Milk diets influence doxorubicin-induced intestinal toxicity in piglets.

PubMed

Shen, Rene L; Pontoppidan, Peter E L; Rathe, Mathias; Jiang, Pingping; Hansen, Carl Frederik; Buddington, Randal K; Heegaard, Peter M H; Müller, Klaus; Sangild, Per T

2016-08-01

Chemotherapy-induced gastrointestinal (GI) toxicity is a common adverse effect of cancer treatment. We used preweaned piglets as models to test our hypothesis that the immunomodulatory and GI trophic effects of bovine colostrum would reduce the severity of GI complications associated with doxorubicin (DOX) treatment. Five-day-old pigs were administered DOX (1 × 100 mg/m(2)) or an equivalent volume of saline (SAL) and either fed formula (DOX-Form, n = 9, or SAL-Form, n = 7) or bovine colostrum (DOX-Colos, n = 9, or SAL-Colos, n = 7). Pigs were euthanized 5 days after initiation of chemotherapy to assess markers of small intestinal function and inflammation. All DOX-treated animals developed diarrhea, growth deficits, and leukopenia. However, the intestines of DOX-Colos pigs had lower intestinal permeability, longer intestinal villi with higher activities of brush border enzymes, and lower tissue IL-8 levels compared with DOX-Form (all P < 0.05). DOX-Form pigs, but not DOX-Colos pigs, had significantly higher plasma C-reactive protein, compared with SAL-Form. Plasma citrulline was not affected by DOX treatment or diet. Thus a single dose of DOX induces intestinal toxicity in preweaned pigs and may lead to a systemic inflammatory response. The toxicity is affected by type of enteral nutrition with more pronounced GI toxicity when formula is fed compared with bovine colostrum. The results indicate that bovine colostrum may be a beneficial supplementary diet for children subjected to chemotherapy and subsequent intestinal toxicity. Copyright © 2016 the American Physiological Society.

Comparative effects of fumonisins on sphingolipid metabolism and toxicity in ducks and turkeys.

PubMed

Benlasher, Emad; Geng, Xiuyu; Nguyen, Ngoc Thanh Xuan; Tardieu, Didier; Bailly, Jean-Denis; Auvergne, Alain; Guerre, Philippe

2012-03-01

Fumonisins (FBs) are mycotoxins that are found worldwide in maize and maize products. Their main toxic effects have been well characterized in poultry, but differences between species have been demonstrated. Ducks appeared very sensitive to toxicity, whereas turkeys are more resistant. At the same time, alterations of sphingolipid metabolism, with an increase of the concentration of the free sphinganine (Sa) in serum and liver, have been demonstrated in the two species, but the link between the toxicity of FBs and Sa accumulation remains difficult to interpret. The aim of the present work was to compare the effects of FBs (10 mg FB1 + FB2/kg body weight) on sphingolipid metabolism in ducks and turkeys. Growth, feed consumption, and serum biochemistry were also investigated to evaluate toxicity. The main results showed that FBs increased Sa concentrations in liver and serum in ducks and turkeys, but these accumulations were not directly correlated with toxicity. Sa accumulation was higher in the livers of turkeys than in ducks, whereas Sa levels were higher in the sera of ducks than in turkeys. Hepatic toxicity was more pronounced in ducks than in turkeys and accompanied a decrease of body weight and an increase of serum biochemistry in ducks but not in turkeys. So, although FBs increase Sa concentration in the livers of both species, this effect is not directly proportional to toxicity. The mechanisms of FB toxicity and/or the mechanisms of protection of ducks and turkeys to the Sa accumulation within the liver remain to be established.

cDNA-AFLP analysis reveals the adaptive responses of citrus to long-term boron-toxicity.

PubMed

Guo, Peng; Qi, Yi-Ping; Yang, Lin-Tong; Ye, Xin; Jiang, Huan-Xin; Huang, Jing-Hao; Chen, Li-Song

2014-10-28

Boron (B)-toxicity is an important disorder in agricultural regions across the world. Seedlings of 'Sour pummelo' (Citrus grandis) and 'Xuegan' (Citrus sinensis) were fertigated every other day until drip with 10 μM (control) or 400 μM (B-toxic) H3BO3 in a complete nutrient solution for 15 weeks. The aims of this study were to elucidate the adaptive mechanisms of citrus plants to B-toxicity and to identify B-tolerant genes. B-toxicity-induced changes in seedlings growth, leaf CO2 assimilation, pigments, total soluble protein, malondialdehyde (MDA) and phosphorus were less pronounced in C. sinensis than in C. grandis. B concentration was higher in B-toxic C. sinensis leaves than in B-toxic C. grandis ones. Here we successfully used cDNA-AFLP to isolate 67 up-regulated and 65 down-regulated transcript-derived fragments (TDFs) from B-toxic C. grandis leaves, whilst only 31 up-regulated and 37 down-regulated TDFs from B-toxic C. sinensis ones, demonstrating that gene expression is less affected in B-toxic C. sinensis leaves than in B-toxic C. grandis ones. These differentially expressed TDFs were related to signal transduction, carbohydrate and energy metabolism, nucleic acid metabolism, protein and amino acid metabolism, lipid metabolism, cell wall and cytoskeleton modification, stress responses and cell transport. The higher B-tolerance of C. sinensis might be related to the findings that B-toxic C. sinensis leaves had higher expression levels of genes involved in photosynthesis, which might contribute to the higher photosyntheis and light utilization and less excess light energy, and in reactive oxygen species (ROS) scavenging compared to B-toxic C. grandis leaves, thus preventing them from photo-oxidative damage. In addition, B-toxicity-induced alteration in the expression levels of genes encoding inorganic pyrophosphatase 1, AT4G01850 and methionine synthase differed between the two species, which might play a role in the B-tolerance of C. sinensis. C. sinensis leaves could tolerate higher level of B than C. grandis ones, thus improving the B-tolerance of C. sinensis plants. Our findings reveal some novel mechanisms on the tolerance of plants to B-toxicity at the gene expression level.

Gender and age differences in mixed metal exposure and urinary excretion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Berglund, Marika, E-mail: Marika.Berglund@ki.se; Lindberg, Anna-Lena; Rahman, Mahfuzar

Background: Little is known about the variation in exposure to toxic metals by age and gender and other potential modifying factors. We evaluated age and gender differences by measurements of metal/element concentrations in urine in a rural population in Matlab, Bangladesh, in three age groups: 8-12 (N=238), 14-15 (N=107) and 30-88 (N=710) years of age, living in an area with no point sources of metal exposure but where elevated water arsenic concentrations are prevalent. Results: We found marked differences in urine concentrations of metals and trace elements by gender, age, tobacco use, socioeconomic and nutritional status. Besides a clearly elevatedmore » urinary arsenic concentration in all age groups (medians 63-85 {mu}g As/L), and despite the low degree of contamination from industries and traffic, the urine concentrations of toxic metals such as cadmium and lead were clearly elevated, especially in children (median 0.31 {mu}g Cd/L and 2.9 {mu}g Pb/L, respectively). In general, women had higher urinary concentrations of toxic metals, especially Cd (median 0.81 {mu}g/L) compared to men (0.66 {mu}g/L) and U (median 10 ng/L in women, compared to 6.4 ng/L in men), while men had higher urinary concentrations of the basic and essential elements Ca (69 mg/L in men, 30-50 years, compared to 52 mg/L in women), Mg (58 mg/L in men compared to 50 mg/L in women), Zn (182 {mu}g/L in men compared to 117 {mu}g/L in women) and Se (9.9 {mu}g/L in men compared to 8.7 {mu}g/L in women). Manganese was consistently higher in females than in males in all age groups, suggesting a biological difference between females and males in Mn metabolism. Increasing socioeconomic status decreased the toxic metal exposure significantly in children and especially in men. Poor iron status was detected in 17% of children, adolescents and women, but only in 6% of men. Also zinc deficiency was more prevalent in females than in males. Conclusions: Women and children seemed to be more at risk for toxic metal exposure than men and at the same time more vulnerable to micronutrient deficiency. Higher concentrations of the toxic metals in urine in women are likely to reflect an increased gastrointestinal absorption of these metals at micronutrient deficiency, such as low body iron stores and Zn deficiency. Higher urinary concentrations of the essential elements in men likely reflect a better nutritional status. There is a need for information on exposure, lifestyle and socioeconomic factors, stratified by gender and age, for the purpose of conducting balanced risk assessment and management that considers such differences.« less

Leachates from solid wastes: chemical and eco(geno)toxicological differences between leachates obtained from fresh and stabilized industrial organic sludge.

PubMed

Chiochetta, Claudete G; Goetten, Luís C; Almeida, Sônia M; Quaranta, Gaetana; Cotelle, Sylvie; Radetski, Claudemir M

2014-01-01

The chemical and ecotoxicological characteristics of fresh and stabilized industrial organic sludge leachates were compared to obtain information regarding how the stabilization process can influence the ecotoxic potential of this industrial waste, which could be used for the amendment of degraded soil. Physicochemical analysis of the sludge leachates, as well as a battery of eco(geno)toxicity tests on bacteria, algae, daphnids, and higher plants (including Vicia faba genotoxicity test) and the determination of hydrolytic enzyme activity, was performed according to standard methods. The chemical comparison of the two types of leachate showed that the samples obtained from stabilized sludge had a lower organic content and higher metal content than leachates of the fresh sludge. The eco(geno)toxicological results obtained with aquatic organisms showed that the stabilized sludge leachate was more toxic than the fresh sludge leachate, both originating from the same industrial organic sludge sample. Nevertheless, phytotoxicity tests carried out with a reference peat soil irrigated with stabilized sludge leachate showed the same toxicity as the fresh sludge leachate. In the case of the industrial solid organic sludge studied, stabilization through a biodegradation process promoted a higher metal mobility/bioavailability/eco(geno)toxicity in the stabilized sludge leachate compared to the fresh sludge leachate.

Drug Release Kinetics, Cell Uptake, and Tumor Toxicity of Hybrid VVVVVVKK Peptide-Assembled Polylactide Nanoparticles

PubMed Central

Jabbari, Esmaiel; Yang, Xiaoming; Moeinzadeh, Seyedsina; He, Xuezhong

2013-01-01

An exciting approach to tumor delivery is encapsulation of the drug in self-assembled polymer-peptide nanoparticles. The objective of this work was to synthesize a conjugate of low molecular weight polylactide (LMW PLA) and V6K2 peptide, and investigate self-assembly, drug release kinetics, cell uptake and toxicity, drug pharmacokinetics, and tumor cell invasion with Doxorubicin (DOX) or paclitaxel (PTX). The results for PLA-V6K2 self-assembled NPs were compared with those of polyethylene glycol stabilized PLA (PLA-EG) NPs. The size of PLA-V6K2 and PLA-EG NPs were 100±20 and 130±50 nm, respectively, with polydispersity index of 1.04 and 1.14. The encapsulation efficiency of DOX in PLA-V6K2 and PLA-EG NPs was 44±9% and 55±5%, respectively, and that of PTX was >90 for both NP types. The release of DOX and PTX from PLA-V6K2 was slower than that of PLA-EG and the release rate was relatively constant with time. Based on molecular dynamic simulation, the less hydrophobic DOX was distributed in the lactide core as well as the peptide shell while the hydrophobic PTX was localized mainly to the lactide core. PLA-V6K2 NPs had significantly higher cell uptake by 4T1 mouse breast carcinoma cells compared to PLA-EG NPs, which was attributed to the electrostatic interactions between the peptide and negatively charged moieties on the cell membrane. PLA-V6K2 NPs showed no toxicity to marrow stromal cells. DOX loaded PLA-V6K2 NPs showed higher toxicity to 4T1 cells and the DNA damage response and apoptosis was delayed compared to the free DOX. DOX or PTX encapsulated in PLA-V6K2 NPs significantly reduced invasion of 4T1 cells compared to those cells treated with the drug in PLA-EG NPs. Invasion of 4T1 cells treated with DOX in PLA-V6K2 and PLA-EG NPs was 5±1% and 30±5%, respectively, and that of PTX was 11±2% and 40±7%. The AUC of DOX in PLA-V6K2 NPs was 67% and 21% higher than those of free DOX and PLA-EG NPs, respectively. DOX loaded PLA-V6K2 NPs injected in C3HeB/FeJ mice inoculated with MTCL syngeneic breast cancer cells displayed higher tumor toxicity than PLA-EG NPs and lower host toxicity than the free DOX. Cationic PLA-V6K2 NPs with higher tumor toxicity than the PLA-EG NPs are potentially useful in chemotherapy. PMID:23275111

Sexual Maturity and Life Stage Influences Toxic Metal Accumulation in Croatian Brown Bears.

PubMed

Lazarus, Maja; Sekovanić, Ankica; Orct, Tatjana; Reljić, Slaven; Jurasović, Jasna; Huber, Đuro

2018-02-01

The influence of reproductive and (early) life stages on toxic metal levels was investigated in the brown bear (Ursus arctos), the largest mammalian predator species in Croatia. The purpose was to examine critical clusters in a population that might be at a higher risk of adverse health effects caused by metals as environmental contaminants. Levels of cadmium, mercury and lead in muscle, liver and kidney cortex of 325 male and 139 female bears, quantified by inductively coupled plasma mass spectrometry, were analysed according to distinct bear life stages (young: cub, yearling, subadult; mature: adult). Metal levels did not differ among sexes in young animals (< 4 years), except for mercury in muscles (higher in females), and adult females had higher cadmium and mercury. A trend of renal cadmium accumulation with age in immature male animals disappeared once they reached maturity, whereas for females this trend has only slowly declined in mature compared to immature bears. In early life stage (< 1 year), bear cubs had lower cadmium, comparable mercury, and higher lead in the kidneys than the bears of the following age category (yearlings). Due to a higher proportion of renal lead transfer from the mother to the cub compared with cadmium, it may be that the high burden of cadmium found in kidneys of older females has lower toxicological concern for their cubs than the lead content. Sex, reproductive, and life stages of bears were confirmed as important in assessing toxic metal burden.

Comparative toxicity of two glyphosate-based formulations to Eisenia andrei under laboratory conditions.

PubMed

Piola, Lucas; Fuchs, Julio; Oneto, María Luisa; Basack, Silvana; Kesten, Eva; Casabé, Norma

2013-04-01

Glyphosate-based products are the leading post-emergent agricultural herbicides in the world, particularly in association with glyphosate tolerant crops. However, studies on the effects of glyphosate-based formulations on terrestrial receptors are scarce. This study was conducted to evaluate the comparative toxicity of two glyphosate-based products: Roundup FG (monoammonium salt, 72% acid equivalent, glyphosate-A) and Mon 8750 (monoammonium salt, 85.4% acid equivalent, glyphosate-B), towards the earthworm Eisenia andrei. Median lethal concentration (LC50) showed that glyphosate-A was 4.5-fold more toxic than glyphosate-B. Sublethal concentrations caused a concentration-dependent weight loss, consistent with the reported effect of glyphosate as uncoupler of oxidative phosphorylation. Glyphosate-A showed deleterious effects on DNA and lysosomal damage at concentrations close to the applied environmental concentrations (14.4 μg ae cm(-2)). With glyphosate-B toxic effects were observed at higher doses, close to its LC50, suggesting that the higher toxicity of formulate A could be attributed to the effects of some of the so-called "inert ingredients", either due to a direct intrinsic toxicity, or to an enhancement in the bioavailability and/or bioaccumulation of the active ingredient. Our results highlight the importance of ecotoxicological assessment not only of the active ingredients, but also of the different formulations usually employed in agricultural practices. Copyright © 2012 Elsevier Ltd. All rights reserved.

The taste of toxicity: A quantitative analysis of bitter and toxic molecules.

PubMed

Nissim, Ido; Dagan-Wiener, Ayana; Niv, Masha Y

2017-12-01

The role of bitter taste-one of the few basic taste modalities-is commonly assumed to signal toxicity and alert animals against consuming harmful compounds. However, it is known that some toxic compounds are not bitter and that many bitter compounds have negligible toxicity while having important health benefits. Here we apply a quantitative analysis of the chemical space to shed light on the bitterness-toxicity relationship. Using the BitterDB dataset of bitter molecules, The BitterPredict prediction tool, and datasets of toxic compounds, we quantify the identity and similarity between bitter and toxic compounds. About 60% of the bitter compounds have documented toxicity and only 56% of the toxic compounds are known or predicted to be bitter. The LD 50 value distributions suggest that most of the bitter compounds are not very toxic, but there is a somewhat higher chance of toxicity for known bitter compounds compared to known nonbitter ones. Flavonoids and alpha acids are more common in the bitter dataset compared with the toxic dataset. In contrast, alkaloids are more common in the toxic datasets compared to the bitter dataset. Interestingly, no trend linking LD 50 values with the number of activated bitter taste receptors (TAS2Rs) subtypes is apparent in the currently available data. This is in accord with the newly discovered expression of TAS2Rs in several extra-oral tissues, in which they might be activated by yet unknown endogenous ligands and play non-gustatory physiological roles. These results suggest that bitter taste is not a very reliable marker for toxicity, and is likely to have other physiological roles. © 2017 IUBMB Life, 69(12):938-946, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

Toxicity evaluation of cordycepin and its delivery system for sustained in vitro anti-lung cancer activity

NASA Astrophysics Data System (ADS)

Aramwit, Pornanong; Porasuphatana, Supatra; Srichana, Teerapol; Nakpheng, Titpawan

2015-03-01

In the previous study, we have found that the cordycepin which was extracted from Cordyceps mycelia produced by growing Cordyceps militaris on the dead larva of Bombyx mori silkworms showed the anti-proliferative effect toward lung cancer cells without toxicity to non-cancer cells. In this work, the cordycepin was tested for its in vitro mutagenicity and in vivo toxicity. From the Ames test and subacute toxicity test using oral administration in a rat model, the cordycepin was proved to be a non-mutagenic and non-toxic compound. The hematology and blood chemistry as well as the microanatomical characteristic of the tissues of rats fed with cordycepin every day for consecutive 30 days were comparable to those of the normal ones. Then, the cordycepin was incorporated in gelatin type A (GA) and gelatin type B (GB) nanoparticles aimed to sustain its release and activity. The cordycepin incorporated in both GA and GB nanoparticles showed the sustained release profiles. GA nanoparticles could encapsulate cordycepin at higher encapsulation efficiency due to the attractive electrostatic interaction between the positive-charged GA and the negative-charged cordycepin. However, GA nanoparticles released cordycepin at the higher amount possibly because of the large surface area of small size nanoparticles. Comparing to GB nanoparticles, the higher amount of cordycepin released from GA nanoparticles showed the higher anti-proliferative and anti-migratory effects on A549 lung cancer cells. In conclusion, GA nanoparticles were suggested as a suitable carrier for the sustained release of cordycepin. The GA nanoparticles releasing cordycepin could be an effective and non-invasive material for the treatment of lung cancer cells.

DOE Office of Scientific and Technical Information (OSTI.GOV)

van Gestel, C.A.; Ma, W.C.

The acute toxicity of five chlorophenols for two earthworm species was determined in two sandy soils differing in organic matter content and the results were compared with adsorption data. Adsorption increased with increasing organic matter content of the soils, but for tetra- and pentachlorophenol was also influenced by soil pH. Earthworm toxicity was significantly higher in the soil with a low level of organic matter. This difference disappeared when LC50 values were recalculated to concentrations in soil solution using adsorption data. Eisenia fetida andrei showed LC50 values lower than those of Lumbricus rubellus although bioaccumulation was generally higher in themore » latter species. Toxicity and bioaccumulation based on soil solution concentrations increased with increasing lipophilicity of the chlorophenols. The present results indicate that the toxicity and bioaccumulation and therefore the bioavailability of chlorophenols in soil to earthworms are dependent on the concentration in soil solution and can be predicted on the basis of adsorption data. Both the toxicity of and bioaccumulation data on chlorophenols in earthworms demonstrated surprisingly good agreement with those on chlorophenols in fish.« less

Pre-ingestive selection capacity and endoscopic analysis in the sympatric bivalves Mulinia edulis and Mytilus chilensis exposed to diets containing toxic and non-toxic dinoflagellates

PubMed Central

Widdows, John; Chaparro, Oscar R.; Ortíz, Alejandro; Mellado, Carla; Villanueva, Paola A.

2018-01-01

This study investigates the effects of toxic and non-toxic dinoflatellates on two sympatric bivalves, the clam Mulinia edulis and the mussel Mytilus chilensis. Groups of bivalves were fed one of three diets: (i) the toxic paralytic shellfish producing (PSP) Alexandrium catenella + Isochrysis galbana; (ii) the non-toxic Alexandrium affine + Isochrysis galbana and (iii) the control diet of Isochrysis galbana. Several physiological traits were measured, such as, clearance rate, pre-ingestive selection efficiency and particle transport velocity in the gill. The clearance rates of both M. chilensis and M. edulis showed a significant reduction when fed a mixed toxic diet of 50% Alexandrium catenella: 50% Isochrysis galbana. Similarly, when both species of bivalves were fed with the non-toxic diet (50% A. affine: 50% I. galbana), clearance rate was significantly lower compared with a diet of 100% I. galbana. Under all the experimental diets, M. chilensis showed higher clearance rate values, slightly more than double that of M. edulis. M. edulis and M. chilensis have the ability to select particles at the pre-ingestive level, thus eliminating a larger proportion of the toxic dinoflagellate A. catenella as well as the non-toxic A. affine in the form of pseudofaeces. Higher values of selection efficiency were registered in M. edulis than in M. chilensis when exposed to the toxic diet. Similar results were observed when these two species were exposed to the diet containing the non-toxic dinoflagellate, explained by the fact that the infaunal Mulinia edulis is adapted to dealing with larger particle sizes and higher particle densities (Navarro et al., 1993). The lower transport particle velocity observed in the present work for both species, is related to the reduced clearance rate, the higher particle concentration, and the presence of larger, toxic dinoflagellates. In addition, the species differ in their feeding responses to diets, with and without A. catenella or A. affine, largely reflecting their adaptations to different environmental conditions. The results suggest that the presence of a dinoflagellate bloom, whether toxic or non-toxic spp in Yaldad Bay, is likely to have a greater impact on the Mytilus chilensis than the infaunal Mulinia edulis, based on the combined effects on clearance rate, selection efficiency and particle transport velocity. PMID:29474467

Pre-ingestive selection capacity and endoscopic analysis in the sympatric bivalves Mulinia edulis and Mytilus chilensis exposed to diets containing toxic and non-toxic dinoflagellates.

PubMed

Navarro, Jorge M; Widdows, John; Chaparro, Oscar R; Ortíz, Alejandro; Mellado, Carla; Villanueva, Paola A

2018-01-01

This study investigates the effects of toxic and non-toxic dinoflatellates on two sympatric bivalves, the clam Mulinia edulis and the mussel Mytilus chilensis. Groups of bivalves were fed one of three diets: (i) the toxic paralytic shellfish producing (PSP) Alexandrium catenella + Isochrysis galbana; (ii) the non-toxic Alexandrium affine + Isochrysis galbana and (iii) the control diet of Isochrysis galbana. Several physiological traits were measured, such as, clearance rate, pre-ingestive selection efficiency and particle transport velocity in the gill. The clearance rates of both M. chilensis and M. edulis showed a significant reduction when fed a mixed toxic diet of 50% Alexandrium catenella: 50% Isochrysis galbana. Similarly, when both species of bivalves were fed with the non-toxic diet (50% A. affine: 50% I. galbana), clearance rate was significantly lower compared with a diet of 100% I. galbana. Under all the experimental diets, M. chilensis showed higher clearance rate values, slightly more than double that of M. edulis. M. edulis and M. chilensis have the ability to select particles at the pre-ingestive level, thus eliminating a larger proportion of the toxic dinoflagellate A. catenella as well as the non-toxic A. affine in the form of pseudofaeces. Higher values of selection efficiency were registered in M. edulis than in M. chilensis when exposed to the toxic diet. Similar results were observed when these two species were exposed to the diet containing the non-toxic dinoflagellate, explained by the fact that the infaunal Mulinia edulis is adapted to dealing with larger particle sizes and higher particle densities (Navarro et al., 1993). The lower transport particle velocity observed in the present work for both species, is related to the reduced clearance rate, the higher particle concentration, and the presence of larger, toxic dinoflagellates. In addition, the species differ in their feeding responses to diets, with and without A. catenella or A. affine, largely reflecting their adaptations to different environmental conditions. The results suggest that the presence of a dinoflagellate bloom, whether toxic or non-toxic spp in Yaldad Bay, is likely to have a greater impact on the Mytilus chilensis than the infaunal Mulinia edulis, based on the combined effects on clearance rate, selection efficiency and particle transport velocity.

Bioenergetic strategy of microalgae for the biodegradation of tyrosol and hydroxytyrosol.

PubMed

Papazi, Aikaterini; Ioannou, Andreas; Symeonidi, Myrto; Doulis, Andreas G; Kotzabasis, Kiriakos

2017-05-01

Olive mill wastewater has significant polluting properties due to its high phenolic content [mainly tyrosol (trs) and hydroxytyrosol (htrs)]. Growth kinetics and a series of fluorescence induction measurements for Scenedesmus obliquus cultures showed that microalgae can be tolerant of these phenolic compounds. Changes in the cellular energy reserves and concentration of the phenolic compounds adjust the "toxicity" of these compounds to the microalgae and are, therefore, the main parameters that affect biodegradation. Autotrophic growth conditions of microalgae and high concentrations of trs or htrs induce higher biodegradation compared with mixotrophic conditions and lower phenolic concentrations. When microalgae face trs and htrs simultaneously, biodegradation begins from htrs, the more energetically demanding compound. All these lead to the conviction that microalgae have a "rational" management of cellular energy balance. Low toxicity levels lead to higher growth and lower biodegradation, whereas higher toxicity levels lead to lower growth and higher biodegradation. The selection of appropriate conditions (compatible to the bioenergetic strategies of microalgae) seems to be the key for a successful biodegradation of a series of toxic compounds, thus paving the way for future biotechnological applications for solving complicated pollution problems, like the detoxification of olive mill wastewater.

Safety of nevirapine in HIV-infected pregnant women initiating antiretroviral therapy at higher CD4 counts: a systematic review and meta-analysis.

PubMed

Bera, Ebrahim; Mia, Rafiq

2012-10-08

The package insert for nevirapine (NVP) cautions use in HIV-infected women (including pregnant women) with CD4 counts ≥250 cells/µl. However, recent studies showed that the CD4 count of pregnant women receiving antiretroviral therapy (ART) was not predictive of NVP toxicity. To determine whether ART-naive pregnant women initiating NVP-based ART at higher CD4 counts experience greater toxicity compared with pregnant women at lower CD4 counts. We reviewed studies comparing serious adverse NVP-related events among ART-naive pregnant women who commenced therapy at higher v. lower CD4 counts. Relevant studies were extracted from PubMed, SCOPUS and EMBASE, major journals and conference proceedings prior to December 2011. Authors were contacted for additional data. Data were independently extracted and entered into Review Manager. Fourteen studies (2 663 participants) were included for analysis. The odds ratio (OR) for overall NVP toxicity among pregnant women with CD4 <250 cells/µl was 0.61 (95% confidence interval (CI) 0.43 - 0.85). When analysis was restricted to prospective studies only (7 studies, 1 318 participants), the results were consistent for overall NVP toxicity (OR 0.43; 95% CI 0.25 - 0.73) and severe hepatotoxicity (OR 0.45; 95% CI 0.22 - 0.90), but not for severe cutaneous reaction (OR 0.53; 95% CI 0.26 - 1.10). Initiating NVP-based ART during pregnancy at CD4 ≥250 cells/µl increases toxicity risk and should be avoided, necessitating urgent revision of current guidelines supporting this practice.

Antiretroviral Therapy-Induced Mitochondrial Toxicity: Potential Mechanisms Beyond Polymerase-γ Inhibition

PubMed Central

Selvaraj, Shanmugapriya; Ghebremichael, Musie; Li, Min; Foli, Yram; Langs-Barlow, Allison; Ogbuagu, Arit; Barakat, Lydia; Tubridy, Elizabeth; Edifor, Regina; Lam, Wing; Cheng, Yung-Chi; Paintsil, Elijah

2014-01-01

We hypothesized that competition between NRTI-triphosphate and endogenous deoxyribonucleoside triphosphate (dNTP) may lead to depletion of dNTP pools and mitochondrial dysfunction independent of Pol-γ inhibition. We collected peripheral blood mononuclear cells from 75 adults (25 cases: HIV-infected with mitochondrial toxicity, 25 HIV-infected positive controls, and 25 HIV-negative controls). We observed statistically significant individual and group differences in ribonucleotide (RN) and deoxyribonucleotide (dRN) pools. The median RN pool was 10062 (IQR, 7090 – 12590), 4360 (IQR, 3058 –6838), and 2968 (IQR, 2538 – 4436) pmol/106 cells for negative controls, positive controls, and cases, respectively. Cases had significantly higher absolute mtDNA copy number compared to negative controls (p<0.05). Cases had significantly higher expression of Pol-γ, nucleoside transporters, cellular kinases, and ABC compared to controls. Antiretroviral therapy perturbs ribonucleotide and deoxyribonucleotide pools. Depletion of RN and dRN pools may be associated with ART-induced mitochondrial toxicity independent of Pol-γ inhibition. PMID:24637942

Characterization of a highly toxic strain of Bacillus thuringiensis serovar kurstaki very similar to the HD-73 strain.

PubMed

Reinoso-Pozo, Yaritza; Del Rincón-Castro, Ma Cristina; Ibarra, Jorge E

2016-09-01

The LBIT-1200 strain of Bacillus thuringiensis was recently isolated from soil, and showed a 6.4 and 9.5 increase in toxicity, against Manduca sexta and Trichoplusia ni, respectively, compared to HD-73. However, LBIT-1200 was still highly similar to HD-73, including the production of bipyramidal crystals containing only one protein of ∼130 000 kDa, its flagellin gene sequence related to the kurstaki serotype, plasmid and RepPCR patterns similar to HD-73, no production of β-exotoxin and no presence of VIP genes. Sequencing of its cry gene showed the presence of a cry1Ac-type gene with four amino acid differences, including two amino acid replacements in domain III, compared to Cry1Ac1, which may explain its higher toxicity. In conclusion, the LBIT-1200 strain is a variant of the HD-73 strain but shows a much higher toxicity, which makes this new strain an important candidate to be developed as a bioinsecticide, once it passes other tests, throughout its biotechnological development. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Influence of Fractionation Scheme and Tumor Location on Toxicities After Stereotactic Body Radiation Therapy for Large (≥5 cm) Non-Small Cell Lung Cancer: A Multi-institutional Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Verma, Vivek; Shostrom, Valerie K.; Zhen, Weining

Purpose: To describe the impact of fractionation scheme and tumor location on toxicities in stereotactic body radiation therapy (SBRT) for ≥5-cm non-small cell lung cancer (NSCLC), as part of a multi-institutional analysis. Methods: Patients with primary ≥5-cm N0 M0 NSCLC who underwent ≤5-fraction SBRT were examined across multiple high-volume SBRT centers. Collected data included clinical/treatment parameters; toxicities were prospectively assessed at each institution according to the Common Terminology Criteria for Adverse Events. Patients treated daily were compared with those treated every other day (QOD)/other nondaily regimens. Stratification between central and peripheral tumors was also performed. Results: Ninety-two patients from 12 institutionsmore » were evaluated (2004-2016), with median follow-up of 12 months. In total there were 23 (25%) and 6 (7%) grade ≥2 and grade ≥3 toxicities, respectively. Grades 2 and 3 pulmonary toxicities occurred in 9% and 4%, respectively; 1 patient treated daily experienced grade 5 radiation pneumonitis. Of the entire cohort, 46 patients underwent daily SBRT, and 46 received QOD (n=40)/other nondaily (n=6) regimens. Clinical/treatment parameters were similar between groups; the QOD/other group was more likely to receive 3-/4-fraction schemas. Patients treated QOD/other experienced significantly fewer grade ≥2 toxicities as compared with daily treatment (7% vs 43%, P<.001). Patients treated daily also had higher rates of grade ≥2 pulmonary toxicities (P=.014). Patients with peripheral tumors (n=66) were more likely to receive 3-/4-fraction regimens than those with central tumors (n=26). No significant differences in grade ≥2 toxicities were identified according to tumor location (P>.05). Conclusions: From this multi-institutional study, toxicity of SBRT for ≥5-cm lesions is acceptable, and daily treatment was associated with a higher rate of toxicities.« less

Influence of Fractionation Scheme and Tumor Location on Toxicities After Stereotactic Body Radiation Therapy for Large (≥5 cm) Non-Small Cell Lung Cancer: A Multi-institutional Analysis.

PubMed

Verma, Vivek; Shostrom, Valerie K; Zhen, Weining; Zhang, Mutian; Braunstein, Steve E; Holland, John; Hallemeier, Christopher L; Harkenrider, Matthew M; Iskhanian, Adrian; Jabbour, Salma K; Attia, Albert; Lee, Percy; Wang, Kyle; Decker, Roy H; McGarry, Ronald C; Simone, Charles B

2017-03-15

To describe the impact of fractionation scheme and tumor location on toxicities in stereotactic body radiation therapy (SBRT) for ≥5-cm non-small cell lung cancer (NSCLC), as part of a multi-institutional analysis. Patients with primary ≥5-cm N0 M0 NSCLC who underwent ≤5-fraction SBRT were examined across multiple high-volume SBRT centers. Collected data included clinical/treatment parameters; toxicities were prospectively assessed at each institution according to the Common Terminology Criteria for Adverse Events. Patients treated daily were compared with those treated every other day (QOD)/other nondaily regimens. Stratification between central and peripheral tumors was also performed. Ninety-two patients from 12 institutions were evaluated (2004-2016), with median follow-up of 12 months. In total there were 23 (25%) and 6 (7%) grade ≥2 and grade ≥3 toxicities, respectively. Grades 2 and 3 pulmonary toxicities occurred in 9% and 4%, respectively; 1 patient treated daily experienced grade 5 radiation pneumonitis. Of the entire cohort, 46 patients underwent daily SBRT, and 46 received QOD (n=40)/other nondaily (n=6) regimens. Clinical/treatment parameters were similar between groups; the QOD/other group was more likely to receive 3-/4-fraction schemas. Patients treated QOD/other experienced significantly fewer grade ≥2 toxicities as compared with daily treatment (7% vs 43%, P<.001). Patients treated daily also had higher rates of grade ≥2 pulmonary toxicities (P=.014). Patients with peripheral tumors (n=66) were more likely to receive 3-/4-fraction regimens than those with central tumors (n=26). No significant differences in grade ≥2 toxicities were identified according to tumor location (P>.05). From this multi-institutional study, toxicity of SBRT for ≥5-cm lesions is acceptable, and daily treatment was associated with a higher rate of toxicities. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparative performances of eggs and embryos of sea urchin (Paracentrotus lividus) in toxicity bioassays used for assessment of marine sediment quality.

PubMed

Khosrovyan, A; Rodríguez-Romero, A; Salamanca, M J; Del Valls, T A; Riba, I; Serrano, F

2013-05-15

The potential toxicity of sediments from various ports was assessed by means of two different liquid-phase toxicity bioassays (acute and chronic) with embryos and eggs of sea urchin Paracentrotus lividus. Performances of embryos and eggs of P. lividus in these bioassays were compared for their interchangeable applicability in integrated sediment quality assessment. The obtained endpoints (percentages of normally developed plutei and fertilized eggs) were linked to physical and chemical properties of sediments and demonstrated dependence on sediment contamination. The endpoints in the two bioassays were strongly correlated and generally exhibited similar tendency throughout the samples. Therein, embryos demonstrated higher sensitivity to elutriate exposure, compared to eggs. It was concluded that these tests could be used interchangeably for testing toxicity of marine sediments. Preferential use of any of the bioassays can be determined by the discriminatory capacity of the test or vulnerability consideration of the test subject to the surrounding conditions. Copyright © 2013 Elsevier Ltd. All rights reserved.

Blood Lead Toxicity Analysis of Multipurpose Canines and Military Working Dogs.

PubMed

Reid, Paul; George, Clinton; Byrd, Christopher M; Miller, Laura; Lee, Stephen J; Motsinger-Reif, Alison; Breen, Matthew; Hayduk, Daniel W

Special Operations Forces and their accompanying tactical multipurpose canines (MPCs) who are involved in repeated live-fire exercises and military operations have the potential for increased blood lead levels and toxicity due to aerosolized and environmental lead debris. Clinical lead-toxicity symptoms can mimic other medical disorders, rendering accurate diagnosis more challenging. The objective of this study was to examine baseline lead levels of MPCs exposed to indoor firing ranges compared with those of nontactical military working dogs (MWDs) with limited or no exposure to the same environment. In the second part of the study, results of a commercially available, human-blood lead testing system were compared with those of a benchtop inductively coupled plasma-mass spectrometry (ICP-MS) analysis technique. Blood samples from 18 MPCs were tested during routine clinical blood draws, and six samples from a canine group with limited exposure to environmental lead (nontactical MWDs) were tested for comparison. There was a high correlation between results of the commercial blood-testing system compared with ICP-MS when blood lead levels were higher than 4.0µg/dL. Both testing methods recorded higher blood lead levels in the MPC blood samples than in those of the nontactical MWDs, although none of the MPC samples tested contained lead levels approaching those at which symptoms of lead toxicity have previously been reported in animals (i.e., 35µg/dL). 2018.

Assessment of the Toxicity of CuO Nanoparticles by Using Saccharomyces cerevisiae Mutants with Multiple Genes Deleted

PubMed Central

Bao, Shaopan; Lu, Qicong; Dai, Heping; Zhang, Chao

2015-01-01

To develop applicable and susceptible models to evaluate the toxicity of nanoparticles, the antimicrobial effects of CuO nanoparticles (CuO-NPs) on various Saccharomyces cerevisiae (S. cerevisiae) strains (wild type, single-gene-deleted mutants, and multiple-gene-deleted mutants) were determined and compared. Further experiments were also conducted to analyze the mechanisms associated with toxicity using copper salt, bulk CuO (bCuO), carbon-shelled copper nanoparticles (C/Cu-NPs), and carbon nanoparticles (C-NPs) for comparisons. The results indicated that the growth inhibition rates of CuO-NPs for the wild-type and the single-gene-deleted strains were comparable, while for the multiple-gene deletion mutant, significantly higher toxicity was observed (P < 0.05). When the toxicity of the CuO-NPs to yeast cells was compared with the toxicities of copper salt and bCuO, we concluded that the toxicity of CuO-NPs should be attributed to soluble copper rather than to the nanoparticles. The striking difference in adverse effects of C-NPs and C/Cu-NPs with equivalent surface areas also proved this. A toxicity assay revealed that the multiple-gene-deleted mutant was significantly more sensitive to CuO-NPs than the wild type. Specifically, compared with the wild-type strain, copper was readily taken up by mutant strains when cell permeability genes were knocked out, and the mutants with deletions of genes regulated under oxidative stress (OS) were likely producing more reactive oxygen species (ROS). Hence, as mechanism-based gene inactivation could increase the susceptibility of yeast, the multiple-gene-deleted mutants should be improved model organisms to investigate the toxicity of nanoparticles. PMID:26386067

Pictorial health warning label content and smokers’ understanding of smoking-related risks—a cross-country comparison

PubMed Central

Swayampakala, Kamala; Thrasher, James F.; Hammond, David; Yong, Hua-Hie; Bansal-Travers, Maansi; Krugman, Dean; Brown, Abraham; Borland, Ron; Hardin, James

2015-01-01

The aim of the present study was to assess smokers’ level of agreement with smoking-related risks and toxic tobacco constituents relative to inclusion of these topics on health warning labels (HWLs). 1000 adult smokers were interviewed between 2012 and 2013 from online consumer panels of adult smokers from each of the three countries: Australia (AU), Canada (CA) and Mexico (MX). Generalized estimating equation models were estimated to compare agreement with smoking-related risks and toxic tobacco constituents. For disease outcomes described on HWLs across all three countries, there were few statistical differences in agreement with health outcomes (e.g. emphysema and heart attack). By contrast, increases in agreement where the HWLs were revised or introduced on HWLs for the first time (e.g. blindness in AU and CA, bladder cancer in CA). Similarly, samples from countries that have specific health content or toxic constituents on HWLs showed higher agreement for that particular disease or toxin than countries without (e.g. higher agreement for gangrene and blindness in AU, higher agreement for bladder cancer and all toxic constituents except nitrosamines and radioactive polonium in CA). Pictorial HWL content is associated with greater awareness of smoking-related risks and toxic tobacco constituents. PMID:24848554

Evaluation of Potential Exposure to Metals in Laundered Shop Towels

PubMed Central

Greenberg, Grace; Beck, Barbara D.

2013-01-01

We reported in 2003 that exposure to metals on laundered shop towels (LSTs) could exceed toxicity criteria. New data from LSTs used by workers in North America document the continued presence of metals in freshly laundered towels. We assessed potential exposure to metals based on concentrations of metals on the LSTs, estimates of LST usage by employees, and the transfer of metals from LST-to-hand, hand-to-mouth, and LST-to-lip, under average- or high-exposure scenarios. Exposure estimates were compared to toxicity criteria. Under an average-exposure scenario (excluding metals' data outliers), exceedances of the California Environmental Protection Agency, U.S. Environmental Protection Agency, and the Agency for Toxic Substances and Disease Registry toxicity criteria may occur for aluminum, cadmium, cobalt, copper, iron, and lead. Calculated intakes for these metals were up to more than 400-fold higher (lead) than their respective toxicity criterion. For the high-exposure scenario, additional exceedances may occur, and high-exposure intakes were up to 1,170-fold higher (lead) than their respective toxicity criterion. A sensitivity analysis indicated that alternate plausible assumptions could increase or decrease the magnitude of exceedances, but were unlikely to eliminate certain exceedances, particularly for lead. PMID:24453472

Abnormal chemical element concentrations in lichens of Isle Royale National Park

USGS Publications Warehouse

Bennett, J.P.

1995-01-01

Lichens have been used for many years to monitor changes in deposited airborne chemical elements in many areas, but few studies have focused on areas suspected of experiencing slightly elevated pollution. Detection of subtle patterns of slightly elevated pollutants calls for developing several lines of evidence as opposed to single line studies used in heavily polluted areas. This study of two lichen species, Hypogymnia physodes and Evernia mesomorpha, in Isle Royale National Park, Michigan compares the concentrations and ranks of elements with the concentrations and ranks of the elements in the earth's crust, changes in element concentrations over a nine year period, and the geography of element concentrations in the park. S, Zn, Pb, Cd and Se were elevated in both species and higher in rank compared to the concentrations and ranks in the earth's crust. Toxic elements increased 123% in Hypogymnia and 62% in Evernia over 9 years, compared to increases of 45% and 59% for non-toxic elements in each species, respectively. Geographically, the lichens at certain localities with higher exposures experienced higher than average element concentrations. Finally, tissue concentrations of Mn, S and Se at some localities were above levels known to be either toxic or similar to those found in polluted areas. These four lines of evidence suggest that Isle Royale National Park is experiencing the onset of chronic air pollution stress from a number of sources.

Bacterial toxicity comparison between nano- and micro-scaled oxide particles.

PubMed

Jiang, Wei; Mashayekhi, Hamid; Xing, Baoshan

2009-05-01

Toxicity of nano-scaled aluminum, silicon, titanium and zinc oxides to bacteria (Bacillus subtilis, Escherichia coli and Pseudomonas fluorescens) was examined and compared to that of their respective bulk (micro-scaled) counterparts. All nanoparticles but titanium oxide showed higher toxicity (at 20 mg/L) than their bulk counterparts. Toxicity of released metal ions was differentiated from that of the oxide particles. ZnO was the most toxic among the three nanoparticles, causing 100% mortality to the three tested bacteria. Al(2)O(3) nanoparticles had a mortality rate of 57% to B. subtilis, 36% to E. coli, and 70% to P. fluorescens. SiO(2) nanoparticles killed 40% of B. subtilis, 58% of E. coli, and 70% of P. fluorescens. TEM images showed attachment of nanoparticles to the bacteria, suggesting that the toxicity was affected by bacterial attachment. Bacterial responses to nanoparticles were different from their bulk counterparts; hence nanoparticle toxicity mechanisms need to be studied thoroughly.

Spin labelled nitrosoureas and triazenes and their non-labelled clinically used analogues--a comparative study on their physicochemical properties and antimelanomic effects.

PubMed

Zheleva, A M; Gadjeva, V G

2001-01-16

Physicochemical properties, such as half life time (tau0.5), alkylating and carbamoylating activity and in vivo antimelanomic effects against B16 melanoma of spin labeled (containing nitroxyl free radical moiety) amino acid nitrosoureas, synthesized in our laboratory, have been studied and compared to those of the antitumor drug N'-cyclohexyl-N-(2-chloroethyl)-N-nitrosourea (lomustine, CCNU). We have shown that the introduction of amino acid moieties and the replacement of cyclohexylamine with nitroxyl moiety leads to a faster decomposition, higher alkylating, lower carbamoylating activity, better antimelanomic activity and lower general toxicity, when compared to those of CCNU. It was also established that spin labeled triazenes, previously synthesized by us, were more stable in phosphate saline than their nonlabeled analogue, 5-(3,3-dimethyltriazene-1-yl)-imidazole-4-carboxamide (dacarbazine, DTIC). A higher cytotoxicity to B16 melanoma cells than to YAC-1 and lymphocytes was demonstrated for all spin labeled triazenes, in comparison with DTIC. An assumption has been made to explain the lower general toxicity of the spin labeled nitrosoureas compared to that of CCNU. Based on the results presented, we accept that a new trend for synthesis of more selective and less toxic nitrosourea and triazene derivatives as potential antimelanomic drugs might be developed.

Comparative study of late rectal toxicity in prostate cancer patients treated with low-dose-rate brachytherapy: With or without supplemental external beam radiotherapy.

PubMed

Serrano, Nicholas; Moghanaki, Drew; Asher, David; Karlin, Jeremy; Schutzer, Matthew; Chang, Michael; Hagan, Michael P

2016-01-01

Supplemental external beam radiation therapy (sEBRT) is often prescribed in men undergoing low-dose-rate (LDR) brachytherapy. A population of patients was analyzed to assess the effect of sEBRT on late rectal toxicity. It was hypothesized that sEBRT + LDR would be associated with a higher risk of late rectal toxicity. This retrospective cohort study examined LDR brachytherapy patients, treated with or without sEBRT, with a minimum of 5-year followup. Longitudinal assessments were evaluated using the computerized patient record system. The Kaplan-Meier method was used for analysis. Median followup was 7.5 years for 245 patients from 2004 to 2007. sEBRT was administered to 33.5%. Followup beyond 5 years was available for 89%. Overall rates of Grade ≥2 and ≥3 rectal toxicities were 6.9% and 2.9%, respectively. The risk of Grade ≥2 rectal toxicity was 2.8-fold higher for patients receiving sEBRT (95% confidence interval: 1.1-7.2; p = 0.02). The risk of Grade ≥3 rectal toxicity was 11.9-fold higher for patients who received sEBRT (1.5-97.4, 95% confidence interval; p = 0.003). Six of seven patients with a Grade ≥3 rectal toxicity received sEBRT, including one who required an abdominoperineal resection. Median post-LDR D90, V150, V200, and R100 values were 103.3%, 59.4%, 30.1%, and 0.5 cc. In a cohort of LDR brachytherapy patients with high rates of followup, sEBRT + LDR was associated with significantly higher risk of Grade ≥2 and ≥3 late rectal toxicity. This analysis supports previous findings and maintains concern about the supplemental use of external beam radiation therapy with LDR brachytherapy while its benefit for tumor control has yet to be prospectively validated. Published by Elsevier Inc.

Heavy metal speciation and toxicity characteristics of tannery sludge

NASA Astrophysics Data System (ADS)

Juel, Md. Ariful Islam; Chowdhury, Zia Uddin Md.; Ahmed, Tanvir

2016-07-01

Heavy metals present in tannery sludge can get mobilized in the environment in various forms and can be a cause for concern for the natural ecosystem and human health. The speciation of metals in sludge provides valuable information regarding their toxicity in the environment and determines their suitability for land application or disposal in landfills. Concentrations of seven heavy metals (Cr, Pb, Cd, Ni, Zn, As and Cu) in tannery sludge were determined to evaluate their toxicity levels. Metal contents ranged over the following intervals: As: 1.52-2.07 mg/kg; Pb: 57.5-67 mg/kg; Cr: 15339-26501 mg/kg; Cu: 261.3-579.5 mg/kg; Zn: 210.2-329.1 mg/kg and Ni: 137.5-141.3 mg/kg (dry weight basis). The concentrations of all heavy metals in the sludge samples were lower compared to EPA guidelines except chromium which was found to be several orders of magnitude higher than the guideline value. Toxicity Characteristics Leaching Procedure (TCLP) test indicated that the leaching potential of chromium was higher compared to the other heavy metals and exceeded the EPA land disposal restriction limits. To quantitatively assess the environmental burden of the chromium associated with tannery sludge, the IMPACT 2002+ methodology was adopted under the SimaPro software environment. Considering the USEPA limit for chromium as the baseline scenario, it was found that chromium in the tannery sludge had 6.41 times higher impact than the baseline in the categories of aquatic ecotoxicity, terrestrial ecotoxicity and non-carcinogens. Chromium has the highest contribution to toxicity in the category of aquatic ecotoxicity while copper is the major contributor to the category of terrestrial ecotoxicity in the tannery sludge.

Toxicity after post-prostatectomy image-guided intensity-modulated radiotherapy using Australian guidelines.

PubMed

Chin, Stephen; Aherne, Noel J; Last, Andrew; Assareh, Hassan; Shakespeare, Thomas P

2017-12-01

We evaluated single institution toxicity outcomes after post-prostatectomy radiotherapy (PPRT) via image-guided intensity-modulated radiation therapy (IG-IMRT) with implanted fiducial markers following national eviQ guidelines, for which late toxicity outcomes have not been published. Prospectively collected toxicity data were retrospectively reviewed for 293 men who underwent 64-66 Gy IG-IMRT to the prostate bed between 2007 and 2015. Median follow-up after PPRT was 39 months. Baseline grade ≥2 genitourinary (GU), gastrointestinal (GI) and sexual toxicities were 20.5%, 2.7% and 43.7%, respectively, reflecting ongoing toxicity after radical prostatectomy. Incidence of new (compared to baseline) acute grade ≥2 GU and GI toxicity was 5.8% and 10.6%, respectively. New late grade ≥2 GU, GI and sexual toxicity occurred in 19.1%, 4.7% and 20.2%, respectively. However, many patients also experienced improvements in toxicities. For this reason, prevalence of grade ≥2 GU, GI and sexual toxicities 4 years after PPRT was similar to or lower than baseline (21.7%, 2.6% and 17.4%, respectively). There were no grade ≥4 toxicities. Post-prostatectomy IG-IMRT using Australian contouring guidelines appears to have tolerable acute and late toxicity. The 4-year prevalence of grade ≥2 GU and GI toxicity was virtually unchanged compared to baseline, and sexual toxicity improved over baseline. This should reassure radiation oncologists following these guidelines. Late toxicity rates of surgery and PPRT are higher than following definitive IG-IMRT, and this should be taken into account if patients are considering surgery and likely to require PPRT. © 2017 The Royal Australian and New Zealand College of Radiologists.

Interactive effects of λ-cyhalothrin, soil moisture, and temperature on Folsomia candida and Sinella curviseta (Collembola).

PubMed

Bandow, Cornelia; Coors, Anja; Karau, Nora; Römbke, Jörg

2014-03-01

The authors investigated whether and how 2 environmental factors could influence the toxicity of a pyrethroid to 2 representatives of an important group of soil organisms. The impacts of different temperatures (20 °C and 26 °C) and soil moisture levels (30%, 50%, and 70% of water holding capacity) were investigated in combination with the insecticide λ-cyhalothrin on the reproduction success of Folsomia candida and Sinella curviseta in a full factorial design. Testing was based on the standard collembolan reproduction test (Organisation for Economic Co-operation and Development, guideline 232) following an effect concentration design. The results showed an effect of environmental and chemical factors on the number of juveniles of these animals. Particularly in dry soil, the reproduction of both species was reduced, while higher soil moisture levels influenced the number of juveniles positively compared with the middle soil moisture level. In general, however, higher soil moisture led to increased sensitivity to λ-cyhalothrin. In both organisms, temperature affected the toxicity of the pesticide but in different directions: high temperature led to higher toxicity in F. candida but to lower toxicity in S. curviseta. © 2013 SETAC.

Comparison of ethylene glycol and propylene glycol for the vitrification of immature porcine oocytes.

PubMed

Somfai, Tamás; Nakai, Michiko; Tanihara, Fuminori; Noguchi, Junko; Kaneko, Hiroyuki; Kashiwazaki, Naomi; Egerszegi, István; Nagai, Takashi; Kikuchi, Kazuhiro

2013-01-01

Our aim was to optimize a cryoprotectant treatment for vitrification of immature porcine cumulus-oocyte complexes (COCs). Immature COCs were vitrified either in 35% ethylene glycol (EG), 35% propylene glycol (PG) or a combination of 17.5% EG and 17.5% PG. After warming, the COCs were in vitro matured (IVM), and surviving oocytes were in vitro fertilized (IVF) and cultured. The mean survival rate of vitrified oocytes in 35% PG (73.9%) was higher (P<0.05) than that in 35% EG (27.8%). Oocyte maturation rates did not differ among vitrified and non-vitrified control groups. Blastocyst formation in the vitrified EG group (10.8%) was higher (P<0.05) than that in the vitrified PG group (2.0%) but was lower than that in the control group (25.0%). Treatment of oocytes with 35% of each cryoprotectant without vitrification revealed a higher toxicity of PG on subsequent blastocyst development compared with EG. The combination of EG and PG resulted in 42.6% survival after vitrification. The maturation and fertilization rates of the surviving oocytes were similar in the vitrified, control and toxicity control (TC; treated with EG+PG combination without cooling) groups. Blastocyst development in the vitrified group was lower (P<0.05) than that in the control and TC groups, which in turn had similar development rates (10.7%, 18.1% and 23.3%, respectively). In conclusion, 35% PG enabled a higher oocyte survival rate after vitrification compared with 35% EG. However, PG was greatly toxic to oocytes. The combination of 17.5% EG and 17.5% PG yielded reasonable survival rates without toxic effects on embryo development.

Cadmium toxicity in Maize (Zea mays L.): consequences on antioxidative systems, reactive oxygen species and cadmium accumulation.

PubMed

Anjum, Shakeel Ahmad; Tanveer, Mohsin; Hussain, Saddam; Bao, Mingchen; Wang, Longchang; Khan, Imran; Ullah, Ehsan; Tung, Shahbaz Atta; Samad, Rana Abdul; Shahzad, Babar

2015-11-01

Increased cadmium (Cd) accumulation in soils has led to tremendous environmental problems, with pronounced effects on agricultural productivity. Present study investigated the effects of Cd stress imposed at various concentrations (0, 75, 150, 225, 300, 375 μM) on antioxidant activities, reactive oxygen species (ROS), Cd accumulation, and productivity of two maize (Zea mays L.) cultivars viz., Run Nong 35 and Wan Dan 13. Considerable variations in Cd accumulation and in behavior of antioxidants and ROS were observed under Cd stress in both maize cultivars, and such variations governed by Cd were concentration dependent. Exposure of plant to Cd stress considerably increased Cd concentration in all plant parts particularly in roots. Wan Dan 13 accumulated relatively higher Cd in root, stem, and leaves than Run Nong 35; however, in seeds, Run Nong 35 recorded higher Cd accumulation. All the Cd toxicity levels starting from 75 μM enhanced H2O2 and MDA concentrations and triggered electrolyte leakage in leaves of both cultivars, and such an increment was more in Run Nong 35. The ROS were scavenged by the enhanced activities of superoxide dismutase, peroxidase, catalase, ascorbate peroxidase, and glutathione peroxidase in response to Cd stress, and these antioxidant activities were higher in Wan Dan 13 compared with Run Nong 35 at all Cd toxicity levels. The grain yield of maize was considerably reduced particularly for Run Nong 35 under different Cd toxicity levels as compared with control. The Wan Dan 13 was better able to alleviate Cd-induced oxidative damage which was attributed to more Cd accumulation in roots and higher antioxidant activities in this cultivar, suggesting that manipulation of these antioxidants and enhancing Cd accumulation in roots may lead to improvement in Cd stress tolerance.

Comparative chronic toxicity of imidacloprid, clothianidin, and thiamethoxam to Chironomus dilutus and estimation of toxic equivalency factors.

PubMed

Cavallaro, Michael C; Morrissey, Christy A; Headley, John V; Peru, Kerry M; Liber, Karsten

2017-02-01

Nontarget aquatic insects are susceptible to chronic neonicotinoid insecticide exposure during the early stages of development from repeated runoff events and prolonged persistence of these chemicals. Investigations on the chronic toxicity of neonicotinoids to aquatic invertebrates have been limited to a few species and under different laboratory conditions that often preclude direct comparisons of the relative toxicity of different compounds. In the present study, full life-cycle toxicity tests using Chironomus dilutus were performed to compare the toxicity of 3 commonly used neonicotinoids: imidacloprid, clothianidin, and thiamethoxam. Test conditions followed a static-renewal exposure protocol in which lethal and sublethal endpoints were assessed on days 14 and 40. Reduced emergence success, advanced emergence timing, and male-biased sex ratios were sensitive responses to low-level neonicotinoid exposure. The 14-d median lethal concentrations for imidacloprid, clothianidin, and thiamethoxam were 1.52 μg/L, 2.41 μg/L, and 23.60 μg/L, respectively. The 40-d median effect concentrations (emergence) for imidacloprid, clothianidin, and thiamethoxam were 0.39 μg/L, 0.28 μg/L, and 4.13 μg/L, respectively. Toxic equivalence relative to imidacloprid was estimated through a 3-point response average of equivalencies calculated at 20%, 50%, and 90% lethal and effect concentrations. Relative to imidacloprid (toxic equivalency factor [TEF] = 1.0), chronic (lethality) 14-d TEFs for clothianidin and thiamethoxam were 1.05 and 0.14, respectively, and chronic (emergence inhibition) 40-d TEFs were 1.62 and 0.11, respectively. These population-relevant endpoints and TEFs suggest that imidacloprid and clothianidin exert comparable chronic toxicity to C. dilutus, whereas thiamethoxam induced comparable effects only at concentrations an order of magnitude higher. However, the authors caution that under field conditions, thiamethoxam readily degrades to clothianidin, thereby likely enhancing toxicity. Environ Toxicol Chem 2017;36:372-382. © 2016 SETAC. © 2016 SETAC.

Mechanism of chloroform-induced renal toxicity: Non-involvement of hepatic cytochrome P450-dependent metabolism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fang Cheng; Behr, Melissa; Xie Fang

2008-02-15

Chloroform causes hepatic and renal toxicity in a number of species. In vitro studies have indicated that chloroform can be metabolized by P450 enzymes in the kidney to nephrotoxic intermediate, although direct in vivo evidence for the role of renal P450 in the nephrotoxicity has not been reported. This study was to determine whether chloroform renal toxicity persists in a mouse model with a liver-specific deletion of the P450 reductase (Cpr) gene (liver-Cpr-null). Chloroform-induced renal toxicity and chloroform tissue levels were compared between the liver-Cpr-null and wild-type mice at 24 h following differing doses of chloroform. At a chloroform dosemore » of 150 mg/kg, the levels of blood urea nitrogen (BUN) were five times higher in the exposed group than in the vehicle-treated one for the liver-Cpr-null mice, but they were only slightly higher in the exposed group than in the vehicle-treated group for the wild-type mice. Severe lesions were found in the kidney of the liver-Cpr-null mice, while only mild lesions were found in the wild-type mice. At a chloroform dose of 300 mg/kg, severe kidney lesions were observed in both strains, yet the BUN levels were still higher in the liver-Cpr-null than in the wild-type mice. Higher chloroform levels were found in the tissues of the liver-Cpr-null mice. These findings indicated that loss of hepatic P450-dependent chloroform metabolism does not protect against chloroform-induced renal toxicity, suggesting that renal P450 enzymes play an essential role in chloroform renal toxicity.« less

Pictorial health warning label content and smokers' understanding of smoking-related risks-a cross-country comparison.

PubMed

Swayampakala, Kamala; Thrasher, James F; Hammond, David; Yong, Hua-Hie; Bansal-Travers, Maansi; Krugman, Dean; Brown, Abraham; Borland, Ron; Hardin, James

2015-02-01

The aim of the present study was to assess smokers' level of agreement with smoking-related risks and toxic tobacco constituents relative to inclusion of these topics on health warning labels (HWLs). 1000 adult smokers were interviewed between 2012 and 2013 from online consumer panels of adult smokers from each of the three countries: Australia (AU), Canada (CA) and Mexico (MX). Generalized estimating equation models were estimated to compare agreement with smoking-related risks and toxic tobacco constituents. For disease outcomes described on HWLs across all three countries, there were few statistical differences in agreement with health outcomes (e.g. emphysema and heart attack). By contrast, increases in agreement where the HWLs were revised or introduced on HWLs for the first time (e.g. blindness in AU and CA, bladder cancer in CA). Similarly, samples from countries that have specific health content or toxic constituents on HWLs showed higher agreement for that particular disease or toxin than countries without (e.g. higher agreement for gangrene and blindness in AU, higher agreement for bladder cancer and all toxic constituents except nitrosamines and radioactive polonium in CA). Pictorial HWL content is associated with greater awareness of smoking-related risks and toxic tobacco constituents. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Group Waterpipe Tobacco Smoking Increases Smoke Toxicant Concentration

PubMed Central

Ramôa, Carolina P.; Shihadeh, Alan; Salman, Rola

2016-01-01

Abstract Introduction: Waterpipe tobacco smoking is a global health concern. Laboratory research has focused on individual waterpipe users while group use is common. This study examined user toxicant exposure and smoke toxicant yield associated with individual and group waterpipe smoking. Methods: Twenty-two pairs of waterpipe smokers used a waterpipe individually and as a dyad. Before and after smoking, blood was sampled and expired carbon monoxide (CO) measured; puff topography was recorded throughout. One participant from each pair was selected randomly and their plasma nicotine and expired air CO concentrations were compared when smoking alone to when smoking as part of a dyad. Recorded puff topography was used to machine-produce smoke that was analyzed for toxicant content. Results: There was no difference in mean plasma nicotine concentration when an individual smoked as part of a dyad (mean = 14.9ng/ml; standard error of the mean [ SEM ] = 3.0) compared to when smoking alone (mean = 10.0ng/ml; SEM = 1.5). An individual smoking as part of as a dyad had, on average, lower CO (mean = 15.8 ppm; SEM = 2.0) compared to when smoking alone (mean= 21.3 ppm; SEM = 2.7). When two participants smoked as a dyad they took, on average, more puffs (mean = 109.8; SEM = 7.6) than a singleton smoker (mean = 77.7; SEM = 8.1) and a shorter interpuff interval (IPI; dyad mean = 23.8 seconds; SEM = 1.9; singleton mean = 40.8 seconds; SEM = 4.8). Higher concentrations of several toxicants were observed in dyad-produced smoke. Discussion: Dyad smoking may increase smoke toxicant content, likely due to the dyad’s shorter IPIs and greater puff number. More work is needed to understand if group waterpipe smoking alters the health risks of waterpipe tobacco smoking. Implications: This study is the first to measure toxicants in smoke generated from a waterpipe when used by a dyad. Relative to smoke generated by a singleton, dyad smoke had higher concentration of some toxicants. These differences may be attributed to differences in puffing behavior, specifically the shorter IPI and greater puff number observed in the dyad condition. Relative to singleton smokers, dyad smokers were exposed to less CO, but nicotine exposure did not differ. More work is needed to assess the health effects of inhalation of more toxicant-laden smoke during group waterpipe use. PMID:26659913

Building-related symptoms are linked to the in vitro toxicity of indoor dust and airborne microbial propagules in schools: A cross-sectional study.

PubMed

Salin, J T; Salkinoja-Salonen, M; Salin, P J; Nelo, K; Holma, T; Ohtonen, P; Syrjälä, H

2017-04-01

Indoor microbial toxicity is suspected to cause some building-related symptoms, but supporting epidemiological data are lacking. We examined whether the in vitro toxicity of indoor samples from school buildings was associated with work-related health symptoms (building-related symptoms, BRS). Administrators of the Helsinki City Real Estate Department selected 15 schools for the study, and a questionnaire on symptoms connected to work was sent to the teachers in the selected schools for voluntary completion. The cellular toxicity of classroom samples was determined by testing substances extracted from wiped indoor dust and by testing microbial biomass that was cultured on fallout plates. Boar sperm cells were used as indicator cells, and motility loss was the indicator for toxic effects. The effects were expressed as the half maximal effective concentration (EC 50 ) at which >50% of the exposed boar sperm cells were immobile compared to vehicle control. Completed symptom questionnaires were received from 232 teachers [median age, 43 years; 190 (82.3%) women] with a median time of 6 years working at their school. Samples from their classrooms were available and were assessed for cellular toxicity. The Poisson regression model showed that the impact of extracts of surface-wiped school classroom dust on teacher work-related BRS was 2.8-fold (95% CI: 1.6-4.9) higher in classrooms with a toxic threshold EC 50 of 6µgml -1 versus classrooms with insignificant EC 50 values (EC 50 >50µgml -1 ); P<0.001. The number of symptoms that were alleviated during vacation was higher in school classrooms with high sperm toxicity compared to less toxic sites; the RR was 1.9 (95% CI: 1.1-3.3, P=0.03) for wiped dust extracts. Teachers working in classrooms where the samples showed high sperm toxicity had more BRS. The boar sperm cell motility inhibition assay appears promising as a tool for demonstrating the presence of indoor substances associated with BRS. Copyright © 2017 Elsevier Inc. All rights reserved.

Toxicity Assessment of Silica Coated Iron Oxide Nanoparticles and Biocompatibility Improvement by Surface Engineering

PubMed Central

Malvindi, Maria Ada; De Matteis, Valeria; Galeone, Antonio; Brunetti, Virgilio; Anyfantis, George C.; Athanassiou, Athanassia; Cingolani, Roberto; Pompa, Pier Paolo

2014-01-01

We have studied in vitro toxicity of iron oxide nanoparticles (NPs) coated with a thin silica shell (Fe3O4/SiO2 NPs) on A549 and HeLa cells. We compared bare and surface passivated Fe3O4/SiO2 NPs to evaluate the effects of the coating on the particle stability and toxicity. NPs cytotoxicity was investigated by cell viability, membrane integrity, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) assays, and their genotoxicity by comet assay. Our results show that NPs surface passivation reduces the oxidative stress and alteration of iron homeostasis and, consequently, the overall toxicity, despite bare and passivated NPs show similar cell internalization efficiency. We found that the higher toxicity of bare NPs is due to their stronger in-situ degradation, with larger intracellular release of iron ions, as compared to surface passivated NPs. Our results indicate that surface engineering of Fe3O4/SiO2 NPs plays a key role in improving particles stability in biological environments reducing both cytotoxic and genotoxic effects. PMID:24465736

Radiotherapy for malignancy in patients with scleroderma: The Mayo Clinic experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gold, Douglas G.; Miller, Robert C.; Petersen, Ivy A.

2007-02-01

Purpose: To determine the frequency of acute and chronic adverse effects in patients with scleroderma who receive radiotherapy for treatment of cancer. Methods and Materials: Records were reviewed of 20 patients with scleroderma who received radiotherapy. Acute and chronic toxic effects attributable to radiotherapy were analyzed, and freedom from radiation-related toxicity was calculated. Results: Of the 20 patients, 15 had acute toxic effects, with Grade 3 or higher toxicity for 3 patients. Seven patients had self-limited Grade 1 or 2 radiation dermatitis, and no patient had Grade 3 or higher radiation dermatitis. Thirteen patients had chronic toxic effects, with Grademore » 3 or higher chronic toxicity for 3 patients. The median estimated time to any grade chronic toxicity was 0.4 years, and the median estimated time to Grade 3 or higher chronic toxicity has not been reached. Conclusions: The results suggest that although some patients with scleroderma treated with radiation experience considerable toxic effects, the occurrence of Grade 3 or higher toxicity may be less than previously anticipated.« less

The Risk of Major NSAID Toxicity with Celecoxib, Ibuprofen, or Naproxen: A Secondary Analysis of the PRECISION Trial.

PubMed

Solomon, Daniel H; Husni, M Elaine; Libby, Peter A; Yeomans, Neville D; Lincoff, A Michael; Lϋscher, Thomas F; Menon, Venu; Brennan, Danielle M; Wisniewski, Lisa M; Nissen, Steven E; Borer, Jeffrey S

2017-12-01

The relative safety of long-term use of nonsteroidal anti-inflammatory drugs is unclear. Patients and providers are interested in an integrated view of risk . We examined the risk of major nonsteroidal anti-inflammatory drug toxicity in the PRECISION trial. We conducted a post hoc analysis of a double-blind, randomized, controlled, multicenter trial enrolling 24,081 patients with osteoarthritis or rheumatoid arthritis at moderate or high cardiovascular risk. Patients were randomized to receive celecoxib 100 to 200 mg twice daily, ibuprofen 600 to 800 mg thrice daily, or naproxen 375 to 500 mg twice daily. All patients were provided with a proton pump inhibitor. The outcome was major nonsteroidal anti-inflammatory drug toxicity, including time to first occurrence of major adverse cardiovascular events, important gastrointestinal events, renal events, and all-cause mortality. During follow-up, 4.1% of subjects sustained any major toxicity in the celecoxib arm, 4.8% in the naproxen arm, and 5.3% in the ibuprofen arm. Analyses adjusted for aspirin use and geographic region found that subjects in the naproxen arm had a 20% (95% CI 4-39) higher risk of major toxicity than celecoxib users and that 38% (95% CI 19-59) higher risk. These risks translate into numbers needed to harm of 135 (95% CI, 72-971) for naproxen and 82 (95% CI, 53-173) for ibuprofen, both compared with celecoxib. Among patients with symptomatic arthritis who had moderate to high risk of cardiovascular events, approximately 1 in 20 experienced a major toxicity over 1 to 2 years. Patients using naproxen or ibuprofen experienced significantly higher risk of major toxicity than those using celecoxib. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of antibacterial agents, levofloxacin and clarithromycin, on aquatic organisms.

PubMed

Yamashita, N; Yasojima, M; Nakada, N; Miyajima, K; Komori, K; Suzuki, Y; Tanaka, H

2006-01-01

Contamination of surface waters by pharmaceutical chemicals is an emerging environmental problem. This study evaluated the toxic effects of the antibacterial agents levofloxacin (LVFX) and clarithromycin (CAM), which are widely used in Japan, on aquatic organisms. Ecotoxicity tests using a bacterium, alga and crustacean were conducted. Microtox test using a marine fluorescent bacterium showed that LVFX and CAM have no acute toxicity to the bacterium. From the results of the Daphnia immobilisation test, LVFX and CAM did not show acute toxicity to the crustacean. Meanwhile, an algal growth inhibition test revealed that LVFX and CAM have high toxicity to the microalga. The phytotoxicity of CAM was about 100-fold higher than that of LVFX from a comparison of EC50 (median effective concentration) value. From the Daphnia reproduction test, LVFX and CAM also showed chronic toxicity to the crustacean. Concentrations of LVFX and CAM in the aquatic environment were compared with PNEC (predicted no effect concentration) to evaluate the ecological risk. As a result, the ecological risk of LVFX is considered to be low, but that of CAM is higher, suggesting that CAM discharged into an aquatic environment after therapeutic use may affect organisms in the aquatic environment.

Conjunctival and corneal reactions in rabbits following short- and repeated exposure to preservative-free tafluprost, commercially available latanoprost and 0.02% benzalkonium chloride

PubMed Central

Liang, H; Baudouin, C; Pauly, A; Brignole-Baudouin, F

2008-01-01

Aim: To compare the conjunctival and corneal reactions of commercially available solution of latanoprost (Xalatan) and preservative-free (PF) tafluprost in rabbits. Methods: The rabbits received 50 μl of phosphate-buffered saline (PBS), PF-tafluprost 0.0015%, latanoprost 0.005% or benzalkonium chloride (BAK) 0.02%; all solutions were applied at 5 min intervals for a total of 15 times. The ocular surface toxicity was investigated using slit-lamp biomicroscopy examination, flow cytometry (FCM) and on imprints for CD45 and tumour necrosis factor-receptor 1 (TNFR1) conjunctival impression cytology (CIC) and corneal in vivo confocal microscopy (IVCM). Standard immunohistology also assessed inflammatory/apoptotic cells. Results: Clinical observation and IVCM images showed the highest ocular surface toxicity with latanoprost and BAK, while PF-tafluprost and PBS eyes presented almost normal corneoconjunctival aspects. FCM showed a higher expression of CD45+ and TNFR1+ in latanoprost- or BAK-instilled groups, compared with PF-tafluprost and PBS groups. Latanoprost induced fewer positive cells for inflammatory marker expressions in CIC specimens compared with BAK-alone, both of which were higher than with PF-tafluprost or PBS. Immunohistology showed the same tendency of toxic ranking. Conclusion: The authors confirm that rabbit corneoconjunctival surfaces presented a better tolerance when treated with PF-tafluprost compared with commercially available latanoprost or BAK solution. PMID:18723745

Mdr1a plays a crucial role in regulating the analgesic effect and toxicity of aconitine by altering its pharmacokinetic characteristics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, Lijun; Wu, Jinjun; Zhao, Min

Aconitine (AC) is the primary bioactive/toxic alkaloid in plants of the Aconitum species. Our previous study demonstrated that Mdr1 was involved in efflux of AC. However, the mechanism by which Mdr1 regulates the efficacy/toxicity of AC in vivo remains unclear. The present study aimed to determine the effects of Mdr1a on the efficacy/toxicity and pharmacokinetics of AC in wild-type and Mdr1a{sup −/−} FVB mice. After oral administration of AC, significantly higher analgesic effect was observed in Mdr1a{sup −/−} mice (49% to 105%) compared to wild-type mice (P < 0.05). The levels of s100-β protein and creatine kinase, which indicate cerebralmore » and myocardial damage, respectively, were also significantly increased (P < 0.05) in Mdr1a{sup −/−} mice. Histopathological examination revealed that the Mdr1a{sup −/−} mice suffered from evident cerebral and myocardial damages, but the wild-type mice did not. These findings suggested that Mdr1a deficiency significantly promoted the analgesic effect of AC and exacerbated its toxicity. Pharmacokinetic experiments showed that T{sub 1/2} of AC in the Mdr1a{sup −/−} mice was significantly higher (from 87% to 300%) than that in wild-type mice (P < 0.05). The distribution of AC in the brain of Mdr1a{sup −/−} mice was 2- to 32-fold higher than that in the brains of wild-type mice (P < 0.05). Toxic reactions were more severe in Mdr1a{sup −/−} mice compared to wild-type mice. In conclusion, Mdr1a deficiency significantly enhanced the analgesic effect of AC and exacerbated its toxicity by upregulating its distribution to the brain and decreasing its plasma elimination rate. Thus, Mdr1a dysfunction may cause severe AC poisoning. - Highlights: • The efficacy and toxicity of aconitine were significantly enhanced in Mdr1a{sup −/−} mice. • The distribution of aconitine to the brain was remarkably increased in Mdr1a{sup −/−} mice. • The elimination rate of aconitine was significantly decreased in Mdr1a{sup −/−} mice.« less

The newly described heterotrophic dinoflagellate Gyrodinium moestrupii, an effective protistan grazer of toxic dinoflagellates.

PubMed

Yoo, Yeong Du; Yoon, Eun Young; Jeong, Hae Jin; Lee, Kyung Ha; Hwang, Yeong Jong; Seong, Kyeong Ah; Kim, Jae Seong; Park, Jae Yeon

2013-01-01

Few protistan grazers feed on toxic dinoflagellates, and low grazing pressure on toxic dinoflagellates allows these dinoflagellates to form red-tide patches. We explored the feeding ecology of the newly described heterotrophic dinoflagellate Gyrodinium moestrupii when it fed on toxic strains of Alexandrium minutum, Alexandrium tamarense, and Karenia brevis and on nontoxic strains of A. tamarense, Prorocentrum minimum, and Scrippsiella trochoidea. Specific growth rates of G. moestrupii feeding on each of these dinoflagellates either increased continuously or became saturated with increasing mean prey concentration. The maximum specific growth rate of G. moestrupii feeding on toxic A. minutum (1.60/d) was higher than that when feeding on nontoxic S. trochoidea (1.50/d) or P. minimum (1.07/d). In addition, the maximum growth rate of G. moestrupii feeding on the toxic strain of A. tamarense (0.68/d) was similar to that when feeding on the nontoxic strain of A. tamarense (0.71/d). Furthermore, the maximum ingestion rate of G. moestrupii on A. minutum (2.6 ng C/grazer/d) was comparable to that of S. trochoidea (3.0 ng C/grazer/d). Additionally, the maximum ingestion rate of G. moestrupii on the toxic strain of A. tamarense (2.1 ng C/grazer/d) was higher than that when feeding on the nontoxic strain of A. tamarense (1.3 ng C/grazer/d). Thus, feeding by G. moestrupii is not suppressed by toxic dinoflagellate prey, suggesting that it is an effective protistan grazer of toxic dinoflagellates. © 2012 The Author(s) Journal of Eukaryotic Microbiology © 2012 International Society of Protistologists.

Prediction of toxicity of zinc and nickel mixtures to Artemia sp. at various salinities: From additivity to antagonism.

PubMed

Damasceno, Évila Pinheiro; de Figuerêdo, Lívia Pitombeira; Pimentel, Marcionília Fernandes; Loureiro, Susana; Costa-Lotufo, Letícia Veras

2017-08-01

Few studies have examined the toxicity of metal mixtures to marine organisms exposed to different salinities. The aim of the present study was to investigate the acute toxicity of zinc and nickel exposures singly and in combination to Artemia sp. under salinities of 10, 17, and 35 psu. The mixture concentrations were determined according to individual toxic units (TUs) to follow a fixed ratio design. Zinc was more toxic than nickel, and both their individual toxicities were higher at lower salinities. These changes in toxicity can be attributed to the Biotic Ligand Model (BLM) rather than to metal speciation. To analyze the mixture effect, the observed data were compared with the expected mixture effects predicted by the concentration addition (CA) model and by deviations for synergistic/antagonistic interactions and dose-level and dose-ratio dependencies. For a salinity of 35 psu, the mixture had no deviations; therefore, the effects were additive. After decreasing the salinity to 17 psu, the toxicity pattern changed to antagonism at low concentrations and synergism at higher equivalent LC 50 levels. For the lowest salinity tested (10 psu), antagonism was observed. The speciations of both metals were similar when in a mixture and when isolated, and changes in toxicity patterns are more related to the organism's physiology than metal speciation. Therefore, besides considering chemical interactions in real-world scenarios, where several chemicals can be present, the influence of abiotic factors, such as salinity, should also be considered. Copyright © 2017 Elsevier Inc. All rights reserved.

Particle size effects on bioaccessible amounts of ingestible soil-borne toxic elements.

PubMed

Qin, Junhao; Nworie, Obinna Elijah; Lin, Chuxia

2016-09-01

The unified BARGE method was used to examine the effects of soil particle size on the bioaccessible amounts of potentially toxic elements in multi-contaminated soils from a closed landfill site. The results show that bioaccessible As, Al, Cd, Cr, Cu, Mn, Ni, Pb and Zn increased with decreasing soil particle size and the <0.002 mm soil fraction contained much greater amounts of the bioaccessible elements, as compared to other soil fractions (0.002-0.063 mm, 0.063-0.125 mm, and 0.125-0.250 mm). As, Al and Cr had much lower bioaccessibility, as compared to the six cationic heavy metals. In contrast with other elements, As bioaccessibility tended to be higher in the gastrointestinal phase than in the gastric phase. There was a significant soil particle size effect on bioaccessibility of As and Al in the gastrointestinal phase: As bioaccessibility decreased with decreasing particle size, and the finer soil fractions tended to have a higher Al bioaccessibility, as compared to the coarser soil fractions. The research findings prompt the need for further division of soil particle size fractions in order to more accurately assess the bioaccessible amounts of soil-borne potentially toxic elements in contaminated lands. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparison of Toxicity Between Intensity-Modulated Radiotherapy and 3-Dimensional Conformal Radiotherapy for Locally Advanced Non-small-cell Lung Cancer.

PubMed

Ling, Diane C; Hess, Clayton B; Chen, Allen M; Daly, Megan E

2016-01-01

The role of intensity-modulated radiotherapy (IMRT) in reducing treatment-related toxicity for locally advanced non-small-cell lung cancer (NSCLC) remains incompletely defined. We compared acute toxicity and oncologic outcomes in a large cohort of patients treated with IMRT or 3-dimensional conformal radiotherapy (3-DCRT), with or without elective nodal irradiation (ENI). A single-institution retrospective review was performed evaluating 145 consecutive patients with histologically confirmed stage III NSCLC treated with definitive chemoradiotherapy. Sixty-five (44.8%) were treated with 3-DCRT using ENI, 43 (30.0%) with 3-DCRT using involved-field radiotherapy (IFRT), and 37 (25.5%) with IMRT using IFRT. All patients received concurrent chemotherapy. Comparison of acute toxicities by treatment technique (IMRT vs. 3-DCRT) and extent of nodal irradiation (3-DCRT-IFRT vs. 3-DCRT-ENI) was performed for grade 2 or higher esophagitis or pneumonitis, number of acute hospitalizations, incidence of opioid requirement, percutaneous endoscopic gastrostomy utilization, and percentage weight loss during treatment. Local control and overall survival were analyzed by the Kaplan-Meier method. We identified no significant differences in any measures of acute toxicity by treatment technique or extent of nodal irradiation. There was a trend toward lower rates of grade 2 or higher pneumonitis among IMRT patients compared to 3-DCRT patients (5.4% vs. 23.0%; P = .065). Local control and overall survival were similar between cohorts. Acute and subacute toxicities were similar for patients treated with IMRT and with 3-DCRT with or without ENI, with a nonsignificant trend toward a reduction in pneumonitis with IMRT. Larger studies are needed to better define which patients will benefit from IMRT. Copyright © 2016 Elsevier Inc. All rights reserved.

Suitability of Daphnia similis as an alternative organism in ecotoxicological tests: implications for metal toxicity.

PubMed

Rodgher, Suzelei; Espíndola, Evaldo Luiz Gaeta; Lombardi, Ana Teresa

2010-08-01

The acute toxicity of metals to Daphnia similis was determined and compared to other daphnid species to evaluate the suitability of this organism in ecotoxicology bioassays. To verify the performance D. similis in toxicity tests, we also investigated the effect of Pseudokirchneriella subcapitata at 1 x 10(5) and 1 x 10(6) cells ml(-1) on Cd and Cr acute toxicity to the cladoceran. Daphnid neonates were exposed to a range of chromium and cadmium concentrations in the absence and presence of the algal cells. Metal speciation calculations using MINEQL(+) showed that total dissolved metal concentrations in zooplankton culture corresponded to 96.2% free Cd and 100% free Cr concentrations. Initial total dissolved metal concentrations were used for 48 h-LC(50) determination. LC(50) for D. similis was 5.15 x 10(-7) mol l(-1) dissolved Cd without algal cells, whereas with 1 x 10(5) cells ml(-1), it was significantly higher (7.15 x 10(-7) mol l(-1) dissolved Cd). For Cr, the 48 h-LC(50) value of 9.17 x 10(-7) mol l(-1) obtained for the cladoceran in tests with 1 x 10(6) cells ml(-1) of P. subcapitata was also significantly higher than that obtained in tests without algal cells (5.28 x 10(-7) mol l(-1) dissolved Cr). The presence of algal cells reduced the toxicity of metals to D. similis, as observed in other studies that investigated the effects of food on metal toxicity to standard cladocerans. Comparing our results to those of literature, we observed that D. similis is as sensitive to metals as other standardized Daphnia species and may serve as a potential test species in ecotoxicological evaluations.

A Multi-institutional Analysis of Trimodality Therapy for Esophageal Cancer in Elderly Patients.

PubMed

Lester, Scott C; Lin, Steven H; Chuong, Michael; Bhooshan, Neha; Liao, Zhongxing; Arnett, Andrea L; James, Sarah E; Evans, Jaden D; Spears, Grant M; Komaki, Ritsuko; Haddock, Michael G; Mehta, Minesh P; Hallemeier, Christopher L; Merrell, Kenneth W

2017-07-15

The therapeutic gains of neoadjuvant chemoradiation therapy (nCRT) followed by esophagectomy may be offset by increased incidences of morbidity and mortality in elderly patients. This study aimed to determine the impact of age on the risks and benefits of trimodality therapy for esophageal cancer. We evaluated 571 patients treated with trimodality therapy at 3 high-volume tertiary cancer centers in the United States from 2007 to 2013. Two hundred two of 571 (35%) patients were 65 years or older at diagnosis and were classified as elderly. Toxicity and treatment parameters for the elderly cohort were compared with the younger cohort (ages 22-64) by the use of univariate (UVA) and multivariable (MVA) logistic analyses. Age was analyzed as a continuous hazard for cardiac and pulmonary toxicities. Survival was assessed by the Kaplan-Meier method. Elderly patients had a higher risk for postoperative cardiac toxicities (UVA: odds ratio [OR] 2.2, P<.001; MVA: OR 2.07, P=.004) and pulmonary toxicities (UVA: OR 2.0, P<.001; MVA: OR 2.03, P<.001) and a higher 90-day postoperative mortality (5.4% vs 2.2%, P=.049). Of the elderly patients, 6.9% experienced acute respiratory distress syndrome compared with 3.8% of younger patients (P=.11). Cardiac toxicity was linearly associated with age, and the relative risk increased by 61% for every additional decade of age. There was no difference in postoperative gastrointestinal or wound adverse events or in length of hospital stay. Grade 3+ acute toxicities from nCRT were infrequent and were clinically similar regardless of age. Freedom from esophageal cancer and disease-free survival were similar, but overall survival was significantly shorter in the elderly cohort. Elderly patients experienced more postoperative cardiopulmonary toxicities and mortality than did younger patients after nCRT. Compared with contemporary outcomes for trimodality therapy, both cohorts had acceptable rates for adverse events and disease control. For appropriately selected elderly patients, trimodality therapy for esophageal cancer is a reasonable treatment option. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparative Toxicity and Dosimetric Profile of Whole-Pelvis Versus Prostate Bed-Only Intensity-Modulated Radiation Therapy After Prostatectomy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deville, Curtiland, E-mail: deville@uphs.upenn.edu; Vapiwala, Neha; Hwang, Wei-Ting

2012-03-15

Purpose: To assess whether whole-pelvis (WP) intensity modulated radiation therapy (IMRT) for prostate cancer (PCa) after prostatectomy is associated with increased toxicity compared to prostate-bed only (PB) IMRT. Methods and Materials: All patients (n = 67) undergoing postprostatectomy IMRT to 70.2 Gy at our institution from January 2006 to January 2009 with minimum 12-month follow-up were divided into WP (n = 36) and PB (n = 31) comparison groups. WP patients received initial pelvic nodal IMRT to 45 Gy. Pretreatment demographics, bladder and rectal dose-volume histograms, and maximum genitourinary (GU) and gastrointestinal (GI) toxicities were compared. Logistic regression models evaluatedmore » uni- and multivariate associations between pretreatment demographics and toxicities. Results: Pretreatment demographics including age and comorbidities were similar between groups. WP patients had higher Gleason scores, T stages, and preoperative prostate-specific antigen (PSA) levels, and more WP patients underwent androgen deprivation therapy (ADT). WP minimum (Dmin) and mean bladder doses, bladder volumes receiving more than 5 Gy (V5) and V20, rectal Dmin, and PB bladder and rectal V65 were significantly increased. Maximum acute GI toxicity was Grade 2 and was increased for WP (61%) vs. PB (29%) patients (p = 0.001); there was no significant difference in acute Grade {>=}2 GU toxicity (22% WP vs. 10% PB; p = 0.193), late Grade {>=}2 GI toxicity (3% WP vs. 0% PB; p = 0.678), or late Grade {>=}2 GU toxicity (28% WP vs. 19% PB; p = 0.274) with 25-month median follow-up (range, 12-44 months). On multivariate analysis, long-term ADT use was associated with Grade {>=}2 late GU toxicity (p = 0.02). Conclusion: Despite dosimetric differences in irradiated bowel, bladder, and rectum, WP IMRT resulted only in clinically significant increased acute GI toxicity in comparison to that with PB IMRT, with no differences in GU or late GI toxicity.« less

Ecotoxicity of quinoline and hydroxylated derivatives and their occurrence in groundwater of a tar-contaminated field site.

PubMed

Neuwoehner, Judith; Reineke, Anne-Kirsten; Hollender, Juliane; Eisentraeger, Adolf

2009-03-01

In the groundwater of a timber impregnation site higher concentrations of hydroxylated quinolines compared to their parent compounds quinoline and isoquinoline were found. Studying the toxicity of parent compounds and metabolites, genotoxicity was found with metabolic activation in the SOS-Chromotest and Ames fluctuation test only for quinoline. An adverse effect on algae was observed only for the parent compounds quinoline and isoquinoline, while in the Daphnia magna immobilization assay most hydroxylated quinoline derivatives showed toxicity. The highest ecotoxic potential was observed in the Vibrio fischeri luminescence-inhibition assay. Comparing experimental EC50-values with QSAR predicted ones, for all compounds apart from isoquinoline and 2(1H)-quinolinone in the V. fischeri test baseline toxicity or polar nacrosis is indicated. In conclusion, the hydroxylation of quinoline leads to a detoxification of the genotoxic potential, while taken additive mixture toxicity and a safety factor into account parent compounds and metabolites are found of ecotoxicological relevance in the groundwater.

Effect of bis(tributyltin) oxide on reproduction and population growth rate of calanoid copepod Schmackeria poplesia

NASA Astrophysics Data System (ADS)

Huang, Ying; Zhu, Liyan; Qiu, Xuchun; Zhang, Tianwen

2010-03-01

A full life-cycle toxicity test, combined with histology, on calanoid copepod Schmackeria poplesia was used to study the effect of bis(tributyltin) oxide (TBTO). The results indicate no sex-specific differences in TBTO toxicity. Long-term mortalities of the copepods exposed to concentrations higher than 20 ng TBTO L-1 were significantly elevated compared with that of control, and larval development was inhibited when they were exposed to 40 and 60 ng TBTO L-1. The percentages of ovigerous females were reduced compared with the control ( P<0.01) after 24 days exposure to concentrations higher than 10 ng TBTO L-1. Histological examinations suggest that exposure to TBTO might block the posterior end of the diverticula and inhibits the production of egg sacs. A modified Euler-Lotka equation was used to calculate a population-level endpoint, the intrinsic rate of natural increase ( r m), from individual life-table endpoints, i.e. mortality rate, time of release of first brood, sex ratio, the fraction of ovigerous females among all females as well as the number of nauplii per ovigerous female. Apart from the highest TBTO concentration (60 ng L-1), where all females aborted their egg sacs, 20 ng TBTO L-1 was the only concentration that significantly decreased r m compared with that of control (an effect associated with decreased sex ratio). The results show that the S. poplesia is affected by prolonged exposure to low concentrations of TBTO. The full life-cycle toxicity test combined with histology experiments provides more integral understanding of the toxicity of endocrine disrupters.

Toxicity of waters from the Rochester Embayment Area of Concern to the plankton species Pseudokirchneriella subcapitata and Ceriodaphnia dubia

USGS Publications Warehouse

Baldigo, Barry P.; Duffy, Brian T.; Smith, Alexander J.; George, Scott D.

2016-01-01

The lower Genesee River and Rochester Embayment of Lake Ontario are a designated Area of Concern (AOC) under the binational Great Lakes Water Quality Agreement. The “degradation of phytoplankton and zooplankton populations” or plankton Beneficial Use Impairment (BUI) was classified as unknown and in need of further assessment in this AOC because water quality data suggested plankton communities could be effected and community data were either unavailable or indicated impacts. The plankton BUI may now be obsolete because local contaminant sources have been largely eliminated. The present study was conducted between July 2013 and August 2014 to assess the BUI-removal criteria: “AOC plankton bioassays confirm that toxicity in ambient waters (i.e., no growth inhibition) is not significantly higher than comparable non-AOC controls”. Acute and chronic toxicity of waters from 13 sites were quantified seasonally using standardized bioassays with the green alga Pseudokirchneriella subcapitata and water flea Ceriodaphnia dubia to test the hypothesis that toxicity of waters from AOC sites was not higher than that of waters from comparable non-AOC reference sites. Survival and reproduction of C. dubia did not differ significantly between site types, systems, or months. The growth of P. subcapitata did not differ between site types, but differed among systems and months. All results indicate that waters from AOC sites were no more toxic to both plankton species than waters from reference sites. Assuming test species represent natural plankton assemblages, water quality should not negatively affect survival and growth of resident plankton populations in the Rochester Embayment AOC.

Reduced toxicity with equivalent outcomes using three-dimensional volumetric (3DV) image-based versus nonvolumetric point-based (NV) brachytherapy in a cervical cancer population.

PubMed

Thomas, Kimberly M; Maquilan, Genevieve; Stojadinovic, Strahinja; Medin, Paul; Folkert, Michael R; Albuquerque, Kevin

Brachytherapy (BT) techniques have historically used a two-dimensional nonvolumetric (NV) system involving dose prescribed to a point fixed in space. We compared dosimetric, toxicity, and oncologic outcomes for volumetric planning (3DV) versus CT point-based planning. Patients treated with external beam radiation therapy and high dose rate (HDR) intracavitary BT were included (n = 71). Patients planned with NV BT treated from 2009 to 2011 (n = 37) were compared to patients planned with 3DV BT treated from 2012 to 2014 (n = 34). Investigators delineated volumes for organs at risk clinical target volumes for the 2009-2011 NV cohort. Acute and chronic toxicity data were graded. The mean HDR clinical target volume D90 received in the NV and 3DV cohorts were significantly different (p < 0.001). The mean dose to point A was significantly higher in the NV cohort than in the 3DV cohort (p < 0.001). There were significantly more Grade 3 or higher gastrointestinal toxicities in the NV cohort (p = 0.048). There was a nonsignificant trend toward improved oncologic outcomes for patients undergoing CT-based planning. 3DV BT allows for a significant reduction of dose to critical structures, resulting in decreased gastrointestinal toxicity, while delivering noninferior doses to the high-risk clinical target volume. Outcomes were improved in the 3D cohort trending toward statistical significance. Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Risk of hematologic toxicities with programmed cell death-1 inhibitors in cancer patients: a meta-analysis of current studies.

PubMed

Sui, Jiang-Dong; Wang, Ying; Wan, Yue; Wu, Yong-Zhong

2018-01-01

Programmed cell death-1 (PD-1) inhibitor-related hematologic toxicities are a category of rare but clinically serious and potentially life-threatening adverse events; however, little is known about their risks across different treatment regimens and tumor types. The objective of this study was to compare the incidences of PD-1 inhibitor-related hematologic toxicities among different therapeutic regimens and tumor types. Twenty-six original articles on PD-1 inhibitor trials were identified based on a PubMed search completed on September 26, 2017. The incidences of hematologic toxicities were collected. A total of 26 studies containing 5,088 patients were included in the meta-analysis. PD-1 inhibitor monotherapy was associated with an increased risk of all-grade anemia in cancer patients (5%, 95% CI 4%-6%), particularly in patients with renal cell carcinoma (RCC) (8%, 95% CI 6%-12%), compared with all-grade thrombocytopenia (2%, 95% CI 1%-5%), leukopenia (2%, 95% CI 1%-3%), and neutropenia (1%, 95% CI 0-1%). However, low incidences of high-grade hematologic toxicities were observed in cancer patients treated with PD-1 inhibitor monotherapy. The use of PD-1 inhibitors in combination with ipilimumab, peptide vaccines, or chemotherapy had significantly higher risks than PD-1 inhibitor monotherapy for all-grade anemia (13%, 95% CI 5%-31%), thrombocytopenia (6%, 95% CI 2%-18%), leukopenia (5%, 95% CI 1%-35%), neutropenia (4%, 95% CI 1%-26%), and only high-grade thrombocytopenia (4%, 95% CI 1%-15%). In addition, all-grade and high-grade hematologic toxicities in chemotherapy and everolimus treatment arms were more frequent than in PD-1 inhibitor monotherapy arms. The risks of PD-1 inhibitor-related hematologic toxicities were higher in RCC than in other cancers, and during combination therapy. These results may contribute toward enhancing awareness among clinicians about frequent clinical monitoring when managing PD-1 inhibitors.

Nontoxic Hydroxylammonium Nitrate (HAN) Monopropellant Propulsion

NASA Technical Reports Server (NTRS)

McKechnie, Timothy N.

2015-01-01

Nontoxic monopropellants have been developed that provide better performance than toxic hydrazine. Formulations based on HAN have superior performance as compared to hydrazine with enhanced specific impulse (Isp), higher density and volumetric impulse, lower melting point, and much lower toxicity. However, HAN-based monopropellants require higher chamber temperatures (2,083 K vs. 883 K) to combust. Current hydrazine-based combustion chamber technology (Inconel® or niobium C103 and silicide coating) and catalyst (Shell 405) are inadequate. In Phase I, state-of-the-art iridium-lined rhenium chambers and innovative new foam catalysts were demonstrated in pulse and 10-second firings. Phase II developed and tested a flight-weight thruster for an environmentally green monopropellant.

Antiretroviral therapy-induced mitochondrial toxicity: potential mechanisms beyond polymerase-γ inhibition.

PubMed

Selvaraj, S; Ghebremichael, M; Li, M; Foli, Y; Langs-Barlow, A; Ogbuagu, A; Barakat, L; Tubridy, E; Edifor, R; Lam, W; Cheng, Y-C; Paintsil, E

2014-07-01

We hypothesized that competition between nucleotide reverse-transcriptase inhibitor triphosphate and endogenous deoxyribonucleotide triphosphate (dNTP) may lead to depletion of dNTP pools and mitochondrial dysfunction independent of polymerase-γ (pol-γ) inhibition. We collected peripheral blood mononuclear cells from 75 adults (25 cases: HIV-infected patients with mitochondrial toxicity, 25 HIV-infected positive controls, and 25 HIV-negative controls). We observed statistically significant individual and group differences in ribonucleotide (RN) and deoxyribonucleotide (dRN) pools. The median values for the RN pools were 10,062 (interquartile range (IQR): 7,090-12,590), 4,360 (IQR: 3,058-6,838), and 2,968 (IQR: 2,538-4,436) pmol/10(6) cells for negative controls, positive controls, and cases, respectively. Cases had significantly higher absolute mitochondrial DNA copy number as compared with negative controls (P < 0.05). Moreover, cases had significantly higher expression levels of pol-γ, nucleotide transporters, cellular kinases, and adenosine triphosphate (ATP)-binding cassette (ABC) proteins as compared with controls. Antiretroviral therapy (ART) perturbs RN and dRN pools. Depletion of RN and dRN pools may be associated with ART-induced mitochondrial toxicity independent of pol-γ inhibition.

Comparative study of the nutritional composition and toxic elements of farmed and wild Chanodichthys mongolicus

NASA Astrophysics Data System (ADS)

Jiang, Haifeng; Cheng, Xiaofei; Geng, Longwu; Tang, Shizhan; Tong, Guangxiang; Xu, Wei

2017-07-01

Information of the difference in quality between farmed and wild fish is central to better ensuring fish products produced in aquaculture meet regulatory and consumer requirements. Proximate composition, amino acid and fatty acid profiles, and toxic elements contents of farmed and wild Chanodichthys mongolicus were established and compared. Significantly higher crude protein content while lower moisture content in farmed fish compared to wild fish were observed ( P<0.05). The percentages of total amino acids (TAA), total essential amino acids (TEAA), total non-essential amino acids (TNEAA) and total delicious amino acids (TDAA) in farmed fish were all significantly higher than those in the wild equivalent ( P<0.05). Compared to the FAO/WHO recommended reference values, the ratios of TEAA/TAA (39.84%-40.33%) were comparable to 40% and TEAA / TNEAA (66.22%-67.60%) were above 60%. Fatty acid profiles in both farmed and wild C. mongolicus were dominated by monounsaturated fatty acid (MUFA), with farmed fish contained much more MUFA content compared to wild counterpart ( P<0.05). Notably, wild fish exhibited significantly higher levels of total polyunsaturated fatty acid (PUFA) including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) than farmed fish ( P<0.05). The EPA (C20:5n3) and linoleic acid (C18:2n6) were the predominant PUFA in wild and farmed C. mongolicus, respectively. Moreover, farmed fish displayed an overall lower toxic element levels (As, Cd, Pb and Hg) in comparison with wild fish, and both were far lower than the established limit standard. In conclusion, our results suggest that the nutritional quality of farmed C. mongolicus was inferior to their wild counterpart with respect to fatty acids nutrition, and therefore further studies should focus on the improving C. mongolicus diet in order to enhance the overall nutritional composition.

Preclinical evaluations of norcantharidin-loaded intravenous lipid microspheres with low toxicity.

PubMed

Lin, Xia; Zhang, Bo; Zhang, Keru; Zhang, Yu; Wang, Juan; Qi, Na; Yang, Shenshen; He, Haibing; Tang, Xing

2012-12-01

The aim of this study was to perform a systematic preclinical evaluation of norcantharidin (NCTD)-loaded intravenous lipid microspheres (NLM). Pharmacokinetics, biodistribution, antitumor efficacy and drug safety assessment (including acute toxicity, subchronic toxicity, hemolysis testing, intravenous stimulation and injection anaphylaxis) of NLM were carried out in comparison with the commercial product disodium norcantharidate injection (NI). The pharmacokinetics of NLM in rats was similar to that of NI, and a non-linear correlation was observed between AUC and dose. A comparable antitumor efficacy of NLM and NI was observed in mice inoculated with A549, BEL7402 and BCAP-37 cell lines. It was worth noting that the NLM produced a lower drug concentration in heart compared with NI, and significantly reduced the cardiac and renal toxicity. The LD(50) of NLM was twice higher than that of NI. In NLM, over 80% of NCTD was loaded in the lipid phase or bound with phospholipids. Thus, NCTD was sequestered by direct contacting with body fluids and largely avoided distribution into tissues, consequently leading to significantly reduced cardiac and renal toxicity. These preclinical results suggested that NLM could be a useful potential carrier for parenteral administration of NCTD, while providing a superior safety profile.

Interactions of metal-based engineered nanoparticles with aquatic higher plants: A review of the state of current knowledge.

PubMed

Thwala, Melusi; Klaine, Stephen J; Musee, Ndeke

2016-07-01

The rising potential for the release of engineered nanoparticles (ENPs) into aquatic environments requires evaluation of risks to protect ecological health. The present review examines knowledge pertaining to the interactions of metal-based ENPs with aquatic higher plants, identifies information gaps, and raises considerations for future research to advance knowledge on the subject. The discussion focuses on ENPs' bioaccessibility; uptake, adsorption, translocation, and bioaccumulation; and toxicity effects on aquatic higher plants. An information deficit surrounds the uptake of ENPs and associated dynamics, because the influence of ENP characteristics and water quality conditions has not been well documented. Dissolution appears to be a key mechanism driving bioaccumulation of ENPs, whereas nanoparticulates often adsorb to plant surfaces with minimal internalization. However, few reports document the internalization of ENPs by plants; thus, the role of nanoparticulates' internalization in bioaccumulation and toxicity remains unclear, requiring further investigation. The toxicities of metal-based ENPs mainly have been associated with dissolution as a predominant mechanism, although nano toxicity has also been reported. To advance knowledge in this domain, future investigations need to integrate the influence of ENP characteristics and water physicochemical parameters, as their interplay determines ENP bioaccessibility and influences their risk to health of aquatic higher plants. Furthermore, harmonization of test protocols is recommended for fast tracking the generation of comparable data. Environ Toxicol Chem 2016;35:1677-1694. © 2016 SETAC. © 2016 SETAC.

Wastewater toxicity of tannin- versus chromium-based leather tanneries in Marrakesh, Morocco.

PubMed

De Nicola, E; Meriç, S; Della Rocca, C; Gallo, M; Iaccarino, M; Manini, P; Petruzzelli, D; Belgiorno, V; Cheggour, M; Di Gennaro, A; Moukrim, A; Tünay, O; Pagano, G

2007-10-01

The toxicity of leather tanning wastewater from a traditional tannery (TT), which is based on vegetable tannin (VT), was compared with wastewater from a tannery combining the use of chromium-based tanning (CT) with VT-based tanning operations. Wastewater samples from a TT and a CT plant as well as from five sewer sampling points were collected in Marrakesh, Morocco, and the concentrations of VT and some selected inorganics were measured. A set of bioassays were used to test wastewater toxicity in sea urchin (Paracentrotus lividus) embryos and sperm, in Daphnia magna, and in marine microalgae (Dunaliella tertiolecta). Toxicity end points included: (1) developmental defects, embryonic mortality, sperm fertilization success, and offspring damage in sea urchins; (2) D. magna immobilization; and (3) algal growth rate inhibition. Toxicity tests on TT and CT effluents (TTE and CTE) were run at dilutions ranging from 0.1% to 2% (sea urchins and algae) or up to 12% in D. magna. Parallel bioassays were run on VT extract (VTE) at nominal tannin concentrations ranging from 0.1 to 10 mg l(-1). The results showed higher toxicity of CTE compared with TTE. CTE toxicity in sea urchins and algae showed concentration-related trends, whereas TTE exerted hormetic effects at levels of 0.1% to 0.2% and toxic effects at levels >or=1%. The same trends were observed for VTE, suggesting a prevailing role of tannin in TTE-associated effects. The moderate wastewater toxicity of VT-based tanneries might prompt interest in the VT tanning process.

Group Waterpipe Tobacco Smoking Increases Smoke Toxicant Concentration.

PubMed

Ramôa, Carolina P; Shihadeh, Alan; Salman, Rola; Eissenberg, Thomas

2016-05-01

Waterpipe tobacco smoking is a global health concern. Laboratory research has focused on individual waterpipe users while group use is common. This study examined user toxicant exposure and smoke toxicant yield associated with individual and group waterpipe smoking. Twenty-two pairs of waterpipe smokers used a waterpipe individually and as a dyad. Before and after smoking, blood was sampled and expired carbon monoxide (CO) measured; puff topography was recorded throughout. One participant from each pair was selected randomly and their plasma nicotine and expired air CO concentrations were compared when smoking alone to when smoking as part of a dyad. Recorded puff topography was used to machine-produce smoke that was analyzed for toxicant content. There was no difference in mean plasma nicotine concentration when an individual smoked as part of a dyad (mean = 14.9 ng/ml; standard error of the mean [SEM] = 3.0) compared to when smoking alone (mean = 10.0 ng/ml; SEM = 1.5). An individual smoking as part of as a dyad had, on average, lower CO (mean = 15.8 ppm; SEM = 2.0) compared to when smoking alone (mean= 21.3 ppm; SEM = 2.7). When two participants smoked as a dyad they took, on average, more puffs (mean = 109.8; SEM = 7.6) than a singleton smoker (mean = 77.7; SEM = 8.1) and a shorter interpuff interval (IPI; dyad mean = 23.8 seconds; SEM = 1.9; singleton mean = 40.8 seconds; SEM = 4.8). Higher concentrations of several toxicants were observed in dyad-produced smoke. Dyad smoking may increase smoke toxicant content, likely due to the dyad's shorter IPIs and greater puff number. More work is needed to understand if group waterpipe smoking alters the health risks of waterpipe tobacco smoking. This study is the first to measure toxicants in smoke generated from a waterpipe when used by a dyad. Relative to smoke generated by a singleton, dyad smoke had higher concentration of some toxicants. These differences may be attributed to differences in puffing behavior, specifically the shorter IPI and greater puff number observed in the dyad condition. Relative to singleton smokers, dyad smokers were exposed to less CO, but nicotine exposure did not differ. More work is needed to assess the health effects of inhalation of more toxicant-laden smoke during group waterpipe use. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Pulmonary toxicity study in rats with PM 10 and PM 2.5: Differential responses related to scale and composition

NASA Astrophysics Data System (ADS)

Zhang, Wei; Lei, Tian; Lin, Zhi-Qing; Zhang, Hua-Shan; Yang, Dan-Feng; Xi, Zhu-Ge; Chen, Jian-Hua; Wang, Wei

2011-02-01

ObjectionTo study the pollution of atmospheric particles at winter in Beijing and compare the lung toxicity which induced by particle samples from different sampling sites. MethodWe collected samples from two sampling points during the winter for toxicity testing and chemical analysis. Wistar rats were administered with particles by intratracheal instillation. After exposure, biochemically index, esimmunity indexes, histopathology and DNA damage were detected in rat pulmonary cells. ResultThe elements with enrichment factors (EF) larger than 10 were As, Cd, Cu, Zn, S and Pb in the four experiment groups. The priority control of the total concentration of polycyclic aromatic hydrocarbons (PAHs) in PM 10 and PM 2.5 of Near-traffic source was much higher than that of Far-traffic source, it demonstrated that near the traffic source of PAHs pollution was heavier than that of Far-traffic source, as it was close to main roads Beiyuan Road, motor vehicle emissions were much higher. The pathology of lung showed that the degree of inflammation was increased with the particle diameter minished, it was the same as the detection of biochemical parameters such as lactate dehydrogenase (LDH), Total antioxidant status(T-AOC) and total protein (TP) in BALF and inflammation cytokine(interleukin-1, interleukin-6 and tumor necrosis factor-alpha) in lung homogenate. The indexes of DNA damage including the content of DNA and Olive empennage of PM 2.5 were significant higher than that of PM 10 at the same surveillance point ( P < 0.05), near-traffic particles were higher than the far-traffic particles at the same diameter, ( P < 0.05). ConclusionNear-traffic area particles had certain pollution at winter in Beijing. Meanwhile, atmospheric particulate matters on lung toxicity were related to the particles size and distance related sites which were exposed: smaller size, more toxicity; nearer from traffic, more toxicity.

Developmental toxicity in flounder embryos exposed to crude oils derived from different geographical regions.

PubMed

Jung, Jee-Hyun; Lee, Eun-Hee; Choi, Kwang-Min; Yim, Un Hyuk; Ha, Sung Yong; An, Joon Geon; Kim, Moonkoo

2017-06-01

Crude oils from distinct geographical regions have distinct chemical compositions, and, as a result, their toxicity may be different. However, developmental toxicity of crude oils derived from different geographical regions has not been extensively characterized. In this study, flounder embryos were separately exposed to effluents contaminated by three crude oils including: Basrah Light (BLO), Pyrenees (PCO), and Sakhalin Vityaz (SVO), in addition to a processed fuel oil (MFO-380), to measure developmental toxicity and for gene expressions. Each oil possessed a distinct chemical composition. Edema defect was highest in embryos exposed to PCO and MFO-380 that both have a greater fraction of three-ring PAHs (33% and 22%, respectively) compared to BLO and SVO. Observed caudal fin defects were higher in embryos exposed to SVO and MFO-380, which are both dominated by naphthalenes (81% and 52%, respectively). CYP1A gene expressions were also highest in embryos exposed to SVO and MFO-380. Higher incidence of cardiotoxicity and lower nkx 2.5 expression were detected in embryos exposed to PCO. Unique gene expression profiles were observed in embryos exposed to crude oils with distinct compositions. This study demonstrates that crude oils of different geographical origins with different compositional characteristics induce developmental toxicity to different degrees. Copyright © 2017 Elsevier Inc. All rights reserved.

Bacillus pumilus KatX2 confers enhanced hydrogen peroxide resistance to a Bacillus subtilis PkatA::katX2 mutant strain.

PubMed

Handtke, Stefan; Albrecht, Dirk; Zühlke, Daniela; Otto, Andreas; Becher, Dörte; Schweder, Thomas; Riedel, Kathrin; Hecker, Michael; Voigt, Birgit

2017-04-26

Bacillus pumilus cells exhibit a significantly higher resistance to hydrogen peroxide compared to closely related Bacilli like Bacillus subtilis. In this study we analyzed features of the catalase KatX2 of B. pumilus as one of the most important parts of the cellular response to hydrogen peroxide. KatX2, the vegetative catalase expressed in B. pumilus, was compared to the vegetative catalase KatA of B. subtilis. Data of our study demonstrate that B. pumilus can degrade toxic concentrations of hydrogen peroxide faster than B. subtilis. By replacing B. subtilis katA gene by katX2 we could significantly enhance its resistance to H 2 O 2 and its potential to eliminate this toxic compound. Mutant cells showed a 1.5- to 2-fold higher survival to toxic concentrations of hydrogen peroxide compared to wild type cells. Furthermore, we found reversible but also irreversible oxidations of the KatX2 protein which, in contrast to KatA, contains several cysteine residues. Our study indicates that the catalase KatX2 plays a major role in the increased resistance of B. pumilus to oxidative stress caused by hydrogen peroxide. Resistance to hydrogen peroxide of other Bacilli can be enhanced by exchanging the native catalase in the cells with katX2.

Low muscle mass is associated with chemotherapy-induced haematological toxicity in advanced non-small cell lung cancer.

PubMed

Sjøblom, Bjørg; Grønberg, Bjørn H; Benth, Jūratė Šaltytė; Baracos, Vickie E; Fløtten, Øystein; Hjermstad, Marianne J; Aass, Nina; Jordhøy, Marit

2015-10-01

Recent research suggests a significant relationship between lean body mass (LBM) and toxicity from chemotherapeutic agents. We investigated if higher drug doses per kg LBM were associated with increased toxicity in stage IIIB/IV non-small cell lung cancer (NSCLC) patients receiving a first-line chemotherapy regimen dosed according to body surface area (BSA). Data from patients randomised to receive intravenous gemcitabine 1000 mg/m(2) plus orally vinorelbine 60 mg/m(2) days 1 and 8 in a phase III trial comparing two chemotherapy regimens were analysed. LBM was estimated from assessment of the cross-sectional muscle area at the third lumbar level (L3) on computed tomography images obtained before chemotherapy commenced. Common terminology criteria for adverse events (CTCAE) grade 3-4 haematological toxicity and dose reduction and/or stop of treatment after the first course of chemotherapy were defined as primary and secondary toxicity outcomes. The study sample included 153 patients, mean age was 66 years, 55% were men, 87% had disease stage IV and 75% had performance status (PS) 0-1. Gemcitabine doses per kg LBM varied from 23.2 to 53.1 mg/kg LBM, and vinorelbine doses from 1.5 to 3.3 mg/kg LBM. Higher doses of gemcitabine per kg LBM were significantly associated with grade 3-4 haematological toxicity in bivariate (OR=1.12, 95% CI 1.03-1.23, p=0.008) and multivariate analyses (OR=1.15, 95% CI 1.01-1.29, p=0.018), as were also higher doses of vinorelbine per kg LBM. No significant association was found between drug doses per kg LBM and dose reduction and/or stop of treatment. The study showed that dose estimates according to BSA lead to a substantial variation in drug dose per kg LBM, and higher doses per kg LBM are a significant predictor for chemotherapy-induced haematological toxicity. The results indicate that taking LBM into account may lead to a better dose individualisation of chemotherapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Complex Mixture-Associated Hormesis and Toxicity: The Case of Leather Tanning Industry

PubMed Central

Pagano, Giovanni; Castello, Giuseppe; Gallo, Marialuisa; Borriello, Ilaria; Guida, Marco

2008-01-01

A series of studies investigated the toxicities of tannery-derived complex mixtures, i.e. vegetable tannin (VT) from Acacia sp. or phenol-based synthetic tannin (ST), and waste-water from tannin-based vs. chromium-based tanneries. Toxicity was evaluated by multiple bioassays including developmental defects and loss of fertilization rate in sea urchin embryos and sperm (Paracentrotus lividus and Sphaerechinus granularis), and algal growth inhibition (Dunaliella tertiolecta and Selenastrum capricornutum). Both VT and ST water extracts resulted in hormetic effects at concentrations ranging 0.1 to 0.3%, and toxicity at levels ≥1%, both in sea urchin embryo and sperm, and in algal growth bioassays. When comparing tannin-based tannery wastewater (TTW) vs. chromium-based tannery effluent (CTE), a hormesis to toxicity trend was observed for TTW both in terms of developmental and fertilization toxicity in sea urchins, and in algal growth inhibition, with hormetic effects at 0.1 to 0.2% TTW, and toxicity at TTW levels ≥1%. Unlike TTW, CTE showed a monotonic toxicity increase from the lowest tested level (0.1%) and CTE toxicity at higher levels was significantly more severe than TTW-induced toxicity. The results support the view that leather production utilizing tannins might be regarded as a more environmentally friendly procedure than chromium-based tanning process. PMID:19088903

Complex mixture-associated hormesis and toxicity: the case of leather tanning industry.

PubMed

Pagano, Giovanni; Castello, Giuseppe; Gallo, Marialuisa; Borriello, Ilaria; Guida, Marco

2008-01-01

A series of studies investigated the toxicities of tannery-derived complex mixtures, i.e. vegetable tannin (VT) from Acacia sp. or phenol-based synthetic tannin (ST), and waste-water from tannin-based vs. chromium-based tanneries. Toxicity was evaluated by multiple bioassays including developmental defects and loss of fertilization rate in sea urchin embryos and sperm (Paracentrotus lividus and Sphaerechinus granularis), and algal growth inhibition (Dunaliella tertiolecta and Selenastrum capricornutum). Both VT and ST water extracts resulted in hormetic effects at concentrations ranging 0.1 to 0.3%, and toxicity at levels > or =1%, both in sea urchin embryo and sperm, and in algal growth bioassays. When comparing tannin-based tannery wastewater (TTW) vs. chromium-based tannery effluent (CTE), a hormesis to toxicity trend was observed for TTW both in terms of developmental and fertilization toxicity in sea urchins, and in algal growth inhibition, with hormetic effects at 0.1 to 0.2% TTW, and toxicity at TTW levels > or =1%. Unlike TTW, CTE showed a monotonic toxicity increase from the lowest tested level (0.1%) and CTE toxicity at higher levels was significantly more severe than TTW-induced toxicity. The results support the view that leather production utilizing tannins might be regarded as a more environmentally friendly procedure than chromium-based tanning process.

GHS additivity formula: can it predict the acute systemic toxicity of agrochemical formulations that contain acutely toxic ingredients?

PubMed

Van Cott, Andrew; Hastings, Charles E; Landsiedel, Robert; Kolle, Susanne; Stinchcombe, Stefan

2018-02-01

In vivo acute systemic testing is a regulatory requirement for agrochemical formulations. GHS specifies an alternative computational approach (GHS additivity formula) for calculating the acute toxicity of mixtures. We collected acute systemic toxicity data from formulations that contained one of several acutely-toxic active ingredients. The resulting acute data set includes 210 formulations tested for oral toxicity, 128 formulations tested for inhalation toxicity and 31 formulations tested for dermal toxicity. The GHS additivity formula was applied to each of these formulations and compared with the experimental in vivo result. In the acute oral assay, the GHS additivity formula misclassified 110 formulations using the GHS classification criteria (48% accuracy) and 119 formulations using the USEPA classification criteria (43% accuracy). With acute inhalation, the GHS additivity formula misclassified 50 formulations using the GHS classification criteria (61% accuracy) and 34 formulations using the USEPA classification criteria (73% accuracy). For acute dermal toxicity, the GHS additivity formula misclassified 16 formulations using the GHS classification criteria (48% accuracy) and 20 formulations using the USEPA classification criteria (36% accuracy). This data indicates the acute systemic toxicity of many formulations is not the sum of the ingredients' toxicity (additivity); but rather, ingredients in a formulation can interact to result in lower or higher toxicity than predicted by the GHS additivity formula. Copyright © 2018 Elsevier Inc. All rights reserved.

A Dosimetric Comparison of Proton and Intensity Modulated Radiation Therapy in Pediatric Rhabdomyosarcoma Patients Enrolled on a Prospective Phase II Proton Study

PubMed Central

Ladra, Matthew M.; Edgington, Samantha K.; Mahajan, Anita; Grosshans, David; Szymonifka, Jackie; Khan, Fazal; Moteabbed, Maryam; Friedmann, Alison M.; MacDonald, Shannon M.; Tarbell, Nancy J.; Yock, Torunn I.

2015-01-01

Background Pediatric rhabdomyosarcoma (RMS) is highly curable, however, cure may come with significant radiation related toxicity in developing tissues. Proton therapy (PT) can spare excess dose to normal structures, potentially reducing the incidence of adverse effects. Methods Between 2005 and 2012, 54 patients were enrolled on a prospective multi-institutional phase II trial using PT in pediatric RMS. As part of the protocol, intensity modulated radiation therapy (IMRT) plans were generated for comparison with clinical PT plans. Results Target coverage was comparable between PT and IMRT plans with a mean CTV V95 of 100% for both modalities (p=0.82). However, mean integral dose was 1.8 times higher for IMRT (range 1.0-4.9). By site, mean integral dose for IMRT was 1.8 times higher for H&N (p<0.01) and GU (p=0.02), 2.0 times higher for trunk/extremity (p<0.01), and 3.5 times higher for orbit (p<0.01) compared to PT. Significant sparing was seen with PT in 26 of 30 critical structures assessed for orbital, head and neck, pelvic, and trunk/extremity patients. Conclusions Proton radiation lowers integral dose and improves normal tissue sparing when compared to IMRT for pediatric RMS. Correlation with clinical outcomes is necessary once mature long-term toxicity data are available. PMID:25443861

Breast cancer in Latinas: gene expression, differential response to treatments, and differential toxicities in Latinas compared with other population groups.

PubMed

Patel, Tejal A; Colon-Otero, Gerardo; Bueno Hume, Celyne; Copland, John A; Perez, Edith A

2010-01-01

Disparities in clinical outcomes of breast cancer have been described among different racial and ethnic groups in the U.S. Convincing data exist showing that Latina women have a lower incidence of breast cancer but a higher breast cancer-related mortality rate compared with white women. Noticeable differences in breast cancer incidence are present even within different Latina subsets with a higher incidence in second- and third-generation women compared with foreign born. An increasing amount of data exists pointing to significant differences in the genetics and biology of breast cancer in Latinas as a significant contributor to the higher mortality, including a higher incidence of triple-negative breast cancers (which do not overexpress HER-2 protein and are negative for estrogen receptors and progesterone receptors). Other social and environmental factors are likely to play a significant role as well, including a lower rate of screening mammography, variable access to medical care, among others. Recent data are inconclusive regarding differences among racial/ethnic groups in the response to chemotherapy. Data on racial/ethnic variations in the pharmacogenomics of chemotherapy, endocrine treatments, and toxicity are more limited, with some data suggesting differences in frequencies of polymorphisms of genes involved in the metabolism of some of these agents. Further studies are needed on this subject.

Biological effects of carbon black nanoparticles are changed by surface coating with polycyclic aromatic hydrocarbons.

PubMed

Lindner, Karina; Ströbele, Michael; Schlick, Sandra; Webering, Sina; Jenckel, André; Kopf, Johannes; Danov, Olga; Sewald, Katherina; Buj, Christian; Creutzenberg, Otto; Tillmann, Thomas; Pohlmann, Gerhard; Ernst, Heinrich; Ziemann, Christina; Hüttmann, Gereon; Heine, Holger; Bockhorn, Henning; Hansen, Tanja; König, Peter; Fehrenbach, Heinz

2017-03-21

Carbon black nanoparticles (CBNP) are mainly composed of carbon, with a small amount of other elements (including hydrogen and oxygen). The toxicity of CBNP has been attributed to their large surface area, and through adsorbing intrinsically toxic substances, such as polycyclic aromatic hydrocarbons (PAH). It is not clear whether a PAH surface coating changes the toxicological properties of CBNP by influencing their physicochemical properties, through the specific toxicity of the surface-bound PAH, or by a combination of both. Printex ® 90 (P90) was used as CBNP; the comparators were P90 coated with either benzo[a]pyrene (BaP) or 9-nitroanthracene (9NA), and soot from acetylene combustion that bears various PAHs on the surface (AS-PAH). Oxidative stress and IL-8/KC mRNA expression were determined in A549 and bronchial epithelial cells (16HBE14o-, Calu-3), mouse intrapulmonary airways and tracheal epithelial cells. Overall toxicity was tested in a rat inhalation study according to Organization for Economic Co-operation and Development (OECD) criteria. Effects on cytochrome monooxygenase (Cyp) mRNA expression, cell viability and mucociliary clearance were determined in acute exposure models using explanted murine trachea. All particles had similar primary particle size, shape, hydrodynamic diameter and ζ-potential. All PAH-containing particles had a comparable specific surface area that was approximately one third that of P90. AS-PAH contained a mixture of PAH with expected higher toxicity than BaP or 9NA. PAH-coating reduced some effects of P90 such as IL-8 mRNA expression and oxidative stress in A549 cells, granulocyte influx in the in vivo OECD experiment, and agglomeration of P90 and mucus release in the murine trachea ex vivo. Furthermore, P90-BaP decreased particle transport speed compared to P90 at 10 μg/ml. In contrast, PAH-coating induced IL-8 mRNA expression in bronchial epithelial cell lines, and Cyp mRNA expression and apoptosis in tracheal epithelial cells. In line with the higher toxicity compared to P90-BaP and P90-9NA, AS-PAH had the strongest biological effects both ex vivo and in vivo. Our results demonstrate that the biological effect of CBNP is determined by a combination of specific surface area and surface-bound PAH, and varies in different target cells.

Influence of salinity and dissolved organic carbon on acute Cu toxicity to the rotifer Brachionus plicatilis.

PubMed

Cooper, Christopher A; Tait, Tara; Gray, Holly; Cimprich, Giselle; Santore, Robert C; McGeer, James C; Wood, Christopher M; Smith, D Scott

2014-01-21

Acute copper (Cu) toxicity tests (48-h LC50) using the euryhaline rotifer Brachionus plicatilis were performed to assess the effects of salinity (3, 16, 30 ppt) and dissolved organic carbon (DOC, ∼ 1.1, ∼ 3.1, ∼ 4.9, ∼ 13.6 mg C L(-1)) on Cu bioavailability. Total Cu was measured using anodic stripping voltammetry, and free Cu(2+) was measured using ion-selective electrodes. There was a protective effect of salinity observed in all but the highest DOC concentrations; at all other DOC concentrations the LC50 value was significantly higher at 30 ppt than at 3 ppt. At all salinities, DOC complexation significantly reduced Cu toxicity. At higher concentrations of DOC the protective effect increased, but the increase was less than expected from a linear extrapolation of the trend observed at lower concentrations, and the deviation from linearity was greatest at the highest salinity. Light-scattering data indicated that salt induced colloid formation of DOC could be occurring under these conditions, thereby decreasing the number of available reactive sites to complex Cu. When measurements of free Cu across DOC concentrations at each individual salinity were compared, values were very similar, even though the total Cu LC50 values and DOC concentrations varied considerably. Furthermore, measured free Cu values and predicted model values were comparable, highlighting the important link between the concentration of bioavailable free Cu and Cu toxicity.

Comparison of toxicity values across zebrafish early life stages and mammalian studies: Implications for chemical testing.

PubMed

Ducharme, Nicole A; Reif, David M; Gustafsson, Jan-Ake; Bondesson, Maria

2015-08-01

With the high cost and slow pace of toxicity testing in mammals, the vertebrate zebrafish has become a tractable model organism for high throughput toxicity testing. We present here a meta-analysis of 600 chemicals tested for toxicity in zebrafish embryos and larvae. Nineteen aggregated and 57 individual toxicity endpoints were recorded from published studies yielding 2695 unique data points. These data points were compared to lethality and reproductive toxicology endpoints analyzed in rodents and rabbits and to exposure values for humans. We show that although many zebrafish endpoints did not correlate to rodent or rabbit acute toxicity data, zebrafish could be used to accurately predict relative acute toxicity through the rat inhalation, rabbit dermal, and rat oral exposure routes. Ranking of the chemicals based on toxicity and teratogenicity in zebrafish, as well as human exposure levels, revealed that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), benzo(a)pyrene, and chlorpyrifos ranked in the top nine of all chemicals for these three categories, and as such should be considered high priority chemicals for testing in higher vertebrates. Copyright © 2014 Elsevier Inc. All rights reserved.

Comparative toxicity of bentazon and molinate on growth, photosynthetic pigments, photosynthesis, and respiration of the Portuguese ricefield cyanobacterium Nostoc muscorum.

PubMed

Galhano, Victor; Peixoto, Francisco; Gomes-Laranjo, José; Fernández-Valiente, Eduardo

2010-04-01

Bentazon and molinate are selective herbicides recommended for integrated weed management in rice. Their toxicity on growth and some biochemical and physiological parameters of Nostoc muscorum, an abundant cyanobacterium in Portuguese rice fields, was evaluated under laboratory conditions during time- and concentration-dependent exposure for 72 h. Results showed that toxic concentrations (0.75-2 mM) of both herbicides have pleiotropic effects on the cyanobacterium. Molinate was more toxic than bentazon to growth, respiration, chlorophyll-a, carotenoids, and phycobiliproteins contents. Protein content was increased by both herbicides although the effect was particularly evident with higher concentrations of molinate (1.5-2 mM). The herbicides had contrasting effects on carbohydrates content: molinate increased this organic fraction whereas bentazon decreased it. Photosynthesis and respiration were inhibited by both herbicides.

Toxicity of thiamethoxam to Tetranychus urticae Koch and Phytoseiulus persimilis Athias-Henriot (Acari Tetranychidae, Phytoseiidae) through different routes of exposure.

PubMed

Pozzebon, Alberto; Duso, Carlo; Tirello, Paola; Ortiz, Paulina Bermudez

2011-03-01

Knowledge of the impact of insecticides on Tetranychus urticae Koch and its predator Phytoseiulus persimilis Athias-Henriot is crucial for IPM. This study evaluates the effect of thiamethoxam on T. urticae and its predator by considering different routes of exposure (topical, residual and contaminated food exposures) and their combinations. Thiamethoxam effects on T. urticae were higher when residual and contaminated food exposures were considered. The total effect was higher than 90% where contaminated food exposure was involved. On P. persimilis, the total effect was higher in residual and contaminated prey exposures compared with topical exposure, and all combinations of routes of exposure attained a total effect higher than 90%. Thiamethoxam was found to be toxic to T. urticae and P. persimilis; however, the impact of the insecticide depended on the routes of exposure and their combinations. Lethal and sublethal effects occurred in residual and contaminated food exposures, while only sublethal effects occurred in topical exposure of predators and prey. The toxicity of thiamethoxam on prey and predator increased with the number of exposure routes involved. By limiting exposure to thiamethoxam to ingestion of contaminated food only, the impact of the pesticide was more favourable to P. persimilis than to its prey. Copyright © 2010 Society of Chemical Industry.

The effect of soil properties on the toxicity and bioaccumulation of Ag nanoparticles and Ag ions in Enchytraeus crypticus.

PubMed

Topuz, Emel; van Gestel, Cornelis A M

2017-10-01

Standard natural Lufa soils (2.2, 2.3 and 5M) with different organic carbon contents (0.67-1.61%) and pH CaCl2 (5.5-7.3) were spiked with ionic Ag (AgNO 3 ) and polyvinyl pyrrolidone (AgNP-PVP) and citrate (AgNP-Cit) coated Ag nanoparticles (NPs). Enchytraeus crypticus were exposed for 21 days to assess effects on survival and reproduction. Soil, pore water and animals were analyzed for Ag. AgNP-Cit had a strong increasing effect on soil pH, leading to high enchytraeid mortality at concentrations higher than 60-100mg Ag/kg dry soil which made it impossible to determine the influence of soil properties on its toxicity. LC50s were lower for AgNO 3 than for AgNP-PVP (92-112 and 335-425mg Ag/kg dry soil, respectively) and were not affected by soil properties. AgNO 3 and AgNP-PVP had comparable reproductive toxicity with EC50s of 26.9-75.2 and 28.2-92.3mg Ag/kg dry soil, respectively; toxicity linearly increased with decreasing organic carbon content of the soils but did not show a clear effect of soil pH. Ag uptake in the enchytraeids was higher at higher organic carbon content, but could not explain differences in toxicity between soils. This study indicates that the bioavailability of both ionic and nanoparticulate Ag is mainly affected by soil organic carbon, with little effect of soil pH. Copyright © 2017. Published by Elsevier Inc.

Antibacterial activity and toxicity of silver - nanosilver versus ionic silver

NASA Astrophysics Data System (ADS)

Kvitek, L.; Panacek, A.; Prucek, R.; Soukupova, J.; Vanickova, M.; Kolar, M.; Zboril, R.

2011-07-01

The in vitro study of antibacterial activity of silver nanoparticles (NPs), prepared via modified Tollens process, revealed high antibacterial activity even at very low concentrations around several units of mg/L. These concentrations are comparable with concentrations of ionic silver revealing same antibacterial effect. However, such low concentrations of silver NPs did not show acute cytotoxicity to mammalian cells - this occurs at concentrations higher than 60 mg/L of silver, while the cytotoxic level of ionic silver is much more lower (approx. 1 mg/L). Moreover, the silver NPs exhibit lower acute ecotoxicity against the eukaryotic organisms such as Paramecium caudatum, Monoraphidium sp. and D. melanogaster. The silver NPs are toxic to these organisms at the concentrations higher than 30 mg/L of silver. On contrary, ionic silver retains its cytoxicity and ecotoxicity even at the concentration equal to 1 mg/L. The performed experiments demonstrate significantly lower toxicity of silver NPs against the eukaryotic organisms than against the prokaryotic organisms.

Acute and subacute toxicities effect of oxytetracycline pharmaceutical wastewater on Zebrafish

NASA Astrophysics Data System (ADS)

Wu, Pengpeng; Shen, Hong-Yan

2018-02-01

Oxytetracycline wastewater is a major category of pharmaceutical wastewater, and its toxic effects on aquatic organisms have aroused people’s attention. In this study, Zebrafish were separately exposed to four Oxytetracycline wastewater treatments (20%, 40%, 60%, 80%) and a control group were sampled on days 3, 6, 9, 12, and 15. Superoxide dismutase (SOD) activities showed significant inhibition, but the highest SOD activity was found in 20% and 40% the treatment groups (195.12U/mgprot, 187.43U/mgprot, respectively) on the 12th day. MDA contents increased significantly compared with control group. MDA contents showed that the higher the volume concentration, the higher the contents of MDA with the increase of exposure time. The highest MDA content shown in 60% exposure group (5.49nmol/mgprot) on the 12th day. And SOD activities and MDA contents showed a trend of “Λ” type. In conclusion, Oxytetracycline wastewater induced oxidative stress and toxicity in Zebrafish muscle tissue.

Effects of endosulfan, thiamethoxam, and indoxacarb in combination with atrazine on multi-biomarkers in Gammarus kischineffensis.

PubMed

Demirci, Özlem; Güven, Kemal; Asma, Dilek; Öğüt, Serdal; Uğurlu, Pelin

2018-01-01

Studies addressing the toxicity of pesticides towards non-target organisms focus on the median lethal concentration and biochemical response of individual pesticides. However, when determining environmental risks, it is important to test the combined effects of pesticides, such as insecticides and herbicides, which are frequently used together in agricultural areas. Here we aimed to investigate the toxic effects of the combined use of the herbicide atrazine and the insecticides, endosulfan, indoxacarb, and thiamethoxam on Gammarus kischineffensis. To do this, we tested the activities of oxidative stress, detoxification, and neurotoxicity biomarkers. Compared to atrazine alone, we detected higher glutathione-S-transferase, catalase and superoxide dismutase activities (oxidative stress biomarkers) when atrazine was combined with either endosulfan or indoxacarb. However, higher IBR values were determined in organisms where pesticide mixtures were used according to individual use. Based on these results, mixtures of atrazine and other pesticides may cause synergistic effects and may be evidence of increased toxicity and oxidative stress. Copyright © 2017 Elsevier Inc. All rights reserved.

Acute toxicity of an acid mine drainage mixing zone to juvenile bluegill and largemouth bass

USGS Publications Warehouse

Henry, T.B.; Irwin, E.R.; Grizzle, J.M.; Wildhaber, M.L.; Brumbaugh, W.G.

1999-01-01

The toxicity of an acid mixing zone produced at the confluence of a stream that was contaminated by acid mine drainage (AMD) and a pH-neutral stream was investigated in toxicity tests with juvenile bluegill Lepomis macrochirus and largemouth bass Micropterus salmoides. Fish mortalities in instream cages located in the mixing zone, below the mixing zone, and upstream in both tributaries were compared to determine relative toxicity at each site. In all tests and for both species, significantly higher mortality was observed in the mixing zone than at any other location, including the acid stream, which had lower pH (2.9-4.3). The mixing zone was defined chemically by rapid precipitation of dissolved aluminum and iron, which arrived from the low-pH stream, and by the presence of white precipitates, which were attached to the substratum and which extended below the confluence. Possible seasonal changes in mixing zone toxicity were investigated by conducting field tests with bluegill in June, July, and August 1996 and in January 1997 and by conducting field tests with largemouth bass in April and May 1997. Toxicity was not significantly different at the extremes of temperature, pH, and metal concentration that occurred in June and July, as compared with January. Toxicity was significantly lower in August; however, elevated stream discharge during the August test may have disturbed mixing zone characteristics. High toxicity in AMD mixing zones may lower the survival of fishes in streams, reduce available habitat, and impede movements of migratory fish.

Acute Toxicity of TiO2 Nanoparticles to Ceriodaphnia dubia under Visible Light and Dark Conditions in a Freshwater System

PubMed Central

Dalai, Swayamprava; Pakrashi, Sunandan; Chandrasekaran, Natarajan; Mukherjee, Amitava

2013-01-01

The ever increasing industrial and consumer applications of titanium dioxide nanoparticles (TiO2 NPs) raise concern over the possible risk associated with their environmental exposure. Still, the knowledge regarding nanoparticle behavior in a freshwater ecosystem is lacking. The current study focuses on the toxicity of TiO2 NPs towards Ceriodaphnia dubia (a dominant daphnid isolated from the freshwater) under two different conditions; (1) light and dark photoperiod (16:8 h) and (2) continuous dark conditions, for a period of 48 h. An increase in toxicity was observed with an increase in the concentration, until a certain threshold level (under both photoperiod and dark conditions), and beyond which, reduction was noted. The decrease in toxicity would have resulted from the aggregation and settling of NPs, making them less bioavailable. The oxidative stress was one of the major contributors towards cytotoxicity under both photoperiod and dark conditions. The slow depuration of TiO2 NPs under the photoperiod conditions confirmed a higher NP bioaccumulation and thus a higher bioconcentration factor (BCF) compared to dark conditions. The transmission electron micrographs confirmed the bioaccumulation of NPs and damage of tissues in the gut lining. PMID:23658658

Assessment of diclofenac LC50 reference values in juvenile and embryonic stages of the zebrafish (Danio rerio).

PubMed

Praskova, E; Voslarova, E; Siroka, Z; Plhalova, L; Macova, S; Marsalek, P; Pistekova, V; Svobodova, Z

2011-01-01

The aim of the study was to compare the acute toxicity of diclofenac to juvenile and embryonic stages of the zebrafish (Danio rerio). Acute toxicity tests were performed on the aquarium fish Danio rerio, which is one of the model organisms most commonly used in toxicity testing. The tests were performed using a semi-static method according to OECD guideline No. 203 (Fish, acute toxicity test). Embryo toxicity tests were performed in zebrafish embryos (Danio rerio) in compliance with OECD No. 212 methodology (Fish, short-term toxicity test on embryo and sac-fry stages). The results were subjected to a probit analysis using the EKO-TOX 5.2 programme to determine 96hLC50 and 144hLC50 (median lethal concentration, 50% mortality after a 96 h or 144 h interval, respectively) values of diclofenac. The statistical significance of the difference between LC50 values in juvenile and embryonic stages of Danio rerio was tested using the Mann-Whitney non-parametric test implemented in the Unistat 5.1 programme. The LC50 mean value of diclofenac was 166.6 +/- 9.8 mg/L in juvenile Danio rerio, and 6.11 +/- 2.48 mg/L in embryonic stages of Danio rerio. The study demonstrated a statistically higher sensitivity to diclofenac (P < 0.05) in embryonic stages compared to the juvenile fish.

Comparative toxicological assessment of PAMAM and thiophosphoryl dendrimers using embryonic zebrafish

PubMed Central

Pryor, Joseph B; Harper, Bryan J; Harper, Stacey L

2014-01-01

Dendrimers are well-defined, polymeric nanomaterials currently being investigated for biomedical applications such as medical imaging, gene therapy, and tissue targeted therapy. Initially, higher generation (size) dendrimers were of interest because of their drug carrying capacity. However, increased generation was associated with increased toxicity. The majority of studies exploring dendrimer toxicity have focused on a small range of materials using cell culture methods, with few studies investigating the toxicity across a wide range of materials in vivo. The objective of the present study was to investigate the role of surface charge and generation in dendrimer toxicity using embryonic zebrafish (Danio rerio) as a model vertebrate. Due to the generational and charge effects observed at the cellular level, higher generation cationic dendrimers were hypothesized to be more toxic than lower generation anionic or neutral dendrimers with the same core composition. Polyamidoamine (PAMAM) dendrimers elicited significant morbidity and mortality as generation was decreased. No significant adverse effects were observed from the suite of thiophosphoryl dendrimers studied. Exposure to ≥50 ppm cationic PAMAM dendrimers G3-amine, G4-amine, G5-amine, and G6-amine caused 100% mortality by 24 hours post-fertilization. Cationic PAMAM G6-amine at 250 ppm was found to be statistically more toxic than both neutral PAMAM G6-amidoethanol and anionic PAMAM G6-succinamic acid at the same concentration. The toxicity observed within the suite of varying dendrimers provides evidence that surface charge may be the best indicator of dendrimer toxicity. Dendrimer class and generation are other potential contributors to the toxicity of dendrimers. Further studies are required to better understand the relative role each plays in driving the toxicity of dendrimers. To the best of our knowledge, this is the first in vivo study to address such a broad range of dendrimers. PMID:24790436

Effect of surfactant in mitigating cadmium oxide nanoparticle toxicity: Implications for mitigating cadmium toxicity in environment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Balmuri, Sricharani Rao

Cadmium (Cd), classified as human carcinogen, is an extremely toxic heavy metal pollutant, and there is an increasing environmental concern for cadmium exposure through anthropogenic sources including cigarette smoke. Though Cd based nanoparticles such as cadmium oxide (CdO) are being widely used in a variety of clinical and industrial applications, the toxicity of CdO nanoparticles has not been well characterized. Herein we report the toxicity of CdO nanoparticles employing zebrafish as a model. Two different CdO nanoparticles were prepared, calcination of Cd(OH){sub 2} without any organic molecule (CdO-1) and calcination of Cd-citrate coordination polymer (CdO-2), to evaluate and compare themore » toxicity of these two different CdO nanoparticles. Results show that zebrafish exposed to CdO-2 nanoparticles expressed reduced toxicity as judged by lower oxidative stress levels, rescue of liver carboxylesterases and reduction in metallothionein activity compared to CdO-1 nanoparticles. Histopathological observations also support our contention that CdO-1 nanoparticles showed higher toxicity relative to CdO-2 nanoparticles. The organic unit of Cd-citrate coordination polymer might have converted into carbon during calcination that might have covered the surface of CdO nanoparticles. This carbon surface coverage can control the release of Cd{sup 2+} ions in CdO-2 compared to non-covered CdO-1 nanoparticles and hence mitigate the toxicity in the case of CdO-2. This was supported by atomic absorption spectrophotometer analyses of Cd{sup 2+} ions release from CdO-1 and CdO-2 nanoparticles. Thus the present study clearly demonstrates the toxicity of CdO nanoparticles in an aquatic animal and also indicates that the toxicity could be substantially reduced by carbon coverage. This could have important implications in terms of anthropogenic release and environmental pollution caused by Cd and human exposure to Cd{sup 2+} from sources such as cigarette smoke. - Highlights: • Toxicity of CdO nanoparticles can be mitigated by the use of sodium citrate. • Sodium citrate covers the CdO surface and reduces Cd{sup 2+} ion release. • Use of sodium citrate reduces both biochemical and histopathological changes. • Sodium citrate can be a remediation strategy against CdO nanoparticles toxicity.« less

Comparative toxicity of inorganic contaminants released by placer mining to early life stages of salmonids

USGS Publications Warehouse

Buhl, Kevin J.; Hamilton, Steven J.

1990-01-01

The acute toxicities of four trace inorganics associated with placer mining were determined, individually and in environmentally relevant mixtures, to early life stages of Arctic grayling (Thymallus arcticus) from Alaska and Montana, coho salmon (Oncorhynchus kitsutch) from Alaska and Washington, and rainbow trout (Oncorhynchus mykiss) from Montana. The descending rank order of toxicity to all species and life stages was copper > zinc > lead > arsenic. For each of the three species, sensitivity to the inorganics was greater in juveniles than in alvenins or in swim-up fry. Arctic grayling from Alaska were more sensitive than the other species tested, including Arctic grayling from Montana. For Arctic grayling, sensitivity to all four inorganics was significantly greater in swim-up fry from Alaska than in alevins from Montana, and sensitivity to arsenic and copper was significantly greater in juveniles from Alaska than in juveniles from Montana. In tests with environmentally relevant mixtures (based on ratios of concentrations measured in streams with placer mining) of these four inorganics, copper was identified as the major toxic component because it accounted for ⩾97% of the summed toxic units of the mixture, and an equitoxic mixture of these inorganics showed less-than-additive toxicity. Total and total recoverable copper concentrations reported in five Alaskan streams with active placer mines were higher than the acutely toxic concentrations, either individually or in mixtures, that the authors found to be acutely toxic to Arctic grayling and coho salmon from Alaska. However, caution should be used when comparing our results obtained in “clear” water to field situations, because speciation and toxicity of these inorganics may be altered in the presence of sediments suspended by placer mining activities.

Dose Escalation to the Dominant Intraprostatic Lesion Defined by Sextant Biopsy in a Permanent Prostate I-125 Implant: A Prospective Comparative Toxicity Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gaudet, Marc; Vigneault, Eric; Aubin, Sylviane

2010-05-01

Purpose: Using real-time intraoperative inverse-planned permanent seed prostate implant (RTIOP/PSI), multiple core biopsy maps, and three-dimensional ultrasound guidance, we planned a boost volume (BV) within the prostate to which hyperdosage was delivered selectively. The aim of this study was to investigate the potential negative effects of such a procedure. Methods and Materials: Patients treated with RTIOP/PSI for localized prostate cancer with topographic biopsy results received an intraprostatic boost (boost group [BG]). They were compared with patients treated with a standard plan (reference group [RG]). Plans were generated using a simulated annealing inverse planning algorithm. Prospectively recorded urinary, rectal, and sexualmore » toxicities and dosimetric parameters were compared between groups. Results: The study included 120 patients treated with boost technique who were compared with 70 patients treated with a standard plan. Boost technique did not significantly change the number of seeds (55.1/RG vs. 53.6/BG). The intraoperative prostate V150 was slightly higher in BG (75.2/RG vs. 77.2/BG, p = 0.039). Urethra V100, urethra D90, and rectal D50 were significantly lower in the BG. No significant differences were seen in acute or late urinary, rectal, or sexual toxicities. Conclusions: Because there were no differences between the groups in acute and late toxicities, we believe that BV can be planned and delivered to the dominant intraprostatic lesion without increasing toxicity. It is too soon to say whether a boost technique will ultimately increase local control.« less

Acute lethal toxicity of environmental pollutants to aquatic organisms.

PubMed

Yen, Jui-Hung; Lin, Kuo-Hsiung; Wang, Yei-Shung

2002-06-01

The acute lethal toxicity of environment pollutants including chlorophenol, haloalkane, quinone, and substituted nitrobenzene (i.e., nitrophenol, nitrobenzene, nitrotoluene, and aniline) compounds to aquatic organisms was determined. Determination of toxicity of chemicals was performed with chlorella, daphnia, carp, and tilapia. The toxicity of chlorophenols had no relation to the number of chlorine atoms on the benzene ring, but monochlorophenol had lower activity than more chlorine-substituted compounds. The tolerance levels of daphnia and carp to haloalkanes was found to be higher than that of chlorella; toxicity to chlorella was several hundred times higher than to daphnia. The toxicity of naphthoquinone compounds to chlorella and carp was higher than that of anthraquinone. A compound with a monochloride substitution on anthraquinone ring was less toxic to carp than those substituted with amine, hydroxyl, and dichlorine groups. Nitrobenzene compounds with an additional substitution group on the p position were extremely toxic to daphnia and carp. (c) 2002 Elsevier Science (USA).

In vitro toxicity of nanoparticles in BRL 3A rat liver cells.

PubMed

Hussain, S M; Hess, K L; Gearhart, J M; Geiss, K T; Schlager, J J

2005-10-01

This study was undertaken to address the current deficient knowledge of cellular response to nanosized particle exposure. The study evaluated the acute toxic effects of metal/metal oxide nanoparticles proposed for future use in industrial production methods using the in vitro rat liver derived cell line (BRL 3A). Different sizes of nanoparticles such as silver (Ag; 15, 100 nm), molybdenum (MoO(3); 30, 150 nm), aluminum (Al; 30, 103 nm), iron oxide (Fe(3)O(4); 30, 47 nm), and titanium dioxide (TiO(2); 40 nm) were evaluated for their potential toxicity. We also assessed the toxicity of relatively larger particles of cadmium oxide (CdO; 1 microm), manganese oxide (MnO(2); 1-2 microm), and tungsten (W; 27 microm), to compare the cellular toxic responses with respect to the different sizes of nanoparticles with different core chemical compositions. For toxicity evaluations, cellular morphology, mitochondrial function (MTT assay), membrane leakage of lactate dehydrogenase (LDH assay), reduced glutathione (GSH) levels, reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) were assessed under control and exposed conditions (24h of exposure). Results showed that mitochondrial function decreased significantly in cells exposed to Ag nanoparticles at 5-50 microg/ml. However, Fe(3)O(4), Al, MoO(3) and TiO(2) had no measurable effect at lower doses (10-50 microg/ml), while there was a significant effect at higher levels (100-250 microg/ml). LDH leakage significantly increased in cells exposed to Ag nanoparticles (10-50 microg/ml), while the other nanoparticles tested displayed LDH leakage only at higher doses (100-250 microg/ml). In summary the Ag was highly toxic whereas, MoO(3) moderately toxic and Fe(3)O(4), Al, MnO(2) and W displayed less or no toxicity at the doses tested. The microscopic studies demonstrated that nanoparticle-exposed cells at higher doses became abnormal in size, displaying cellular shrinkage, and an acquisition of an irregular shape. Due to toxicity of silver, further study conducted with reference to its oxidative stress. The results exhibited significant depletion of GSH level, reduced mitochondrial membrane potential and increase in ROS levels, which suggested that cytotoxicity of Ag (15, 100 nm) in liver cells is likely to be mediated through oxidative stress.

Effect of aluminum (Al) speciation on erythrocytic antioxidant defense process: Correlations between lipid membrane peroxidation and morphological characteristics.

PubMed

Cheng, Dai; Tang, Jinlei; Wang, Xuerui; Zhang, Xinyu; Wang, Shuo

2018-08-15

Al contamination becomes a growing problem in human society. Accumulation of Al in blood could destroy the structure and disorder function of erythrocyte, and finally cause blood diseases. In the present study, AlCl 3 and Al(malt) 3 are respectively used in the erythrocyte system, in order to investigate the comparative toxic effect on erythrocyte fragility, the influence on cellular biochemical components and lipid peroxidation level. We find that the osmotic fragility, the number of Heinz bodies, the content of MDA and advanced oxidation protein product of the AlCl 3 treated erythrocytes were higher than the Al(malt) 3 treated erythrocytes at the same concentrations of Al(Ⅲ). The morphological and membrane protein changes of the AlCl 3 treated group show superior to the Al(malt) 3 treated group. In summary, we conclude that the comparative effect on the erythrocyte between organic aluminum and inorganic aluminum is significantly different, and the prime comparative difference between the toxic effects of both the compounds is oxidative stress. Further research should focus on in vivo experiments to confirm the differential toxicity and to elucidate the molecular mechanisms underlying Al-induced erythrocyte toxicity in order to prevent hematological disorders. Copyright © 2018 Elsevier Inc. All rights reserved.

Associations between dioxins/furans and dioxin-like PCBs in estuarine sediment and blue crab

USGS Publications Warehouse

Liebens, J.; Mohrherr, C.J.; Karouna-Renier, N. K.; Snyder, R.A.; Rao, K.R.

2011-01-01

The objective of the present study was to evaluate the relationships between the quantity, toxicity, and compositional profile of dioxin/furan compounds (PCDD/Fs) and dioxin-like polychlorinated biphenyls (DL-PCBs) in estuarine sediment and in the blue crab (Callinectes sapidus). Sediment and blue crab samples were collected in three small urban estuaries that are in relatively close proximity to each other. Results show that differences between PCDD/F and DL-PCB mass concentrations and total toxic equivalents (TEQ) toxicity in sediments of the three estuaries are reflected in those of the blue crab. TEQs are higher in the hepatopancreas of the crabs than in the sediment, but the concentration factor is inversely proportional to the TEQ in the sediments. Congener profiles in the crabs are systematically different from those in the sediments, and the difference is more pronounced for PCDD/Fs than for DL-PCBs, possibly due to differences in metabolization rates. Compared with sediment profiles, more lesser-chlorinated PCDD/Fs that have higher TEFs accumulate in crab hepatopancreas. This selective bioaccumulation of PCDD/Fs results in a TEQ augmentation in crab hepatopancreas compared with sediments. The bioaccumulation in the blue crab is also selective for PCDD/Fs over DL-PCBs. ?? 2011 Springer Science+Business Media B.V.

The impact of iodinated X-ray contrast agents on formation and toxicity of disinfection by-products in drinking water.

PubMed

Jeong, Clara H; Machek, Edward J; Shakeri, Morteza; Duirk, Stephen E; Ternes, Thomas A; Richardson, Susan D; Wagner, Elizabeth D; Plewa, Michael J

2017-08-01

The presence of iodinated X-ray contrast media (ICM) in source waters is of high concern to public health because of their potential to generate highly toxic disinfection by-products (DBPs). The objective of this study was to determine the impact of ICM in source waters and the type of disinfectant on the overall toxicity of DBP mixtures and to determine which ICM and reaction conditions give rise to toxic by-products. Source waters collected from Akron, OH were treated with five different ICMs, including iopamidol, iopromide, iohexol, diatrizoate and iomeprol, with or without chlorine or chloramine disinfection. The reaction product mixtures were concentrated with XAD resins and the mammalian cell cytotoxicity and genotoxicity of the reaction mixture concentrates was measured. Water containing iopamidol generated an enhanced level of mammalian cell cytotoxicity and genotoxicity after disinfection. While chlorine disinfection with iopamidol resulted in the highest cytotoxicity overall, the relative iopamidol-mediated increase in toxicity was greater when chloramine was used as the disinfectant compared with chlorine. Four other ICMs (iopromide, iohexol, diatrizoate, and iomeprol) expressed some cytotoxicity over the control without any disinfection, and induced higher cytotoxicity when chlorinated. Only iohexol enhanced genotoxicity compared to the chlorinated source water. Copyright © 2017. Published by Elsevier B.V.

Heavy metal concentrations and toxicity in water and sediment from stormwater ponds and sedimentation tanks.

PubMed

Karlsson, Kristin; Viklander, Maria; Scholes, Lian; Revitt, Mike

2010-06-15

Sedimentation is a widely used technique in structural best management practices to remove pollutants from stormwater. However, concerns have been expressed about the environmental impacts that may be exerted by the trapped pollutants. This study has concentrated on stormwater ponds and sedimentation tanks and reports on the accumulated metal concentrations (Cd, Cr, Ni, Pb, and Zn) and the associated toxicity to the bacteria Vibrio fischeri. The metal concentrations are compared with guidelines and the toxicity results are assessed in relation to samples for which metal concentrations either exceed or conform to these values. The water phase metal concentrations were highest in the ponds whereas the sedimentation tanks exhibited a distinct decrease towards the outlet. However, none of the water samples demonstrated toxicity even though the concentrations of Cu, Pb, and Zn exceeded the threshold values for the compared guidelines. The facilities with higher traffic intensities had elevated sediment concentrations of Cr, Cu, Ni, and Zn which increased towards the outlet for the sedimentation tanks in agreement with the highest percentage of fine particles. The sediments in both treatment facilities exhibited the expected toxic responses in line with their affinity for heavy metals but the role of organic carbon content is highlighted. Copyright 2010 Elsevier B.V. All rights reserved.

Life-Stage PBPK Models for Multiple Routes of Ethanol Exposure in the Rat

EPA Science Inventory

Ethanol is commonly blended with gasoline (10% ethanol) in the US, and higher ethanol concentrations are being considered. While the pharmacokinetics and toxicity of orally-ingested ethanol are widely reported, comparable work is limited for inhalation exposure (IE), particularly...

Pharmacological evaluation of total alkaloids from nux vomica: effect of reducing strychnine contents.

PubMed

Chen, Jun; Qu, Yange; Wang, Dongyue; Peng, Pei; Cai, Hao; Gao, Ying; Chen, Zhipeng; Cai, Baochang

2014-04-10

The aim of the study was to investigate the possibility of improving the therapeutic efficacy of the total alkaloid fraction (TAF) extracted from processed nux vomica by reducing the strychnine contents. Most strychnine was removed from TAF to obtain the modified total alkaloid fraction (MTAF). The toxicity and pharmacokinetics of TAF and MTAF were further investigated and compared besides their antitumor, analgesic and anti-inflammatory activities. The results showed that the ratios of brucine to strychnine were 1:2.05 and 2.2:1 for TAF and MTAF, respectively, and the toxicity of TAF was about 3.17-fold higher than that of MTAF. Compared to brucine alone, the elimination of brucine was found to be inhibited by other alkaloids in TAF or MTAF except strychnine. Significantly increased pharmacological activities when administered by the oral route were obtained with MTAF in comparison to TAF and nux vomica powder (NVP). In summary, MTAF might replace NVP and TAF in the clinical application of Chinese medicine to obtain much higher efficacy.

Relationship between toxic metals exposure via cigarette smoking and rheumatoid arthritis.

PubMed

Afridi, Hassan Imran; Kazi, Tasneem Gul; Talpur, Farah Naz; Naher, Sumsun; Brabazon, Dermot

2014-01-01

The incidence of Rheumatoid Arthritis (RA) has increased among people who smoke tobacco. In the present study, the association between toxic metals exposure via cigarette smoking and rheumatoid arthritis incidence in the population living in Dublin, Ireland, is investigated. The different brands of cigarettes (filler tobacco, filter and ash) consumed by the population studied were analysed for Cd, Ni, and Pb. The concentrations of toxic elements in biological samples and different components of cigarettes were measured by inductively coupled plasma atomic emission spectrophotometer after microwave-assisted acid digestion. The validity and accuracy of the methodology were checked using certified reference materials. The filler tobacco of different branded cigarettes contain Cd, Ni, and Pb concentrations in the ranges of 1.73-2.02, 0.715-1.52, and 0.378-1.16 μg/cigarette, respectively. The results of this study showed that the mean values of cadmium nickel, and lead were significantly higher in scalp hair and blood samples of rheumatoid arthritis patients when related to healthy controls, while the difference was significant in the case of smoker patients (p < 0.001). The levels of all three toxic metals were 2- to 3-fold higher in scalp hair and blood samples of non arthritis smoker subjects as compared to nonsmoker controls. The high exposure of toxic metals as a result of cigarette smoking may be synergistic with risk factors associated with rheumatoid arthritis.

Quality of life and toxicity in breast cancer patients using adjuvant TAC (docetaxel, doxorubicin, cyclophosphamide), in comparison with FAC (doxorubicin, cyclophosphamide, 5-fluorouracil).

PubMed

Hatam, N; Ahmadloo, N; Ahmad Kia Daliri, A; Bastani, P; Askarian, M

2011-07-01

The aim of this study was to compare two regimens of chemotherapy in patients with breast cancer, including FAC (doxorubicin, cyclophosphamide, and 5-fluorouracil) and TAC (docetaxel, doxorubicin and cyclophosphamide); and analyze the toxicity of these treatments and observe patient's health-related quality of life. Health-related quality of life was assessed for up to 4 months (from the beginning to the end of chemotherapy cycles), using European organization and cancer treatment quality of life questionnaire (EORTC) QLQ-C30. A group of 100 patients, with node-positive breast cancer were studied in order to compare the toxicity of adjuvant therapy TAC with FAC and the subsequent effects on the patient's quality of life. After a 4-month follow-up of patients, our findings showed that despite having the same mean score of QOL at the start of adjuvant chemotherapy, the QOL in TAC arm was decreased more as a result of the higher range of toxicity in TAC regimen. In spite of increase in disease-free patients who received TAC regimen and increase their survival rate, there is significant toxicity and decrease in QOL in TAC protocol compare to FAC protocol. Using prophylactic granulocyte colony stimulating factor (G-CSF) along with increased education aimed at improving patient's knowledge and also the provision of a supportive group involving psychiatrics and patients that have successfully experienced the same treatment may be helpful.

Tissue distribution and acute toxicity of silver after single intravenous administration in mice: nano-specific and size-dependent effects.

PubMed

Recordati, Camilla; De Maglie, Marcella; Bianchessi, Silvia; Argentiere, Simona; Cella, Claudia; Mattiello, Silvana; Cubadda, Francesco; Aureli, Federica; D'Amato, Marilena; Raggi, Andrea; Lenardi, Cristina; Milani, Paolo; Scanziani, Eugenio

2016-02-29

Silver nanoparticles (AgNPs) are an important class of nanomaterials used as antimicrobial agents for a wide range of medical and industrial applications. However toxicity of AgNPs and impact of their physicochemical characteristics in in vivo models still need to be comprehensively characterized. The aim of this study was to investigate the effect of size and coating on tissue distribution and toxicity of AgNPs after intravenous administration in mice, and compare the results with those obtained after silver acetate administration. Male CD-1(ICR) mice were intravenously injected with AgNPs of different sizes (10 nm, 40 nm, 100 nm), citrate-or polyvinylpyrrolidone-coated, at a single dose of 10 mg/kg bw. An equivalent dose of silver ions was administered as silver acetate. Mice were euthanized 24 h after the treatment, and silver quantification by ICP-MS and histopathology were performed on spleen, liver, lungs, kidneys, brain, and blood. For all particle sizes, regardless of their coating, the highest silver concentrations were found in the spleen and liver, followed by lung, kidney, and brain. Silver concentrations were significantly higher in the spleen, lung, kidney, brain, and blood of mice treated with 10 nm AgNPs than those treated with larger particles. Relevant toxic effects (midzonal hepatocellular necrosis, gall bladder hemorrhage) were found in mice treated with 10 nm AgNPs, while in mice treated with 40 nm and 100 nm AgNPs lesions were milder or negligible, respectively. In mice treated with silver acetate, silver concentrations were significantly lower in the spleen and lung, and higher in the kidney than in mice treated with 10 nm AgNPs, and a different target organ of toxicity was identified (kidney). Administration of the smallest (10 nm) nanoparticles resulted in enhanced silver tissue distribution and overt hepatobiliary toxicity compared to larger ones (40 and 100 nm), while coating had no relevant impact. Distinct patterns of tissue distribution and toxicity were observed after silver acetate administration. It is concluded that if AgNPs become systemically available, they behave differently from ionic silver, exerting distinct and size-dependent effects, strictly related to the nanoparticulate form.

Oil and oil dispersant do not cause synergistic toxicity to fish embryos.

PubMed

Adams, Julie; Sweezey, Michael; Hodson, Peter V

2014-01-01

Atlantic herring (Clupea harengus) embryos were exposed to water accommodated fractions (WAFs; oil dissolved in water) and chemically enhanced water accommodated fractions (CEWAFs; oil dispersed in water with Corexit 9500A) of Medium South American (MESA) crude oil. The CEWAF was approximately 100-fold more toxic than WAF based on nominal loadings of test solutions (% v/v). In contrast, the ratio of WAF and CEWAF toxicity expressed as measured oil concentrations approximated 1.0, indicating that the higher toxicity of CEWAFs was caused by an increase in exposure to hydrocarbons with chemical dispersion. In a second experiment, the chronic toxicity of Corexit 9500A and chemically dispersed heavy fuel oil 7102 (HFO 7102) to rainbow trout (Oncorhynchus mykiss) embryos was compared to chemically dispersed Nujol, a nontoxic mineral oil. Dispersant alone was toxic, but caused different signs of toxicity than HFO 7102. Nujol at a dispersant-to-oil ratio of 1:20 was nontoxic, suggesting that dispersant was sequestered by oil and not present at toxic concentrations. In contrast, the same nominal loadings of dispersed HFO 7102 caused concentration-dependent increases in toxicity. Both experiments suggest that chemically dispersed oil was more toxic to fish embryos than solutions created by mechanical mixing due to the increased exposure of fish to petroleum hydrocarbons and not to changes in hydrocarbon toxicity. The Nujol control discriminated between the toxicity of oil and chemical dispersant and would be a practical addition to programs of dispersant testing.

[An in vitro study on toxic effect of vanadium-titanium-magnetite dust on alveolar macrophage in rabbits].

PubMed

Song, Y; Chen, Q; Guan, Y

1998-11-01

To study the toxic effect of vanadium-titanium-magnetite (VTM) dust on alveolar macrophage (AM) and its hazardous extent. Survival rates, morphology and function of AM were compared in rabbits exposed to dust of VTM, vanadium oxide, titanium dioxide and silica in various doses and length of time with in vitro cell culture and putamen membrane cover glass transmission electron microscopy, and changes in activities of lactic dehydrogenase (LDH) and acid phosphatase (ACP) in cell culture were measured. Exposure to all the four kinds of dust could lead to decrease in survival rate of AM, increase in activities of LDH and ACP in the cell culture, and changes in their morphology and function to the extent dependent on the nature of dust. Toxic effect of exposure to VTM dust was lower than that to vanadium oxide and silica, but higher than that to titanium dioxide, which had slight toxic effect.

[Relationship between the methylenetetrahydrofolate reductase gene polymorphism and adverse reactions of high-dose methotrexate in children with acute lymphocytic leukemia].

PubMed

Zheng, Miao-Miao; Yue, Li-Jie; Chen, Xiao-Wen; Wen, Fei-Qiu; Li, Chang-Gang; Yang, Chun-Lan; Xie, Cai; Ding, Hui

2013-03-01

To study the association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and toxicities after high-dose methotrexate (HD-MTX) infusion in children with acute lymphocytic leukemia (ALL). MTHFR variants in 52 children with ALL were determined by reverse transcriptase-polymerase chain reaction-denaturing gradient gel electrophoresis and sequencing. Toxicities of children who received HD-MTX chemotherapy were evaluated according to the National Cancer Institute-Common Toxicity Criteria (NCI-CTC). The children carrying MTHFR 1298AC had a higher risk of developing thrombocytopenia compared with the carriers of the 1298 AA genotype (OR=13.7, 95%CI=1.18-159.36, P=0.036). There was no significant difference in HD-MTX chemotherapy-related adverse effects between the patients with different MTHFR C677T or G1793A genotypes. MTHFR A1298C polymorohism may associate with the toxicity of HD-MTX chemotherapy in children with ALL.

Tunable Biodegradable Nanocomposite Hydrogel for Improved Cisplatin Efficacy on HCT-116 Colorectal Cancer Cells and Decreased Toxicity in Rats.

PubMed

Abdel-Bar, Hend Mohamed; Osman, Rihab; Abdel-Reheem, Amal Youssef; Mortada, Nahed; Awad, Gehanne A S

2016-02-08

This work describes the development of a modified nanocomposite thermosensitive hydrogel for controlled cisplatin release and improved cytotoxicity with decreased side effects. The system was characterized in terms of physical properties, morphological architecture and in vitro cisplatin release. Cytotoxicity was tested against human colorectal carcinoma HCT-116. In vivo studies were conducted to evaluate the acute toxicity in terms of rats' survival rate and body weight loss. Nephro and hepatotoxicities were evaluated followed by histopathological alterations of various tissue organs. Nanocomposite thermosensitive hydrogel containing nanosized carrier conferred density and stiffness allowing a zero order drug release for 14 days. Enhanced cytotoxicity with 2-fold decrease in cisplatin IC50 was accomplished. A linear in vivo-in vitro correlation was proved for the system degradation. Higher animal survival rate and lower tissue toxicities proved the decreased toxicity of cisplatin nanocomposite compared to its solution.

Calculation and evaluation of sediment effect concentrations for the amphipod Hyalella azteca and the midge Chironomus riparius

USGS Publications Warehouse

Ingersoll, Christopher G.; Haverland, Pamela S.; Brunson, Eric L.; Canfield, Timothy J.; Dwyer, F. James; Henke, Chris; Kemble, Nile E.; Mount, David R.; Fox, Richard G.

1996-01-01

Procedures are described for calculating and evaluating sediment effect concentrations (SECs) using laboratory data on the toxicity of contaminants associated with field-collected sediment to the amphipod Hyalella azteca and the midge Chironomus riparius. SECs are defined as the concentrations of individual contaminants in sediment below which toxicity is rarely observed and above which toxicity is frequently observed. The objective of the present study was to develop SECs to classify toxicity data for Great Lake sediment samples tested with Hyalella azteca and Chironomus riparius. This SEC database included samples from additional sites across the United States in order to make the database as robust as possible. Three types of SECs were calculated from these data: (1) Effect Range Low (ERL) and Effect Range Median (ERM), (2) Threshold Effect Level (TEL) and Probable Effect Level (PEL), and (3) No Effect Concentration (NEC). We were able to calculate SECs primarily for total metals, simultaneously extracted metals, polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs). The ranges of concentrations in sediment were too narrow in our database to adequately evaluate SECs for butyltins, methyl mercury, polychlorinated dioxins and furans, or chlorinated pesticides. About 60 to 80% of the sediment samples in the database are correctly classified as toxic or not toxic depending on type of SEC evaluated. ERMs and ERLs are generally as reliable as paired PELs and TELs at classifying both toxic and non-toxic samples in our database. Reliability of the SECs in terms of correctly classifying sediment samples is similar between ERMs and NECs; however, ERMs minimize Type I error (false positives) relative to ERLs and minimize Type II error (false negatives) relative to NECs. Correct classification of samples can be improved by using only the most reliable individual SECs for chemicals (i.e., those with a higher percentage of correct classification). SECs calculated using sediment concentrations normalized to total organic carbon (TOC) concentrations did not improve the reliability compared to SECs calculated using dry-weight concentrations. The range of TOC concentrations in our database was relatively narrow compared to the ranges of contaminant concentrations. Therefore, normalizing dry-weight concentrations to a relatively narrow range of TOC concentrations had little influence on relative concentra of contaminants among samples. When SECs are used to conduct a preliminary screening to predict the potential for toxicity in the absence of actual toxicity testing, a low number of SEC exceedances should be used to minimize the potential for false negatives; however, the risk of accepting higher false positives is increased.

Updated efficacy and toxicity analysis of irinotecan and oxaliplatin (IROX) : intergroup trial N9741 in first-line treatment of metastatic colorectal cancer.

PubMed

Ashley, Amanda C; Sargent, Daniel J; Alberts, Steven R; Grothey, Axel; Campbell, Megan E; Morton, Roscoe F; Fuchs, Charles S; Ramanathan, Ramesh K; Williamson, Stephen K; Findlay, Brian P; Pitot, Henry C; Goldberg, Richard M

2007-08-01

Efficacy and toxicity of oxaliplatin (Eloxatin; Sanofi-Aventis, Paris, France) combined with irinotecan (IROX) were examined in 383 patients enrolled on the IROX arm of Intergroup Study N9741. This IROX regimen was oxaliplatin 85 mg/m(2) and irinotecan 200 mg/m(2) administered every 3 weeks. The relation between adverse events on IROX to selected characteristics was analyzed. Time to progression (TTP), response rate, and overall survival for patients treated with IROX compared with patients treated with oxaliplatin with 5- fluorouracil (FOLFOX) were updated in this article. Grade >or=3 gastrointestinal and hematologic toxicities were common with 39% patients experiencing neutropenia, 28% diarrhea, and 21% vomiting. Patients ages >70 years experienced higher rates of grade >or=3 toxicity, with significantly higher rates of grade >or=3 hematologic toxicities (P = .02). Long-term toxicity was uncommon, and nearly all cases of grade >or=3 neurotoxicity resolved within 10 months. Fifty-two percent of patients required dose reductions for adverse events, and 26% experienced 119 hospitalizations related to complications of treatment or their disease, with 5 treatment-related deaths. This analysis confirmed prior findings that FOLFOX is superior to IROX in terms of response rate (43% vs 36%, p = 0.002), TTP (9.2 months vs 6.7 months, P < .0001), and overall survival (19.5 months vs 17.3 months, P = .0001). IROX was found to be less active than FOLFOX but with a similar toxicity profile except in patients ages >70 years. Although IROX may be considered in patients intolerant of 5-FU or in patients known to have a dihydropyrimidine dehydrogenase (DPD) deficiency, it should be used with caution in older patients. (c) 2007 American Cancer Society.

Low doses of six toxicants change plant size distribution in dense populations of Lactuca sativa.

PubMed

Belz, Regina G; Patama, Marjo; Sinkkonen, Aki

2018-08-01

Toxicants are known to have negligible or stimulatory, i.e. hormetic, effects at low doses below those that decrease the mean response of a plant population. Our earlier observations indicated that at such low toxicant doses the growth of very fast- and slow-growing seedlings is selectively altered, even if the population mean remains constant. Currently, it is not known how common these selective low-dose effects are, whether they are similar among fast- and slow-growing seedlings, and whether they occur concurrently with hormetic effects. We tested the response of Lactuca sativa in complete dose-response experiments to six different toxicants at doses that did not decrease population mean and beyond. The tested toxicants were IAA, parthenin, HHCB, 4-tert-octylphenol, glyphosate, and pelargonic acid. Each experiment consisted of 14,400-16,800 seedlings, 12-14 concentrations, 24 replicates per concentration and 50 germinated seeds per replicate. We analyzed the commonness of selective low-dose effects and explored if toxic effects and hormetic stimulation among fast- and slow-growing individuals occurred at the same concentrations as they occur at the population level. Irrespective of the observed response pattern and toxicant, selective low-dose effects were found. Toxin effects among fast-growing individuals usually started at higher doses compared to the population mean, while the opposite was found among slow-growing individuals. Very low toxin exposures tended to homogenize plant populations due to selective effects, while higher, but still hormetic doses tended to heterogenize plant populations. Although the extent of observed size segregation varied with the specific toxin tested, we conclude that a dose-dependent alteration in size distribution of a plant population may generally apply for many toxin exposures. Copyright © 2018 Elsevier B.V. All rights reserved.

Toxic effects of lead and nickel nitrate on rat liver chromatin components.

PubMed

Rabbani-Chadegani Iii, Azra; Fani, Nesa; Abdossamadi, Sayeh; Shahmir, Nosrat

2011-01-01

The biological activity of heavy metals is related to their physicochemical interaction with biological receptors. In the present study, the effect of low concentrations of nickel nitrate and lead nitrate (<0.3 mM) on rat liver soluble chromatin and histone proteins was examined. The results showed that addition of various concentrations of metals to chromatin solution preceded the chromatin into aggregation and precipitation in a dose-dependant manner; however, the extent of absorbance changes at 260 and 400 nm was different between two metals. Gel electrophoresis of histone proteins and DNA of the supernatants obtained from the metal-treated chromatin and the controls revealed higher affinity of lead nitrate to chromatin compared to nickel nitrate. Also, the binding affinity of lead nitrate to histone proteins free in solution was higher than nickel. On the basis of the results, it is concluded that lead reacts with chromatin components even at very low concentrations and induce chromatin aggregation through histone-DNA cross-links. Whereas, nickel nitrate is less effective on chromatin at low concentrations, suggesting higher toxicity of lead nitrate on chromatin compared to nickel. Copyright © 2010 Wiley Periodicals, Inc.

Influence of titanium dioxide nanoparticles on the toxicity of arsenate in Nannochloropsis maritima.

PubMed

Yang, Fan; Yan, Changzhou

2018-06-13

Interest is growing in the role that nanoparticles play in modifying the biological effects of contaminants. This study aimed to determine whether nano-TiO 2 exhibited pronounced influence on arsenate (As(V)) toxicity levels to the marine microalgae Nannochloropsis maritima. We compared individual and combined toxicity levels of As(V) and nano-TiO 2 by assessing the inhibition percentages of algal growth. Compared to groups treated with As(V) alone, an EC 50 of 53.0 mg/L decreased by 28.8% after the addition of nanoparticles. This enhanced toxicity was attributed to the inhibition of As methylation and the promotion of lipid peroxidation in the presence of nano-TiO 2 . Additionally, transmission electron microscopy (TEM) and scanning electron microscopy (SEM) also showed that algal cells exhibited different degrees of shrinkage, that cell wall were destroyed in the process, and that the photosynthetic apparatus was virtually indiscernible after the addition of nano-TiO 2 . In addition, for low As(V) concentration exposure groups, nano-TiO 2 could alleviate As(V) toxicity to some extent by reducing As sorption onto algal cells and subcellular distribution in organelles, but this alleviation effect could not protect against the combined toxicity (both As(V) and nano-TiO 2 ) effect on N. maritima, which was verified by the higher inhibition percentage of the algal growth rate in the combined exposure group treatment compared to the As(V) exposure treatment alone. Our results suggest that more attention must be paid to the potential impact of nanoparticles on the bioavailability and biotransformation of contaminants in phytoplankton. Copyright © 2018 Elsevier Ltd. All rights reserved.

Comparative study on the biodegradability of morpholinium herbicidal ionic liquids.

PubMed

Ławniczak, Łukasz; Materna, Katarzyna; Framski, Grzegorz; Szulc, Alicja; Syguda, Anna

2015-07-01

This study focused on evaluating the toxicity as well as primary and ultimate biodegradability of morpholinium herbicidal ionic liquids (HILs), which incorporated MCPA, MCPP, 2,4-D or Dicamba anions. The studied HILs were also subjected to determination of surface active properties in order to assess their influence on toxicity and biodegradability. The study was carried out with microbiota isolated from different environmental niches: sediments from river channel, garden soil, drainage trench collecting agricultural runoff stream, agricultural soil and municipal waste repository. The obtained results revealed that resistance to toxicity and biodegradation efficiency of the microbiota increased in the following order: microbiota from the waste repository > microbiota from agricultural soil ≈ microbiota from an agricultural runoff stream > microbiota from garden soil > microbiota from the river sludge. It was observed that the toxicity of HILs increased with the hydrophobicity of the cation, however the influence of the anion was more notable. The highest toxicity was observed when MCPA was used as the anion (EC50 values ranging from 60 to 190 mg L(-1)). The results of ultimate biodegradation tests indicated that only HILs with 2,4-D as the anion were mineralized to some extent, with slightly higher values for HILs with the 4-decyl-4-ethylmorpholinium cation (10-31 %) compared to HILs with the 4,4-didecylmorpholinium cation (9-20 %). Overall, the cations were more susceptible (41-94 %) to primary biodegradation compared to anions (0-61 %). The obtained results suggested that the surface active properties of the studied HILs may influence their toxicity and biodegradability by bacteria in different environmental niches.

Comparison of in vivo toxicity, antioxidant and immunomodulatory activities of coconut, nipah and pineapple juice vinegars.

PubMed

Mohamad, Nurul Elyani; Keong Yeap, Swee; Beh, Boon Keen; Romli, Muhammad Firdaus; Yusof, Hamidah Mohd; Kristeen-Teo, Ye Wen; Sharifuddin, Shaiful Adzni; Long, Kamariah; Alitheen, Noorjahan Banu

2018-01-01

Vinegar is widely used as a food additive, in food preparation and as a food supplement. This study compared the phenolic acid profiles and in vivo toxicities, and antioxidant and immunomodulatory effects of coconut, nipah and pineapple juice vinegars, which were respectively prepared via a two-step fermentation using Saccharomyces cerevisiae 7013 INRA and Acetobacter aceti vat Europeans. Pineapple juice vinegar, which had the highest total phenolic acid content, also exhibited the greatest in vitro antioxidant capacity compared to coconut juice and nipah juice vinegars. Following acute and sub-chronic in vivo toxicity evaluation, no toxicity and mortality were evident and there were no significant differences in the serum biochemical profiles between mice administered the vinegars versus the control group. In the sub-chronic toxicity evaluation, the highest liver antioxidant levels were found in mice fed with pineapple juice vinegar, followed by coconut juice and nipah juice vinegars. However, compared to the pineapple juice and nipah juice vinegars, the mice fed with coconut juice vinegar, exhibited a higher population of CD4 + and CD8 + T-lymphocytes in the spleen, which was associated with greater levels of serum interleukin-2 and interferon-γ cytokines. Overall, the data suggested that not all vinegar samples cause acute and sub-chronic toxicity in vivo. Moreover, the in vivo immunity and organ antioxidant levels were enhanced, to varying extents, by the phenolic acids present in the vinegars. The results obtained in this study provide appropriate guidelines for further in vivo bioactivity studies and pre-clinical assessments of vinegar consumption. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Toxicity of copper on the growth of marine microalgae Pavlova sp. and its chlorophyll-a

NASA Astrophysics Data System (ADS)

Purbonegoro, T.; Suratno; Puspitasari, R.; Husna, N. A.

2018-02-01

Marine microalgae is the primary producer at the base of the marine food chain. Their sensitivity to metal contamination provides important information for predicting the environmental impact of pollution. Toxicity testing using marine microalgae Pavlova sp. was carried out to assess the toxicity of copper on the growth and chlorophyll-a content. Results of this study show that adverse effects were observed by the increase of copper concentration. Cell number began to decrease at the lowest concentration (13 μg/L) and reduced drastically at 98 μg/L. Minimum cell number was observed at the highest concentration (890 μg/L). The inhibition concentration (IC50) value of copper for Pavlova sp. was 51.46 μg/L and at concentrations >29 μgL-1 the chlorophyll-a content decreased dramatically compared to the control. A variation in cell size and morphology was also observed at the higher concentration by the increase in the cell size and loss of setae compared to normal cells.

Relationship between chronic lead toxicity and plasma neurotransmitters in autistic patients from Saudi Arabia.

PubMed

El-Ansary, Afaf K; Bacha, Abir Ben; Ayahdi, Layla Y Al-

2011-09-01

This study aims to clarify the relationship between blood Pb(2+) concentration as a ubiquitous environmental pollutant and plasma neurotransmitters as biochemical parameters that reflect brain function in Saudi autistic patients. RBC's lead content together with plasma concentration of gamma aminobutyric acid (GABA), serotonin (5HT) and dopamine (DA) were measured in 25 Saudi autistic patients and compared to 16 age-matching control samples. The obtained data recorded that Saudi autistic patients have a remarkable higher levels of Pb(2+) and significantly elevated levels of GABA, 5HT and DA compared to healthy subjects. ROC analysis revealed satisfactory values of specificity and sensitivity of the measured parameters. This study suggests that postnatal lead toxicity in autistic patients of Saudi Arabia could represent a causative factor in the pathogenesis of autism. Elevated GABA, 5HT and DA were discussed in relation to the chronic lead toxicity recorded in the investigated autistic samples. Copyright © 2011. Published by Elsevier Inc.

Comparative analyses of physiological responses of Cynodon dactylon accessions from Southwest China to sulfur dioxide toxicity.

PubMed

Li, Xi; Wang, Ling; Li, Yiqiao; Sun, Lingxia; Cai, Shizhen; Huang, Zhuo

2014-01-01

Sulfur dioxide (SO2), a major air pollutant in developing countries, is highly toxic to plants. To achieve better air quality and landscape, planting appropriate grass species in severe SO2 polluted areas is very critical. Cynodon dactylon, a widely used warm season turfgrass species, has good SO2-tolerant ability. In this study, we selected 9 out of 38 C. dactylon accessions from Southwest China as representatives of high, intermediate SO2-tolerant and SO2-sensitive accessions to comparatively analyze their physiological differences in leaves under SO2 untreated and treated conditions. Our results revealed that SO2-tolerant C. dactylon accessions showed higher soluble sugar, proline, and chlorophyll a contents under both SO2 treated and untreated conditions; higher chlorophyll b and carotenoid under SO2 treated condition; lower reactive oxygen species (ROS) level, oxidative damages, and superoxide dismutase (SOD) activities under SO2 treated condition; and higher peroxidase (POD) activities under SO2 untreated condition. Further results indicated that SO2-tolerant C. dactylon accessions had higher sulfur contents under both SO2 treated and untreated conditions, consistent with higher SO activities under both SO2 treated and untreated conditions, and higher SiR activities under SO2 treated condition. Taken together, our results indicated that SO2 tolerance of C. dactylon might be largely related to soluble sugar, proline and chlorophyll a contents, and SO enzyme activity.

Comparative Analyses of Physiological Responses of Cynodon dactylon Accessions from Southwest China to Sulfur Dioxide Toxicity

PubMed Central

Wang, Ling; Li, Yiqiao; Cai, Shizhen

2014-01-01

Sulfur dioxide (SO2), a major air pollutant in developing countries, is highly toxic to plants. To achieve better air quality and landscape, planting appropriate grass species in severe SO2 polluted areas is very critical. Cynodon dactylon, a widely used warm season turfgrass species, has good SO2-tolerant ability. In this study, we selected 9 out of 38 C. dactylon accessions from Southwest China as representatives of high, intermediate SO2-tolerant and SO2-sensitive accessions to comparatively analyze their physiological differences in leaves under SO2 untreated and treated conditions. Our results revealed that SO2-tolerant C. dactylon accessions showed higher soluble sugar, proline, and chlorophyll a contents under both SO2 treated and untreated conditions; higher chlorophyll b and carotenoid under SO2 treated condition; lower reactive oxygen species (ROS) level, oxidative damages, and superoxide dismutase (SOD) activities under SO2 treated condition; and higher peroxidase (POD) activities under SO2 untreated condition. Further results indicated that SO2-tolerant C. dactylon accessions had higher sulfur contents under both SO2 treated and untreated conditions, consistent with higher SO activities under both SO2 treated and untreated conditions, and higher SiR activities under SO2 treated condition. Taken together, our results indicated that SO2 tolerance of C. dactylon might be largely related to soluble sugar, proline and chlorophyll a contents, and SO enzyme activity. PMID:25097893

Environmental impacts of remediation of a trichloroethene-contaminated site: life cycle assessment of remediation alternatives.

PubMed

Lemming, Gitte; Hauschild, Michael Z; Chambon, Julie; Binning, Philip J; Bulle, Cécile; Margni, Manuele; Bjerg, Poul L

2010-12-01

The environmental impacts of remediation of a chloroethene-contaminated site were evaluated using life cycle assessment (LCA). The compared remediation options are (i) in situ bioremediation by enhanced reductive dechlorination (ERD), (ii) in situ thermal desorption (ISTD), and (iii) excavation of the contaminated soil followed by off-site treatment and disposal. The results showed that choosing the ERD option will reduce the life-cycle impacts of remediation remarkably compared to choosing either ISTD or excavation, which are more energy-demanding. In addition to the secondary impacts of remediation, this study includes assessment of local toxic impacts (the primary impact) related to the on-site contaminant leaching to groundwater and subsequent human exposure via drinking water. The primary human toxic impacts were high for ERD due to the formation and leaching of chlorinated degradation products, especially vinyl chloride during remediation. However, the secondary human toxic impacts of ISTD and excavation are likely to be even higher, particularly due to upstream impacts from steel production. The newly launched model, USEtox, was applied for characterization of primary and secondary toxic impacts and combined with a site-dependent fate model of the leaching of chlorinated ethenes from the fractured clay till site.

Maternal-child transfer of essential and toxic elements through breast milk in a mine-waste polluted area.

PubMed

Castro, Francisca; Harari, Florencia; Llanos, Miguel; Vahter, Marie; Ronco, Ana Maria

2014-11-01

To determine the daily intake of essential micronutrients and toxic elements through breast milk in exclusive and nonexclusive breastfed infants living in an area with major mine tailing deposition (n = 24), compared with a control area (n = 11). The milk volume ingested by 2 to 4 and 4 to 6 month infants was measured by a stable isotopic method. Elements in milk, maternal and infant urine, and drinking water were measured by inductively coupled plasma mass spectrometry (ICP-MS). Similar breast milk volume and essential micronutrients intake in groups of exclusively breastfed infants, but more cadmium, boron, and lithium through breastfeeding in experimental area was found. This exposure was even higher in the nonexclusively breastfed infants, who also ingested more arsenic, boron, and lithium than exclusive breastfed infants. The use of the deuterium and the ICP-MS methods made it possible to evaluate the exact amount of essential and toxic elements ingested by infants through breast milk demonstrating that lower amount of toxic elements are transferred to exclusive breastfed infants compared with those who additionally received nonmaternal milk. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Treating chronic arsenic toxicity with high selenium lentil diets.

PubMed

Sah, Shweta; Vandenberg, Albert; Smits, Judit

2013-10-01

Arsenic (As) toxicity causes serious health problems in humans, especially in the Indo-Gangetic plains and mountainous areas of China. Selenium (Se), an essential micronutrient is a potential mitigator of As toxicity due to its antioxidant and antagonistic properties. Selenium is seriously deficient in soils world-wide but is present at high, yet non-toxic levels in the great plains of North America. We evaluate the potential of dietary Se in counteracting chronic As toxicity in rats through serum biochemistry, blood glutathione levels, immunotoxicity (antibody response), liver peroxidative stress, thyroid response and As levels in tissues and excreta. To achieve this, we compare diets based on high-Se Saskatchewan (SK) lentils versus low-Se lentils from United States. Rats drank control (0ppm As) or As (40ppm As) water while consuming SK lentils (0.3ppm Se) or northwestern USA lentils (<0.01ppm Se) diets for 14weeks. Rats on high Se diets had higher glutathione levels regardless of As exposure, recovered antibody responses in As-exposed group, higher fecal and urinary As excretion and lower renal As residues. Selenium deficiency caused greater hepatic peroxidative damage in the As exposed animals. Thyroid hormones, triiodothyronine (T3) and thyroxine (T4), were not different. After 14weeks of As exposure, health indicators in rats improved in response to the high Se lentil diets. Our results indicate that high Se lentils have a potential to mitigate As toxicity in laboratory mammals, which we hope will translate into benefits for As exposed humans. Copyright © 2013 Elsevier Inc. All rights reserved.

Clarithromycin (Biaxin)-lenalidomide-low-dose dexamethasone (BiRd) versus lenalidomide-low-dose dexamethasone (Rd) for newly diagnosed myeloma.

PubMed

Gay, Francesca; Rajkumar, S Vincent; Coleman, Morton; Kumar, Shaji; Mark, Tomer; Dispenzieri, Angela; Pearse, Roger; Gertz, Morie A; Leonard, John; Lacy, Martha Q; Chen-Kiang, Selina; Roy, Vivek; Jayabalan, David S; Lust, John A; Witzig, Thomas E; Fonseca, Rafael; Kyle, Robert A; Greipp, Philip R; Stewart, A Keith; Niesvizky, Ruben

2010-09-01

The objective of this case-matched study was to compare the efficacy and toxicity of the addition of clarithromycin (Biaxin) to lenalidomide/low-dose dexamethasone (BiRd) vs. lenalidomide/low-dose dexamethasone (Rd) for newly diagnosed myeloma. Data from 72 patients treated at the New York Presbyterian Hospital-Cornell Medical Center were retrospectively compared with an equal number of matched pair mates selected among patients seen at the Mayo Clinic who received Rd. Case matching was blinded and was performed according to age, gender, and transplant status. On intention-to-treat analysis, complete response (45.8% vs. 13.9%, P < 0.001) and very-good-partial-response or better (73.6% vs. 33.3%, P < 0.001) were significantly higher with BiRd. Time-to-progression (median 48.3 vs. 27.5 months, P = 0.071), and progression-free survival (median 48.3 vs. 27.5 months, P = 0.044) were higher with BiRd. There was a trend toward better OS with BiRd (3-year OS: 89.7% vs. 73.0%, P = 0.170). Main grade 3-4 toxicities of BiRd were hematological, in particular thrombocytopenia (23.6% vs. 8.3%, P = 0.012). Infections (16.7% vs. 9.7%, P = 0.218) and dermatological toxicity (12.5% vs. 4.2%, P = 0.129) were higher with Rd. Results of this case-matched analysis suggest that there is significant additive value when clarithromycin is added to Rd. Randomized phase III trials are needed to confirm these results. © 2010 Wiley-Liss, Inc.

Two rice plasma membrane intrinsic proteins, OsPIP2;4 and OsPIP2;7, are involved in transport and providing tolerance to boron toxicity.

PubMed

Kumar, Kundan; Mosa, Kareem A; Chhikara, Sudesh; Musante, Craig; White, Jason C; Dhankher, Om Parkash

2014-01-01

Boron (B) toxicity is responsible for low cereal crop production in a number of regions worldwide. In this report, we characterized two rice genes, OsPIP2;4 and OsPIP2;7, for their involvement in B permeability and tolerance. Transcript analysis demonstrated that the expression of OsPIP2;4 and OsPIP2;7 were downregulated in shoots and strongly upregulated in rice roots by high B treatment. Expression of both OsPIP2;4 and OsPIP2;7 in yeast HD9 strain lacking Fps1, ACR3, and Ycf1 resulted in an increased B sensitivity. Furthermore, yeast HD9 strain expressing OsPIP2;4 and OsPIP2;7 accumulated significantly higher B as compared to empty vector control, which suggests their involvement in B transport. Overexpression of OsPIP2;4 and OsPIP2;7 in Arabidopsis imparted higher tolerance under B toxicity. Arabidopsis lines overexpressing OsPIP2;4 and OsPIP2;7 showed significantly higher biomass production and greater root length, however there was no difference in B accumulation in long term uptake assay. Short-term uptake assay using tracer B (¹⁰B) in shoots and roots demonstrated increased ¹⁰B accumulation in Arabidopsis lines expressing OsPIP2;4 and OsPIP2;7, compare to wild type control plants. Efflux assay of B in the roots showed that ¹⁰B was effluxed from the Arabidopsis transgenic plants overexpressing OsPIP2;4 or OsPIP2;7 during the initial 1-h of assay. These data indicate that OsPIP2;4 and OsPIP2;7 are involved in mediating B transport in rice and provide tolerance via efflux of excess B from roots and shoot tissues. These genes will be highly useful in developing B tolerant crops for enhanced yield in the areas affected by high B toxicity.

The role of the anion in the toxicity of imidazolium ionic liquids.

PubMed

Biczak, Robert; Pawłowska, Barbara; Bałczewski, Piotr; Rychter, Piotr

2014-06-15

From the environmental protection point of view, the growing interest of ionic liquids in various industrial branches has raised concerns for the toxicity assessment of these compounds. The paper discusses the effect of salts containing the shared 1-ethyl-3-methylimidazolium [EMIM] cation as coupled with five different anions: bromide [Br], nitrate [NO3], p-toluenesulfonate (tosylate) [Ts], dimethylphosphate [dMP] and methanesulfonate [MS] on the growth and development of higher land plants - spring barley and common radish. The experiment was done according to the ISO Standard 11269-2:1995 and the OECD/OCDE Guide 208/2006. As the indications of phytotoxicity, the percentage of sprouts and the level of dry and fresh plant mass were used; in addition, the visual assessment of any signs of damage to the examined plant species, such as growth inhibition and chlorotic changes, was also made. Results of our study has proved the negative impact of ILs on the tested plants and the toxic effect of imidazolium salts was dependent primarily on the applied ionic liquids concentration. The common radish revealed the higher tolerance to the imidazolium as compared to spring barley. The anion type of ionic liquid was crucial for the toxicity against common radish. Copyright © 2014 Elsevier B.V. All rights reserved.

Comparative study of toxicity of 4-nitrophenol and 2,4-dinitrophenol in newborn and young rats.

PubMed

Koizumi, M; Yamamoto, Y; Ito, Y; Takano, M; Enami, T; Kamata, E; Hasegawa, R

2001-12-01

The toxicities of 4-nitrophenol and 2,4-dinitrophenol in newborn and young rats was examined and the susceptibility of newborn rats was analyzed in terms of presumed unequivocally toxic and no observed adverse effect levels (NOAELs). In the 18-day repeated dose newborn rat study, 4-nitrophenol was orally given from Day 4 to Day 21 after birth but did not induce any toxicity up to 160 mg/kg in the main study, although it induced death in one of six males at 160 mg/kg, and three of six males and one of six females at 230 mg/kg in a prior dose-finding study. In the 28-day repeated dose oral toxicity study starting at 6 weeks of age, 4-nitrophenol caused the death of most males and females at 1,000 mg/kg but was not toxic at 400 mg/kg except for male rat-specific renal toxicity. As unequivocally toxic levels were considered to be 230 mg/kg/day in newborn rats and 600 to 800 mg/kg/day in young rats, and NOAELs were 110 mg/kg/day in newborn rats and 400 mg/kg/day in young rats, the susceptibility of the newborn to 4-nitrophenol appears to be 2.5 to 4 times higher than that of young animals. In the newborn rat study of 2,4-dinitrophenol, animals died at 30 mg/kg in the dose-finding study and significant lowering of body and organ weights was observed at 20 mg/kg in the main study. In the 28-day young rat study, clear toxic signs followed by death occurred at 80 mg/kg but there was no definitive toxicity at 20 mg/kg. As unequivocally toxic levels and NOAELs were considered to be 30 and 10 mg/kg/day in newborn rats and 80 and 20 mg/kg/day in young rats, respectively, the toxicity of 2,4-dinitrophenol in newborns again seems to be 2 to 3 times stronger than in young rats. Abnormalities of external development and reflex ontogeny in the newborn were not observed with either chemical. Based on these results, it can be concluded that the toxic response in newborn rats is at most 4 times higher than that in young rats, at least in the cases of 4-nitrophenol and 2,4-dinitrophenol.

Comparative study on the toxic effects of red tide flagellates Heterocapsa circularisquama and Chattonella marina on the short-necked clam (Ruditapes philippinarum).

PubMed

Kim, Daekyung; Choi, Kwang-Sik; Hong, Hyun-Ki; Jiang, Zedong; Zou, Yanan; Choi, Kyu-Sung; Yamasaki, Yasuhiro; Matsuyama, Yukihiko; Yamaguchi, Kenichi; Oda, Tatsuya

2011-01-01

Heterocapsa circularisquama showed much higher toxic effects on short-necked clams than Chattonella marina. Clams exposed to H. circularisquama exhibited morphological changes concomitant with an accumulation of mucus-like substances in the gills, a profound reduction in filtration activity, and lysosomal destabilization in hemocytes. Chattonella marina was less effective than H. circularisquama, and Heterocapsa triquetra was almost harmless in all these criteria. These results suggest that H. circularisquama exerted its lethal effect on short-necked clams through gill tissue damage and subsequent induction of physiological stress.

Toxicity tests of soil contaminated by recycling of scrap plastics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wong, M.H.; Chui, V.W.

The present investigation studied the toxicity of soil contaminated by untreated discharge from a factory that recycles used plastics. The nearby agricultural areas and freshwater fish ponds were polluted with high concentrations of Cu, Ni, and Mn. Water extracts from the contaminated soil retarded root growth of Brassica chinensis (Chinese white cabbage) and Cynodon dactylon (Bermuda grass) where their seeds were obtained commercially. The contaminated populations of C. dactylon, Panicum repen (panic grass), and Imperata cylindrica (wooly grass) were able to withstand higher concentrations of Cu, Ni, and Mn, especially C. dactylon, when compared with their uncontaminated counterparts.

Boron-toxicity tolerance in barley arising from efflux transporter amplification.

PubMed

Sutton, Tim; Baumann, Ute; Hayes, Julie; Collins, Nicholas C; Shi, Bu-Jun; Schnurbusch, Thorsten; Hay, Alison; Mayo, Gwenda; Pallotta, Margaret; Tester, Mark; Langridge, Peter

2007-11-30

Both limiting and toxic soil concentrations of the essential micronutrient boron represent major limitations to crop production worldwide. We identified Bot1, a BOR1 ortholog, as the gene responsible for the superior boron-toxicity tolerance of the Algerian barley landrace Sahara 3771 (Sahara). Bot1 was located at the tolerance locus by high-resolution mapping. Compared to intolerant genotypes, Sahara contains about four times as many Bot1 gene copies, produces substantially more Bot1 transcript, and encodes a Bot1 protein with a higher capacity to provide tolerance in yeast. Bot1 transcript levels identified in barley tissues are consistent with a role in limiting the net entry of boron into the root and in the disposal of boron from leaves via hydathode guttation.

Efficacy and toxicity of a paediatric protocol in teenagers and young adults with Philadelphia chromosome negative acute lymphoblastic leukaemia: results from UKALL 2003.

PubMed

Hough, Rachael; Rowntree, Clare; Goulden, Nick; Mitchell, Chris; Moorman, Anthony; Wade, Rachel; Vora, Ajay

2016-02-01

Despite the substantial outcome improvements achieved in paediatric acute lymphoblastic leukaemia (ALL), survival in teenage and young adult (TYA) patients has remained inferior. We report the treatment outcomes and toxicity profiles observed in TYA patients treated on the UK paediatric ALL trial, UKALL2003. UKALL2003 was a multi-centre, prospective, randomized phase III trial, investigating treatment intensification or de-escalation according to minimal residual disease (MRD) kinetics at the end of induction. Of 3126 patients recruited to UKALL2003, 229 (7·3%) were aged 16-24 years. These patients were significantly more likely to have high risk MRD compared to 10-15 year olds (47·9% vs. 36·6%, P = 0·004). Nonetheless, 5-year event-free survival for the TYA cohort (aged 16-24 years) was 72·3% [95% confidence interval (CI): 66·2-78·4] overall and 92·6% (95% CI: 85·5-99·7) for MRD low risk patients. The risk of serious adverse events was higher in patients aged ≥10 years compared to those aged 9 or younger (P < 0·0001) and novel age-specific patterns of treatment-related toxicity were observed. TYA patients obtain excellent outcomes with a risk- and response-adapted paediatric chemotherapy protocol. Whilst those aged 10 years and older have excess toxicity compared with younger patients, the age association is specific to individual toxicities. © 2015 John Wiley & Sons Ltd.

Oxaliplatin-Based Doublets Versus Cisplatin or Carboplatin-Based Doublets in the First-Line Treatment of Advanced Nonsmall Cell Lung Cancer.

PubMed

Yu, Jing; Xiao, Jing; Yang, Yifan; Cao, Bangwei

2015-07-01

The efficacy and toxicity of oxaliplatin-based versus carboplatin/cisplatin-based doublets in patients with previously untreated nonsmall cell lung cancer (NSCLC) have been compared.We searched published randomized controlled trials of oxaliplatin-based or carboplatin/cisplatin-based medications for NSCLC. A fixed effect model was used to analyze outcomes which were expressed as the hazard ratio for overall survival (OS) and time-to-progression (TTP), relative risk, overall response rate (ORR), disease control rate (DCR), 1-year survival, and the odds ratios for toxicity were pooled.Eight studies involving 1047 patients were included. ORR tended to favor carboplatin/cisplatin but the effect was not significantly different compared with oxaliplatin doublets (P = 0.05). The effects of OS, TTP, DCR, and 1-year survival between the 2 regimens were comparable. Oxaliplatin doublets caused less grade 3/4 leukocytopenia and neutropenia. Grades 3 to 4 nonhematological toxicities and grades 3 to 4 hematological toxicities showed little difference between oxaliplatin doublets and carboplatin/cisplatin doublets.Meta-analysis shows that the efficacy of oxaliplatin doublets is similar to that of other currently used platinum doublets. The lack of significant differences in the statistic analysis does not preclude genuine differences in clinical efficacy, because higher diversities between the studies covered differences between the 2 groups in each study. Oxaliplatin combined with a third-generation agent should be considered for use as alternative chemotherapy in patients who cannot tolerate conventional platinum-based regimens because the toxicity profile is much more favorable.

Differential effects of thiopurine methyltransferase (TPMT) and multidrug resistance-associated protein gene 4 (MRP4) on mercaptopurine toxicity.

PubMed

Liu, Chengcheng; Janke, Laura J; Yang, Jun J; Evans, William E; Schuetz, John D; Relling, Mary V

2017-08-01

Mercaptopurine plays a pivotal role in treatment of acute lymphoblastic leukemia (ALL) and autoimmune diseases, and inter-individual variability in mercaptopurine tolerance can influence treatment outcome. Thiopurine methyltransferase (TPMT) and multi-drug resistant Protein 4 (MRP4) have both been associated with mercaptopurine toxicity in clinical studies, but their relative contributions remain unclear. We studied the metabolism of and tolerance to mercaptopurine in murine knockout models of Tpmt, Mrp4, and both genes simultaneously. Upon mercaptopurine treatment, Tpmt -/- Mrp4 -/- mice had the highest concentration of bone marrow thioguanine nucleotides (8.5 pmol/5 × 10 6 cells, P = 7.8 × 10 -4 compared with 2.7 pmol/5 × 10 6 cells in wild-types), followed by those with Mrp4 or Tpmt deficiency alone (6.1 and 4.3 pmol/5 × 10 6 cells, respectively). Mrp4-deficient mice accumulated higher concentrations of methylmercaptopurine metabolites compared with wild-type (76.5 vs. 23.2 pmol/5 × 10 6 cells, P = 0.027). Mice exposed to a clinically relevant mercaptopurine dosing regimen displayed differences in toxicity and survival among the genotypes. The double knock-out of both genes experienced greater toxicity and shorter survival compared to the single knockout of either Tpmt (P = 1.7 × 10 -6 ) or Mrp4 (P = 7.4 × 10 -10 ). We showed that both Tpmt and Mrp4 influence mercaptopurine disposition and toxicity.

Solubility of chrysotile asbestos and basalt fibers in relation to their fibrogenic and carcinogenic action.

PubMed

Kogan, F M; Nikitina, O V

1994-10-01

Fiber length and persistence are thought to be determinants for the development of toxic, fibrogenic, and carcinogenic effects of fibrous dusts. When the solubilities of chrysotile asbestos (CA) and basalt fibers (BF) were compared by measuring the loss of silica and magnesium in Leineweber's solution, CA was shown to be the more soluble. In a 6-month inhalation experiment, chrysotile at a mean concentration of 25 mg/m3 had a higher clearance rate than other comparable dusts. In acute toxicity studies, chrysotile and basalt fibers were administered intraperitoneally. At a dose of 1.7 g/kg body weight of CA, one third of the animals died. A dose of 2.7 g/kg body weight killed all the animals. With BF, even at a dose of 10 g/kg body weight all the animals survived. When the two fibers were administered over a 6-month period, either intratracheally or by inhalation, fibrotic lesions were more common in the group that received CA. Intraperitoneal administration of CA led to three times as many deaths from peritoneal mesothelioma as administration of BF. It appears, therefore, that in spite of its higher solubility and lower persistence, CA was the more toxic, fibrogenic and carcinogenic fiber, which gives rise to the hypothesis that the surface chemistry of the fibers is the determinant for biological activity.

Solubility of chrysotile asbestos and basalt fibers in relation to their fibrogenic and carcinogenic action.

PubMed Central

Kogan, F M; Nikitina, O V

1994-01-01

Fiber length and persistence are thought to be determinants for the development of toxic, fibrogenic, and carcinogenic effects of fibrous dusts. When the solubilities of chrysotile asbestos (CA) and basalt fibers (BF) were compared by measuring the loss of silica and magnesium in Leineweber's solution, CA was shown to be the more soluble. In a 6-month inhalation experiment, chrysotile at a mean concentration of 25 mg/m3 had a higher clearance rate than other comparable dusts. In acute toxicity studies, chrysotile and basalt fibers were administered intraperitoneally. At a dose of 1.7 g/kg body weight of CA, one third of the animals died. A dose of 2.7 g/kg body weight killed all the animals. With BF, even at a dose of 10 g/kg body weight all the animals survived. When the two fibers were administered over a 6-month period, either intratracheally or by inhalation, fibrotic lesions were more common in the group that received CA. Intraperitoneal administration of CA led to three times as many deaths from peritoneal mesothelioma as administration of BF. It appears, therefore, that in spite of its higher solubility and lower persistence, CA was the more toxic, fibrogenic and carcinogenic fiber, which gives rise to the hypothesis that the surface chemistry of the fibers is the determinant for biological activity. PMID:7882932

Abiotic Degradation and Toxicological Impacts of Pharmaceuticals and Personal Care Products (PPCPs) in Surface Waters: Roles of Mineral Sediments and Solar Radiation

NASA Astrophysics Data System (ADS)

Rubasinghege, G. R. S.; Rijal, H.; Maldonado-Torres, S.; Gurung, R.; Rogelj, S.; Piyasena, M.

2017-12-01

The growing medical and personal needs of human populations have escalated release of pharmaceuticals and personal care products into surface waters. This work investigates abiotic degradation pathways of a particular PPCP, ibuprofen, in the presence of a major mineral component of sedimentation (kaolinite clay), as well as the health effects of the primary compound and its degradation products. Results from these studies showed that the rate and extent of ibuprofen degradation is greatly influenced by the presence of sedimentation particles and solar radiation. In the absence of solar radiation, the dominant reaction mechanism was observed to be the adsorption of ibuprofen onto sedimentation particle surface where surface silanol groups play a key role. In contrast, under solar radiation and in the presence of clay particles, ibuprofen breaks down to several fractions. The decay rates were at least 6-fold higher for irradiated samples compared to those of dark conditions. Toxicity of primary ibuprofen and its secondary residues were tested on three microorganisms: Bacillus megaterium, Pseudoaltermonas atlantica; and algae from the Chlorella genus. The results from the biological assays show that primary PPCP is more toxic than the mixture of secondary products. Overall, however, biological assays carried out using only 4-acetylbenzoic acid, the most abundant secondary product, show a higher toxic effect on algae compared to its parent compound.

Antiplasmodial Activity and Toxicological Assessment of Curcumin PLGA-Encapsulated Nanoparticles

PubMed Central

Busari, Zulaikha A.; Dauda, Kabiru A.; Morenikeji, Olajumoke A.; Afolayan, Funmilayo; Oyeyemi, Oyetunde T.; Meena, Jairam; Sahu, Debasis; Panda, Amulya K.

2017-01-01

Curcumin is a polyphenolic pigment isolated from the rhizomes of Curcuma longa (turmeric), a medicinal plant widely used in the ancient Indian and Chinese medicine. The antiplasmodial activity of curcumin is often hampered by its fast metabolism and poor water solubility, thus its incorporation into a delivery system could circumvent this problem. This study aimed to evaluate the in vivo antiplasmodial activity and the toxicity assessment of curcumin incorporated into poly (lactic-co-glycolic) acid (PLGA) nanoparticles. Curcumin was loaded with poly (D,L-lactic-co-glycolic acid) (PLGA) using solvent evaporation from oil-in-water single emulsion method. The nanoparticles were characterized and evaluated in vivo for antimalarial activities using Peter’s 4-day suppressive protocol in mice model. Hematological and hepatic toxicity assays were performed on whole blood and plasma, respectively. In vivo anti-parasitic test and toxicity assays for free and encapsulated drug were performed at 5 and 10 mg/kg. In vitro cytotoxicity of free and PLGA encapsulated curcumin (Cur-PLGA) to RAW 264.7 cell line was also determined at varying concentrations (1000–7.8 μg/mL). The size and entrapment efficiency of the nanoparticulate drug formulated was 291.2 ± 82.1 nm and 21.8 ± 0.4 respectively. The percentage parasite suppression (56.8%) at 5 mg/kg was significantly higher than in free drug (40.5%) of similar concentration (p < 0.05) but not at 10 mg/kg (49.5%) at 4-day post-treatment. There were no significant differences in most of the recorded blood parameters in free curcumin and PLGA encapsulated nanoparticulate form (p > 0.05) except in lymphocytes which were significantly higher in Cur-PLGA compared to the free drug (p < 0.05). There were no significant differences in hepatotoxic biomarkers; aspartate aminotransferase and alanine aminotransferase concentrations in various treatment groups (p > 0.05). At higher concentrations (1000 and 500 μg/mL), Cur-PLGA entrapped nanoparticle showed higher toxicity compared with the free drug (p < 0.05) in exposed RAW 264.7 cell line. The cell viability was, however, higher in Cur-PLGA nanoparticles than in free curcumin at lower concentrations (p > 0.05). The antiplasmodial activity and safety of Cur-PLGA was better at lower concentration. PMID:28932197

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meier, J.R.; Chang, L.W.; Meckes, M.C.

Soil from a site heavily contaminated with polychlorinated biphenyls (PCBs) was treated with a pilot-scale, solvent extraction technology. Bioassays in earthworms and plants were used to examine the efficacy of the remediation process for reducing the toxicity of the soil. The earthworm toxicity bioassays were the 14-d survival test and 21-d reproduction test, using Lumbricus terrestris and Eisenia fetida andrei. The plant bioassays included phytotoxicity tests for seed germination and root elongation in lettuce and oats, and a genotoxicity test (anaphase aberrations) in Allium cepa (common onion). Although the PCB content of the soil was reduced by 99% (below themore » remediation goal), toxicity to earthworm reproduction remained essentially unchanged following remediation. Furthermore, phytotoxicity and genotoxicity were higher for the remediated soil compared to the untreated soil. The toxicity remaining after treatment appeared to be due to residual solvent introduced during the remediation process, and/or to heavy metals or other inorganic contaminants not removed by the treatment. Mixture studies involving isopropanol and known toxicants indicated possible synergistic effects of the extraction solvent and soil contaminants. The toxicity in plants was essentially eliminated by a postremediation, water-rinsing step. These results demonstrate a need for including toxicity measurements in the evaluation of technologies used in hazardous waste site remediations, and illustrate the potential value of such measurements for making modifications to remediation processes.« less

Effects of three related amides on microecosystem stability

DOE Office of Scientific and Technical Information (OSTI.GOV)

Flum, T.F.; Shannon, L.J.

1987-04-01

Three related amides (diuron, 2-(octyloxy) acetanilide, and salicylanilide) were evaluated for toxicity to aquatic microcosm communities. Effects were measured at the ecosystem level using changes in pH, Eh (redox potential), and dissolved oxygen as indicators of toxicity. These values were used to calculate the resistance, resilience, and relative instability of the microecosystems to each compound at comparable dose levels of approximately 2500 micrograms/liter. Such measures have often been used in a theoretical context, but have not received wide practical application. The systems showed low resistance and no resilience to diuron, high resistance and low resilience to 2-(octyloxy) acetanilide, and nomore » response to salicylanilide. At a higher exposure level (9800 micrograms/liter salicylanilide), the systems showed low resistance and high resilience. Both this approach and more traditional dose-response measures of toxicity indicated that diuron was clearly the most toxic compound, followed by 2-(octyloxy) acetanilide and salicylanilide. While microcosm toxicity tests were slightly less sensitive than some single species tests, they provided important additional information on the extent of perturbations and the rate of ecosystem recovery.« less

Lethal and sublethal endpoints observed for Artemia exposed to two reference toxicants and an ecotoxicological concern organic compound.

PubMed

Manfra, Loredana; Canepa, Sara; Piazza, Veronica; Faimali, Marco

2016-01-01

Swimming speed alteration and mortality assays with the marine crustacean Artemia franciscana were carried out. EC50 and LC50 values after 24-48h exposures were calculated for two reference toxicants, copper sulphate pentahydrate (CuSO4·5H2O) and Sodium Dodecyl Sulphate (SDS), and an ecotoxicological concern organic compound, Diethylene Glycol (DEG). Different end-points have been evaluated, in order to point out their sensitivity levels. The swimming speed alteration (SSA) was compared to mortality values and also to the hatching rate inhibition (literature data). SSA resulted to be more sensitive than the mortality and with a sensitivity comparable to (or even higher than) the hatching rate endpoint. Copyright © 2015 Elsevier Inc. All rights reserved.

Removal potential of toxic 2378-substituted PCDD/F from incinerator flue gases by waste-derived activated carbons.

PubMed

Hajizadeh, Yaghoub; Onwudili, Jude A; Williams, Paul T

2011-06-01

The application of activated carbons has become a commonly used emission control protocol for the removal or adsorption of persistent organic pollutants from the flue gas streams of waste incinerators. In this study, the 2378-substituted PCDD/F removal efficiency of three types of activated carbons derived from the pyrolysis of refuse derived fuel, textile waste and scrap tyre was investigated and compared with that of a commercial carbon. Experiments were carried out in a laboratory scale fixed-bed reactor under a simulated flue gas at 275°C with a reaction period of four days. The PCDD/F in the solid matrices and exhaust gas, were analyzed using gas chromatography coupled with a triple quadrupole mass spectrometer. In the absence of activated carbon adsorbent, there was a significant increase in the concentration of toxic PCDD/F produced in the reacted flyash, reaching up to 6.6 times higher than in the raw flyash. In addition, there was a substantial release of PCDD/F into the gas phase, which was found in the flue gas trapping system. By application of the different commercial, refuse derived fuel, textile and tyre activated carbons the total PCDD/F toxic equivalent removal efficiencies in the exhaust gas stream were 58%, 57%, 64% and 52%, respectively. In general, the removal of the PCDDs was much higher with an average of 85% compared to PCDFs at 41%. Analysis of the reacted activated carbons showed that there was some formation of PCDD/F, for instance, a total of 60.6 μg I-TEQ kg(-1) toxic PCDD/F was formed in the refuse derived fuel activated carbon compared to 34 μg I-TEQ kg(-1) in the commercial activated carbon. The activated carbons derived from the pyrolysis of waste, therefore, showed good potential as a control material for PCDD/F emissions in waste incinerator flue gases. Copyright © 2011 Elsevier Ltd. All rights reserved.

California wildfires of 2008: coarse and fine particulate matter toxicity.

PubMed

Wegesser, Teresa C; Pinkerton, Kent E; Last, Jerold A

2009-06-01

During the last week of June 2008, central and northern California experienced thousands of forest and brush fires, giving rise to a week of severe fire-related particulate air pollution throughout the region. California experienced PM(10-2.5) (particulate matter with mass median aerodynamic diameter > 2.5 mum to < 10 mum; coarse ) and PM(2.5) (particulate matter with mass median aerodynamic diameter < 2.5 mum; fine) concentrations greatly in excess of the air quality standards and among the highest values reported at these stations since data have been collected. These observations prompt a number of questions about the health impact of exposure to elevated levels of PM(10-2.5) and PM(2.5) and about the specific toxicity of PM arising from wildfires in this region. Toxicity of PM(10-2.5) and PM(2.5) obtained during the time of peak concentrations of smoke in the air was determined with a mouse bioassay and compared with PM samples collected under normal conditions from the region during the month of June 2007. Concentrations of PM were not only higher during the wildfire episodes, but the PM was much more toxic to the lung on an equal weight basis than was PM collected from normal ambient air in the region. Toxicity was manifested as increased neutrophils and protein in lung lavage and by histologic indicators of increased cell influx and edema in the lung. We conclude that the wildfire PM contains chemical components toxic to the lung, especially to alveolar macrophages, and they are more toxic to the lung than equal doses of PM collected from ambient air from the same region during a comparable season.

Pregnenolone protects the PC-12 cell line against amyloid beta peptide toxicity but its sulfate ester does not.

PubMed

Akan, Pinar; Kizildag, Servet; Ormen, Murat; Genc, Sermin; Oktem, Mehmet Ali; Fadiloglu, Meral

2009-01-15

Pregnenolone (P), the main precursor of the steroids, and its sulfate ester, pregnenolone sulfate (PS), are the major neurosteroids produced in the neural tissue. Many neuroendocrinological studies stressed the neuroprotective role of neurosteroids although it has been suggested that the inhibition of P and PS synthesis can delay neuronal cell death. The potential roles of P and PS in vital neuronal functions and in amyloid beta peptide (Abeta) toxicity are not clearly identified. This work aims to investigate the effects of P and PS on cell viability and Abeta peptide toxicity in a concentration and exposure time-dependent manner in rat PC-12 cells. The cells were treated with 20muM Abeta peptide 25-35 and variable concentrations of P and PS ranging from 0.5muM to 100muM. To examine the effects of steroid treatment on Abeta peptide toxicity, 0.5muM (low) and 50muM (high) neurosteroids were used. The cell viability and lactate dehydrogenase release of cells were evaluated after 24, 48 and 72h. Morphological changes of cells were also examined. The treatment with higher than 1muM concentrations of P and PS significantly decreased the cell viability comparing to untreated cells. At lower concentrations, P and PS had no toxic actions until 72h. The Abeta treatment resulted in a significant decrease in cell viability comparing to untreated cells. P showed a dose-dependent protective effect against Abeta peptide in PC-12 cells. But its sulfate ester did not have the same effect on Abeta peptide toxicity, even it significantly decreased cell viability in Abeta-treated cells. Consequently, the discrepant effects of P and PS on Abeta peptide toxicity may provide insight on the pathogenesis of Alzheimer's disease.

Reduced toxicity of diuron to the freshwater green alga Pseudokirchneriella subcapitata in the presence of black carbon.

PubMed

Knauer, Katja; Sobek, Anna; Bucheli, Thomas D

2007-06-15

Black carbon (BC) is known to act as supersorbent for many organic contaminants. Its presence in surface waters at a level of a few mg/L, which may occur, e.g., after storm events in urban areas, might result in a reduced bioavailability of many contaminants and thus greatly impact their potential toxicity. Photosynthesis-inhibiting phenyl urea derivatives, such as diuron, are widely used as herbicides and diuron is regularly measured in European freshwater systems. In this study, the toxicity of diuron to the freshwater green alga Pseudokirchneriella subcapitata was investigated in the presence of BC in its native and combusted form. As a toxicity endpoint, the in vivo chlorophyll fluorescence was determined and used to indicate the bioavailability of diuron. Fifty milligrams native BC/L reduced effects of 5mugdiuron/L on photosynthesis by 10+/-2%, whereas photosynthesis was completely restored in the presence of the same concentration of combusted BC, suggesting a significantly enhanced adsorption of diuron to the BC fraction compared to the organic carbon fraction. Assuming an environmentally realistic concentration of approximately 1.5mg of combusted BC/L, diuron toxicity would be reduced by approximately 20% in surface waters due to the presence of BC. Higher BC concentrations after storm events might reduce the toxicity even further. A calculation of the Freundlich sorption coefficient K(F,BC,tox) via the toxicity endpoint, resulted in a log K(F,BC,tox) of the combusted BC of 5.7, which is comparable to values obtained by classical sorption experiments. This study contributes to a refined risk assessment of micropollutants in surface waters taking into account the presence of potentially relevant sorbents and, consequently, reduced bioavailability.

Cytotoxicity of Spent Pot Liner on Allium cepa root tip cells: A comparative analysis in meristematic cell type on toxicity bioassays.

PubMed

Palmieri, Marcel José; Andrade-Vieira, Larissa Fonseca; Campos, José Marcello Salabert; Dos Santos Gedraite, Leonardo; Davide, Lisete Chamma

2016-11-01

Spent Pot Liner (SPL) is a waste generated during the production of aluminum. It is comprised of a mixture of substances most of which, like cyanide, aluminum and fluoride, are toxic. Previous studies indicate the highly toxic nature of SPL. However studies using cells of the differentiation/elongation zone of the root meristem (referred as M2 cells in this study) after a proper recovery period in water were never considered. Using these cells could be useful to further understanding the toxicity mechanisms of SPL. A comparative approach between the effects on M2 cells and meristematic cells of the proximal meristem zone (referred as M1 cells in this study) could lead to understanding how DNA damage caused by SPL behaves on successive generations of cells. Allium cepa cells were exposed to 4 different concentrations of SPL (2.5, 5, 7.5 and 10gL(-1)) mixed with soil and diluted in a CaCl2 0.01M to simulate the ionic forces naturally encountered on the environment. A solution containing only soil diluted on CaCl2 0.01M was used as control. M1 and M2 cells were evaluated separately, taking into account four different parameters: (1) mitotic alterations (MA); (2) presence of condensed nuclei (CN); (3) mitotic index (MI); (4) presence of micronucleus (MCN). Significant differences were observed between M1 and M2 roots tip cells for these four parameters accessed. M1 cells was more prompt to reveal citogenotoxicity through the higher frequency of MA observed. Meanwhile, for M2 cells higher frequencies of MCN and CN was noticed, followed by a reduction of MI. Also, it was possible to detect significant differences between the tested treatments and the control on every case. These results indicate SPL toxic effects carries on to future cells generations. This emphasizes the need to properly manage this waste. Joint evaluation of cells from both M1 and M2 regions was proven valuable for the evaluation of a series of parameters on all toxicity tests. Copyright © 2016. Published by Elsevier Inc.

Toxicity and elemental composition of particulate matter from outdoor and indoor air of elementary schools in Munich, Germany.

PubMed

Oeder, S; Dietrich, S; Weichenmeier, I; Schober, W; Pusch, G; Jörres, R A; Schierl, R; Nowak, D; Fromme, H; Behrendt, H; Buters, J T M

2012-04-01

Outdoor particulate matter (PM(10)) is associated with detrimental health effects. However, individual PM(10) exposure occurs mostly indoors. We therefore compared the toxic effects of classroom, outdoor, and residential PM(10). Indoor and outdoor PM(10) was collected from six schools in Munich during teaching hours and in six homes. Particles were analyzed by scanning electron microscopy and X-ray spectroscopy (EDX). Toxicity was evaluated in human primary keratinocytes, lung epithelial cells and after metabolic activation by several human cytochromes P450. We found that PM(10) concentrations during teaching hours were 5.6-times higher than outdoors (117 ± 48 μg/m(3) vs. 21 ± 15 μg/m(3), P < 0.001). Compared to outdoors, indoor PM contained more silicate (36% of particle number), organic (29%, probably originating from human skin), and Ca-carbonate particles (12%, probably originating from paper). Outdoor PM contained more Ca-sulfate particles (38%). Indoor PM at 6 μg/cm(2) (10 μg/ml) caused toxicity in keratinocytes and in cells expressing CYP2B6 and CYP3A4. Toxicity by CYP2B6 was abolished with the reactive oxygen species scavenger N-acetylcysteine. We concluded that outdoor PM(10) and indoor PM(10) from homes were devoid of toxicity. Indoor PM(10) was elevated, chemically different and toxicologically more active than outdoor PM(10). Whether the effects translate into a significant health risk needs to be determined. Until then, we suggest better ventilation as a sensible option. Indoor air PM(10) on an equal weight base is toxicologically more active than outdoor PM(10). In addition, indoor PM(10) concentrations are about six times higher than outdoor air. Thus, ventilation of classrooms with outdoor air will improve air quality and is likely to provide a health benefit. It is also easier than cleaning PM(10) from indoor air, which has proven to be tedious. © 2011 John Wiley & Sons A/S.

Comparative analysis of microbial fuel cell based biosensors developed with a mixed culture and Shewanella loihica PV-4 and underlying biological mechanism.

PubMed

Yi, Yue; Xie, Beizhen; Zhao, Ting; Liu, Hong

2018-06-13

Microbial fuel cell based biosensors (MFC-biosensors) utilize anode biofilms as biological recognition elements to monitor biochemical oxygen demand (BOD) and biotoxicity. However, the relatively poor sensitivity constrains the application of MFC-biosensors. To address this limitation, this study provided a systematic comparison of sensitivity between the MFC-biosensors constructed with two inocula. Higher biomass density and viability were both observed in the anode biofilm of the mixed culture MFC, which resulted in better sensitivity for BOD assessment. Compared with using mixed culture as inoculum, the anode biofilm developed with Shewanella loihica PV-4 presented lower content of extracellular polymeric substances and poorer ability to secrete protein under toxic shocks. Moreover, the looser structure in the S. loihica PV-4 biofilm further facilitated its susceptibilities to toxic agents. Therefore, the MFC-biosensor with a pure culture of S. loihica PV-4 delivered higher sensitivity for biotoxicity monitoring. This study proposed a new perspective to enhance sensor performance. Copyright © 2018 Elsevier Ltd. All rights reserved.

Enhanced cytotoxicity of anticancer drug delivered by novel nanoscale polymeric carrier

NASA Astrophysics Data System (ADS)

Stoika, R.; Boiko, N.; Senkiv, Y.; Shlyakhtina, Y.; Panchuk, R.; Finiuk, N.; Filyak, Y.; Bilyy, R.; Kit, Y.; Skorohyd, N.; Klyuchivska, O.; Zaichenko, A.; Mitina, N.; Ryabceva, A.

2013-04-01

We compared in vitro action of highly toxic anticancer drug doxorubicin under its delivery to the mammalian tumor cells in free form and after encapsulation in novel bio-functionalized nanoscale polymeric carrier. Such encapsulation was found to enhance significantly drug uptake by the targeted cells, as well as its cytotoxic action. 10 times higher cytotoxicity of the carrier-immobilized doxorubicin comparing to its free form was demonstrated by direct cell counting, and 5 times higher cytotoxicity of encapsulated doxorubicin was shown by FACS analysis. The polymeric carrier itself did not possess significant toxicity in vitro or in vivo (laboratory mice). The carrier protected against negative side effects of doxorubicin in mice with experimental NK/Ly lymphoma. The life duration of tumor-bearing animals treated with doxorubicin-carrier complex was significantly longer than life duration in animals treated with free doxorubicin. Besides, the effective treatment dose of the carrier-delivered doxorubicin in tumor-bearing mice was 10 times lower than such dose of free doxorubicin. Thus, novel nanoscale polymers possess high potential as drug carrier.

Effect of exogenous nitric oxide on antioxidative system and S-nitrosylation in leaves of Boehmeria nivea (L.) Gaud under cadmium stress.

PubMed

Wang, Dafei; Liu, Yunguo; Tan, Xiaofei; Liu, Hongyu; Zeng, Guangming; Hu, Xinjiang; Jian, Hao; Gu, Yanling

2015-03-01

Cadmium (Cd)-induced growth inhibition is one of the primary factors limiting phytoremediation effect of Boehmeria nivea (L.) Gaud in contaminated soil. Sodium nitroprusside (SNP), a donor of nitric oxide (NO), has been evidenced to alleviate Cd toxicity in many plants. However, as an important mechanism of NO in orchestrating cellular functions, S-nitrosylation is still poorly understood in its relation with Cd tolerance of plants. In this study, higher exogenous NO levels were found to coincide with higher S-nitrosylation level expressed as content of S-nitrosothiols (SNO). The addition of low concentration (100 μM) SNP increased the SNO content, and it simultaneously induced an alleviating effect against Cd toxicity by enhancing the activities of superoxide dismutase (SOD), ascorbate peroxidase (APX), and glutathione reductase (GR) and reduced the accumulation of H2O2 as compared with Cd alone. Application of S-nitrosoglutathione reductase (GSNOR) inhibitors dodecanoic acid (DA) in 100 μM SNP group brought in an extra elevation in S-nitrosylation level and further reinforced the effect of SNP. While the additions of 400 μM SNP and 400 μM SNP + 50 μM DA further elevated the S-nitrosylation level, it markedly weakened the alleviating effect against Cd toxicity as compared with the addition of 100 μM SNP. This phenomenon could be owing to excess consumption of glutathione (GSH) to form SNO under high S-nitrosylation level. Therefore, the present study indicates that S-nitrosylation is involved in the ameliorating effect of SNP against Cd toxicity. This involvement exhibited a concentration-dependent property.

Biological activity of Xanthium strumarium seed extracts on different cancer cell lines and Aedes caspius, Culex pipiens (Diptera: Culicidae).

PubMed

Al-Mekhlafi, Fahd A; Abutaha, Nael; Mashaly, Ashraf M A; Nasr, Fahd A; Ibrahim, Khalid E; Wadaan, Mohamed A

2017-05-01

Effects of methanol extracts of Xanthium strumarium on different cancer cell lines and on the mortality rates of Aedes caspius, Culex pipiens (Diptera: Culicidae) were investigated. Among the cell lines tested, the Jurkat cell line was the most sensitive to the methanol extract and ethyl acetate fraction, with reported LC 50 values of 50.18 and 48.73 μg/ml respectively. Conversely, methanol extracts were not that toxic to the A549 cell line though the toxicity increased on further purification. The percentage of growth inhibition was dose dependent for the methanol extract and ethyl acetate fraction. The ethyl acetate fraction showed higher toxicity to all cell lines tested when compared to the methanol extract. The results showed that methanol extracts of plant seeds caused 100% mortality of mosquito larvae at a concentration of 1000 μg/ml after 24 h of treatment. The LC 50 and LC 90 values of X. strumarium were found to be 531.07 and 905.95 μg/ml against Ae. caspius and 502.32 and 867.63 μg/ml against Cx. Pipiens, respectively. From the investigations, it was concluded that the crude extract of X. strumarium showed a weak potential for controlling the larval instars of Ae. caspius and Cx. pipiens . However, on further purification the extract lost the larvicidal activity. The ethyl acetate fraction showed higher toxicity to all cell lines tested when compared to the methanol extract. The ethyl acetate fraction investigated in this study appears to have a weak larvicidal activity but a promising cytotoxic activity. Future studies will include purification and investigation in further detail of the action of X. strumarium on Cancer Cell Lines and mosquitoes.

UVΑ pre-irradiation to P25 titanium dioxide nanoparticles enhanced its toxicity towards freshwater algae Scenedesmus obliquus.

PubMed

Roy, Barsha; Chandrasekaran, Hemamalini; Palamadai Krishnan, Suresh; Chandrasekaran, Natarajan; Mukherjee, Amitava

2018-04-02

There has recently been an increase in the usage of TiO 2 nanoparticles (NPs). P25 TiO 2 NPs, a mixture of anatase and rutile phase in 3:1 ratio, are generally used for photocatalytic applications because both phases exhibit a synergistic effect on the photocatalytic activity of the TiO 2 NPs. In the present study, increased toxicity of UVA-pre-irradiated P25 TiO 2 NPs on freshwater algae Scenedesmus obliquus was assessed under visible light and dark exposure conditions at actual low concentrations (0.3, 3 and 35 μM of Ti). Photocatalytic property of P25 TiO 2 NPs caused disaggregation of UVA-pre-irradiated NPs, thus significantly decreasing the mean hydrodynamic diameter (MHD) (188.74 ± 0.54 nm) than that of non-irradiated NPs (232.26 ± 0.44). This decrease in diameter of UVA-pre-irradiated NPs may increase its biological activity towards algal samples. All concentrations of pre-irradiated NPs, under both light and dark conditions, showed a significantly lesser cell viability (p < 0.001) when compared with non-irradiated NPs. Increased production of ROS, antioxidant enzymes and lipid peroxidation supported the viability data. Higher exopolysaccharide production and more nuclear damage were observed for pre-irradiated NPs. NP uptake was also more for the pre-irradiated NPs on treated samples when compared with non-irradiated NPs on treated samples, which, in turn, established the higher toxic potential of UVA-pre-irradiated TiO 2 NPs. This study improves our understanding of the toxic effects of UVA-pre-irradiated TiO 2 NPs on freshwater algae, thereby emphasising the need for ecological risk assessments of metal oxide nanoparticles in a natural experimental medium.

Inter-regional differences in baseline toxicity of Bemisia argentifolii (Homoptera: Aleyrodidae) to the two insect growth regulators, buprofezin and pyriproxyfen.

PubMed

Toscano, N C; Prabhaker, N; Castle, S J; Henneberry, T J

2001-12-01

A survey of 53 Bemisia argentifolii Bellows & Perring populations from different agricultural regions in California and Arizona was conducted from 1997 to 1999 to establish baseline toxicological responses to buprofezin and pyriproxyfen. Although both compounds proved to be highly toxic even in minute quantities to specific stages, geographical and temporal differences in responses were detected using a leaf spray bioassay technique. Monitoring for three years revealed that six to seven populations had higher LC50 values but not greater survival when exposed to these two insecticides. A significant difference in relative susceptibility to buprofezin was first observed in late season 1997 in San Joaquin Valley populations with LC50s ranging from 16 to 22 microg (AI)/liter(-1) compared with IC50s of 1 to 3 mg (AI)/liter(-1) in Imperial, Palo Verde Valley and Yuma populations. Whiteflies collected in subsequent years from these and other locations showed an increase in susceptibility to buprofezin. Regional differences in susceptibilities to pyriproxyfen were minimal within the same years. Three years of sampling revealed consistently higher LC50s to pyriproxyfen in populations from Palo Verde Valley, CA, compared with whiteflies from Imperial, San Joaquin Valley or Yuma. As was the case with buprofezin, a decline in LC50s to pyriproxyfen was observed in whiteflies from all locations sampled in 1999. However, no correlation was observed between buprofezin and pyriproxyfen toxicity in any of the strains. The variable toxicities observed to both compounds over a period of 3 yr may be due principally to inherent differences among geographical populations or due to past chemical use which may confer positive or negative cross-resistance to buprofezin or pyriproxyfen.

Detection of CYP2E1, a genetic biomarker of susceptibility to benzene metabolism toxicity in immortal human lymphocytes derived from the Han Chinese Population.

PubMed

Zhang, Juan; Yin, Lihong; Liang, Geyu; Liu, Ran; Fan, Kaihong; Pu, Yuepu

2011-06-01

Cytochrome P450 2E1 (CYP2E1) is an important metabolizing enzyme involved in oxidative stress responses to benzene, a chemical associated with bone marrow toxicity and leukemia. We aimed to identify the CYP2E1 genetic biomarkers of susceptibility to benzene toxicity in support of environmental and occupational exposure prevention, and to test whether a model using immortal human lymphocytes might be an efficient tool for detecting genetic biomarkers. Immortalized human lymphocyte cell lines with independent genotypes on four CYP2E1 SNP sites were induced with 0.01% phenol, a metabolite of benzene. CYP2E1 gene function was evaluated by mRNA expression and enzyme activity. DNA damage was measured by Single-Cell Gel Electrophoresis (SCGE). Among the four SNPs, cells with rs2070673TT and rs2030920CC showed higher levels of CYP2E1 transcription and enzymatic activity than the other genotypes in the same SNP site. Cells with higher gene expression genotypes also showed higher comet rates compared with lower gene expression genotypes. These results suggest that CYP2E1 rs2070673 and rs2030920 might be the genetic biomarkers of susceptibility to benzene toxicity and that the immortalized human lymphocytes model might be an efficient tool for the detection of genetic biomarkers of susceptibility to chemicals. Copyright © 2011 The Editorial Board of Biomedical and Environmental Sciences. Published by Elsevier B.V. All rights reserved.

QSAR Modeling of Rat Acute Toxicity by Oral Exposure

PubMed Central

Zhu, Hao; Martin, Todd M.; Ye, Lin; Sedykh, Alexander; Young, Douglas M.; Tropsha, Alexander

2009-01-01

Few Quantitative Structure-Activity Relationship (QSAR) studies have successfully modeled large, diverse rodent toxicity endpoints. In this study, a comprehensive dataset of 7,385 compounds with their most conservative lethal dose (LD50) values has been compiled. A combinatorial QSAR approach has been employed to develop robust and predictive models of acute toxicity in rats caused by oral exposure to chemicals. To enable fair comparison between the predictive power of models generated in this study versus a commercial toxicity predictor, TOPKAT (Toxicity Prediction by Komputer Assisted Technology), a modeling subset of the entire dataset was selected that included all 3,472 compounds used in the TOPKAT’s training set. The remaining 3,913 compounds, which were not present in the TOPKAT training set, were used as the external validation set. QSAR models of five different types were developed for the modeling set. The prediction accuracy for the external validation set was estimated by determination coefficient R2 of linear regression between actual and predicted LD50 values. The use of the applicability domain threshold implemented in most models generally improved the external prediction accuracy but expectedly led to the decrease in chemical space coverage; depending on the applicability domain threshold, R2 ranged from 0.24 to 0.70. Ultimately, several consensus models were developed by averaging the predicted LD50 for every compound using all 5 models. The consensus models afforded higher prediction accuracy for the external validation dataset with the higher coverage as compared to individual constituent models. The validated consensus LD50 models developed in this study can be used as reliable computational predictors of in vivo acute toxicity. PMID:19845371

Quantitative structure-activity relationship modeling of rat acute toxicity by oral exposure.

PubMed

Zhu, Hao; Martin, Todd M; Ye, Lin; Sedykh, Alexander; Young, Douglas M; Tropsha, Alexander

2009-12-01

Few quantitative structure-activity relationship (QSAR) studies have successfully modeled large, diverse rodent toxicity end points. In this study, a comprehensive data set of 7385 compounds with their most conservative lethal dose (LD(50)) values has been compiled. A combinatorial QSAR approach has been employed to develop robust and predictive models of acute toxicity in rats caused by oral exposure to chemicals. To enable fair comparison between the predictive power of models generated in this study versus a commercial toxicity predictor, TOPKAT (Toxicity Prediction by Komputer Assisted Technology), a modeling subset of the entire data set was selected that included all 3472 compounds used in TOPKAT's training set. The remaining 3913 compounds, which were not present in the TOPKAT training set, were used as the external validation set. QSAR models of five different types were developed for the modeling set. The prediction accuracy for the external validation set was estimated by determination coefficient R(2) of linear regression between actual and predicted LD(50) values. The use of the applicability domain threshold implemented in most models generally improved the external prediction accuracy but expectedly led to the decrease in chemical space coverage; depending on the applicability domain threshold, R(2) ranged from 0.24 to 0.70. Ultimately, several consensus models were developed by averaging the predicted LD(50) for every compound using all five models. The consensus models afforded higher prediction accuracy for the external validation data set with the higher coverage as compared to individual constituent models. The validated consensus LD(50) models developed in this study can be used as reliable computational predictors of in vivo acute toxicity.

Difference of toxicity and accumulation of methylated and inorganic arsenic in arsenic-hyperaccumulating and -hypertolerant plants.

PubMed

Huang, Ze-Chun; Chen, Tong-Bin; Lei, Mei; Liu, Ying-Ru; Hu, Tian-Dou

2008-07-15

The arsenic (As) hyperaccumulators, Pteris vittata and Pteris cretica and an As-tolerant plant Boehmeria nivea, were selected to compare the toxicity, uptake, and transportation of inorganic arsenate (As(V)) and its methylated counterpart dimethylarsinic acid (DMA). The XANES method was used to elucidate the effect of As species transformation on As toxicity and accumulation characteristics. Significantly higher toxicity and lower accumulation of DMAthan inorganic As(V) was shown in the As hyperaccumulators and the As-tolerant plant. Reduction of As(V) was commonly found in the plants. Arsenic complexation with thiols, which have less mobility in plants and usually occur in As-tolerant plants, was also found in rhizoids of P. cretica. Plants with greater ability to form As-thiolate have lower ability for upward transport of As. Demethylation of DMA occurred in the three plants. The DMA component decreased from the rhizoids to the fronds in both hyperaccumulators, while this tendency is reverse in B. nivea.

Ozonation of trimethoprim in aqueous solution: identification of reaction products and their toxicity.

PubMed

Kuang, Jiangmeng; Huang, Jun; Wang, Bin; Cao, Qiming; Deng, Shubo; Yu, Gang

2013-05-15

This work aimed to better understand the ozonation process of a typical antibiotic pharmaceutical, trimethoprim in aqueous solution. The parent compound was almost completely degraded with ozone dose up to 3.5 mg/L with no mineralization. Twenty one degradation products were identified using an electrospray quadrupole time-of-flight mass spectrometer. Several ozonation pathways were proposed including hydroxylation, demethylation, carbonylation, deamination and methylene group cleavage. Two species of luminescent bacteria Photobacterium phosphoreum and Vibrio qinghaiensis were selected to assess the toxicity of ozonation products. For P. phosphoreum, higher level of toxicity was observed compared to the parent compound, but a negligible toxicity change was observed for V. qinghaiensis, indicating different modes of action for the same water sample. This was further confirmed by quantitative structure-active relationship analysis. This work proves the dominant role of ozone rather than hydroxyl radicals in the reaction and the potential risk after ozonation. Copyright © 2013 Elsevier Ltd. All rights reserved.

Impact of an electronic tool in prescribing primary prophylaxis with ciprofloxacin or granulocyte colony-stimulating factor for breast cancer patients receiving TC chemotherapy.

PubMed

Sulpher, Jeffrey; Giguere, Pierre; Hopkins, Sean; Dent, Susan

2016-07-01

The US Oncology Trial 9735 (doxorubicin and cyclophosphamide (AC) versus docetaxel and cyclophosphamide (TC)) reported febrile neutropenia (FN) in 5 % of patients receiving TC chemotherapy, in the absence of routine primary prophylaxis with granulocyte colony-stimulating factor (G-CSF) or antibiotics. In contrast, higher rates of FN have been reported in the 'real world' setting. This retrospective study compares the incidence and severity of FN and other TC-related toxicities before and after implementation of a primary prophylaxis computerized prescribing tool. Medical records of 207 patients receiving adjuvant TC between May 1, 2006, and November 1, 2011, were reviewed for toxicity. The incidence for each TC adverse event was measured by an incident rate ratio (IRR), and chi-square analysis was used to compare the differences in severity of TC toxicities before and after use of a primary prophylaxis computerized prescribing tool, and to compare G-CSF and ciprofloxacin groups. The implementation of a computerized prescribing tool significantly increased the proportion of patients prescribed primary prophylaxis (18.2 vs. 97.4 %; p < 0.001). Prior to the change in practice, the incidence of FN (incidence rate ratio 3.87; 95 % CI [1.3, 11.5]) and neutropenia (OR 4.8; 95 % CI [2.0, 11.7]) was significantly higher. Primary prophylaxis significantly reduced the rate of febrile neutropenia (20 vs. 5.3 %, p = 0.003). No significant differences were found in incidence and severity of other TC-related toxicities. Patients who did not receive G-CSF were at a greater risk for neutropenia (OR 5.1, 95 % CI [1.06, 24.3]). There were insufficient patients treated with antibiotics alone to compare to those treated with G-CSF. Implementation of a computerized prescribing tool significantly increased the use of primary prophylaxis by treating physicians in patients receiving TC chemotherapy, which was associated with reduced incidence of febrile neutropenia. Further research efforts should focus on the incorporation and routine use of evidence-based practices using tools such as alerts and prompts, in order to optimize patient care and improve outcomes.

Differences in venom toxicity and antigenicity between females and males Tityus nororientalis (Buthidae) scorpions

PubMed Central

De Sousa, Leonardo; Borges, Adolfo; Vásquez-Suárez, Aleikar; Op den Camp, Huub JM; Chadee-Burgos, Rosa I; Romero-Bellorín, Mirna; Espinoza, Jorge; De Sousa-Insana, Leonardo; Pino-García, Oscar

2010-01-01

Venom from male and female specimens of the medically important Venezuelan scorpion Tityus nororientalis have been compared. Males showed a significantly higher venom yield (2.39mg/individual) compared to female scorpions (0.98mg/individual). Female venom was significantly more toxic than that of males, with a median lethal dose (LD50) in C57BL/6 mice of 9.46 μg venom protein/gm body weight [95% confidence interval (8.91-9.94)] whereas LD50 for males was 13.36(12.58-14.03) μg/gm. Mass spectral analyses by MALDI-TOF revealed differences in venom composition between males and females. From a clinical standpoint, the time course of toxicity course indicated a tendency, in the case of the female venom, to elicit the earlier occurrence of severe signs such as sialorrhea, dyspnea (bradypnea/apnea) and exophthalmus particularly in the late toxicity phase. Female venom was significantly less efficient than male venom to inhibit the binding of anti-T. discrepans antibodies to immobilized T. discrepans venom in ELISA assays, suggesting sex-related differences in the bioactive surfaces of T. nororientalis toxins. These results indicate that males and females of T. nororientalis produce venoms with different composition and activity which may have epidemiological implications. PMID:21544184

Comet assay and micronucleus tests on Oreochromis niloticus (Perciforme: Cichlidae) exposed to raw sugarcane vinasse and to phisicochemical treated vinasse by pH adjustment with lime (CaO).

PubMed

Correia, Jorge E; Christofoletti, Cintya Ap; Ansoar-Rodríguez, Yadira; Guedes, Thays A; Fontanetti, Carmem S

2017-04-01

In Brazil vinasse, a main sugarcane distillery residue, stands out because every liter of alcohol generates 10-15 L of vinasse as waste. An alternative for the disposal of this waste is the fertirrigation of the sugarcane culture itself. However, the high amount released can saturate the soil and through leaching/percolation contaminate water resources. The aim of this study is verifying the toxic potential of vinasse in tilapias and effectiveness of the physicalchemical treatment of this waste with pH adjustment with lime (CaO). The comet assay and the micronucleus test were applied on animals exposed to dilutions of raw vinasse and vinasse adjusted to neutral pH. Bioassays with raw vinasse dilutions indicated a toxic and genotoxic potential; fish exposed to the highest concentration died less than 48 h after the exposure; the incidence of micronucleus was significantly higher when compared to negative control for all dilutions. For the comet assay, the scores of damage were statistically higher for all dilutions, with the exception of the 1% dillution. However, in the bioassay with the chemically treated vinasse (neutral pH), most fish in the 10% dilution survived and there was no significant difference when compared to the control. Damage scores in the comet assay were similar to the results of the untreated vinasse. The chemical treatment of vinasse with lime to neutralize the pH proved to be an effective alternative for the toxicity reduction of this residue, since it reduced the mortality of fish at higher concentrations and the incidence of damage to DNA. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparative study on the sensitivity of turions and active fronds of giant duckweed (Spirodela polyrhiza (L.) Schleiden) to heavy metal treatments.

PubMed

Oláh, Viktor; Hepp, Anna; Mészáros, Ilona

2015-08-01

Standard ecotoxicological test procedures use only active forms of aquatic plants. The potential effects of toxicants on vegetative propagules, which play an important role in the survival of several aquatic plant species, is not well understood. Because turion-like resting propagules overwinter on the water bottom in temperate regions, they could be exposed to contaminants for longer periods than active plants. Due to its turion producing capability, giant duckweed (Spirodela polyrhiza) is widely used in studying morphogenesis, dormancy, and activation mechanisms in plants. It is also suitable for ecotoxicological purposes. The present work aims to compare the growth inhibition sensitivity of active (normal frond) and overwintering (turion) forms of S. polyrhiza to concentrations of nickel (Ni), cadmium (Cd) and hexavalent chromium (Cr) ranging from 0 to 100mgL(-1). The results indicated that in general, resting turions have higher heavy metal tolerance than active fronds. Cd proved to be the most toxic heavy metal to S. polyrhiza active frond cultures because it induced rapid turion formation. In contrast, the toxicity of Ni and Cr were found to be similar but lower than the effects of Cd. Cr treatments up to 10mgL(-1) did not result in any future negative effects on turion activation. Turions did not survive heavy metal treatments at higher concentrations of Cr. Cd and Ni treatments affected both the floating-up and germination of turions but did not significantly affect the vigor of sprouts. Higher concentrations (of 100mgL(-1)) Cd completely inhibited germination. Copyright © 2015 Elsevier Ltd. All rights reserved.

High-dose-rate stereotactic body radiation therapy for postradiation therapy locally recurrent prostatic carcinoma: Preliminary prostate-specific antigen response, disease-free survival, and toxicity assessment.

PubMed

Fuller, Donald B; Wurzer, James; Shirazi, Reza; Bridge, Stephen S; Law, Jonathan; Mardirossian, George

2015-01-01

Patients with locally recurrent adenocarcinoma of the prostate following radiation therapy (RT) present a challenging problem. We prospectively evaluated the use of "high-dose-rate-like" prostate stereotactic body RT (SBRT) salvage for this circumstance, evaluating prostate-specific antigen response, disease-free survival, and toxicity. Between February 2009 and March 2014, 29 patients with biopsy-proven recurrent locally prostate cancer >2 years post-RT were treated. Median prior RT dose was 73.8 Gy and median interval to SBRT salvage was 88 months. Median recurrence Gleason score was 7 (79% was ≥7). Pre-existing RT toxicity >grade 1 was a reason for exclusion. Magnetic resonance imaging-defined prostate volume including any suspected extraprostatic extension, comprising the planning target volume. A total of 34 Gy/5 fractions was given, delivering a heterogeneous, high-dose-rate-like dose-escalation pattern. Toxicities were assessed using Common Terminology Criteria for Adverse Events, version 3.0, criteria. Twenty-nine treated patients had a median 24-month follow-up (range, 3-60 months). A median pre-SBRT salvage baseline prostate-specific antigen level of 3.1 ng/mL decreased to 0.65 ng/mL and 0.16 ng/mL at 1 and 2 years, respectively. Actuarial 2-year biochemical disease-free survival measured 82%, with no local failures. Toxicity >grade 1 was limited to the genitourinary domain, with 18% grade 2 or higher and 7% grade 3 or higher. No gastrointestinal toxicity >grade 1 occurred. Two-year disease-free survival is encouraging, and the prostate-specific antigen response kinetic appears comparable with that seen in de novo patients treated with SBRT, albeit still a preliminary finding. Grade ≥2 genitourinary toxicity was occasionally seen with no obvious predictive factor. Noting that our only brachytherapy case was 1 of the 2 cases with ≥grade 3 genitourinary toxicity, caution is recommended treating these patients. SBRT salvage of post-RT local recurrence appears clinically feasible, with longer term evaluation required to assess ultimate efficacy and late toxicity rates. Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Toxic effect of cadmium adsorbed by different sizes of nano-hydroxyapatite on the growth of rice seedlings.

PubMed

Huang, Yifan; Qiu, Weiwen; Yu, Zhihong; Song, Zhengguo

2017-06-01

Information regarding the toxic effects of cadmium (Cd) adsorbed by nano-hydroxyapatite (NHAP-Cd) on the growth of crop plants remain limited. We investigated the mechanism of NHAP-Cd (diameters, 20 and 40nm; NHAP 20 -Cd and NHAP 40 -Cd, respectively) phytotoxicity. Rice seedlings treated with Cd and NHAP 20 -Cd showed more severe growth retardation compared to those treated with NHAP 40 -Cd, for the same Cd concentration. Transmission electron microscopy revealed NHAP in the seedlings. The nanoparticles entered the rice seedlings with no Cd 2+ signals in the NHAP treatments compared to -0.47pmolcm -2 s -1 of Cd 2+ fluxes in the Cd treatment. The higher Cd 2+ content in the leaves and mesocotyl of NHAP 20 -Cd-treated rice seedlings suggested that smaller NHAP-Cd can translocate easily to the aboveground parts. Further, NHAP-Cd increased oxidative stress, which was determined as catalase activity changes in this study. Thus, NHAP-Cd particles in the growth medium can be transported to rice seedlings and cause toxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

Biodiesel versus diesel exposure: Enhanced pulmonary inflammation, oxidative stress, and differential morphological changes in the mouse lung

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yanamala, Naveena, E-mail: wqu1@cdc.gov; Hatfield, Meghan K., E-mail: wla4@cdc.gov; Farcas, Mariana T., E-mail: woe7@cdc.gov

2013-10-15

The use of biodiesel (BD) or its blends with petroleum diesel (D) is considered to be a viable approach to reduce occupational and environmental exposures to particulate matter (PM). Due to its lower particulate mass emissions compared to D, use of BD is thought to alleviate adverse health effects. Considering BD fuel is mainly composed of unsaturated fatty acids, we hypothesize that BD exhaust particles could induce pronounced adverse outcomes, due to their ability to readily oxidize. The main objective of this study was to compare the effects of particles generated by engine fueled with neat BD and neat petroleum-basedmore » D. Biomarkers of tissue damage and inflammation were significantly elevated in lungs of mice exposed to BD particulates. Additionally, BD particulates caused a significant accumulation of oxidatively modified proteins and an increase in 4-hydroxynonenal. The up-regulation of inflammatory cytokines/chemokines/growth factors was higher in lungs upon BD particulate exposure. Histological evaluation of lung sections indicated presence of lymphocytic infiltrate and impaired clearance with prolonged retention of BD particulate in pigment laden macrophages. Taken together, these results clearly indicate that BD exhaust particles could exert more toxic effects compared to D. - Highlights: • Exposure of mice to BDPM caused higher pulmonary toxicity compared to DPM. • Oxidative stress and inflammation were higher in BD vs to D exposed mice. • Inflammatory lymphocyte infiltrates were seen only in lungs of mice exposed to BD. • Ineffective clearance, prolonged PM retention was present only after BD exposure.« less

Seed priming with KNO3 mediates biochemical processes to inhibit lead toxicity in maize (Zea mays L.).

PubMed

Nawaz, Fahim; Naeem, Muhammad; Akram, Asim; Ashraf, Muhammad Y; Ahmad, Khawaja S; Zulfiqar, Bilal; Sardar, Hasan; Shabbir, Rana N; Majeed, Sadia; Shehzad, Muhammad A; Anwar, Irfan

2017-11-01

Accumulation of lead (Pb) in agricultural soils has become a major factor for reduced crop yields and poses serious threats to humans consuming agricultural products. The present study investigated the effects of KNO 3 seed priming (0 and 0.5% KNO 3 ) on growth of maize (Zea mays L.) seedlings exposed to Pb toxicity (0, 1300 and 2550 mg kg -1 Pb). Pb exposure markedly reduced the growth of maize seedlings and resulted in higher Pb accumulation in roots than shoots. Pretreatment of seeds with KNO 3 significantly improved the germination percentage and increased physiological indices. A stimulating effect of KNO 3 seed priming was also observed on pigments (chlorophyll a, b, total chlorophyll and carotenoid contents) of Pb-stressed plants. Low translocation of Pb from roots to shoots caused an increased accumulation of total free amino acids and higher activities of catalase, peroxidase, superoxide dismutase and ascorbate peroxidase in roots as compared to shoot, which were further enhanced by exogenous KNO 3 supply to prevent Pb toxicity. Maize accumulates more Pb in roots than shoot at early growth stages. Priming of seeds with KNO 3 prevents Pb toxicity, which may be exploited to improve seedling establishment in crop species grown under Pb contaminated soils. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Increased levels of dioxin-like substances in adipose tissue in patients with deep infiltrating endometriosis.

PubMed

Martínez-Zamora, M A; Mattioli, L; Parera, J; Abad, E; Coloma, J L; van Babel, B; Galceran, M T; Balasch, J; Carmona, F

2015-05-01

Are the levels of biologically active and the most toxic dioxin-like substances in adipose tissue of patients with deep infiltrating endometriosis (DIE) higher than in a control group without endometriosis? DIE patients have higher levels of dioxins and polychlorinated biphenyls (PCBs) in adipose tissue compared with controls without endometriosis. Some studies have investigated the levels of dioxin-like substances, in serum samples, in patients with endometriosis, with inconsistent results. Case-control study including two groups of patients. The study group (DIE group) consisted of 30 patients undergoing laparoscopic surgery because of DIE. In all patients, an extensive preoperative work-up was performed including clinical exploration, magnetic resonance imaging (MRI) and transvaginal sonography. All patients with DIE underwent a confirmatory histological study for DIE after surgery. The non-endometriosis control group (control group), included the next consecutive patient undergoing laparoscopic surgery in our center due to adnexal benign gynecological disease (ovarian or tubal procedures other than endometriosis) after each DIE patient, and who did not present any type of endometriosis. During the surgical procedure 1-2 g of adipose tissue from the omentum were obtained. Dioxin-like substances were analyzed in adipose tissue in DIE patients and controls without endometriosis. The total toxic equivalence and concentrations of both dioxins and PCBs were significantly higher in patients with DIE in comparison with the control group (P < 0.05), mainly due to the significantly higher values of the two most toxic dioxins (2,3,7,8-tetrachlorodibenzo-p-dioxin [2,3,7,8-TCDD] and 1,2,3,7,8-pentachlorodibenzo-p-dioxin [1,2,3,7,8-PeCDD]) (P < 0.01 for each compound). The levels of furan 2,3,4,7,8-PeCDF were statistically higher in the DIE group compared with controls. Only four congeners of PCBs had toxic equivalence values and concentrations that were statistically higher in patients with DIE, but these included the most toxic and carcinogenic PCB-126 (PCB-114 P < 0.05; PCB-156 P < 0.05; PCB-189 P = 0.04; PCB-126 P < 0.01). Since few patients were recruited, the study is only exploratory. Our results need to be confirmed in larger and more heterogeneous population studies since environmental and even genetic factors involved in determining dioxins and PCBs widely vary in different countries. Furthermore, the strict eligibility criteria used may preclude generalization of the results to other populations and the surgery-based sampling frame may induce a selection bias. Finally, adipose tissue was obtained only from the omentum, and not from other adipose tissue of the body. Our results suggest a potential role of dioxin-like substances in the pathogenesis of DIE. Further studies are warranted to confirm our findings. None. Not applicable. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Testicular distribution and toxicity of a novel LTA4H inhibitor in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ward, P.D., E-mail: pward4@its.jnj.com; La, D.

JNJ 40929837, a novel leukotriene A4 hydrolase inhibitor in drug development, was reported to induce testicular toxicity in rats. The mechanism of toxicity was considered to be rodent specific and not relevant to humans. To further investigate this finding in rats, the distribution and toxicokinetics of JNJ 40929837 and its two metabolites, M1 and M2, were investigated. A quantitative whole body autoradiography study showed preferential distribution and retention of JNJ 40929837-derived radioactivity in the testes consistent with the observed site of toxicity. Subsequent studies with unlabeled JNJ 40929837 showed different metabolite profiles between the plasma and testes. Following a singlemore » oral 50 mg/kg dose of JNJ 40929837, M2 was the primary metabolite in plasma whereas M1 was the primary metabolite in testes. The exposure of M1 was 386-fold higher in the testes compared to plasma whereas M2 had limited exposure in testes. Furthermore, the T{sub max} of M1 was 48 h in testes suggesting a large accumulation potential of this metabolite in testes compared to plasma. Following six months of repeated daily oral dosing, M1 accumulated approximately five-fold in the testes whereas the parent did not accumulate. These results indicate that the toxicokinetic profiles of JNJ 40929837 and its two metabolites in testes are markedly different compared to plasma and support the importance of understanding the toxicokinetic profiles of compounds and their metabolites in organs/tissues where toxicity is observed. - Highlights: • JNJ 40929837-derived radioactivity preferentially distributed into testes • Primary metabolite flip-flop in plasma and testes • The primary metabolite in testes accumulated 5-fold but not parent.« less

Clinico-hematological and micronuclear changes induced by cypermethrin in broiler chicks: Their attenuation with vitamin E and selenium.

PubMed

Sharaf, Summaira; Khan, Ahrar; Khan, Muhammad Zargham; Aslam, Faiza; Saleemi, Muhammad Kashif; Mahmood, Fazal

2010-07-01

This study was carried out on 90 one-day-old broiler chicks to know clinico-hematological alterations, DNA damage caused by cypermethrin (CY), and attenuation of toxic effects by vitamin E (Vit E) and selenium (Se). Birds were randomly divided into five equal groups. Groups 1-4 received CY (600mlkg(-1)b.wt) daily for 30 days by crop tubing. In addition to CY, groups 2, 3 and 4 received Vit E (150mgkg(-1)b.wt), Se (0.25mgkg(-1)b.wt), and Vit E (150mgkg(-1)b.wt)+Se (0.25mgkg(-1)b.wt), respectively. Group 5 served as control. Birds were monitored twice daily for clinical signs. They were weighed and blood samples were collected at experimental days 10, 20 and 30 for hematological studies. CY-treated birds showed more prominent signs of toxicity compared to CY+Vit E, CY+Se and CY+Vit E+Se birds. Body weight in groups 1-3 was significantly (P<0.05) smaller at days 20 and 30 when compared with the control group. Significantly (P<0.001) higher numbers of micronuclei appeared in chicks treated with CY compared to CY+Vit E- and CY+Se-treated birds. Significantly decreased total erythrocyte counts (TEC), hemoglobin (Hb) concentration and packed cell volume (PCV) in all treated groups were recorded. Treated birds suffered from macrocytic hypochromic anemia. Leukocytosis in early stage and later leucopenia was seen in treated birds. It can be concluded that CY induces toxic effects in broilers chicks; however, these toxic effects can be ameliorated by Vit E or Se. Combination of Vit E and Se was more effective to ameliorate toxic effects of cypermethrin.

Acute toxicity study of cisplatin loaded long-circulating and pH-sensitive liposomes administered in mice.

PubMed

Leite, Elaine A; Lana, Angela M Q; Junior, Alvaro D Carvalho; Coelho, Luiz G V; De Oliveira, Mônica C

2012-04-01

Cisplatin (CDDP) is a very active and cytotoxic agent but causes severe side effects, namely nephrotoxicity, which limits the therapy. The present study aimed to evaluate the acute toxicity of long-circulating and pH-sensitive liposomes containing cisplatin (SpHL-CDDP), as compared to free CDDP, after their intravenous administration in mice. After the administration of free CDDP or SpHL-CDDP at different doses, the body weight was recorded and the LD50 and the maximum tolerated dose (MTD) were calculated. Blood samples were collected for hematological and biochemical analysis. Kidneys, liver, spleen, and bone marrow were removed for histopathological examination. A reduction of body weight of less than 15% could be observed in male and female mice after treatment with free CDDP and SpHL-CDDP at doses of < or = 10 mg/kg and 20 mg/kg, respectively. The LD50 and MTD values obtained after SpHL-CDDP administration were approximately two and three times higher, respectively, than those obtained using free CDDP. Changes in hematological parameters and hematopoietic tissue morphology showed the appearance of toxicity induced by free CDDP. By contrast, the absence of mielotoxicity after SpHL-CDDP treatment could be observed. As regards nephrotoxicity, no alteration in blood urea and creatinine levels, nor morphological change in kidneys, could be observed in mice treated with SpHL-CDDP, as compared to saline-treatment control group. The results showed that SpHL-CDDP at its MTD (20 mg/kg), as compared to the administration of free CDDP at its MTD (7.5 mg/kg), significantly reduced the renal toxicity. Thus, SpHL-CDDP can eliminate CDDP-induced toxicity and is a promising candidate for the intravenous therapy of solid tumors.

Toxicity and trophic transfer of P25 TiO2 NPs from Dunaliella salina to Artemia salina: Effect of dietary and waterborne exposure.

PubMed

Bhuvaneshwari, M; Thiagarajan, Vignesh; Nemade, Prateek; Chandrasekaran, N; Mukherjee, Amitava

2018-01-01

The recent increase in nanoparticle (P25 TiO 2 NPs) usage has led to concerns regarding their potential implications on environment and human health. The food chain is the central pathway for nanoparticle transfer from lower to high trophic level organisms. The current study relies on the investigation of toxicity and trophic transfer potential of TiO 2 NPs from marine algae Dunaliella salina to marine crustacean Artemia salina. Toxicity was measured in two different modes of exposure such as waterborne (exposure of TiO 2 NPs to Artemia) and dietary exposure (NP-accumulated algal cells are used to feed the Artemia). The toxicity and accumulation of TiO 2 NPs in marine algae D. salina were also studied. Artemia was found to be more sensitive to TiO 2 NPs (48h LC 50 of 4.21mgL -1 ) as compared to marine algae, D. salina (48h LC 50 of 11.35mgL -1 ). The toxicity, uptake, and accumulation of TiO 2 NPs were observed to be more in waterborne exposure as compared to dietary exposure. Waterborne exposure seemed to cause higher ROS production and antioxidant enzyme (SOD and CAT) activity as compared to dietary exposure of TiO 2 NPs in Artemia. There were no observed biomagnification (BMF) and trophic transfer from algae to Artemia through dietary exposure. Histopathological studies confirmed the morphological and internal damages in Artemia. This study reiterates the possible effects of the different modes of exposure on trophic transfer potential of TiO 2 NPs and eventually the consequences on aquatic environment. Copyright © 2017 Elsevier Inc. All rights reserved.

Memory and Learning Dysfunction Following Copper Toxicity: Biochemical and Immunohistochemical Basis.

PubMed

Kalita, Jayantee; Kumar, Vijay; Misra, Usha K; Bora, Himangsu K

2018-05-01

The prototype disease of Cu toxicity in human is Wilson disease, and cognitive impairment is the presenting symptom of it. There is no study correlating Cu-induced excitotoxicity, apoptosis, and astrocytic reaction with memory dysfunction. We report excitotoxicity, apoptosis, and astrocytic reaction of the hippocampus and frontal cortex with memory dysfunction in rat model of Cu toxicity. Thirty-six rats were divided into group I (control) and group II (100 mg/kgBwt/day CuSO 4 orally). Y-maze was performed for memory and learning at 0, 30, 60, and 90 days. Frontal and hippocampal free Cu concentration, oxidative stress markers [glutathione (GSH), total antioxidant toxicity (TAC), and malondialdehyde (MDA)], and glutamate were measured by atomic absorption spectroscopy, spectrophotometry, and ELISA, respectively. N-methyl-D-aspartate receptors (NMDARs) NR1, NR2A, and NR2B were done by real-time polymerase chain reaction. Immunohistochemistry for caspase-3 and glial fibrillary acidic protein (GFAP) were done and quantified using the ImageJ software. The glutamate level in hippocampus was increased, and NMDAR expression was decreased at 30, 60, and 90 days in group II compared to group I. In the frontal cortex, glutamate was increased at 90 days, but NMDARs were not significantly different in group II compared to group I. Caspase-3 and GFAP expressions were also higher in group II compared to group I, and these changes were more marked in hippocampus than frontal cortex. These changes correlated with respective free tissue Cu, oxidative stress, and Y-maze attention score. Cu toxicity induces apoptosis and astrocytosis of the hippocampus and frontal cortex through direct or glutamate and oxidative stress pathways, and results in impaired memory and learning.

Experimental Assessment of Moringa oleifera Leaf and Fruit for Its Antistress, Antioxidant, and Scavenging Potential Using In Vitro and In Vivo Assays

PubMed Central

Luqman, Suaib; Srivastava, Suchita; Kumar, Ritesh; Maurya, Anil Kumar; Chanda, Debabrata

2012-01-01

We have investigated effect of Moringa oleifera leaf and fruit extracts on markers of oxidative stress, its toxicity evaluation, and correlation with antioxidant properties using in vitro and in vitro assays. The aqueous extract of leaf was able to increase the GSH and reduce MDA level in a concentration-dependent manner. The ethanolic extract of fruit showed highest phenolic content, strong reducing power and free radical scavenging capacity. The antioxidant capacity of ethanolic extract of both fruit and leaf was higher in the in vitro assay compared to aqueous extract which showed higher potential in vivo. Safety evaluation studies showed no toxicity of the extracts up to a dose of 100 mg/kg body weight. Our results support the potent antioxidant activity of aqueous and ethanolic extract of Moringa oleifera which adds one more positive attribute to its known pharmacological importance. PMID:22216055

Enantioselective Bioaccumulation, Tissue Distribution, and Toxic Effects of Myclobutanil Enantiomers in Pelophylax nigromaculatus Tadpole.

PubMed

Cheng, Cheng; Di, Shanshan; Chen, Li; Zhang, Wenjun; Diao, Jinling; Zhou, Zhiqiang

2017-04-19

Research on the enantioselective behavior of chiral pesticides on amphibians has received growing attention, because amphibians are experiencing a population decline and amphibian metamorphosis shares many similarities with human fetal development. In this study, the enantioselective behavior of myclobutanil on Pelophylax nigromaculatus tadpole was studied. The antioxidant enzyme (SOD, GST) activities and malondialdehyde (MDA) content were investigated to assess the different toxic effects when tadpoles were exposed to myclobutanil enantiomers for 96 h. In the chronic exposure experiment, the bioaccumulation concentration of (-)-myclobutanil in tadpoles is significantly higher than that of (+)-myclobutanil, and the concentration of myclobutanil in tadpole intestine and liver was higher compared with other tissues. During the elimination experiment, about 95% of myclobutanil in tadpoles was eliminated within only 24 h. On the basis of these data, the enantiomeric differences should be taken into consideration in the risk assessment of myclobutanil.

PCDDs, PCDFs, and coplanar PCBs in albatross from the North Pacific and Southern Oceans: levels, patterns, and toxicological implications.

PubMed

Tanabe, Shinsuke; Watanabe, Mafumi; Minh, Tu Binh; Kunisue, Tatsuya; Nakanishi, Shigeyuki; Ono, Hitoshi; Tanaka, Hiroyuki

2004-01-15

Concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar polychlorinated biphenyls (coplanar PCBs) were determined in five albatross species collected from the North Pacific and Southern Oceans to assess the north-south differences in residue levels, accumulation patterns, and toxic potential. Black-footed and Laysan albatrosses from the North Pacific Ocean contained higher levels of PCDD/Fs and coplanar PCBs than albatrosses from the Southern Ocean, indicating that emission sources of these contaminants were predominant in the northern hemisphere. Residue levels in albatrosses from the remote North Pacific Ocean far from the point source of pollution were comparable to or higher than those in terrestrial and coastal birds from contaminated areas in developed nations, suggesting the specific exposure and accumulation of PCDD/Fs and coplanar PCBs in albatross. The long life span and ingestion of plastic resin pellets by albatrosses could be the plausible explanations for the elevated accumulation of persistent and lipophilic contaminants including PCDD/Fs and coplanar PCBs in these birds. Relative proportions of PCDFs and coplanar PCBs in albatross were higher than those observed in birds inhabiting terrestrial and coastal areas, suggesting that these toxic chemicals may have higher transportability by air and water than PCDDs. Congener patterns of PCDD/Fs in albatross showed less variability as compared to those in terrestrial species, indicating that contamination patterns of PCDD/Fs were similar within the open ocean environment. Contributions of PCDD/Fs to total TEQs in albatrosses from the open ocean were generally lower than those in terrestrial birds, suggesting different toxic potency of PCDD/Fs and coplanar PCBs on animals inhabiting open ocean and terrestrial environment. Whereas albatrosses from southern oceans retained lower TEQ concentrations, possible adverse effects of PCDD/Fs and coplanar PCBs to black-footed and Laysan albatrosses of the North Pacific Ocean may be suspected from TEQ levels.

High-Content Analysis Provides Mechanistic Insights into the Testicular Toxicity of Bisphenol A and Selected Analogues in Mouse Spermatogonial Cells.

PubMed

Liang, Shenxuan; Yin, Lei; Shengyang Yu, Kevin; Hofmann, Marie-Claude; Yu, Xiaozhong

2017-01-01

Bisphenol A (BPA), an endocrine-disrupting compound, was found to be a testicular toxicant in animal models. Bisphenol S (BPS), bisphenol AF (BPAF), and tetrabromobisphenol A (TBBPA) were recently introduced to the market as alternatives to BPA. However, toxicological data of these compounds in the male reproductive system are still limited so far. This study developed and validated an automated multi-parametric high-content analysis (HCA) using the C18-4 spermatogonial cell line as a model. We applied these validated HCA, including nuclear morphology, DNA content, cell cycle progression, DNA synthesis, cytoskeleton integrity, and DNA damage responses, to characterize and compare the testicular toxicities of BPA and 3 selected commercial available BPA analogues, BPS, BPAF, and TBBPA. HCA revealed BPAF and TBBPA exhibited higher spermatogonial toxicities as compared with BPA and BPS, including dose- and time-dependent alterations in nuclear morphology, cell cycle, DNA damage responses, and perturbation of the cytoskeleton. Our results demonstrated that this specific culture model together with HCA can be utilized for quantitative screening and discriminating of chemical-specific testicular toxicity in spermatogonial cells. It also provides a fast and cost-effective approach for the identification of environmental chemicals that could have detrimental effects on reproduction. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Influence of pH and media composition on suspension stability of silver, zinc oxide, and titanium dioxide nanoparticles and immobilization of Daphnia magna under guideline testing conditions.

PubMed

Cupi, Denisa; Hartmann, Nanna B; Baun, Anders

2016-05-01

In aquatic toxicity testing of engineered nanoparticles (ENPs) the process of agglomeration is very important as it may alter bioavailability and toxicity. In the present study, we aimed to identify test conditions that are favorable for maintaining stable ENP suspensions. We evaluated the influence of key environmental parameters: pH (2-12) and ionic strength using M7, Soft EPA (S EPA) medium, and Very Soft EPA (VS EPA) medium; and observed the influence of these parameters on zeta potential, zeta average, and acute immobilization of Daphnia magna for three different ENPs. Despite being sterically stabilized, test suspensions of silver (Ag) ENPs formed large agglomerates in both VS EPA and M7 media; and toxicity was found to be higher in VS EPA medium due to increased dissolution. Low-agglomerate suspensions for zinc oxide (ZnO) could be obtained at pH 7 in VS EPA medium, but the increase in dissolution caused higher toxicity than in M7 medium. Titanium dioxide (TiO2) ENPs had a point of zero charge in the range of pH 7-8. At pH 7 in VS EPA, agglomerates with smaller hydrodynamic diameters (~200nm) were present compared to the high ionic strength M7 medium where hydrodynamic diameters reached micrometer range. The stable suspensions of TiO2 ENPs caused immobilization of D. magna, 48-h EC50 value of 13.7mgL(-1) (95% CI, 2.4mg-79.1mgL(-1)); whereas no toxicity was seen in the unstable, highly agglomerated M7 medium suspensions, 48-h EC50 >100mgL(-1). The current study provides a preliminary approach for methodology in testing and assessing stability and toxicity of ENPs in aquatic toxicity tests of regulatory relevance. Copyright © 2016 Elsevier Inc. All rights reserved.

A new screening test for toxicity testing of dental materials.

PubMed

Pelka, M; Danzl, C; Distler, W; Petschelt, A

2000-07-01

The development of a micro plate assay for cytotoxicity testing of dental materials based on a bioassay using brine shrimp larvae (artemia salina) as sensitive organisms. Brine shrimp larvae are commonly used for cytotoxicity assays in pharmacology. These larvae are sensitive to toxic substances. The ratio between dead larvae (no motility) and living larvae (high motility) in comparison to a control without any toxic substances is used to estimate the toxicity of the test solutions. The test materials (Arabesk((R)), Solitaire((R)), Pertac((R)) II, Tetric((R)), Herculite((R)) and the compomer materials Dyract((R)), Hytac((R)), Compoglass((R))) were polymerized and consecutively milled. After incubation of 1g in 4ml distilled water at 37 degrees C for 48h, the solid materials were separated by centrifugation. The solutions were equibrilated with NaCl to a salt content of 25g/l. Aliquots of 200microl were distributed in eight micro wells and 50microl of a artemia salina containing (n=8-14) solution were added to each well. As controls eight wells with 250microl salt solution containing a comparable number of brine shrimp were used. At baseline, after 2, 5, 24 and 48h, the dead shrimp were counted using a stereo microscope. Finally all shrimps were sacrificed using Na-acid (5%) and counted to get the number of shrimps per well. All compomers and Solitaire caused 100% brine shrimp lethality after 24h and showed significantly (p<0.01, signed rank test) higher toxicities than the remaining composites. With the exception of Pertac II, all composites showed significantly higher toxic values than the control. Pertac II did not show any differences from the controls used. This new technique has some advantages for toxicity testing of restorative materials, because it can quickly be carried out at low costs. The disadvantage is the high quantity of material used and the low sensitivity.

Numeric Estimates of Teratogenic Severity from Embryo-Fetal Developmental Toxicity Studies.

PubMed

Wise, L David

2016-02-01

A developing organism exposed to a toxicant will have a response that ranges from none to severe (i.e., death or malformation). The response at a given dosage may be termed teratogenic (or developmental toxic) severity and is dependent on exposure conditions. Prenatal/embryo-fetal developmental (EFD) toxicity studies in rodents and rabbits are the most consistent and definitive assessments of teratogenic severity, and teratogenesis screening assays are best validated against their results. A formula is presented that estimates teratogenic severity for each group, including control, within an EFD study. The developmental components include embryonic/fetal death, malformations, variations, and mean fetal weight. The contribution of maternal toxicity is included with multiplication factors to adjust for the extent of mortality, maternal body weight change, and other parameters deemed important. The derivation of the formula to calculate teratogenic severity is described. Various EFD data sets from the literature are presented to highlight considerations to the calculation of the various components of the formula. Each score is compared to the concurrent control group to obtain a relative teratogenic severity. The limited studies presented suggest relative scores of two- to

Encapsulation of cisplatin in long-circulating and pH-sensitive liposomes improves its antitumor effect and reduces acute toxicity.

PubMed

Leite, Elaine A; Souza, Cristina M; Carvalho-Júnior, Alvaro D; Coelho, Luiz G V; Lana, Angela M Q; Cassali, Geovanni D; Oliveira, Mônica C

2012-01-01

Cisplatin (CDDP) is one of the most effective and potent anticancer drugs used as first-line chemotherapy against several solid tumors. However, the severe side effects and its tendency to provoke chemoresistance often limit CDDP therapy. To avoid these inconveniences, the present study's research group developed long-circulating and pH-sensitive liposomes containing CDDP (SpHL-CDDP). The present study aimed to evaluate the antitumor effect and toxicity of SpHL-CDDP, as compared with that of free CDDP, and long-circulating and non- pH-sensitive liposomes containing CDDP (NSpHL-CDDP), after their intravenous administration in solid Ehrlich tumor-bearing mice. Antitumor activity was evaluated by analysis of tumor volume and growth inhibition ratio, serum vascular endothelial growth factor (VEGF) levels, and histomorphometric and immunohistochemical studies. Body weight variation and the histological examination of bone marrow and kidneys were used as toxicity indicators. A significant reduction in the tumor volume and a higher tumor growth inhibition ratio was observed after SpHL-CDDP treatment, compared with free CDDP and NSpHL-CDDP treatments. In addition, complete remission of the tumor was detected in 18.2% of the mice treated with SpHL- CDDP (16 mg/kg). As such, the administration of SpHL-CDDP, as compared with free CDDP and NSpHL-CDDP, led to a decrease in the area of necrosis and in the percentage of positive CDC 47 tumor cells. A significant reduction in the VEGF serum level was also observed after SpHL-CDDP treatment, as compared with free-CDDP treatment. SpHL-CDDP administered in a two-fold higher dose than that of free CDDP presented a loss in body weight and changes in the hematopoietic tissue morphology, which proved to be similar to that of free CDDP. No changes could be verified in the renal tissue after any formulations containing CDDP had been administered. These findings showed that SpHL-CDDP allowed for the administration of higher doses of CDDP, significantly improving its antitumor effect.

[Problems of cardiovascular toxicity of coxibs and non-selective NSA].

PubMed

Forejtová, S

2006-01-01

Non-steroidal antirheumatics (NSA) belong to the most often prescribed drugs. Certain observation studies indicate that they are used by 20 to 30% of population of developed countries. The most common NSA's adverse effects are gastrointestinal complications. Coxibs have been developed as an alternative to conventional non-selective NSA; with similar efficacy, they should reduce the risk of development of gastrointestinal complications. In the few last years, possible toxicity of coxibs and other non-steroidal antirheumatics has been widely discussed. The VIGOR study, which was performed 6 years ago, showed five times higher incidence of nonfatal myocardial infarction in patients with rofecoxib therapy as compared with naproxen. Afterwards, there was much debate about rofecoxib, and coxibs in general, whose cardiotoxicity was supported and confuted at the same time. Possible cardioprotective effect of naproxen was discussed too. Later on, results of the APPROVE study (Adenoma Polyp Prevention on Vioxx) made Merck & Co., Inc. withdraw rofecoxib from all markets voluntarily. In the end of 2004, three controversial studies on celecoxib were published. Although the first study (Adenoma Prevention with Celecoxib study, APC) showed higher cardiovascular risk of celecoxib, the second study (Prevention of Adenomatosus Polyps, PreSAP) did not verify these results. Surprisingly, the third study (Alzheimer Disease and Prevention Trial, ADAPT) proved 50% increase of the risk of cardiovascular (CV) toxicity of naproxen. In the last year, researchers have tried to decide whether CV toxicity is a class effect of coxib group or a class effect of all NSA. Many observation studies proved higher CV risk both of coxibs (particularly rofecoxib) and non-selective NSA including naproxen. These new findings moved the American FDA (Food and Drug Administration) to publish guidance concerning higher CV risk of all coxibs and NSA. For the time being, the EMEA (European Agency for Evaluation of Medicinal Products) does not change its attitude to NSA; coxibs are contraindicated in patients with ischemic heart disease, cerebrovascular disease and peripheral artery disease; they should be used with caution in high-risk patients. Final assessment of the problems of CV toxicity of NSA and coxibs will be a case of a long-term randomized study focused on the incidence of cardiovascular adverse effects.

Extraction of ethanol with higher carboxylic acid solvents and their toxicity to yeast

USDA-ARS?s Scientific Manuscript database

In a screening exercise for ethanol-selective extraction solvents, partitioning of ethanol and water from a 5 wt% aqueous solution into several C8 – C18 carboxylic acids was studied. Results for the acids are compared with those from alcohols of similar structure. In all cases studied, the acids exh...

Toxicity studies of nonylphenol and octylphenol: hormonal, hematological and biochemical effects in Clarias gariepinus.

PubMed

Senthil Kumaran, Satyanarayanan; Kavitha, Chokkalingam; Ramesh, Mathan; Grummt, Tamara

2011-11-01

Among the numerous chemicals discharged into aquatic ecosystems, nonylphenol (NP) and octylphenol (OP) have been shown to have a potent effect on the endocrine system of fish; this issue has been clearly dealt with in several studies. The objective of this study was to assess and compare the general toxicity of these estrogenic chemicals individually on Clarias gariepinus. Fish were exposed to different concentrations of both NP and OP (250, 500, 750 and 1000 μg l(-1) ) under semi-static conditions for a period of 7 days. The adverse effect was evaluated with use of blood cell counting, hemoglobin (Hb), hematocrit (HCT), hematimetric indices, bilirubin, protein, glucose, serum transaminases, serum phosphatases, lactate dehydrogenase and cortisol. The results showed a clear indication of anemia, increases in leukocyte count and bilirubin content and a reduction in plasma protein levels with higher concentrations of both the toxicants compared with controls. Furthermore, with all the concentrations the inevitable increase in serum cortisol and plasma glucose showed primary and secondary stress responses. Moreover, probable tissue damage gave rise to a series of fluctuations of enzyme levels at lower concentrations, but a decrease with higher concentrations showed the severity of the effect. Depending on the parameters examined, OP had a relatively greater effect than NP. Overall, these two chemicals seemingly affected hematology and the activity of some enzymes, leading to serious impairment of the metabolism and physiology of C. gariepinus. 2011 John Wiley & Sons, Ltd.

Sentinel lymph node mapping in endometrial cancer: comparison of fluorescence dye with traditional radiocolloid and blue.

PubMed

Papadia, Andrea; Gasparri, Maria Luisa; Buda, Alessandro; Mueller, Michael D

2017-10-01

Sentinel lymph node (SLN) mapping in endometrial cancer (EMCA) is rapidly gaining acceptance in the clinical community. As compared to a full lymphadenectomy in every patient, to a selective lymphadenectomy after frozen section of uterus in selected patients with intrauterine risk factors or to a strategy in which a lymphadenectomy is always omitted, SLN mapping seems to be a reasonable and oncologically safe middle ground. Various protocols can be used when applying an SLN mapping. In this manuscript we review the characteristics, toxicity and clinical impact of technetium-99m radiocolloid (Tc-99m), of the blue dyes (methylene blue, isosulfan blue and patent blue) and of indocyanine green (ICG). ICG has an excellent toxicity profile, has higher overall and bilateral detection rates as compared to blue dyes and higher bilateral detection rates as compared to a combination of Tc-99m and blue dye. The detrimental effect of BMI on the detection rates is attenuated when ICG is used as a tracer. The ease of use of the ICG SLN mapping is perceived by the patients as a better quality of care delivered. Whenever possible, ICG should be favored over the other tracers for SLN mapping in EMCA patients.

Long- and short-term effects of boron excess to root form and function in two tomato genotypes.

PubMed

Princi, Maria Polsia; Lupini, Antonio; Longo, Caterina; Miller, Anthony J; Sunseri, Francesco; Abenavoli, Maria Rosa

2016-12-01

Boron (B) is an essential plant nutrient, but when present in excess it is toxic. Morphological measurements were made to assess the impact of B toxicity on the growth of two different tomato hybrids, Losna and Ikram. Contrasting long and short-term B responses in these tomato hybrids, were observed. Losna showed less toxicity symptoms, maintaining higher growth and showing much less B content in both root and shoot tissues compared to Ikram. Root morphological differences did not explain the tolerance between the two hybrids. Under excess B supply, a significant inhibition on net nitrate uptake rate was observed in Ikram, but not in Losna. This effect may be explained by a decrease of nitrate transporter transcripts in Ikram, which was not measured in Losna. There was a different pattern of B transporter expression in two tomatoes and this can explain the contrasting tolerance observed. Indeed, Losna may be able to exclude or efflux B resulting in less accumulation in the shoot. Particularly, SlBOR4 expression showed significant differences between the tomato hybrids, with higher expression in Losna explaining the improved B-tolerance. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Life-stage-, sex-, and dose-dependent dietary toxicokinetics and relationship to toxicity of 2,4-dichlorophenoxyacetic acid (2,4-D) in rats: implications for toxicity test dose selection, design, and interpretation.

PubMed

Saghir, Shakil A; Marty, Mary S; Zablotny, Carol L; Passage, Julie K; Perala, Adam W; Neal, Barbara H; Hammond, Larry; Bus, James S

2013-12-01

Life-stage-dependent toxicity and dose-dependent toxicokinetics (TK) were evaluated in Sprague Dawley rats following dietary exposure to 2,4-dichlorophenoxyacetic acid (2,4-D). 2,4-D renal clearance is impacted by dose-dependent saturation of the renal organic anion transporter; thus, this study focused on identifying inflection points of onset of dietary nonlinear TK to inform dose selection decisions for toxicity studies. Male and female rats were fed 2,4-D-fortified diets at doses to 1600 ppm for 4-weeks premating, <2 weeks during mating, and to test day (TD) 71 to parental (P1) males and to P1 females through gestation/lactation to TD 96. F1 offspring were exposed via milk with continuing diet exposure until postnatal day (PND) 35. As assessed by plasma area under the curve for the time-course plasma concentration, nonlinear TK was observed ≥ 1200 ppm (63 mg/kg/day) for P1 males and between 200 and 400 ppm (14-27 mg/kg/day) for P1 females. Dam milk and pup plasma levels were higher on lactation day (LD) 14 than LD 4. Relative to P1 adults, 2,4-D levels were higher in dams during late gestation/lactation and postweaning pups (PND 21-35) and coincided with elevated intake of diet/kg body weight. Using conventional maximum tolerated dose (MTD) criteria based on body weight changes for dose selection would have resulted in excessive top doses approximately 2-fold higher than those identified incorporating critical TK data. These data indicate that demonstration of nonlinear TK, if present at dose levels substantially above real-world human exposures, is a key dose selection consideration for improving the human relevance of toxicity studies compared with studies employing conventional MTD dose selection strategies.

Life-Stage-, Sex-, and Dose-Dependent Dietary Toxicokinetics and Relationship to Toxicity of 2,4-Dichlorophenoxyacetic Acid (2,4-D) in Rats: Implications for Toxicity Test Dose Selection, Design, and Interpretation

PubMed Central

Marty, Mary S.

2013-01-01

Life-stage-dependent toxicity and dose-dependent toxicokinetics (TK) were evaluated in Sprague Dawley rats following dietary exposure to 2,4-dichlorophenoxyacetic acid (2,4-D). 2,4-D renal clearance is impacted by dose-dependent saturation of the renal organic anion transporter; thus, this study focused on identifying inflection points of onset of dietary nonlinear TK to inform dose selection decisions for toxicity studies. Male and female rats were fed 2,4-D-fortified diets at doses to 1600 ppm for 4-weeks premating, <2 weeks during mating, and to test day (TD) 71 to parental (P1) males and to P1 females through gestation/lactation to TD 96. F1 offspring were exposed via milk with continuing diet exposure until postnatal day (PND) 35. As assessed by plasma area under the curve for the time-course plasma concentration, nonlinear TK was observed ≥1200 ppm (63mg/kg/day) for P1 males and between 200 and 400 ppm (14–27mg/kg/day) for P1 females. Dam milk and pup plasma levels were higher on lactation day (LD) 14 than LD 4. Relative to P1 adults, 2,4-D levels were higher in dams during late gestation/lactation and postweaning pups (PND 21–35) and coincided with elevated intake of diet/kg body weight. Using conventional maximum tolerated dose (MTD) criteria based on body weight changes for dose selection would have resulted in excessive top doses approximately 2-fold higher than those identified incorporating critical TK data. These data indicate that demonstration of nonlinear TK, if present at dose levels substantially above real-world human exposures, is a key dose selection consideration for improving the human relevance of toxicity studies compared with studies employing conventional MTD dose selection strategies. PMID:24105888

An in vitro cytotoxic approach to assess the toxicity of heavy metals and their binary mixtures on hippocampal HT-22 cell line.

PubMed

Karri, Venkatanaidu; Kumar, Vikas; Ramos, David; Oliveira, Eliandre; Schuhmacher, Marta

2018-01-05

Humans are exposed to a cocktail of heavy metal toxicants in the environment. Though heavy metals are deleterious, there is a paucity of information on the toxicity of mixtures. In this study, four common neurotoxicity heavy metals lead (Pb) cadmium (Cd), arsenic (As), and methylmercury (MeHg) were exposed individually and as mixtures to HT-22 cell line for 8days. The study established that low dose exposures induced toxicity to the HT-22 cell line during 8days. The results indicates potency dependent response, the toxicity of single metals on the HT-22 cells; MeHg > As > Cd > Pb. The cytotoxicity data of single metals were used to determine the mixtures interaction profile by using the dose additivity and effect additivity method. Metal mixtures showed higher toxicities compared to individual metals. Synergistic, antagonistic or additive effects of the toxicity were observed in different mixtures in low dose exposure. The interactive responses of mixtures depend on the co-exposure metal and their respective concentration. We concluded that the combined effects should be considered in the risk assessment of heavy metal co-exposure and potency. In future, comprehensive mechanistic based investigations needed for understanding the real interactive mixtures effects at molecular level. Copyright © 2017 Elsevier B.V. All rights reserved.

Toxic Element Contamination of Natural Health Products and Pharmaceutical Preparations

PubMed Central

Genuis, Stephen J.; Schwalfenberg, Gerry; Siy, Anna-Kristen J.; Rodushkin, Ilya

2012-01-01

Background Concern has recently emerged regarding the safety of natural health products (NHPs)–therapies that are increasingly recommended by various health providers, including conventional physicians. Recognizing that most individuals in the Western world now consume vitamins and many take herbal agents, this study endeavored to determine levels of toxic element contamination within a range of NHPs. Methods Toxic element testing was performed on 121 NHPs (including Ayurvedic, traditional Chinese, and various marine-source products) as well as 49 routinely prescribed pharmaceutical preparations. Testing was also performed on several batches of one prenatal supplement, with multiple samples tested within each batch. Results were compared to existing toxicant regulatory limits. Results Toxic element contamination was found in many supplements and pharmaceuticals; levels exceeding established limits were only found in a small percentage of the NHPs tested and none of the drugs tested. Some NHPs demonstrated contamination levels above preferred daily endpoints for mercury, cadmium, lead, arsenic or aluminum. NHPs manufactured in China generally had higher levels of mercury and aluminum. Conclusions Exposure to toxic elements is occurring regularly as a result of some contaminated NHPs. Best practices for quality control–developed and implemented by the NHP industry with government oversight–is recommended to guard the safety of unsuspecting consumers. PMID:23185404

Using biodynamic models to reconcile differences between laboratory toxicity tests and field biomonitoring with aquatic insects

USGS Publications Warehouse

Buchwalter, D.B.; Cain, D.J.; Clements, W.H.; Luoma, S.N.

2007-01-01

Aquatic insects often dominate lotic ecosystems, yet these organisms are under-represented in trace metal toxicity databases. Furthermore, toxicity data for aquatic insects do not appear to reflect their actual sensitivities to metals in nature, because the concentrations required to elicit toxicity in the laboratory are considerably higher than those found to impact insect communities in the field. New approaches are therefore needed to better understand how and why insects are differentially susceptible to metal exposures. Biodynamic modeling is a powerful tool for understanding interspecific differences in trace metal bioaccumulation. Because bioaccumulation alone does not necessarily correlate with toxicity, we combined biokinetic parameters associated with dissolved cadmium exposures with studies of the subcellular compartmentalization of accumulated Cd. This combination of physiological traits allowed us to make predictions of susceptibility differences to dissolved Cd in three aquatic insect taxa: Ephemerella excrucians, Rhithrogena morrisoni, and Rhyacophila sp. We compared these predictions with long-term field monitoring data and toxicity tests with closely related taxa: Ephemerella infrequens, Rhithrogena hageni, and Rhyacophila brunea. Kinetic parameters allowed us to estimate steady-state concentrations, the time required to reach steady state, and the concentrations of Cd projected to be in potentially toxic compartments for different species. Species-specific physiological traits identified using biodynamic models provided a means for better understanding why toxicity assays with insects have failed to provide meaningful estimates for metal concentrations that would be expected to be protective in nature. ?? 2007 American Chemical Society.

Modified Toxicity Probability Interval Design: A Safer and More Reliable Method Than the 3 + 3 Design for Practical Phase I Trials

PubMed Central

Ji, Yuan; Wang, Sue-Jane

2013-01-01

The 3 + 3 design is the most common choice among clinicians for phase I dose-escalation oncology trials. In recent reviews, more than 95% of phase I trials have been based on the 3 + 3 design. Given that it is intuitive and its implementation does not require a computer program, clinicians can conduct 3 + 3 dose escalations in practice with virtually no logistic cost, and trial protocols based on the 3 + 3 design pass institutional review board and biostatistics reviews quickly. However, the performance of the 3 + 3 design has rarely been compared with model-based designs in simulation studies with matched sample sizes. In the vast majority of statistical literature, the 3 + 3 design has been shown to be inferior in identifying true maximum-tolerated doses (MTDs), although the sample size required by the 3 + 3 design is often orders-of-magnitude smaller than model-based designs. In this article, through comparative simulation studies with matched sample sizes, we demonstrate that the 3 + 3 design has higher risks of exposing patients to toxic doses above the MTD than the modified toxicity probability interval (mTPI) design, a newly developed adaptive method. In addition, compared with the mTPI design, the 3 + 3 design does not yield higher probabilities in identifying the correct MTD, even when the sample size is matched. Given that the mTPI design is equally transparent, costless to implement with free software, and more flexible in practical situations, we highly encourage its adoption in early dose-escalation studies whenever the 3 + 3 design is also considered. We provide free software to allow direct comparisons of the 3 + 3 design with other model-based designs in simulation studies with matched sample sizes. PMID:23569307

Phytoremediation of soils contaminated with toxic elements and radionuclides

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cornish, J.E.; Goldberg, W.C.; Levine, R.S.

1995-12-31

At many US Department of Energy (US DOE) facilities and other sites, surface soils over relatively large areas are contaminated with heavy metals, radionuclides, and other toxic elements, often at only a relatively small factor above regulatory action levels. Cleanup of such sites presents major challenges, because currently available soil remediation technologies can be very expensive. In response, the US DOE`s Office of Technology Development, through the Western Environmental Technology Office, is sponsoring research in the area of phytoremediation. Phytoremediation is an emerging technology that uses higher plants to transfer toxic elements and radionuclides from surface soils into aboveground biomass.more » Some plants, termed hyperaccumulators, take up toxic elements in substantial amounts, resulting in concentrations in aboveground biomass over 100 times those observed with conventional plants. After growth, the plant biomass is harvested, and the toxic elements are concentrated and reclaimed or disposed of. As growing, harvesting, and processing plant biomass is relatively inexpensive, phytoremediation can be a low-cost technology for remediation of extensive areas having lightly to moderately contaminated soils. This paper reviews the potential of hyper- and moderate accumulator plants in soil remediation, provides some comparative cost estimates, and outlines ongoing work initiated by the US DOE.« less

Linking embryo toxicity with genotoxic responses in the freshwater snail Physa acuta: single exposure to benzo(a)pyrene, fluoxetine, bisphenol A, vinclozolin and exposure to binary mixtures with benzo(a)pyrene.

PubMed

Sánchez-Argüello, Paloma; Aparicio, Natalia; Fernández, Carlos

2012-06-01

Genotoxic effects on fauna after waterborne pollutant exposure have been demonstrated by numerous research programmes. Less effort has been focused on establishing relationship between genotoxicity and long-term responses at higher levels of biological organization. Taking into account that embryos may be more sensitive indicators of reproductive impairment than alterations in fertility, we have developed two assays in multiwell plates to address correlations between embryo toxicity and genotoxicity. The potential teratogenicity was assessed by analyzing abnormal development and mortality of Physa acuta at embryonic stage. Genotoxicity was measured by the micronucleus (MN) test using embryonic cells. Our results showed that linkage between genotoxicity and embryo toxicity depends on mechanisms of action of compounds under study. Embryo toxic responses showed a clear dose-related tendency whereas no clear dose-dependent effect was observed in micronucleus induction. The higher embryo toxicity was produced by benzo(a)pyrene exposure followed by fluoxetine and bisphenol A. Vinclozolin was the lower embryo toxic compound. Binary mixtures with BaP always resulted in higher embryo toxicity than single exposures but antagonistic effects were observed for MN induction. Benzo(a)pyrene produced the higher MN induction at 0.04 mg/L, which also produced clear embryo toxic effects. Fluoxetine did not induce cytogenetic effects but 0.25mg/L altered embryonic development. Bisphenol A significantly reduced hatchability at 0.5mg/L while MN induction appeared with higher treatments than those that start causing teratogenicity. Much higher concentration of vinclozolin (5mg/L) reduced hatchability and induced maximum MN formation. In conclusion, while validating one biomarker of genotoxicity and employing one ecologically relevant effect, we have evaluated the relative sensitivity of a freshwater mollusc for a range of chemicals. The embryo toxicity test is a starting point for the development of a life cycle test with freshwater snails even for undertaking multigeneration studies focused on transgenerational effects. Copyright © 2012 Elsevier Inc. All rights reserved.

Influence of soil pH on the toxicity of zinc oxide nanoparticles to the terrestrial isopod Porcellionides pruinosus.

PubMed

Tourinho, Paula S; van Gestel, Cornelis A M; Lofts, Stephen; Soares, Amadeu M V M; Loureiro, Susana

2013-12-01

The effects of soil pH on the toxicity of ZnO nanoparticles (NPs) to the terrestrial isopod Porcellionides pruinosus were evaluated. Isopods were exposed to a natural soil amended with CaCO3 to reach 3 different pH(CaCl2) levels (4.5, 6.2, and 7.3) and to standard LUFA 2.2 soil (pH 5.5) spiked with ZnO NPs (30 nm), non-nano ZnO (200 nm), and ionic Zn as ZnCl₂. Toxicity was expressed based on total Zn concentration in soil, as well as total Zn and free Zn²⁺ ion concentrations in porewater. Compared with ZnO-spiked soils, the ZnCl₂-spiked soils had lower pH and higher porewater Ca²⁺ and Zn levels. Isopod survival did not differ between Zn forms and soils, but survival was higher for isopods exposed to ZnO NPs at pH 4.5. Median effect concentrations (EC50s) for biomass change showed similar trends for all Zn forms in all soils, with higher values at intermediate pH. Median lethal concentration (LC50) and EC50 values based on porewater Zn or free Zn ion concentrations were much lower for ZnO than for ionic zinc. Zn body concentrations increased in a dose-related manner, but no effect of soil pH was found. It is suggested not only that dissolved or free Zn in porewater contributed to uptake and toxicity, but also that oral uptake (i.e., ingestion of soil particles) could be an important additional route of exposure. © 2013 SETAC.

Cell Wall Pectin and its Methyl-esterification in Transition Zone Determine Al Resistance in Cultivars of Pea (Pisum sativum)

PubMed Central

Li, Xuewen; Li, Yalin; Qu, Mei; Xiao, Hongdong; Feng, Yingming; Liu, Jiayou; Wu, Lishu; Yu, Min

2016-01-01

The initial response of plants to aluminum (Al) is the inhibition of root elongation, while the transition zone is the most Al sensitive zone in the root apex, which may sense the presence of Al and regulate the responses of root to Al toxicity. In the present study, the effect of Al treatment (30 μM, 24 h) on root growth, Al accumulation, and properties of cell wall of two pea (Pisum sativum L.) cultivars, cv Onward (Al-resistant) and cv Sima (Al-sensitive), were studied to disclose whether the response of root transition zone to Al toxicity determines Al resistance in pea cultivars. The lower relative root elongation (RRE) and higher Al content were founded in cv Sima compared with cv Onward, which were related to Al-induced the increase of pectin in root segments of both cultivars. The increase of pectin is more prominent in Al-sensitive cultivar than in Al-resistant cultivar. Aluminum toxicity also induced the increase of pectin methylesterases (PME), which is 2.2 times in root transition zone in Al-sensitive cv Sima to that of Al resistant cv Onward, thus led to higher demethylesterified pectin content in root transition zone of Al-sensitive cv Sima. The higher demethylesterified pectin content in root transition zone resulted in more Al accumulation in the cell wall and cytosol in Al-sensitive cv Sima. Our results provide evidence that the increase of pectin content and PME activity under Al toxicity cooperates to determine Al sensitivity in root transition zone that confers Al resistance in cultivars of pea (Pisum sativum). PMID:26870060

Pentostatin and Rituximab Therapy for Previously Untreated B-CLL

PubMed Central

Kay, Neil E.; Wu, Wenting; Kabat, Brian; LaPlant, Betsy; Lin, Thomas S.; Byrd, John C.; Jelinek, Diane F.; Grever, Michael R.; Zent, Clive S.; Call, Timothy G.; Shanafelt, Tait D.

2010-01-01

We have shown that the combination of pentostatin (P), cyclophosphamide (C) and rituximab (R) achieves an overall response (OR) rate >90% with more than 40% complete responses (CR) in patients with untreated CLL. To evaluate if the tolerability of this regimen could be enhanced without sacrificing efficacy, we conducted a phase II trial of P and R without cyclophosphamide, using a higher P dose (4 mg/m2). Among the 33 patients enrolled, 82% were male, median age was 65 (9 patients ≥70 years) and 64% were Rai stage III-IV. The OR rate was 76% with 9 CR (27%), 5 nPR, and 11 PRs. At the time of this analysis, 29/33 patients are still alive and the median follow up for patients still alive is 14 months (range: 1-34.8 months). Four (12%) patients experienced grade 3 or higher hematologic toxicity and 5 (15%) experienced grade 3 or higher non-hematologic toxicity. Comparison of this trial to our previous PCR trial showed that patients treated with PCR had a higher OR rate (91% vs. 76%) and CR rate (41% vs. 27%) compared to patients treated with PR. Median treatment-free survival for all accrued patients was notably longer in PCR treated patients compared to PR (30 vs. 16 months). These findings suggest that increasing the dose of the purine nucleoside analogue does not eliminate the need for cyclophosphamide in chemoimmunotherapy for treatment of CLL. PMID:20187101

Early skin toxicity predicts better outcomes, and early tumor shrinkage predicts better response after cetuximab treatment in advanced colorectal cancer.

PubMed

Kogawa, T; Doi, A; Shimokawa, M; Fouad, T M; Osuga, T; Tamura, F; Mizushima, T; Kimura, T; Abe, S; Ihara, H; Kukitsu, T; Sumiyoshi, T; Yoshizaki, N; Hirayama, M; Sasaki, T; Kawarada, Y; Kitashiro, S; Okushiba, S; Kondo, H; Tsuji, Y

2015-03-01

Cetuximab-containing treatments for metastatic colorectal cancer have been shown to have higher overall response rates and longer progression-free and overall survival than other systemic therapies. Cetuximab-related manifestations, including severe skin toxicity and early tumor shrinkage, have been shown to be predictors of response to cetuximab. We hypothesized that early skin toxicity is a predictor of response and better outcomes in patients with advanced colorectal carcinoma. We retrospectively evaluated 62 patients with colorectal adenocarcinoma who had unresectable tumors and were treated with cetuximab in our institution. Skin toxicity grade was evaluated on each treatment day. Tumor size was evaluated using computed tomography prior to treatment and 4-8 weeks after the start of treatment with cetuximab.Patients with early tumor shrinkage after starting treatment with cetuximab had a significantly higher overall response rate (P = 0.0001). Patients with early skin toxicity showed significantly longer overall survival (P = 0.0305), and patients with higher skin toxicity grades had longer progression-free survival (P = 0.0168).We have shown that early tumor shrinkage, early onset of skin toxicity, and high skin toxicity grade are predictors of treatment efficacy and/or outcome in patients with advanced colorectal carcinoma treated with cetuximab.

Sex Is a Determinant for Deoxynivalenol Metabolism and Elimination in the Mouse

PubMed Central

Pestka, James J.; Clark, Erica S.; Schwartz-Zimmermann, Heidi E.

2017-01-01

Based on prior observations that deoxynivalenol (DON) toxicity is sex-dependent, we compared metabolism and clearance of this toxin in male and female mice. Following intraperitoneal challenge with 1 mg/kg bw DON, the dose used in the aforementioned toxicity study, ELISA and LC–MS/MS analyses revealed that by 24 h, most DON and DON metabolites were excreted via urine (49–86%) as compared to feces (1.2–8.3%). Females excreted DON and its principal metabolites (DON-3-, DON-8,15 hemiketal-8-, and iso-DON-8-glucuronides) in urine more rapidly than males. Metabolite concentrations were typically 2 to 4 times higher in the livers and kidneys of males than females from 1 to 4 h after dosing. Trace levels of DON-3-sulfate and DON-15-sulfate were found in urine, liver and kidneys from females but not males. Fecal excretion of DON and DON sulfonates was approximately 2-fold greater in males than females. Finally, decreased DON clearance rates in males could not be explained by glucuronidation activities in liver and kidney microsomes. To summarize, increased sensitivity of male mice to DON’s toxic effects as compared to females corresponds to decreased ability to clear the toxin via urine but did not appear to result from differences in toxin metabolism. PMID:28777306

The mysid Siriella armata as a model organism in marine ecotoxicology: comparative acute toxicity sensitivity with Daphnia magna.

PubMed

Pérez, Sara; Beiras, Ricardo

2010-01-01

Siriella armata (Crustacea, Mysidacea) is a component of the coastal zooplankton that lives in swarms in the shallow waters of the European neritic zone, from the North Sea to the Mediterranean. Juveniles of this species were examined as standard test organisms for use in marine acute toxicity tests. The effects of reference toxicants, three trace metals (Copper, Cadmium and Zinc), and one surfactant, sodium dodecyl sulfate (SDS) were studied on S. armata neonates (\\24 h) reared in the laboratory. Acute toxicity tests were carried out with filtered sea water on individual chambers (microplate wells for metals or glass vials for SDS) incubated in an isothermal room at 20 degrees C, with 16 h light: 8 h dark photoperiod for 96 h. Each neonate was fed daily with 10-15 nauplii of Artemia salina. Acute (96 h) LC50 values, in increasing order, were 46.9 lg/L for Cu, 99.3 lg/L for Cd, 466.7 lg/L for Zn and 8.5 mg/L for SDS. The LC(10), NOEC and LOEC values were also calculated. Results were compared with Daphnia magna, a freshwater cladoceran widely used as a standard ecotoxicological test organism. Acute (48 h) LC(50) values were 56.2 lg/L for Cu, 571.5 lg/L for Cd, 1.3 mg/L for Zn and 27.3 mg/L for SDS. For all the reference toxicants studied, the marine mysid Siriella armata showed higher sensitivity than the freshwater model organism Daphnia magna, validating the use of Siriella mysids as model organisms in marine acute toxicity tests.

An ecological risk assessment of the acute and chronic toxicity of the herbicide picloram to the threatened bull trout (salvelinus confluentus) and the rainbow trout (onchorhyncus mykiss)

USGS Publications Warehouse

Fairchild, J.F.; Feltz, K.P.; Sappington, L.C.; Allert, A.L.; Nelson, K.J.; Valle, J.

2009-01-01

We conducted acute and chronic toxicity studies of the effects of picloram acid on the threatened bull trout (Salvelinus confluentus) and the standard coldwater surrogate rainbow trout (Oncorhynchus mykiss). Juvenile fish were chronically exposed for 30 days in a proportional flow-through diluter to measured concentrations of 0, 0.30, 0.60, 1.18, 2.37, and 4.75 mg/L picloram. No mortality of either species was observed at the highest concentration. Bull trout were twofold more sensitive to picloram (30-day maximum acceptable toxic concentration of 0.80 mg/L) compared to rainbow trout (30-day maximum acceptable toxic concentration of 1.67 mg/L) based on the endpoint of growth. Picloram was acutely toxic to rainbow trout at 36 mg/L (96-h ALC50). The acute:chronic ratio for rainbow trout exposed to picloram was 22. The chronic toxicity of picloram was compared to modeled and measured environmental exposure concentrations (EECs) using a four-tiered system. The Tier 1, worst-case exposure estimate, based on a direct application of the current maximum use rate (1.1 kg/ha picloram) to a standardized aquatic ecosystem (water body of 1-ha area and 1-m depth), resulted in an EEC of 0.73 mg/L picloram and chronic risk quotients of 0.91 and 0.44 for bull trout and rainbow trout, respectively. Higher-tiered exposure estimates reduced chronic risk quotients 10-fold. Results of this study indicate that picloram, if properly applied according to the manufacturer's label, poses little risk to the threatened bull trout or rainbow trout in northwestern rangeland environments on either an acute or a chronic basis. ?? 2008 Springer Science+Business Media, LLC.

Toxicity of spray and fumigant products containing cassia oil to Dermatophagoides farinae and Dermatophagoides pteronyssinus (Acari: Pyroglyphidae).

PubMed

Kim, Soon-Ii; Kim, Hyun-Kyung; Koh, Young-Yull; Clark, J Marshall; Ahn, Young-Joon

2006-08-01

The toxicity of formulations of oil of cassia, Cinnamomum cassia Blume, (20 and 50 g L(-1) sprays and 100% oil-based fumigant) to adult Dermatophagoides farinae Hughes and D. pteronyssinus Trouessart was examined using contact and vapour-phase toxicity bioassays. Results were compared with the lethal activity of three commercial acaricides: benzyl benzoate, dibutyl phthalate and diethyl-m-toluamide (deet). The contact toxicity of cassia oil to both dust mite species was comparable with that of benzyl benzoate but was higher than that of the other two acaricides. Sprays containing 20 and 50 g L(-1) cassia oil were effective against both mite species when applied to fabric, glass, paper, plastic, tin or wood substrates. Applications of the 50 g L(-1) spray to different space volumes and surface areas determined that 50-60 mg of cassia oil was needed to control dust mites in 3.4 m(3) or in 1 m(2). In tests with fumigant devices, toxicity varied according to the thickness of non-woven fabric covering the device, the exposure time, the number of fumigant devices used and the volume of the space sprayed. Fumigant toxicity to adult D. pteronyssinus was more pronounced with devices enclosed in thinner (40 microm) versus thicker (45 or 50 microm) non-woven fabric covers. A single fumigant device with a 40 microm thick non-woven fabric cover resulted in substantial control in a space of 0.05 m(3) but exhibited only moderate to weak control in spaces >or= 0.097 m(3) at 4 days after application. Two fumigant devices gave 88% mortality in a space of 1.73 m(3). Cassia oil applied as sprays or in fumigant devices appears to provide effective protection of humans from house dust mites.

Comparison of adverse effects of proton and X-ray chemoradiotherapy for esophageal cancer using an adaptive dose–volume histogram analysis

PubMed Central

Makishima, Hirokazu; Ishikawa, Hitoshi; Terunuma, Toshiyuki; Hashimoto, Takayuki; Yamanashi, Koichi; Sekiguchi, Takao; Mizumoto, Masashi; Okumura, Toshiyuki; Sakae, Takeji; Sakurai, Hideyuki

2015-01-01

Cardiopulmonary late toxicity is of concern in concurrent chemoradiotherapy (CCRT) for esophageal cancer. The aim of this study was to examine the benefit of proton beam therapy (PBT) using clinical data and adaptive dose–volume histogram (DVH) analysis. The subjects were 44 patients with esophageal cancer who underwent definitive CCRT using X-rays (n = 19) or protons (n = 25). Experimental recalculation using protons was performed for the patient actually treated with X-rays, and vice versa. Target coverage and dose constraints of normal tissues were conserved. Lung V5–V20, mean lung dose (MLD), and heart V30–V50 were compared for risk organ doses between experimental plans and actual treatment plans. Potential toxicity was estimated using protons in patients actually treated with X-rays, and vice versa. Pulmonary events of Grade ≥2 occurred in 8/44 cases (18%), and cardiac events were seen in 11 cases (25%). Risk organ doses in patients with events of Grade ≥2 were significantly higher than for those with events of Grade ≤1. Risk organ doses were lower in proton plans compared with X-ray plans. All patients suffering toxicity who were treated with X-rays (n = 13) had reduced predicted doses in lung and heart using protons, while doses in all patients treated with protons (n = 24) with toxicity of Grade ≤1 had worsened predicted toxicity with X-rays. Analysis of normal tissue complication probability showed a potential reduction in toxicity by using proton beams. Irradiation dose, volume and adverse effects on the heart and lung can be reduced using protons. Thus, PBT is a promising treatment modality for the management of esophageal cancer. PMID:25755255

Comparison of distribution and toxicity following repeated oral dosing of different vanadium oxide nanoparticles in mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Eun-Jung, E-mail: pejtoxic@hanmail.net

Vanadium is an important ultra-trace element derived from fuel product combustion. With the development of nanotechnology, vanadium oxide nanoparticles (VO NPs) have been considered for application in various fields, thus the possibility of release into the environment and human exposure is also increasing. Considering that verification of bioaccumulation and relevant biological responses are essential for safe application of products, in this study, we aimed to identify the physicochemical properties that determine their health effects by comparing the biological effects and tissue distribution of different types of VO NPs in mice. For this, we prepared five types of VO NPs, commercialmore » (C)-VO{sub 2} and -V{sub 2}O{sub 5} NPs and synthetic (S)-VO{sub 2}, -V{sub 2}O{sub 3,} and -V{sub 2}O{sub 5} NPs. While the hydrodynamic diameter of the two types of C-VO NPs was irregular and impossible to measure, those of the three types of S-VO NPs was in the range of 125–170 nm. The S- and C-V{sub 2}O{sub 5} NPs showed higher dissolution rates compared to other VO NPs. We orally dosed the five types of VO NPs (70 and 210 μg/mouse, approximately 2 and 6 mg/kg) to mice for 28 days and compared their biodistribution and toxic effects. We found that S-V{sub 2}O{sub 5} and S-V{sub 2}O{sub 3} NPs more accumulated in tissues compared to other three types of VO NPs, and the accumulated level was in order of heart>liver>kidney>spleen. Additionally, tissue levels of redox reaction-related elements and electrolytes (Na{sup +}, K{sup +}, and Ca{sup 2+}) were most clearly altered in the heart of treated mice. Notably, all S- and C-VO NPs decreased the number of WBCs at the higher dose, while total protein and albumin levels were reduced at the higher dose of S-V{sub 2}O{sub 5} and S-V{sub 2}O{sub 3} NPs. Taken together, we conclude that the biodistribution and toxic effects of VO NPs depend on their dissolution rates and size (surface area). Additionally, we suggest that further studies are needed to clarify effects of VO NPs on functions of the heart and the immune system. - Highlights: • We used commercial (C)-VO{sub 2} and -V{sub 2}O{sub 5} and synthetic (S)-VO{sub 2}, -V{sub 2}O{sub 3,} and -V{sub 2}O{sub 5} NPs. • The S- and C-V{sub 2}O{sub 5} NPs showed higher dissolution rates compared to other VO NPs. • S-V{sub 2}O{sub 5} and S-V{sub 2}O{sub 3} NPs more accumulated in tissues compared to other types of VO NPs. • Redox reaction-related elements and electrolytes were clearly altered in the heart. • With decreased body weight, immune and blood-related factors influence by all VO NPs. • Biodistribution and toxicity of VO NPs depend on their dissolution rates and size.« less

Depleted Uranium Toxicity, Accumulation, and Uptake in Cynodon dactylon (Bermuda) and Aristida purpurea (Purple Threeawn).

PubMed

Butler, Afrachanna D; Wynter, Michelle; Medina, Victor F; Bednar, Anthony J

2016-06-01

Yuma Proving Grounds (YPG) in western Arizona is a testing range where Depleted uranium (DU) penetrators have been historically fired. A portion of the fired DU penetrators are being managed under controlled conditions by leaving them in place. The widespread use of DU in armor-penetrating weapons has raised environmental and human health concerns. The present study is focused on the onsite management approach and on the potential interactions with plants local to YPG. A 30 day study was conducted to assess the toxicity of DU corrosion products (e.g., schoepite and meta-schoepite) in two grass species that are native to YPG, Bermuda (Cynodon dactylon) and Purple Threeawn (Aristida purpurea). In addition, the ability for plants to uptake DU was studied. The results of this study show a much lower threshold for biomass toxicity and higher plant concentrations, particularly in the roots than shoots, compared to previous studies.

Cu toxicity on growth and chlorophyll-a of Chaetoceros sp.

NASA Astrophysics Data System (ADS)

Puspitasari, R.; Suratno; Purbonegoro, T.; Agustin, A. T.

2018-02-01

Phytoplankton is a primary producer in marine aquatic ecosystem. Their sensitivity to metal makes them important to study to predict the environmental impact of pollution. Copper is an essential nutrient for aquatic life as micronutrients on an organism but toxic at high levels. The focus of this study was to assess the toxicity of copper to Chaetoceros sp. on growth and chlorophyll-a content. The result shows that inhibition concentration (IC50) of copper on the microalgae, Chaetoceros sp. was 30.25 μg L-1. Growth of Chaetoceros sp. decreased 16.84% in 16 μg L-1 and 81.97% in 44 μg L-1. Chlorophyll-a content decreased dramatically at 44 μg L-1 compared to control. Increase of the cell size, deformation of cell wall and loss of setae were observed at higher concentration of copper.

Effects of symbiotic bacteria on chemical sensitivity of Daphnia magna.

PubMed

Manakul, Patcharaporn; Peerakietkhajorn, Saranya; Matsuura, Tomoaki; Kato, Yasuhiko; Watanabe, Hajime

2017-07-01

The crustacean zooplankton Daphnia magna has been widely used for chemical toxicity tests. Although abiotic factors have been well documented in ecotoxicological test protocols, biotic factors that may affect the sensitivity to chemical compounds remain limited. Recently, we identified symbiotic bacteria that are critical for the growth and reproduction of D. magna. The presence of symbiotic bacteria on Daphnia raised the question as to whether these bacteria have a positive or negative effect on toxicity tests. In order to evaluate the effects of symbiotic bacteria on toxicity tests, bacteria-free Daphnia were prepared, and their chemical sensitivities were compared with that of Daphnia with symbiotic bacteria based on an acute immobilization test. The Daphnia with symbiotic bacteria showed higher chemical resistance to nonylphenol, fenoxycarb, and pentachlorophenol than bacteria-free Daphnia. These results suggested potential roles of symbiotic bacteria in the chemical resistance of its host Daphnia. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pulmonary toxicity of nanomaterials: a critical comparison of published in vitro assays and in vivo inhalation or instillation studies.

PubMed

Landsiedel, Robert; Sauer, Ursula G; Ma-Hock, Lan; Schnekenburger, Jürgen; Wiemann, Martin

2014-11-01

To date, guidance on how to incorporate in vitro assays into integrated approaches for testing and assessment of nanomaterials is unavailable. In addressing this shortage, this review compares data from in vitro studies to results from in vivo inhalation or intratracheal instillation studies. Globular nanomaterials (ion-shedding silver and zinc oxide, poorly soluble titanium dioxide and cerium dioxide, and partly soluble amorphous silicon dioxide) and nanomaterials with higher aspect ratios (multiwalled carbon nanotubes) were assessed focusing on the Organisation for Economic Co-Operation and Development (OECD) reference nanomaterials for these substances. If in vitro assays are performed with dosages that reflect effective in vivo dosages, the mechanisms of nanomaterial toxicity can be assessed. In early tiers of integrated approaches for testing and assessment, knowledge on mechanisms of toxicity serves to group nanomaterials thereby reducing the need for animal testing.

Weekly infusional high-dose 5-fluorouracil and leucovorin and biweekly cisplatin: a convenient treatment option in advanced gastric cancer.

PubMed

Kundel, Yulia; Purim, Ofer; Figer, Arie; Stemmer, Salomon M; Tichler, Thomas; Sulkes, Jaqueline; Sulkes, Aaron; Brenner, Baruch

2008-04-01

To summarize our experience using a regimen of weekly 5-FU and leucovorin (LV) and biweekly cisplatin (CDDP) in advanced gastric cancer (AGC). Patients had previously untreated histologically confirmed AGC. Treatment consisted of intravenous weekly infusional 5-FU and LV and biweekly CDDP, given for 6 weeks followed by a 2-week rest. Initially, a lower dose level was used (5-FU 2000 mg/m(2), LV 500 mg/m(2), CDDP 40 mg/m(2)), which was later increased (5-FU 2600 mg/m(2), LV 500 mg/m(2), CDDP 50 mg/m(2)). Forty-five patients were treated, 18 at the lower dose level and 27 at the higher dose level. The median age was 67 years and 55% were male. Grade > or =3 toxicity was documented in 37% of patients but toxicity related hospitalizations or treatment discontinuation occurred in only 22% and 13%, respectively. There were no toxic deaths. The most common hematological toxicities were anemia and neutropenia and the most common non-hematological toxicities were nausea, vomiting and fatigue. Of the 39 patients evaluable for response, 13 (33%) had partial response (PR) and 11 (28%) had stable disease (SD). Control of disease (PR+SD) was achieved in 61%. The higher dose level was associated with a higher response rate (p=0.07) and an increased toxicity (p=0.01), mostly hematological and gastrointestinal. Median progression-free survival and overall survival were 3.5 and 9.2 months, respectively. This regimen appears safe, with a manageable toxicity profile. Efficacy data resemble those reported for more complex and toxic regimens. The higher dose level had enhanced activity, at the expense of increased toxicity.

Predictors of Grade 3 or Higher Late Bowel Toxicity in Patients Undergoing Pelvic Radiation for Cervical Cancer: Results From a Prospective Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chopra, Supriya, E-mail: schopra@actrec.gov.in; Dora, Tapas; Chinnachamy, Anand N.

Purpose: The present study investigates relationship between dose–volume parameters and severe bowel toxicity after postoperative radiation treatment (PORT) for cervical cancer. Methods and Materials: From June 2010 to December 2012, a total of 71 patients undergoing PORT were included. Small bowel (SB) and large bowel (LB) loops were contoured 2 cm above the target volume. The volume of SB and LB that received 15 Gy, 30 Gy, and 40 Gy was calculated (V15 SB, V15 LB, V30 SB, V30 LB, V40 SB, V 40 LB). On follow-up, bowel toxicity was scored using Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. A reciever operatingmore » characteristic (ROC) curve identified volume thresholds that predicted for grade 3 or higher toxicity with highest specificity. All data was dichotomized across these identified cut-off values. Univariate and multivariate analysis was performed using SPSS, version 15. Results: The median patient age was 47 years (range, 35-65 years). Of the 71 patients, 46 received image-guided intensity modulated radiation therapy, and 25 received conformal radiation (50 Gy in 25 fractions for 5 weeks). Overall, 63 of 71 patients received concurrent chemotherapy. On a median follow-up of 18 months (range, 8-29 months), grade 2 or higher bowel toxicity was seen in 22 of 71 patients (30.9%) and grade 3 or higher bowel toxicity was seen in 9 patients (12.6%). On univariate analysis, V15 SB <275 cc (P=.01), V30 SB <190 cc (P=.02), V40 SB <150 cc (P=.01), and V15 LB <250 cc (P=.03), and V40 LB <90 cc (P=.04) predicted for absence of grade 3 or higher toxicity. No other patient- or treatment-related factors were statistically significant. On multivariate analysis, only V15 SB (P=.002) and V15 LB (P=.03) were statistically significant. Conclusions: V 15 Gy SB and LB are independent predictors of late grade 3 or higher toxicity. Restricting V15 SB and V15 LB to <275 cc and <250 cc can reduce grade 3 or higher toxicity to less than 5%.« less

Radiation Dose-Volume Effects in the Stomach and Small Bowel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kavanagh, Brian D., E-mail: Brian.Kavanagh@ucdenver.ed; Pan, Charlie C.; Dawson, Laura A.

2010-03-01

Published data suggest that the risk of moderately severe (>=Grade 3) radiation-induced acute small-bowel toxicity can be predicted with a threshold model whereby for a given dose level, D, if the volume receiving that dose or greater (VD) exceeds a threshold quantity, the risk of toxicity escalates. Estimates of VD depend on the means of structure segmenting (e.g., V15 = 120 cc if individual bowel loops are outlined or V45 = 195 cc if entire peritoneal potential space of bowel is outlined). A similar predictive model of acute toxicity is not available for stomach. Late small-bowel/stomach toxicity is likely relatedmore » to maximum dose and/or volume threshold parameters qualitatively similar to those related to acute toxicity risk. Concurrent chemotherapy has been associated with a higher risk of acute toxicity, and a history of abdominal surgery has been associated with a higher risk of late toxicity.« less

Weight patterns in children with higher risk ALL: A report from the Children's Oncology Group (COG) for CCG 1961.

PubMed

Withycombe, Janice S; Post-White, Janice E; Meza, Jane L; Hawks, Ria G; Smith, Lynette M; Sacks, Nancy; Seibel, Nita L

2009-12-15

This retrospective analysis defined and described patterns and predictors of weight change during treatment in children with acute lymphocytic leukemia (ALL) with high-risk features who received treatment on Children's Cancer Group protocol CCG 1961. Patients (1,638) were enrolled in CCG 1961 from November 1996 to May 2002. Weight was measured as BMI percent (%), specific for age and gender, and defined as 100 x ln(BMI/median BMI). By the end of treatment, 23% of children were obese (BMI >or=95%), compared with 14% at diagnosis. Children who received post-induction intensified therapy (arms C, D, SER with Doxorubicin or Idarubicin) had higher gastrointestinal toxicities and lower BMI% from consolidation through interim maintenance 1. BMI% then increased for all arms between delayed intensification and maintenance 1 or 2. Children who were of Black or Hispanic race, obese at diagnosis, or who had grade 3 or 4 pancreatitis/glucose toxicities during induction had higher BMI% throughout treatment. Children were more likely to be obese at the end of the study if they were aged 5-9 years at diagnosis or female gender. Cranial radiation was not a predictor of obesity. Successful treatment of higher risk childhood ALL was associated with obesity, independent of cranial irradiation. The beginning of maintenance therapy may be the best time to intervene with nutritional and behavioral interventions, particularly for children who are obese or aged 5-9 years at diagnosis, female, Black or Hispanic, or those with metabolic toxicities during induction. (c) 2009 Wiley-Liss, Inc.

Weight Patterns in Children With Higher Risk ALL: A Report From the Children's Oncology Group (COG) for CCG 1961

PubMed Central

Withycombe, Janice S.; Post-White, Janice E.; Meza, Jane L.; Hawks, Ria G.; Smith, Lynette M.; Sacks, Nancy; Seibel, Nita L.

2011-01-01

Background This retrospective analysis defined and described patterns and predictors of weight change during treatment in children with acute lymphocytic leukemia (ALL) with high-risk features who received treatment on Children's Cancer Group protocol CCG 1961. Procedure Patients (1,638) were enrolled in CCG 1961 from November 1996 to May 2002. Weight was measured as BMI percent (%), specific for age and gender, and defined as 100 × ln(BMI/median BMI). Results By the end of treatment, 23% of children were obese (BMI ≥ 95%), compared with 14% at diagnosis. Children who received post-induction intensified therapy (arms C, D, SER with Doxorubicin or Idarubicin) had higher gastrointestinal toxicities and lower BMI% from consolidation through interim maintenance 1. BMI% then increased for all arms between delayed intensification and maintenance 1 or 2. Children who were of Black or Hispanic race, obese at diagnosis, or who had grade 3 or 4 pancreatitis/glucose toxicities during induction had higher BMI% throughout treatment. Children were more likely to be obese at the end of the study if they were aged 5–9 years at diagnosis or female gender. Cranial radiation was not a predictor of obesity. Conclusions Successful treatment of higher risk childhood ALL was associated with obesity, independent of cranial irradiation. The beginning of maintenance therapy may be the best time to intervene with nutritional and behavioral interventions, particularly for children who are obese or aged 5–9 years at diagnosis, female, Black or Hispanic, or those with metabolic toxicities during induction. PMID:19688832

Comparative toxicity of silver nanoparticles and silver ions to Escherichia coli.

PubMed

Choi, Yoojin; Kim, Hyun-A; Kim, Kyoung-Woong; Lee, Byung-Tae

2018-04-01

With the increase in silver (Ag)-based products in our lives, it is essential to test the potential toxicity of silver nanoparticles (AgNPs) and silver ions (Ag ions) on living organisms under various conditions. Here, we investigated the toxicity of AgNPs with Ag ions to Escherichia coli K-12 strain under various conditions. We observed that both AgNPs and Ag ions display antibacterial activities, and that Ag ions had higher toxicity to E. coli K-12 strain than AgNPs under the same concentrations. To understand the toxicity of AgNPs at a cellular level, reactive oxygen species (ROS) enzymes were detected for use as antioxidant enzymatic biomarkers. We have also studied the toxicity of AgNPs and Ag ions under various coexistence conditions including: fixed total concentration, with a varied the ratio of AgNPs to Ag ions; fixed the AgNPs concentration and then increased the Ag ions concentration; fixed Ag ions concentration and then increasing the AgNPs concentration. Exposure to AgNPs and Ag ions clearly had synergistic toxicity; however, decreased toxicity (for a fixed AgNPs concentration of 5mg/L, after increasing the Ag ions concentration) to E. coli K-12 strain. AgNPs and Ag ions in the presence of L-cysteine accelerated the bacterial cell growth rate, thereby reducing the bioavailability of Ag ions released from AgNPs under the single and coexistence conditions. Further works are needed to consider this potential for AgNPs and Ag ions toxicity across a range of environmental conditions. As silver nanoparticles (AgNPs)-based products are being broadly used in commercial industries, an ecotoxicological understanding of the AgNPs being released into the environment should be further considered. Here, we investigate the comparative toxicity of AgNPs and silver ions (Ag ions) to Escherichia coli K-12 strain, a representative ecotoxicological bioreporter. This study showed that toxicities of AgNPs and Ag ions to E. coli K-12 strain display different relationships when existing individually or when coexisting, and in the presence of L-cysteine materials. These findings suggest that the toxicology research of nanomaterials should consider conditions when NPs coexist with and without their bioavailable ions. Copyright © 2017. Published by Elsevier B.V.

Impact of a More Stringent Blood Lead Level Recommendation for Children (Ages 1-5): Vulnerabilities Related to Housing, Food Security, Vitamins, and Environmental Toxicants

EPA Science Inventory

The adverse health effects of lead (Pb) exposure in young children are well known. Non-Hispanic black children historically have higher blood Pb levels (BLL) compared to Mexican-Americans and non- Hispanic white children (CDC-MMWR). In the past, BLL tests below 10 µg/dL m...

Conspicuousness, color resemblance, and toxicity in geographically diverging mimicry: The pan-Amazonian frog Allobates femoralis.

PubMed

Amézquita, Adolfo; Ramos, Óscar; González, Mabel Cristina; Rodríguez, Camilo; Medina, Iliana; Simões, Pedro Ivo; Lima, Albertina Pimentel

2017-04-01

Predation risk is allegedly reduced in Batesian and Müllerian mimics, because their coloration resembles the conspicuous coloration of unpalatable prey. The efficacy of mimicry is thought to be affected by variation in the unpalatability of prey, the conspicuousness of the signals, and the visual system of predators that see them. Many frog species exhibit small colorful patches contrasting against an otherwise dark body. By measuring toxicity and color reflectance in a geographically variable frog species and the syntopic toxic species, we tested whether unpalatability was correlated with between-species color resemblance and whether resemblance was highest for the most conspicuous components of coloration pattern. Heterospecific resemblance in colorful patches was highest between species at the same locality, but unrelated to concomitant variation in toxicity. Surprisingly, resemblance was lower for the conspicuous femoral patches compared to the inconspicuous dorsum. By building visual models, we further tested whether resemblance was affected by the visual system of model predators. As predicted, mimic-model resemblance was higher under the visual system of simulated predators compared to no visual system at all. Our results indicate that femoral patches are aposematic signals and support a role of mimicry in driving phenotypic divergence or mimetic radiation between localities. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

An assessment of two-step linear regression and a multifactor probit analysis as alternatives to acute to chronic ratios in the estimation of chronic response from acute toxicity data to derive water quality guidelines.

PubMed

Slaughter, Andrew R; Palmer, Carolyn G; Muller, Wilhelmine J

2007-04-01

In aquatic ecotoxicology, acute to chronic ratios (ACRs) are often used to predict chronic responses from available acute data to derive water quality guidelines, despite many problems associated with this method. This paper explores the comparative protectiveness and accuracy of predicted guideline values derived from the ACR, linear regression analysis (LRA), and multifactor probit analysis (MPA) extrapolation methods applied to acute toxicity data for aquatic macroinvertebrates. Although the authors of the LRA and MPA methods advocate the use of extrapolated lethal effects in the 0.01% to 10% lethal concentration (LC0.01-LC10) range to predict safe chronic exposure levels to toxicants, the use of an extrapolated LC50 value divided by a safety factor of 5 was in addition explored here because of higher statistical confidence surrounding the LC50 value. The LRA LC50/5 method was found to compare most favorably with available experimental chronic toxicity data and was therefore most likely to be sufficiently protective, although further validation with the use of additional species is needed. Values derived by the ACR method were the least protective. It is suggested that there is an argument for the replacement of ACRs in developing water quality guidelines by the LRA LC50/5 method.

Field and laboratory investigation of acid effects on largemouth bass, rock bass, black crappie, and yellow perch

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eaton, J.G.; Swenson, W.A.; McCormick, J.H.

1992-01-01

One-half of Little Rock Lake, a small seepage lake in north-central Wisconsin, was gradually acidified by additions of sulfuric acid between August 1983 and November 1990. The ambient pH (6.1) of the lake was reduced at successive 2-year intervals to pH 5.6, 5.1, and 4.7. Responses of largemouth bass Micropterus salmoides, rock bass Ambloplites rupestris, black crappie Pomoxis nigromaculatus, and yellow perch Perca flavescens populations to the pH reductions were recorded and compared to the responses of these species during in situ bioassays and laboratory toxicity tests on embryos and larvae. Laboratory results obtained for largemouth bass and rock bassmore » underestimated, black crappie results overestimated, and yellow perch results were similar to effects observed in field studies. In situ bioassays predicted field responses better than did laboratory toxicity tests. Laboratory results showed that monomeric Al concentrations of approximately 50 microgram/l, which were comparable to Al concentrations in the acidified half of the lake, altered low-pH toxicity. Reduced recruitment was observed in field populations at higher pH than that at which adult mortality was observed. The results indicate that laboratory toxicity tests with early life stages may not accurately predict field population responses and that results from laboratory tests should be field-validated whenever possible.« less

Effects of High Toxic Boron Concentration on Protein Profiles in Roots of Two Citrus Species Differing in Boron-Tolerance Revealed by a 2-DE Based MS Approach

PubMed Central

Sang, Wen; Huang, Zeng-Rong; Yang, Lin-Tong; Guo, Peng; Ye, Xin; Chen, Li-Song

2017-01-01

Citrus are sensitive to boron (B)-toxicity. In China, B-toxicity occurs in some citrus orchards. So far, limited data are available on B-toxicity-responsive proteins in higher plants. Thirteen-week-old seedlings of “Sour pummelo” (Citrus grandis) and “Xuegan” (Citrus sinensis) was fertilized every other day until dripping with nutrient solution containing 10 μM (control) or 400 μM (B-toxicity) H3BO3 for 15 weeks. The typical B-toxic symptom only occurred in 400 μM B-treated C. grandis leaves, and that B-toxicity decreased root dry weight more in C. grandis seedlings than in C. sinensis ones, demonstrating that C. sinensis was more tolerant to B-toxicity than C. grandis. Using a 2-dimensional electrophoresis (2-DE) based MS approach, we identified 27 up- and four down-accumulated, and 28 up- and 13 down-accumulated proteins in B-toxic C. sinensis and C. grandis roots, respectively. Most of these proteins were isolated only from B-toxic C. sinensis or C. grandis roots, only nine B-toxicity-responsive proteins were shared by the two citrus species. Great differences existed in B-toxicity-induced alterations of protein profiles between C. sinensis and C. grandis roots. More proteins related to detoxification were up-accumulated in B-toxic C. grandis roots than in B-toxic C. sinensis roots to meet the increased requirement for the detoxification of the more reactive oxygen species and other toxic compounds such as aldehydes in the former. For the first time, we demonstrated that the active methyl cycle was induced and repressed in B-toxic C. sinensis and C. grandis roots, respectively, and that C. sinensis roots had a better capacity to keep cell wall and cytoskeleton integrity than C. grandis roots in response to B-toxicity, which might be responsible for the higher B-tolerance of C. sinensis. In addition, proteins involved in nucleic acid metabolism, biological regulation and signal transduction might play a role in the higher B-tolerance of C. sinensis. PMID:28261239

PD-L1 inhibitors in the pipeline: Promise and progress.

PubMed

Vanella, Vito; Festino, Lucia; Strudel, Martina; Simeone, Ester; Grimaldi, Antonio M; Ascierto, Paolo A

2017-01-01

Checkpoint inhibitors have improved survival for patients with melanoma, non-small-cell lung cancer (NSCLC), bladder, head and neck and other cancers. Antibodies against PD-L1, including atezolizumab, avelumab and durvalumab, are also being developed and have been approved for various cancers. Compared with anti-CTLA-4 drugs, studies with anti-PD-1/PD-L1 agents have suggested higher response rates and improved survival. Targeting PD-L1 rather than PD-1 may also theoretically offer further benefit, with the potential for improved efficacy and reduced toxicity, although this has not been clearly shown by clinical experience to date. Anti-PD-L1 agents have shown good efficacy and manageable toxicity in several tumor types.

Blood Lead Level in Children with Neurological Disorders.

PubMed

Parhoudeh, Marzieh; Inaloo, Soroor; Zahmatkeshan, Mozhgan; Seratishirazi, Zahra; Haghbin, Saeedeh

2018-01-01

We aimed to investigate the blood lead level (BLL) in children with neurologic disorders of unknown causes and compare with normal children. In this prospective case-control study, 68 patients aged 1 to 18 yr with neurologic disorders of unknown causes, were referred to pediatric neurology clinics and wards, Shiraz, Iran selected during a 12 months period from Sep 2013. They were compared with 1:1 ratio, age, and sex-matched healthy children. BLL was checked from all participants using 3 cc heparinized venous blood sample. Level of ≥5 mcg/dl was considered toxic dose. Totally, 136 children (68 cases and 68 controls) with mean ages of 5.20±4.12 and 4.18±3.86 yr, respectively, were enrolled. Mean BLL was higher in case group than in controls but the difference was not significant ( P =0.84), though they were less than toxic levels in both. In addition, the difference in mean BLLs was not significant in terms of living place, sex, and age. Totally, 17.7% of the study sample had BLL ≥5 mcg/dl. The frequency of BLL ≥5 mcg/dl was significantly higher in case group ( P =0.024) with an odds ratio 2.9 times higher (95% CI: 1.066-7.60). Strategies in public health must focus on practicing primary and secondary preventions of lead exposure in children.

Comparative survey of PAHs incidence in Portuguese traditional meat and blood sausages.

PubMed

Roseiro, L C; Gomes, A; Patarata, L; Santos, C

2012-06-01

Sixteen polycyclic aromatic hydrocarbons (PAHs) in representative traditional sausages produced in "Trás-os-Montes" and "Alentejo", were determined. Light PAHs represented similar overall contents in both regions and showed close decreasing order patterns (ACY, PHE, FLR and NAP), irrespective of the product type considered. Amongst the carcinogenic/mutagenic PAHs analyzed (PAH8), both regions also had greater contents associated to BaA and CHR, with slightly higher values for the former compound in "Alentejo" and, oppositely, for the later in "Trás-os-Montes". However, their quantitative comparison showed that the general mean total PAH content found in "Trás-os-Montes" was almost 3-fold higher than in similar products from "Alentejo" and this factor was about 8-fold superior when the PAH8 and PAH4 indicators were compared, expressing benzo[a]pyrene toxic equivalencies (BaPE), 15 times (total mean toxicity), 34 times (PAH8) and 9 times (PAH4) higher. In general terms, the mean BaP content of all analyzed samples from "Alentejo" was 0.41 μg kg(-1). Differently that value in "Trás-os-Montes" reached 3.57 μg kg(-1), expressing concerning average contents of 5.35, 5.87 and 4.51 μg kg(-1) in Chouriço de Carne, Moura and Salpicão sausages, respectively. Copyright © 2012 Elsevier Ltd. All rights reserved.

Release of elements to natural water from sediments of Lake Roosevelt, Washington, USA

USGS Publications Warehouse

Paulson, Anthony J.; Cox, Stephen E.

2007-01-01

Reservoir sediments from Lake Roosevelt (WA, USA) that were contaminated with smelter waste discharged into the Columbia River (BC, Canada) were examined using three measures of elemental release reflecting varying degrees of physical mixing and time scales. Aqueous concentrations of Cd, Cu, Pb, and Zn in the interstitial water of reservoir sediments, in the gently stirred overlying waters of incubated sediment cores, and in supernatants of aggressively tumbled slurries of reservoir sediments generally were higher than the concentrations from a reference site. When compared to chronic water-quality criteria, all three measures of release suggest that slag-contaminated sediments near the U.S.-Canadian border are potentially toxic as a result of Cu release and Pb release in two of the three measures. All three measures of Cd release suggest potential toxicity for one site farther down the reservoir, probably contaminated as a result of transport and adsorption of Cd from smelter liquid waste. Releases of Zn and As did not appear to be potentially toxic. Carbonate geochemistry indirectly affects the potential toxicity by increasing water hardness.

Export of toxic chemicals - a review of the case of uncontrolled electronic-waste recycling.

PubMed

Wong, M H; Wu, S C; Deng, W J; Yu, X Z; Luo, Q; Leung, A O W; Wong, C S C; Luksemburg, W J; Wong, A S

2007-09-01

This paper reviews the concentrations of persistent organic pollutants such as flame retardants (PBDEs), dioxins/furans (PCDD/Fs), polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs) and heavy metals/metalloid concentrations of different environmental media at Guiyu, a traditional rice-growing village located in southeastern Guangdong Province (PR China), which has turned into an intensive electronic-waste (e-waste) recycling site. Incomplete combustion of e-waste in open air and dumping of processed materials are the major sources of various toxic chemicals. By comparing with existing data available in other areas and also guidelines adopted in different countries, it is obvious that the environment is highly contaminated by these toxic chemicals derived from the recycling processes. For example, the monthly concentration of the sum of 22 PBDE congeners contained in PM(2.5) (16.8ngm(-3)) of air samples at Guiyu was 100 times higher than published data. In order to safeguard the environment and human health, detailed investigations are urgently needed, especially on tracking the exposure pathways of different toxic chemicals which may affect the workers and local residents especially mothers, infants and children.

Bioaccumulation and biological effects of cigarette litter in marine worms

PubMed Central

Wright, Stephanie L.; Rowe, Darren; Reid, Malcolm J.; Thomas, Kevin V.; Galloway, Tamara S.

2015-01-01

Marine debris is a global environmental issue. Smoked cigarette filters are the predominant coastal litter item; 4.5 trillion are littered annually, presenting a source of bioplastic microfibres (cellulose acetate) and harmful toxicants to marine environments. Despite the human health risks associated with smoking, little is known of the hazards cigarette filters present to marine life. Here we studied the impacts of smoked cigarette filter toxicants and microfibres on the polychaete worm Hediste diversicolor (ragworm), a widespread inhabitant of coastal sediments. Ragworms exposed to smoked cigarette filter toxicants in seawater at concentrations 60 fold lower than those reported for urban run-off exhibited significantly longer burrowing times, >30% weight loss, and >2-fold increase in DNA damage compared to ragworms maintained in control conditions. In contrast, ragworms exposed to smoked cigarette filter microfibres in marine sediment showed no significant effects. Bioconcentration factors for nicotine were 500 fold higher from seawater than from sediment. Our results illustrate the vulnerability of organisms in the water column to smoking debris and associated toxicants, and highlight the risks posed by smoked cigarette filter debris to aquatic life. PMID:26369692

Proteomic characterisation of toxins isolated from nematocysts of the South Atlantic jellyfish Olindias sambaquiensis.

PubMed

Weston, Andrew J; Chung, Ray; Dunlap, Walter C; Morandini, André C; Marques, Antonio C; Moura-da-Silva, Ana M; Ward, Malcolm; Padilla, Gabriel; da Silva, Luiziana Ferreira; Andreakis, Nikos; Long, Paul F

2013-09-01

Surprisingly little is known of the toxic arsenal of cnidarian nematocysts compared to other venomous animals. Here we investigate the toxins of nematocysts isolated from the jellyfish Olindias sambaquiensis. A total of 29 unique ms/ms events were annotated as potential toxins homologous to the toxic proteins from diverse animal phyla, including cone-snails, snakes, spiders, scorpions, wasp, bee, parasitic worm and other Cnidaria. Biological activities of these potential toxins include cytolysins, neurotoxins, phospholipases and toxic peptidases. The presence of several toxic enzymes is intriguing, such as sphingomyelin phosphodiesterase B (SMase B) that has only been described in certain spider venoms, and a prepro-haystatin P-IIId snake venom metalloproteinase (SVMP) that activates coagulation factor X, which is very rare even in snake venoms. Our annotation reveals sequence orthologs to many representatives of the most important superfamilies of peptide venoms suggesting that their origins in higher organisms arise from deep eumetazoan innovations. Accordingly, cnidarian venoms may possess unique biological properties that might generate new leads in the discovery of novel pharmacologically active drugs. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Toxicity Evaluation and Anti-Tumor Study of Docetaxel Loaded mPEG-Polyester Micelles for Breast Cancer Therapy.

PubMed

Tan, Li Wei; Ma, Bu Yun; Zhao, Qian; Zhang, Lan; Chen, Li Juan; Peng, Jin Rong; Qian, Zhi Yong

2017-04-01

In this work, docetaxel (DTX) was encapsulated in monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (mPEG-PCL) micelles and monomethoxy poly(ethylene glycol)-poly(D, L-lactic acid) (mPEG-PLA) micelles, respectively. For the further application, the acute/genetic toxicity evaluation and pharmacokinetic/pharmacodynamic study of the two kinds of micellar nanomedicines were performed. In the study of anticancer activity in vitro and in vivo, DTX micelles showed better tumorgrowth inhibition than free DTX. The pharmacokinetic and tissue distribution studies showed that the DTX incorporated in micelles (especially in DTX-mPEG-PCL) retained significantly higher concentration in plasma and tumor tissue compared with free DTX. The acute toxicity and genotoxicity studies indicated that DTX micelles were safer than the docetaxel injection in cancer therapy and DTX-mPEG-PCL had less damage to DNA than DTX-mPEG-PLA. So the micelles had a pronounced effect on reducing acute toxicity and genotoxicity of docetaxel. In conclusion, DTX micelles were efficient and safe on breast carcinoma chemotherapy.

Antitumoral activity and toxicity of PEG-coated and PEG-folate-coated pH-sensitive liposomes containing ¹⁵⁹Gd-DTPA-BMA in Ehrlich tumor bearing mice.

PubMed

Soares, Daniel Crístian Ferreira; Cardoso, Valbert Nascimento; de Barros, André Luís Branco; de Souza, Cristina Maria; Cassali, Geovanni Dantas; de Oliveira, Mônica Cristina; Ramaldes, Gilson Andrade

2012-01-23

In the present study, PEG-coated pH-sensitive and PEG-folate-coated pH-sensitive liposomes containing the ¹⁵⁹Gd-DTPA-BMA were prepared and radiolabeled through neutron activation technique, aiming to study the in vivo antitumoral activity and toxicity on mice bearing a previously-developed solid Ehrlich tumor. The treatment efficacy was verified through tumoral volume increase and histomorphometry studies. The toxicity of formulations was investigated through animal weight variations, as well as hematological and biochemical tests. The results showed that after 31 days of treatment, animals treated with radioactive formulations had a lower increase in tumor volume and a significantly higher percentage of necrosis compared with controls revealed by histomorphometry studies. Furthermore, mice treated with radioactive formulations exhibited lower weight gain without significant hematological or biochemical changes, except for toxicity to hepatocytes which requires more detailed studies. From the results obtained to date, we believe that the radioactive formulations can be considered potential therapeutic agents for cancer. Copyright © 2011 Elsevier B.V. All rights reserved.

Efficacy and pharmacokinetics of a modified acid-labile docetaxel-PRINT(®) nanoparticle formulation against non-small-cell lung cancer brain metastases.

PubMed

Sambade, Maria; Deal, Allison; Schorzman, Allison; Luft, J Christopher; Bowerman, Charles; Chu, Kevin; Karginova, Olga; Swearingen, Amanda Van; Zamboni, William; DeSimone, Joseph; Anders, Carey K

2016-08-01

Particle Replication in Nonwetting Templates (PRINT(®)) PLGA nanoparticles of docetaxel and acid-labile C2-dimethyl-Si-Docetaxel were evaluated with small molecule docetaxel as treatments for non-small-cell lung cancer brain metastases. Pharmacokinetics, survival, tumor growth and mice weight change were efficacy measures against intracranial A549 tumors in nude mice. Treatments were administered by intravenous injection. Intracranial tumor concentrations of PRINT-docetaxel and PRINT-C2-docetaxel were 13- and sevenfold greater, respectively, than SM-docetaxel. C2-docetaxel conversion to docetaxel was threefold higher in intracranial tumor as compared with nontumor tissues. PRINT-C2-docetaxel increased median survival by 35% with less toxicity as compared with other treatments. The decreased toxicity of the PRINT-C2-docetaxel improved treatment efficacy against non-small-cell lung cancer brain metastasis.

Renal and Metabolic Toxicities Following Initiation of HIV-1 Treatment Regimen in a Diverse, Multinational Setting: A Focused Safety Analysis of ACTG PEARLS (A5175)

PubMed Central

Romo, F. Touzard; Smeaton, L.M.; Campbell, T.B.; Riviere, C.; Mngqibisa, R.; Nyirenda, M.; Supparatpinyo, K.; Kumarasamy, N.; Hakim, J.G.; Flanigan, T.P.

2015-01-01

Background Convenient dosing, potency, and low toxicity support use of tenofovir disoproxil fumarate (TDF) as preferred nucleotide reverse transcriptase inhibitor (NRTI) for HIV-1 treatment. However, renal and metabolic safety of TDF compared to other NRTIs has not been well described in resource-limited settings. Methods This was a secondary analysis examining the occurrence of renal abnormalities (RAs) and renal and metabolic serious non-AIDS-defining events (SNADEs) through study follow-up between participants randomized to zidovudine (ZDV)/lamivudine/efavirenz and TDF/emtricitabine/efavirenz treatment arms within A5175/PEARLS trial. Exact logistic regression explored associations between baseline covariates and RAs. Response profile longitudinal analysis compared creatinine clearance (CrCl) over time between NRTI groups. Results Twenty-one of 1,045 participants developed RAs through 192 weeks follow-up; there were 15 out of 21 in the TDF arm (P = .08). Age 41 years or older (odds ratio [OR], 3.35; 95% CI, 1.1–13.1), history of diabetes (OR, 10.7; 95% CI, 2.1–55), and lower baseline CrCl (OR, 3.1 per 25 mL/min decline; 95% CI, 1.7–5.8) were associated with development of RAs. Renal SNADEs occurred in 42 participants; 33 were urinary tract infections and 4 were renal failure/insufficiency; one event was attributed to TDF. Significantly lower CrCl values were maintained among patients receiving TDF compared to ZDV (repeated measures analysis P = .05), however worsening CrCl from baseline was not observed with TDF exposure over time. Metabolic SNADEs were rare, but were higher in the ZDV arm (20 vs 3; P < .001). Conclusions TDF is associated with lower serious metabolic toxicities but not higher risk of RAs, serious renal events, or worsening CrCl over time compared to ZDV in this randomized multinational study. PMID:25433664

Natural Oil-Based Emulsion Containing Allantoin Versus Aqueous Cream for Managing Radiation-Induced Skin Reactions in Patients With Cancer: A Phase 3, Double-Blind, Randomized, Controlled Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chan, Raymond Javan, E-mail: email.rchan@gmail.com; School of Nursing, Queensland University of Technology, Kelvin Grove; Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove

Purpose: To investigate the effects of a natural oil-based emulsion containing allantoin versus aqueous cream for preventing and managing radiation-induced skin reactions. Methods and Materials: A total of 174 patients were randomized and participated in the study. Patients received either cream 1 (the natural oil-based emulsion containing allantoin) or cream 2 (aqueous cream). Skin toxicity, pain, itching, and skin-related quality of life scores were collected for up to 4 weeks after radiation treatment. Results: Patients who received cream 1 had a significantly lower average level of Common Terminology Criteria for Adverse Events at week 3 (P<.05) but had statistically higher averagemore » levels of skin toxicity at weeks 7, 8, and 9 (all P<.001). Similar results were observed when skin toxicity was analyzed by grades. With regards to pain, patients in the cream 2 group had a significantly higher average level of worst pain (P<.05) and itching (P=.046) compared with the cream 1 group at week 3; however, these differences were not observed at other weeks. In addition, there was a strong trend for cream 2 to reduce the incidence of grade 2 or more skin toxicity in comparison with cream 1 (P=.056). Overall, more participants in the cream 1 group were required to use another topical treatment at weeks 8 (P=.049) and 9 (P=.01). Conclusion: The natural oil-based emulsion containing allantoin seems to have similar effects for managing skin toxicity compared with aqueous cream up to week 5; however, it becomes significantly less effective at later weeks into the radiation treatment and beyond treatment completion (week 6 and beyond). There were no major differences in pain, itching, and skin-related quality of life. In light of these results, clinicians and patients can base their decision on costs and preferences. Overall, aqueous cream seems to be a more preferred option.« less

Retinal toxicity related to hydroxychloroquine in patients with systemic lupus erythematosus and rheumatoid arthritis.

PubMed

Telek, Hande Husniye; Yesilirmak, Nilufer; Sungur, Gulten; Ozdemir, Yaprak; Yesil, Nesibe Karahan; Ornek, Firdevs

2017-12-01

To compare the retinal toxicity due to hydroxychloroquine (HCQ) use in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) using multifocal electroretinography (mfERG), fundus autofluorescence (FAF) and optical coherence tomography (OCT). Patients who were using HCQ due to SLE and RA, and healthy subjects evaluated in this study. Central foveal thickness (CFT), inner-outer segment (IS-OS) junction irregularity, retinal nerve fiber layer thickness, mfERG and FAF measurements were performed to evaluate retinal toxicity. Study included 35 eyes of 35 SLE patients, 40 eyes of 40 RA patients and 20 eyes of 20 healthy subjects. In SLE group, retinal abnormality was found in three eyes with mfERG, in one eye with FAF and in four eyes with OCT. In RA group, retinal abnormality was found in 10 eyes with mfERG, in five eyes with FAF and in nine eyes with OCT. A statistically significant difference was found with respect to mfERG between "eyes with abnormal responses and without abnormal responses" and "eyes with abnormal responses and controls" (p < 0.05). A statistically significant difference was found with respect to CFT between "eyes with IS-OS junction irregularities and without IS-OS junction irregularities" and "eyes with/without IS-OS junction irregularities and controls" (p < 0.05). The use of HCQ seems to cause retinal toxicity more often in RA patients compared to SLE patients. For the early detection of retinal changes, OCT and mfERG can be used as screening tools due to their higher sensitivity rates compared to other tests.

Permanganate with a double-edge role in photodegradation of sulfamethoxazole: Kinetic, reaction mechanism and toxicity.

PubMed

Gong, Han; Chu, Wei

2018-01-01

In this study, the double-edge role of permanganate in sulfamethoxazole (SMX) photodegradation with a recyclable catalyst was revealed for the first time. The role of the catalyst under different UV wavelength, the role of permanganate in the treatment process, the effects of permanganate dosage and solution pH on the removal efficiency were investigated. Moreover, the transformation products, TOC reduction and the toxicity of the treated final product to Chlorella vulgaris and Artemia salina were determined. Sole permanganate showed no effect in SMX degradation, while its introduction to the photocatalytic process doubled the reaction rate at the optimal dosage. It is interesting to find that the reaction rate showed a fluctuation trend in terms of permanganate dosage due to the summation of positive effect of permanganate oxidation and the negative effect of the formed MnO 2 at the surface of the catalyst, as well as the light attenuation due to overdosed permanganate. The determined intermediates, the higher inorganic ions release and TOC reduction provided a clue on a higher mineralization compared to SMX degradation in the same process without permanganate. Permanganate above 1 μM may pose a threat to the algae growth, therefore a good monitoring and control of residual permanganate dosage should be incorporated into the process design. A good toxicity reduction to A. salina was observed in the treated effluent; a longer detention is suggested for the complete removal of toxicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Formal recycling of e-waste leads to increased exposure to toxic metals: an occupational exposure study from Sweden.

PubMed

Julander, Anneli; Lundgren, Lennart; Skare, Lizbet; Grandér, Margaretha; Palm, Brita; Vahter, Marie; Lidén, Carola

2014-12-01

Electrical and electronic waste (e-waste) contains multiple toxic metals. However, there is currently a lack of exposure data for metals on workers in formal recycling plants. The objective of this study was to evaluate workers' exposure to metals, using biomarkers of exposure in combination with monitoring of personal air exposure. We assessed exposure to 20 potentially toxic metals among 55 recycling workers and 10 office workers at three formal e-waste recycling plants in Sweden. Workers at two of the plants were followed-up after 6 months. We collected the inhalable fraction and OFC (37-mm) fraction of particles, using personal samplers, as well as spot samples of blood and urine. We measured metal concentrations in whole blood, plasma, urine, and air filters using inductively coupled plasma-mass spectrometry following acid digestion. The air sampling indicated greater airborne exposure, 10 to 30 times higher, to most metals among the recycling workers handling e-waste than among the office workers. The exposure biomarkers showed significantly higher concentrations of chromium, cobalt, indium, lead, and mercury in blood, urine, and/or plasma of the recycling workers, compared with the office workers. Concentrations of antimony, indium, lead, mercury, and vanadium showed close to linear associations between the inhalable particle fraction and blood, plasma, or urine. In conclusion, our study of formal e-waste recycling shows that workers performing recycling tasks are exposed to multiple toxic metals. Copyright © 2014. Published by Elsevier Ltd.

Toxic effects of NH4+-N on embryonic development of Bufo gargarizans and Rana chensinensis.

PubMed

Deng, Hongzhang; Chai, Lihong; Luo, Pingping; Zhou, Meimei; Nover, Daniel; Zhao, Xiaohong

2017-09-01

Although nitrogen fertilizer is commonly used worldwide, little information is currently available about NH 4 + -N toxicity on amphibians. This study determined the acute and chronic toxic effects of NH 4 + -N on two native Chinese amphibian species (Bufo gargarizans and Rana chensinensis), and compared the negative sensitivity of different embryos to NH 4 + -N. Static renewal aqueous exposures were performed using B. gargarizans and R. chensinensis embryos at Gosner stage 2 over 96 h. In terms of 96 h-LC 50 , B. gargarizans and R. chensinensis embryos had significantly different responses to NH 4 + -N, and the latter was more sensitive to NH 4 + -N than the former. In the chronic toxicity test, exposure to 10 mg L -1 NH 4 + -N or higher significantly decreased the hatching rate of embryos in both species. Significant increases in the abnormality rate of embryos at 50 mg L -1 NH 4 + -N or higher were observed and morphological abnormalities were characterized by axial flexures, yolk sac edema, and hyperplasia in both species. Additionally, the total length of embryos decreased in a dose-dependent manner after exposure to NH 4 + -N. The results indicate that NH 4 + -N exposure can increase abnormality and inhibit the hatching and development of embryos in B. gargarizans and R. chensinensis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Decision analytic modeling for the economic analysis of proton radiotherapy for non-small cell lung cancer

PubMed Central

Richard, Patrick J.; Zeng, Jing; Apisarnthanarax, Smith; Rengan, Ramesh; Phillips, Mark H.

2018-01-01

Background Although proton radiation treatments are more costly than photon/X-ray therapy, they may lower overall treatment costs through reducing rates of severe toxicities and the costly management of those toxicities. To study this issue, we created a decision-model comparing proton vs. X-ray radiotherapy for locally advanced non-small cell lung cancer patients. Methods An influence diagram was created to model for radiation delivery, associated 6-month pneumonitis/esophagitis rates, and overall costs (radiation plus toxicity costs). Pneumonitis (age, chemo type, V20, MLD) and esophagitis (V60) predictors were modeled to impact toxicity rates. We performed toxicity-adjusted, rate-adjusted, risk group-adjusted, and radiosensitivity analyses. Results Upfront proton treatment costs exceeded that of photons [$16,730.37 (3DCRT), $23,893.83 (IMRT), $41,061.80 (protons)]. Based upon expected population pneumonitis and esophagitis rates for each modality, protons would be expected to recover $1,065.62 and $1,139.63 of the cost difference compared to 3DCRT or IMRT. For patients treated with IMRT experiencing grade 4 pneumonitis or grade 4 esophagitis, costs exceeded patients treated with protons without this toxicity. 3DCRT patients with grade 4 esophagitis had higher costs than proton patients without this toxicity. For the risk group analysis, high risk patients (age >65, carboplatin/paclitaxel) benefited more from proton therapy. A biomarker may allow patient selection for proton therapy, although the AUC alone is not sufficient to determine if the biomarker is clinically useful. Conclusions The comparison between proton and photon/X-ray radiation therapy for NSCLC needs to consider both the up-front cost of treatment and the possible long term cost of complications. In our analysis, current costs favor X-ray therapy. However, relatively small reductions in the cost of proton therapy may result in a shift to the preference for proton therapy.

Similar efficacy for phase I trials in comparison with DTIC for advanced malignant melanoma: an analysis of melanoma outcomes in CTEP-sponsored phase I trials 1995-2011.

PubMed

Luke, Jason J; Rubinstein, Lawrence V; Smith, Gary L; Ivy, S Percy; Harris, Pamela J

2013-04-01

After ipilimumab, vemurafenib, and interleukin-2, standard of care chemotherapy for melanoma remains dacarbazine (response rate ∼9%). Despite this, many physicians hesitate to refer patients to phase I protocols given a perceived lack of clinical benefit and potential for harm. To better understand the validity of these perceptions, the experience of all patients with melanoma treated on phase I trials sponsored by the National Cancer Institute-Cancer Therapy Evaluation Program (NCI-CTEP) from 1995 to 2011 were analyzed and compared with the pooled results of six contemporary phase III trials of dacarbazine. A total of 937 patients with melanoma were treated in 148 CTEP phase I trials. The majority were men with a median of two prior therapies (46% receiving prior dacarbazine). Response and clinical benefit rates in these trials were not clinically different from those of dacarbazine (phase I: 6.3 and 26.8% vs. dacarbazine: 8.8 and 27.9%) although grades 3 and 4 toxicity was significantly higher (54 vs. 28%). Efficacy and toxicity were generally consistent within phase I subgroups (targeted agents, immunotherapies, or chemotherapeutics) though targeted therapy was associated with a lower response rate, immunotherapy with lower clinical benefit rate, and chemotherapy with higher incidence of grade 4 toxicity. Thus, the perception of limited efficacy of phase I trials for patients with melanoma was disproven, whereas the perception of toxicity was observed. However, this difference in toxicity may have been largely because of the nature of phase I vs. phase III trials (i.e. more heavily pretreated) and because of the phase I trials often being multiagent as opposed to dacarbazine alone. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Different definitions of esophagus influence esophageal toxicity prediction for esophageal cancer patients administered simultaneous integrated boost versus standard-dose radiation therapy.

PubMed

Huang, Bao-Tian; Huang, Rui-Hong; Zhang, Wu-Zhe; Lin, Wen; Guo, Long-Jia; Xu, Liang-Yu; Lin, Pei-Xian; Chen, Jian-Zhou; Li, De-Rui; Chen, Chuang-Zhen

2017-03-09

We aim to evaluate whether different definitions of esophagus (DEs) impact on the esophageal toxicity prediction for esophageal cancer (EC) patients administered intensity-modulated radiation therapy with simultaneous integrated boost (SIB-IMRT) vs. standard-dose IMRT (SD-IMRT). The esophagus for 21 patients diagnosed with primary EC were defined in the following four ways: the whole esophagus, including the tumor (ESO whole ); ESO whole within the treatment field (ESO infield ); ESO infield , excluding the tumor (ESO infield-tumor ) and ESO whole , excluding the tumor (ESO whole-tumor ). The difference in the dose variation, acute esophageal toxicity (AET) and late esophageal toxicity (LET) of four DEs were compared. We found that the mean esophageal dose for ESO whole , ESO infield , ESO infield-tumor and ESO whole-tumor were increased by 7.2 Gy, 10.9 Gy, 4.6 Gy and 2.0 Gy, respectively, in the SIB-IMRT plans. Radiobiological models indicated that a grade ≥ 2 AET was 2.9%, 3.1%, 2.2% and 1.6% higher on average with the Kwint model and 14.6%, 13.2%, 7.2% and 3.4% higher with the Wijsman model for the four DEs. A grade ≥ 3 AET increased by 4.3%, 7.2%, 4.2% and 1.2%, respectively. Additionally, the predicted LET increased by 0.15%, 0.39%, 1.2 × 10 -2 % and 1.5 × 10 -3 %. Our study demonstrates that different DEs influence the esophageal toxicity prediction for EC patients administered SIB-IMRT vs. SD-IMRT treatment.

Honeybees (Apis mellifera) as a biological barrier for contamination of honey by environmental toxic metals.

PubMed

Dżugan, Małgorzata; Wesołowska, Monika; Zaguła, Grzegorz; Kaczmarski, Mateusz; Czernicka, Maria; Puchalski, Czesław

2018-01-27

The aim of the study was to investigate the transfer of toxic metals from honeybee workers (Apis mellifera L.) to bee honey in relation to the ecological state of the environment. The materials of the study consisted of samples of honeybee bodies and varietal honeys taken from the same apiary located in three areas: R1-urbanized (16), R2-ecologically clean (16) and R3-industrialized (15) of south-eastern Poland. The contents of 14 elements in all tested samples, including toxic metals (Cd, Pb, Hg, Al, Ni, Tl) as well as bioelements (K, Mg, Ca, Mn, Fe, Zn, Cu, Se), were analysed by the ICP-OES method with prior microwave mineralization. The concentrations of the majority of the studied elements, excluding aluminum and lead, were significantly higher in bee bodies than in honey samples (P < 0.05). The pollution of bee bodies by toxic metals was dependent on the environmental cleanliness, and the most pollution was observed in the industrialized area. The bee body was the most effective barrier for Cd and Tl transfer to the honey, while the level of Ni was similar in both tested materials. The Al concentration was significantly higher in honey than bee bodies (14.81 ± 24.69 and 6.51 ± 5.83 mg kg -1 , respectively), which suggests the possibility of secondary contamination of honey. The greatest sensitivity to heavy metal pollution was observed in honeydew honey compared to nectar honeys (P < 0.05). It was proved for the first time that bees work as biofilters for toxic metals and prevent honey contamination.

Comparative effect of ZnO NPs, ZnO bulk and ZnSO4 in the antioxidant defences of two plant species growing in two agricultural soils under greenhouse conditions.

PubMed

García-Gómez, Concepción; Obrador, Ana; González, Demetrio; Babín, Mar; Fernández, María Dolores

2017-07-01

The present study has investigated the toxicity of ZnO NPs to bean (Phaseolus vulgaris) and tomato (Solanum lycopersicon) crops grown to maturity under greenhouse conditions using an acidic (soil pH5.4) and a calcareous soil (soil pH8.3). The potentially available Zn in the soils and the Zn accumulation in the leaves from NPs applied to the soil (3, 20 and 225mgZnkg -1 ) and changes in the chlorophylls, carotenoids and oxidative stress biomarkers were measured at 15, 30, 60 and 90days and compared with those caused by bulk ZnO and ZnSO 4 . The available Zn in the soil and the leaf Zn content did not differ among the Zn chemical species, except in the acidic soil at the highest concentration of Zn applied as Zn ions, where the highest values of the two variables were found. The ZnO NPs showed comparable Zn toxicity or biostimulation to their bulk counterparts and Zn salts, irrespective of certain significant differences suggesting a higher activity of the Zn ion. The treatments altered the photosynthetic pigment concentration and induced oxidative stress in plants. ROS formation was observed at Zn plant concentrations ranging from 590 to 760mgkg -1 , but the effects on the rest of the parameters were highly dependent on the plant species, exposure time and especially soil type. In general, the effects were higher in the acidic soil than in the calcareous soil for the bean and the opposite for the tomato. The similar uptakes and toxicities of the different Zn forms suggest that the Zn ions derived from the ZnO NPs exerted a preferential toxicity in plants. However, several results obtained in soils treated with NPs at 3mgZnkg -1 soil indicated that may exist other underlying mechanisms related to the intrinsic nanoparticle properties, especially at low NP concentrations. Copyright © 2017 Elsevier B.V. All rights reserved.

Growth and Photosynthetic Characteristics of Toxic and Non-Toxic Strains of the Cyanobacteria Microcystis aeruginosa and Anabaena circinalis in Relation to Light

PubMed Central

Islam, M. Ashraful; Beardall, John

2017-01-01

Cyanobacteria are major bloom-forming organisms in freshwater ecosystems and many strains are known to produce toxins. Toxin production requires an investment in energy and resources. As light is one of the most important factors for cyanobacterial growth, any changes in light climate might affect cyanobacterial toxin production as well as their growth and physiology. To evaluate the effects of light on the growth and physiological parameters of both toxic and non-toxic strains of Microcystis aeruginosa and Anabaena circinalis, cultures were grown at a range of light intensities (10, 25, 50, 100, 150 and 200 µmol m−2 s−1). The study revealed that the toxic strains of both species (CS558 for M. aeruginosa and CS537 and CS541 for A. circinalis) showed growth (µ) saturation at a higher light intensity compared to the non-toxic strains (CS338 for M. aeruginosa and CS534 for A. circinalis). Both species showed differences in chlorophyll a, carotenoid, allophycocyanin (APC) and phycoerythrin (PE) content between strains. There were also differences in dark respiration (Rd), light saturated oxygen evolution rates (Pmax) and efficiency of light harvesting (α) between strains. All other physiological parameters showed no statistically significant differences between strains. This study suggest that the different strains respond differently to different light habitats. Thus, changes in light availability may affect bloom intensity of toxic and nontoxic strains of cyanobacteria by changing the dominance and succession patterns. PMID:28777340

Tempo and Mode of the Evolution of Venom and Poison in Tetrapods.

PubMed

Harris, Richard J; Arbuckle, Kevin

2016-06-23

Toxic weaponry in the form of venom and poison has evolved in most groups of animals, including all four major lineages of tetrapods. Moreover, the evolution of such traits has been linked to several key aspects of the biology of toxic animals including life-history and diversification. Despite this, attempts to investigate the macroevolutionary patterns underlying such weaponry are lacking. In this study we analyse patterns of venom and poison evolution across reptiles, amphibians, mammals, and birds using a suite of phylogenetic comparative methods. We find that each major lineage has a characteristic pattern of trait evolution, but mammals and reptiles evolve under a surprisingly similar regime, whilst that of amphibians appears to be particularly distinct and highly contrasting compared to other groups. Our results also suggest that the mechanism of toxin acquisition may be an important distinction in such evolutionary patterns; the evolution of biosynthesis is far less dynamic than that of sequestration of toxins from the diet. Finally, contrary to the situation in amphibians, other tetrapod groups show an association between the evolution of toxic weaponry and higher diversification rates. Taken together, our study provides the first broad-scale analysis of macroevolutionary patterns of venom and poison throughout tetrapods.

Tempo and Mode of the Evolution of Venom and Poison in Tetrapods

PubMed Central

Harris, Richard J.; Arbuckle, Kevin

2016-01-01

Toxic weaponry in the form of venom and poison has evolved in most groups of animals, including all four major lineages of tetrapods. Moreover, the evolution of such traits has been linked to several key aspects of the biology of toxic animals including life-history and diversification. Despite this, attempts to investigate the macroevolutionary patterns underlying such weaponry are lacking. In this study we analyse patterns of venom and poison evolution across reptiles, amphibians, mammals, and birds using a suite of phylogenetic comparative methods. We find that each major lineage has a characteristic pattern of trait evolution, but mammals and reptiles evolve under a surprisingly similar regime, whilst that of amphibians appears to be particularly distinct and highly contrasting compared to other groups. Our results also suggest that the mechanism of toxin acquisition may be an important distinction in such evolutionary patterns; the evolution of biosynthesis is far less dynamic than that of sequestration of toxins from the diet. Finally, contrary to the situation in amphibians, other tetrapod groups show an association between the evolution of toxic weaponry and higher diversification rates. Taken together, our study provides the first broad-scale analysis of macroevolutionary patterns of venom and poison throughout tetrapods. PMID:27348001

Ameliorative effect of propolis on the cadmium-induced reproductive toxicity in male albino rats.

PubMed

Çilenk, Kübra Tuğçe; Öztürk, İsmet; Sönmez, Mehmet Fatih

2016-10-01

Propolis is a potent antioxidant and a free radical scavenger. The present study aimed to investigate protective effects of propolis extract on cadmium-induced testicular damage, apoptosis, HIF-1α expression and toxicity in rat's testis tissue. A total of 32 male rats were equally divided into four study groups namely, control, Cd (1mg/kg/day), Cd+propolis (50mg/kg/day) and propolis. The rats were decapitated under ketamine anesthesia and their testes tissues were removed. Serum testosterone, tissue malondialdehyde and HIF-1α levels, HIF-1α expression, apoptosis and histopathological damage scores were then compared. In the Cd group, the diameters of seminiferous tubules, tubular biopsy score of Johnsen and serum testosterone levels were decreased compared control group, but tissue HIF-1α and tissue MDA levels was higher than control group. The immunoreactivity of HIF-1α and the number of apoptotic cells were increased in Cd group. Furthermore, the propolis treated group showed an improved histological appearance in the Cd group. Thus, the results suggest that propolis acts as a potent protective agent against Cd-induced testicular toxicity in rats. Copyright © 2016 Elsevier Inc. All rights reserved.

Assessment of cytogenetic and cytotoxic effects of chlorhexidine digluconate on cultured human lymphocytes.

PubMed

Arabaci, Taner; Türkez, Hasan; Çanakçi, Cenk Fatih; Özgöz, Mehmet

2013-09-01

The aim of this study was to assess the genetic and cellular toxicity of Chlorhexidine digluconate (CHX) on peripheral human lymphocytes in vitro. Micronucleus assay was used to investigate the genotoxicity, while the cell viability and proliferation were evaluated by Trypan blue exclusion test and Nuclear Division Index in control and CHX-treated (0.05, 0.1, 0.2, 0.4, 0.5 mg/ml) human blood cultures. A dose-dependent toxic effect was found depending on CHX incubation on the genetic and cell viability of the lymphocytes. Micronucleus frequency was found to be statistically higher at 0.5 mg/ml concentration compared to lower doses and the control group (p < 0.05). A significant reduction was shown in the cell viability and cell proliferation of the exposed lymphocytes at the concentrations of 0.4 and 0.5 mg/ml (p < 0.05), while no significant toxicity was found at lower concentrations compared to control (p > 0.05). This study showed dose-dependent genotoxic and cytotoxic effects of CHX on human lymphocytes in vitro. It should be considered during periodontal irrigation or novel CHX products at lower concentrations should be manufactured for clinical usage.

Effects of calcium, magnesium, and sodium on alleviating cadmium toxicity to Hyalella azteca

USGS Publications Warehouse

Jackson, B.P.; Lasier, P.J.; Miller, W.P.; Winger, P.V.

2000-01-01

Toxicity of trace metal ions to aquatic organisms, arising through either anthropogenic inputs or acidification of surface waters, continues to be both a regulatory and environmental problem. It is generally accepted that the free metal ion is the major toxic species (Florence et a1.,1992) and that inorganic or organic complexation renders the metal ion non-bioavailable (Meador, 1991, Galvez and Wood, 1997). However, water chemistry parameters such as alkalinity, hardness, dissolved organic carbon and pH influence metal ion toxicity either directly by lowering free metal ion concentration or indirectly through synergistic or antagonistic effects. Alkalinity and salinity can affect the speciation of metal ions by increasing ion-pair formation, thus decreasing free metal ion concentration. For example, Cu was found to be less toxic to rainbow trout in waters of high alkalinity (Miller and Mackay, 1980), due to formation of CuCO3 ion pair, and corresponding reduction in free Cu2+ concentration. The influence of salinity on the toxicity of cadmium to various organisms has been demonstrated in a number of studies (Bervoets et al., 1995, Hall et al., 1995, Lin and Dunson, 1993, Blust et al., 1992). In all these studies the apparent toxicity of cadmium was lowered as salinity was increased due to increased formation of CdC1+ and CDCl2 aqueous complexes that are non-toxic or of much lower toxicity than the free Cd2+ ion. Changes in pH exert both a biological and chemical effect on metal ion toxicity (Campbell and Stokes, 1985). Low pH favors greater metal ion solubility, and, in the absence of complexing ions, reduced speciation of the metal ion, which tends to increase toxicity compared to higher pH. However, Iow pH also enhances competition between H+ and metal ion for cell surface binding sites, which tends to decrease metal ion toxicity.

Comparative toxicity of leachates from 52 textiles to Daphnia magna.

PubMed

Dave, Göran; Aspegren, Pia

2010-10-01

The environmental aspects of textiles are very complex and include production, processing, transport, usage, and recycling. Textiles are made from a variety of materials and can contain a large number of chemicals. Chemicals are used during production of fibres, for preservation and colouring and they are released during normal wear and during washing. The aim of this study was to investigate the release to water of toxic chemicals from various textiles. Altogether 52 samples of textiles made from cotton (21), linen (4), cotton and linen (7), cellulose (3), synthetic fibres (7), cotton and synthetic fibres (8) and wool (2). Seven were eco-labelled. All textiles were cut into squares and placed into Petri dishes with 50 ml ISO test medium in a concentration series (4-256 cm(2)/50 ml) and tested for acute toxicity to Daphnia magna. Estimated EC50s were converted into weight/volume, and 48-h EC50s ranged between <1 and >182 g/L. It was not possible to detect any difference between fibre type and toxicity (ANOVA), but a significantly higher toxicity was found for printed versus unprinted cotton and cotton/linen textiles, while the opposite was found for synthetic textiles. Eco-labelled products were evenly distributed on a toxicity scale, which means that eco-labelling in its present form does not necessarily protect users or the environment from exposure to toxic chemicals. Therefore, the results from the present study suggest that bioassays and toxicity tests should become an integrated part of textile environmental quality control programs. Copyright © 2010 Elsevier Inc. All rights reserved.

Chronic toxicity of an environmentally relevant mixture of pharmaceuticals to three aquatic organisms (alga, daphnid, and fish).

PubMed

Watanabe, Haruna; Tamura, Ikumi; Abe, Ryoko; Takanobu, Hitomi; Nakamura, Ataru; Suzuki, Toshinari; Hirose, Akihiko; Nishimura, Tetsuji; Tatarazako, Norihisa

2016-04-01

Principles of concentration addition and independent action have been used as effective tools to predict mixture toxicity based on individual component toxicity. The authors investigated the toxicity of a pharmaceutical mixture composed of the top 10 detected active pharmaceutical ingredients (APIs) in the Tama River (Tokyo, Japan) in a relevant concentration ratio. Both individual and mixture toxicities of the 10 APIs were evaluated by 3 short-term chronic toxicity tests using the alga Pseudokirchneriella subcapitata, the daphnid Ceriodaphnia dubia, and the zebrafish Danio rerio. With the exception of clarithromycin toxicity to alga, the no-observed-effect concentration of individual APIs for each test species was dramatically higher than the highest concentration of APIs found in the environment. The mixture of 10 APIs resulted in toxicity to alga, daphnid, and fish at 6.25 times, 100 times, and 15,000 times higher concentrations, respectively, than the environmental concentrations of individual APIs. Predictions by concentration addition and independent action were nearly identical for alga, as clarithromycin was the predominant toxicant in the mixture. Both predictions described the observed mixture toxicity to alga fairly well, whereas they slightly underestimated the observed mixture toxicity in the daphnid test. In the fish embryo test, the observed toxicity fell between the predicted toxicity by concentration addition and independent action. These results suggested that the toxicity of environmentally relevant pharmaceutical mixtures could be predicted by individual toxicity using either concentration addition or independent action. © 2015 SETAC.

Environmental toxicants and autism spectrum disorders: a systematic review

PubMed Central

Rossignol, D A; Genuis, S J; Frye, R E

2014-01-01

Although the involvement of genetic abnormalities in autism spectrum disorders (ASD) is well-accepted, recent studies point to an equal contribution by environmental factors, particularly environmental toxicants. However, these toxicant-related studies in ASD have not been systematically reviewed to date. Therefore, we compiled publications investigating potential associations between environmental toxicants and ASD and arranged these publications into the following three categories: (a) studies examining estimated toxicant exposures in the environment during the preconceptional, gestational and early childhood periods; (b) studies investigating biomarkers of toxicants; and (c) studies examining potential genetic susceptibilities to toxicants. A literature search of nine electronic scientific databases through November 2013 was performed. In the first category examining ASD risk and estimated toxicant exposures in the environment, the majority of studies (34/37; 92%) reported an association. Most of these studies were retrospective case–control, ecological or prospective cohort studies, although a few had weaker study designs (for example, case reports or series). Toxicants implicated in ASD included pesticides, phthalates, polychlorinated biphenyls (PCBs), solvents, toxic waste sites, air pollutants and heavy metals, with the strongest evidence found for air pollutants and pesticides. Gestational exposure to methylmercury (through fish exposure, one study) and childhood exposure to pollutants in water supplies (two studies) were not found to be associated with ASD risk. In the second category of studies investigating biomarkers of toxicants and ASD, a large number was dedicated to examining heavy metals. Such studies demonstrated mixed findings, with only 19 of 40 (47%) case–control studies reporting higher concentrations of heavy metals in blood, urine, hair, brain or teeth of children with ASD compared with controls. Other biomarker studies reported that solvent, phthalate and pesticide levels were associated with ASD, whereas PCB studies were mixed. Seven studies reported a relationship between autism severity and heavy metal biomarkers, suggesting evidence of a dose–effect relationship. Overall, the evidence linking biomarkers of toxicants with ASD (the second category) was weaker compared with the evidence associating estimated exposures to toxicants in the environment and ASD risk (the first category) because many of the biomarker studies contained small sample sizes and the relationships between biomarkers and ASD were inconsistent across studies. Regarding the third category of studies investigating potential genetic susceptibilities to toxicants, 10 unique studies examined polymorphisms in genes associated with increased susceptibilities to toxicants, with 8 studies reporting that such polymorphisms were more common in ASD individuals (or their mothers, 1 study) compared with controls (one study examined multiple polymorphisms). Genes implicated in these studies included paraoxonase (PON1, three of five studies), glutathione S-transferase (GSTM1 and GSTP1, three of four studies), δ-aminolevulinic acid dehydratase (one study), SLC11A3 (one study) and the metal regulatory transcription factor 1 (one of two studies). Notably, many of the reviewed studies had significant limitations, including lack of replication, limited sample sizes, retrospective design, recall and publication biases, inadequate matching of cases and controls, and the use of nonstandard tools to diagnose ASD. The findings of this review suggest that the etiology of ASD may involve, at least in a subset of children, complex interactions between genetic factors and certain environmental toxicants that may act synergistically or in parallel during critical periods of neurodevelopment, in a manner that increases the likelihood of developing ASD. Because of the limitations of many of the reviewed studies, additional high-quality epidemiological studies concerning environmental toxicants and ASD are warranted to confirm and clarify many of these findings. PMID:24518398

Diamine Oxidase from White Pea (Lathyrus sativus) Combined with Catalase Protects the Human Intestinal Caco-2 Cell Line from Histamine Damage.

PubMed

Jumarie, Catherine; Séïde, Marilyne; Marcocci, Lucia; Pietrangeli, Paola; Mateescu, Mircea Alexandru

2017-07-01

Diamine oxidase (DAO) administration has been proposed to treat certain gastrointestinal dysfunctions induced by histamine, an immunomodulator, signaling, and pro-inflammatory factor. However, H 2 O 2 resulting from the oxidative deamination of histamine by DAO may be toxic. The purpose of this study was to investigate to which extent DAO from white pea (Lathyrus sativus), alone or in combination with catalase, may modulate histamine toxicity in the human intestinal Caco-2 cell line. The results show that histamine at concentrations higher than 1 mM is toxic to the Caco-2 cells, independently of the cell differentiation status, with a LC 50 of ≅ 10 mM following a 24-h exposure. Depending on its concentration, DAO increased histamine toxicity to a greater extent in differentiated cells compared to undifferentiated cultures. In the presence of catalase, the DAO-induced increase in histamine toxicity was completely abolished in the undifferentiated cells and only partially decreased in differentiated cells, showing differences in the sensitivity of Caco-2 cells to the products resulting from histamine degradation by DAO (H 2 O 2 , NH 3 , or imidazole aldehyde). It appears that treatment of food histaminosis using a combination of vegetal DAO and catalase would protect against histamine toxicity and prevent H 2 O 2 -induced damage that may occur during histamine oxidative deamination.

Safety Assessment of Commonly Used Nanoparticles in Biomedical Applications: Impact on Inflammatory Processes

NASA Astrophysics Data System (ADS)

Alnasser, Yossef

Nanotechnology offers great promise in the biomedical field. Current knowledge of nanoparticles' (NPs) safety and possible mechanisms of various particle types' toxicity is insufficient. The role of particle properties and the route of particles administration in toxic reactions remain unexplored. In this thesis, we aimed to inspect the interrelationship between particle size, chemical composition and toxicological effects of four candidate NPs for drug delivery systems: gold (Au), chitosan, silica, and poly (lactide-co-glycolide) (PLGA). Mice model was combined with in vitro study to explore NPs' safety. We investigated mice survival, weight, behavior, and pro-inflammatory changes. NF-kappaB induction was assessed in vitro using the Luciferase Assay System. As observed in mice, Au NPs had a higher toxicity profile at a shorter duration than the other NPs. This was significantly in concordance with pro-inflammatory changes which may be the key routes of Au NPs toxicity. Although silica NPs induced NF-kappaB, they were less toxic to the mice than Au NPs and did not lead to the pro-inflammatory changes. Chitosan NPs were toxic to the mice but failed to cause significant NF-kappaB induction and pro-inflammatory changes. These findings indicate that chitosan NPs might not have the same pathophysiologic mechanism as the Au NPs. Comparative analysis in this model demonstrated that PLGA NPs is the safest drug delivery candidate to be administered subcutaneously.

Comparison of pharmacokinetics and toxicity after high-dose methotrexate treatments in children with acute lymphoblastic leukemia.

PubMed

Csordas, Katalin; Hegyi, Marta; Eipel, Oliver T; Muller, Judit; Erdelyi, Daniel J; Kovacs, Gabor T

2013-02-01

We carried out a detailed comparative study of the pharmacokinetics and toxicity of methotrexate (MTX) and 7-hydroxy-methotrexate (7-OH-MTX) after high-dose intravenous methotrexate (HD-MTX) in children with acute lymphoblastic leukemia (ALL). Overall, 65 children were treated with 5 g/m2/24 h MTX and 88 children were treated with 2 g/m2/24 h MTX according to ALL-BFM 95 and ALL IC-BFM 2002 protocols (mean age: 6.4 years, range 1.0-17.9 years). A total of 583 HD-MTX courses were analyzed. Serum MTX and 7-OH-MTX levels were measured at 24, 36, and 48 h, and cerebrospinal fluid (CSF) MTX levels were determined 24 h after the initiation of the infusion. The area under the concentration-time curve was calculated. Hepatotoxicity, nephrotoxicity, and bone marrow toxicity were estimated by routine laboratory tests. We investigated pharmacokinetics and toxicity in distinct age groups (< 6 and > 14 years). 5 g/m2/24 h treatments resulted in higher serum and CSF MTX and 7-OH-MTX levels (P < 0.05). The CSF penetration rate of MTX was independent of the MTX dose [2.3% (95% confidence interval: 1.7-2.5%) vs. 2.8% (95% confidence interval: 2.4-3%)]. The CSF MTX concentration was correlated with the 24 h MTX serum level (r = 0.38, P < 0.0001). Repeated treatments did not alter MTX or 7-OH-MTX levels. 7-OH-MTX levels were correlated with nephrotoxicity (r = 0.36, P < 0.0001). Higher MTX levels and toxicity occurred more frequently in children aged older than 14 years (P < 0.05). Therapeutic serum and CSF MTX concentrations can be achieved more reliably with 5 g/m2/24 h treatments. To predict the development of toxicity, monitoring of the level of the 7-OH-MTX is useful. Monitoring of pharmacokinetics is essential to prevent the development of severe adverse events in adolescents.

Copper toxicity and organic matter: Resiliency of watersheds in the Duluth Complex, Minnesota, USA

USGS Publications Warehouse

Piatak, Nadine; Seal, Robert; Jones, Perry M.; Woodruff, Laurel G.

2015-01-01

We estimated copper (Cu) toxicity in surface water with high dissolved organic matter (DOM) for unmined mineralized watersheds of the Duluth Complex using the Biotic Ligand Model (BLM), which evaluates the effect of DOM, cation competition for biologic binding sites, and metal speciation. A sediment-based BLM was used to estimate stream-sediment toxicity; this approach factors in the cumulative effects of multiple metals, incorporation of metals into less bioavailable sulfides, and complexation of metals with organic carbon. For surface water, the formation of Cu-DOM complexes significantly reduces the amount of Cu available to aquatic organisms. The protective effects of cations, such as calcium (Ca) and magnesium (Mg), competing with Cu to complex with the biotic ligand is likely not as important as DOM in water with high DOM and low hardness. Standard hardness-based water quality criteria (WQC) are probably inadequate for describing Cu toxicity in such waters and a BLM approach may yield more accurate results. Nevertheless, assumptions about relative proportions of humic acid (HA) and fulvic acid (FA) in DOM significantly influence BLM results; the higher the HA fraction, the higher calculated resiliency of the water to Cu toxicity. Another important factor is seasonal variation in water chemistry, with greater resiliency to Cu toxicity during low flow compared to high flow.Based on generally low total organic carbon and sulfur content, and equivalent metal ratios from total and weak partial extractions, much of the total metal concentration in clastic streambedsediments may be in bioavailable forms, sorbed on clays or hydroxide phases. However, organicrich fine-grained sediment in the numerous wetlands may sequester significant amount of metals, limiting their bioavailability. A high proportion of organic matter in waters and some sediments will play a key role in the resiliency of these watersheds to potential additional metal loads associated with future mining operations.

Effect of heat treatment on the proximate composition, energy values, and levels of some toxicants in African yam bean (Sphenostylis stenocarpa) seed varieties.

PubMed

Onyeike, Eugene N; Omubo-Dede, Tina T

2002-01-01

The effects of heat treatments on the proximate composition, energy content, and levels of some antinutritional factors in brown and marble-colored African yam bean (AYB) seed flours were investigated. In raw brown and marble-colored AYB seed flours; moisture content, dry matter, crude protein, crude fat, ash, total carbohydrate and caloric value did not differ significantly at the 5% level. Autoclaving and cooking slightly increased the moisture level. Crude protein, crude fat, and ash contents were decreased by autoclaving and were further decreased by cooking. The decrease was not, however, considerable for the AYB that is not eaten raw and whose full nutritional potential as a legume can be derived only when heat treated, as previous reports have indicated for legume seeds. The levels of the toxicants were generally higher in the raw brown AYB compared to the marble-colored, and were generally reduced by both autoclaving and cooking. In the most commonly available and consumed marble-colored AYB, autoclaving at 121 degrees C, 15 psi for 20 min decreased cyanogenic glycosides by 46%, oxalate by 48.9%, tannin by 15.0%, saponin by 14.8% and trypsin inhibitors by 61.3% while cooking for 3.5 hours in tap water decreased these toxic factors by 66.5%, 70.3%, 72.2%, 48.7%, and 86.0%, respectively. The results indicate that for raw samples, varietal difference did not significantly affect nutrient composition though the toxicants were generally higher in the brown AYB than the marble-colored. Autoclaving decreased both nutrient value and the level of toxicants in the two seed types; values were further reduced by cooking. Of the toxicants, trypsin inhibitor was found to be the most heat-labile and of the heat treatment methods, cooking to tenderness is recommendable.

Prostate Cancer Patients With Unmanaged Diabetes or Receiving Insulin Experience Inferior Outcomes and Toxicities After Treatment With Radiation Therapy.

PubMed

Zaorsky, Nicholas G; Shaikh, Talha; Ruth, Karen; Sharda, Pankaj; Hayes, Shelly B; Sobczak, Mark L; Hallman, Mark A; Smaldone, Marc C; Chen, David Y T; Horwitz, Eric M

2017-04-01

The purpose of the study was to determine the effect of type 2 diabetes mellitus (T2DM) on outcomes and toxicities among men with localized prostate cancer receiving definitive radiation therapy. We performed a retrospective review of 3217 patients, from 1998 to 2013, subdivided into 5 subgroups: (I) no T2DM; (II) T2DM receiving oral antihyperglycemic agent that contains metformin, no insulin; (III) T2DM receiving nonmetformin oral agent alone, no insulin; (IV) T2DM receiving any insulin; and (V) T2DM not receiving medication. Outcome measures were overall survival, freedom from biochemical failure (BF), freedom from distant metastasis, cancer-specific survival, and toxicities. Kaplan-Meier analysis, log rank tests, Fine and Gray competing risk regression (to adjust for patient and lifestyle factors), Cox models, and subdistribution hazard ratios (sHRs) were used. Of the 3217 patients, 1295 (40%) were low-risk, 1192 (37%) were intermediate-risk, and 652 (20%) were high risk. The group I to V distribution was 81%, 8%, 5%, 3%, and 4%. The median dose was 78 Gy, and the median follow-up time was 50 (range, 1-190) months. Group V had increased mortality (sHR, 2.1; 95% confidence interval [CI], 0.66-1.54), BF (sHR, 2.14; 0.88-1.83), and cause-specific mortality (sHR, 3.87; 95% CI, 1.31-11). Acute toxicities were higher in group IV versus group I (genitourinary: 38% vs. 26%; P = .01; gastrointestinal: 21% vs. 5%; P = 001). Late toxicities were higher in groups IV and V versus group I (12%-14% vs. 2%-6%; P < .01). Men with T2DM not receiving medication and men with T2DM receiving insulin had worse outcomes and toxicities compared to other patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Extension of a PBPK model for ethylene glycol and glycolic acid to include the competitive formation and clearance of metabolites associated with kidney toxicity in rats and humans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Corley, R.A., E-mail: rick.corley@pnl.gov; Saghir, S.A.; Bartels, M.J.

2011-02-01

A previously developed PBPK model for ethylene glycol and glycolic acid was extended to include glyoxylic acid, oxalic acid, and the precipitation of calcium oxalate that is associated with kidney toxicity in rats and humans. The development and evaluation of the PBPK model was based upon previously published pharmacokinetic studies coupled with measured blood and tissue partition coefficients and rates of in vitro metabolism of glyoxylic acid to oxalic acid, glycine and other metabolites using primary hepatocytes isolated from male Wistar rats and humans. Precipitation of oxalic acid with calcium in the kidneys was assumed to occur only at concentrationsmore » exceeding the thermodynamic solubility product for calcium oxalate. This solubility product can be affected by local concentrations of calcium and other ions that are expressed in the model using an ion activity product estimated from toxicity studies such that calcium oxalate precipitation would be minimal at dietary exposures below the NOAEL for kidney toxicity in the sensitive male Wistar rat. The resulting integrated PBPK predicts that bolus oral or dietary exposures to ethylene glycol would result in typically 1.4-1.6-fold higher peak oxalate levels and 1.6-2-fold higher AUC's for calcium oxalate in kidneys of humans as compared with comparably exposed male Wistar rats over a dose range of 1-1000 mg/kg. The converse (male Wistar rats predicted to have greater oxalate levels in the kidneys than humans) was found for inhalation exposures although no accumulation of calcium oxalate is predicted to occur until exposures are well in excess of the theoretical saturated vapor concentration of 200 mg/m{sup 3}. While the current model is capable of such cross-species, dose, and route-of-exposure comparisons, it also highlights several areas of potential research that will improve confidence in such predictions, especially at low doses relevant for most human exposures.« less

Green synthesis of fluorescent carbon dots from spices for in vitro imaging and tumour cell growth inhibition

PubMed Central

Gallo, Juan; Cerqueira, María de Fátima; Menéndez-Miranda, Mario; Costa-Fernández, José Manuel; Diéguez, Lorena; Espiña, Begoña

2018-01-01

Carbon dots have demonstrated great potential as luminescent nanoparticles in bioapplications. Although such nanoparticles appear to exhibit low toxicity compared to other metal luminescent nanomaterials, today we know that the toxicity of carbon dots (C-dots) strongly depends on the protocol of fabrication. In this work, aqueous fluorescent C-dots have been synthesized from cinnamon, red chilli, turmeric and black pepper, by a one-pot green hydrothermal method. The synthesized C-dots were firstly characterized by means of UV–vis, fluorescence, Fourier transform infrared and Raman spectroscopy, dynamic light scattering and transmission electron microscopy. The optical performance showed an outstanding ability for imaging purposes, with quantum yields up to 43.6%. Thus, the cytotoxicity of the above mentioned spice-derived C-dots was evaluated in vitro in human glioblastoma cells (LN-229 cancer cell line) and in human kidney cells (HK-2 non-cancerous cell line). Bioimaging and viability studies were performed with different C-dot concentrations from 0.1 to 2 mg·mL−1, exhibiting a higher uptake of C-dots in the cancer cultures compared to the non-cancerous cells. Results showed that the spice-derived C-dots inhibited cell viability dose-dependently after a 24 h incubation period, displaying a higher toxicity in LN-229, than in HK-2 cells. As a control, C-dots synthesized from citric acid did not show any significant toxicity in either cancerous or non-cancerous cells, implying that the tumour cell growth inhibition properties observed in the spice-derived C-dots can be attributed to the starting material employed for their fabrication. These results evidence that functional groups in the surface of the C-dots might be responsible for the selective cytotoxicity, as suggested by the presence of piperine in the surface of black pepper C-dots analysed by ESI-QTOF-MS. PMID:29527430

Evaluation of the phytotoxicity of polycontaminated industrial effluents using the lettuce plant (Lactuca sativa) as a bioindicator.

PubMed

Charles, Jérémie; Sancey, Bertrand; Morin-Crini, Nadia; Badot, Pierre-Marie; Degiorgi, François; Trunfio, Giuseppe; Crini, Grégorio

2011-10-01

Industrial wastewater containing heavy metals is generally decontaminated by physicochemical treatment consisting in insolublizing the contaminants and separating the two phases, water and sludge, by a physical process (filtration, settling or flotation). However, chemical precipitation does not usually remove the whole pollution load and the effluent discharged into the environment can be toxic even if it comes up to regulatory standards. To assess the impact of industrial effluent from 4 different surface treatment companies, we performed standardized bioassays using seeds of the lettuce Lactuca sativa. We measured the rate of germination, and the length and mass of the lettuce plantlet. The results were used to compare the overall toxicity of the different effluents: effluents containing copper and nickel had a much higher impact than those containing zinc or aluminum. In addition, germination tests conducted using synthetic solutions confirmed that mixtures of metals have higher toxicity than the sum of their separate constituents. These biological tests are cheap, easy to implement, reproducible and highlight the effects caused by effluent treated with the methods commonly applied in industry today. They could be routinely used to check the impact of industrial discharges, even when they meet regulatory requirements for the individual metals. Copyright © 2011 Elsevier Inc. All rights reserved.

Investigating the chemical profile of regenerated scorpion (Parabuthus transvaalicus) venom in relation to metabolic cost and toxicity.

PubMed

Nisani, Zia; Boskovic, Danilo S; Dunbar, Stephen G; Kelln, Wayne; Hayes, William K

2012-09-01

We investigated the biochemical profile of regenerated venom of the scorpion Parabuthus transvaalicus in relation to its metabolic cost and toxicity. Using a closed-system respirometer, we compared oxygen consumption between milked and unmilked scorpions to determine the metabolic costs associated with the first 192 h of subsequent venom synthesis. Milked scorpions had a substantially (21%) higher mean metabolic rate than unmilked scorpions, with the largest increases in oxygen consumption occurring at approximately 120 h, 162 h, and 186 h post-milking. Lethality tests in crickets indicated that toxicity of the regenerated venom returned to normal levels within 4 d after milking. However, the chemical profile of the regenerated venom, as evaluated by FPLC and MALDI-TOF mass spectrometry, suggested that regeneration of different venom components was asynchronous. Some peptides regenerated quickly, particularly those associated with the scorpion's "prevenom," whereas others required much or all of this time period for regeneration. This asynchrony could explain the different spikes detected in oxygen consumption of milked scorpions as various peptides and other venom components were resynthesized. These observations confirm the relatively high metabolic cost of venom regeneration and suggest that greater venom complexity can be associated with higher costs of venom production. Copyright © 2012 Elsevier Ltd. All rights reserved.

Montmorillonite clay alters toxicity of silver nanoparticles in zebrafish (Danio rerio) eleutheroembryo.

PubMed

Gupta, Govind Sharan; Dhawan, Alok; Shanker, Rishi

2016-11-01

An exponential development in the use of silver nanoparticles (AgNPs) in consumer products has accelerated their release in aquatic environment. As the AgNPs enters into the aquatic systems, their fate may change due to interactions with abiotic (e.g. clay particles) or biotic factors. The abundantly present clay particles are expected to more prone for interaction with nanoparticles in aquatic systems. In the present study, it is demonstrated that AgNPs interacts with clay particles and forms heteroagglomerates. Furthermore, an impact on toxicity potential of AgNPs after interactions with clay particles was assessed by using zebrafish eleutheroembryos (72 h post hatching) as an in vivo model. The mortality rate of zebrafish eleutheroembryos was higher in case of exposure to AgNPs-clay complexes (pH 4.0 and 7.0) as compared to bare AgNPs. In addition, at earlier time points, the eleutheroembryos expressed higher levels of morphological changes in tail, yolk and pericardia, but the edema in yolk sac was followed by cell death. It can be concluded from the observations made in the present study that the inorganic colloids in the aquatic matrices can alter the fate and toxicity potential of nanoparticles. Copyright © 2016 Elsevier Ltd. All rights reserved.

Interaction and cellular uptake of surface-modified carbon dot nanoparticles by J774.1 macrophages

PubMed Central

Thoo, Lester; Fahmi, Mochamad Z; Zulkipli, Ihsan N; Keasberry, Natasha

2017-01-01

Carbon dot (Cdot) nanoparticles are an emerging class of carbon nanomaterials with a promising potential for drug delivery and bio imaging applications. Although the interaction between Cdots and non-immune cell types has been well studied, Cdot interactions with macrophages have not been investigated. Exposure of Cdot nanoparticles to J774.1 cells, a murine macrophage cell line, resulted in minimal toxicity, where notable toxicity was only seen with Cdot concentrations higher than 0.5 mg/ml. Flow cytometric analysis revealed that Cdots prepared from citric acid were internalized at significantly higher levels by macrophages compared with those prepared from bamboo leaves. Interestingly, macrophages preferentially took up phenylboronic acid (PB)-modified nanoparticles. By fluorescence microscopy, strong blue light-specific punctate Cdot fluorescence resembling Cdot structures in the cytosolic space was mostly observed in J774.1 macrophages exposed to PB-modified nanoparticles and not unmodified Cdot nanoparticles. PB binds to sialic acid residues that are overexpressed on diseased cell surfaces. Our findings demonstrate that PB-conjugated Cdots can be taken up by macrophages with low toxicity and high efficiency. These modified Cdots can be used to deliver drugs to suppress or eliminate aberrant immune cells such as macrophages associated with tumors such as tumor-associated macrophages. PMID:29204100

Arbuscular Mycorrhiza Augments Arsenic Tolerance in Wheat (Triticum aestivum L.) by Strengthening Antioxidant Defense System and Thiol Metabolism

PubMed Central

Sharma, Surbhi; Anand, Garima; Singh, Neeraja; Kapoor, Rupam

2017-01-01

Arbuscular mycorrhiza (AM) can help plants to tolerate arsenic (As) toxicity. However, plant responses are found to vary with the host plant and the AM fungal species. The present study compares the efficacy of two AM fungi Rhizoglomus intraradices (M1) and Glomus etunicatum (M2) in amelioration of As stress in wheat (Triticum aestivum L. var. HD-2967). Mycorrhizal (M) and non-mycorrhizal (NM) wheat plants were subjected to four levels of As (0, 25, 50, and 100 mg As kg-1 soil). Although As additions had variable effects on the percentage of root colonized by the two fungal inoculants, each mycobiont conferred benefits to the host plant. Mycorrhizal plants continued to display better growth than NM plants. Formation of AM helped the host plant to overcome As-induced P deficiency and maintained favorable P:As ratio. Inoculation of AMF had variable effects on the distribution of As in plant tissues. While As translocation factor decreased in low As (25 mg kg-1 soil), it increased under high As (50 and 100 mg As kg-1 soil). Further As translocation to grain was reduced (As grain:shoot ratio) in M plants compared with NM plants. Arsenic-induced oxidative stress (generation of H2O2 and lipid peroxidation) in plants reduced significantly by AMF inoculation. The alleviation potential of AM was more evident with increase in severity of As stress. Colonization of AMF resulted in higher activities of the antioxidant enzymes (superoxide dismutase, catalase, and guaiacol peroxidase). It increased the concentrations of the antioxidant molecules (carotenoids, proline, and α-tocopherol) than their NM counterparts at high As addition level. Comparatively higher activities of enzymes of glutathione-ascorbate cycle in M plants led to higher ascorbate:dehydroascorbate (AsA:DHA) and glutathione:glutathione disulphide (GSH:GSSG) ratios. Inoculation by AMF also augmented the glyoxalase system by increasing the activities of both glyoxalase I and glyoxalase II enzymes. Mycorrhizal colonization increased concentrations of cysteine, glutathione, non-protein thiols, and activity of glutathione-S-transferase that facilitated sequestration of As into non-toxic complexes. The study reveals multifarious role of AMF in alleviation of As toxicity. PMID:28642762

Cetuximab Plus Various Chemotherapy Regimens for Patients with KRAS Wild-Type Metastatic Colorectal Cancer.

PubMed

Azadeh, Payam; Mortazavi, Nafiseh; Tahmasebi, Arezoo; Hosseini Kamal, Farnaz; Novin, Kambiz

2016-01-01

The aim of this study was to compare the efficacy and hematologic toxicity of cetuximab combined with various types of chemotherapy regimens in patients with KRAS wild-type metastatic colorectal cancer (mCRC). The response rate, progression-free survival (PFS) and overall survival of the patients were analyzed. In total, 45 patients were included in the study. The overall response rate for the combination of cetuximab and FOLFOX, FOLFIRI and CAPOX was 20, 46 and 30%, respectively, but the differences were not statistically significant. The median PFS for the three groups were 8, 6 and 3.5 months, respectively, but again these differences were not significant. All-grade leukopenia and anemia for the cetuximab plus FOLFOX group were significantly higher than for the other chemotherapy regimens. Our findings suggest that the combination of cetuximab and the three standard chemotherapy regimens resulted in the same outcomes in our patient population of mCRC, with higher hematologic toxicities among the FOLFOX subgroup. © 2015 S. Karger AG, Basel.

Comparison of solid-phase bioassays and ecoscores to evaluate the toxicity of contaminated soils.

PubMed

Lors, Christine; Ponge, Jean-François; Martínez Aldaya, Maite; Damidot, Denis

2010-08-01

Five bioassays (inhibition of lettuce germination and growth, earthworm mortality, inhibition of springtail population growth, avoidance by springtails) were compared, using four coke factory soils contaminated by PAHs and trace elements, before and after biotreatment. For each bioassay, several endpoints were combined in an 'ecoscore', a measure of test sensitivity. Ecoscores pooled over all tested bioassays revealed that most organisms were highly sensitive to the concentration of 3-ring PAHs. When four soils were combined, behavioural tests using the springtail Folsomia candida showed higher ecoscores, i.e. they were most sensitive to soil contamination. However, despite overall higher sensitivity of behavioural tests, which could be used for cheap and rapid assessment of soil toxicity, especially at low levels of contamination, some test endpoints were more sensitive than others, and this may differ from a soil to another, pointing to the need for a battery of bioassays when more itemized results are expected. Copyright 2010 Elsevier Ltd. All rights reserved.

Identification of Metabolism and Excretion Differences of Procymidone between Rats and Humans Using Chimeric Mice: Implications for Differential Developmental Toxicity.

PubMed

Abe, Jun; Tomigahara, Yoshitaka; Tarui, Hirokazu; Omori, Rie; Kawamura, Satoshi

2018-02-28

A metabolite of procymidone, hydroxylated-PCM, causes rat-specific developmental toxicity due to higher exposure to it in rats than in rabbits or monkeys. When procymidone was administered to chimeric mice with rat or human hepatocytes, the plasma level of hydroxylated-PCM was higher than that of procymidone in rat chimeric mice, and the metabolic profile of procymidone in intact rats was well reproduced in rat chimeric mice. In human chimeric mice, the plasma level of hydroxylated-PCM was less, resulting in a much lower exposure. The main excretion route of hydroxylated-PCM-glucuronide was bile (the point that hydroxylated-PCM enters the enterohepatic circulation) in rat chimeric mice, and urine in human chimeric mice. These data suggest that humans, in contrast to rats, extensively form the glucuronide and excrete it in urine, as do rabbits and monkeys. Overall, procymidone's potential for causing teratogenicity in humans must be low compared to that in rats.

LC-MS based metabolomics and chemometrics study of the toxic effects of copper on Saccharomyces cerevisiae.

PubMed

Farrés, Mireia; Piña, Benjamí; Tauler, Romà

2016-08-01

Copper containing fungicides are used to protect vineyards from fungal infections. Higher residues of copper in grapes at toxic concentrations are potentially toxic and affect the microorganisms living in vineyards, such as Saccharomyces cerevisiae. In this study, the response of the metabolic profiles of S. cerevisiae at different concentrations of copper sulphate (control, 1 mM, 3 mM and 6 mM) was analysed by liquid chromatography coupled to mass spectrometry (LC-MS) and multivariate curve resolution-alternating least squares (MCR-ALS) using an untargeted metabolomics approach. Peak areas of the MCR-ALS resolved elution profiles in control and in Cu(ii)-treated samples were compared using partial least squares regression (PLSR) and PLS-discriminant analysis (PLS-DA), and the intracellular metabolites best contributing to sample discrimination were selected and identified. Fourteen metabolites showed significant concentration changes upon Cu(ii) exposure, following a dose-response effect. The observed changes were consistent with the expected effects of Cu(ii) toxicity, including oxidative stress and DNA damage. This research confirmed that LC-MS based metabolomics coupled to chemometric methods are a powerful approach for discerning metabolomics changes in S. cerevisiae and for elucidating modes of toxicity of environmental stressors, including heavy metals like Cu(ii).

Differential toxicity of arsenic on renal oxidative damage and urinary metabolic profiles in normal and diabetic mice.

PubMed

Yin, Jinbao; Liu, Su; Yu, Jing; Wu, Bing

2017-07-01

Diabetes is a common metabolic disease, which might influence susceptibility of the kidney to arsenic toxicity. However, relative report is limited. In this study, we compared the influence of inorganic arsenic (iAs) on renal oxidative damage and urinary metabolic profiles of normal and diabetic mice. Results showed that iAs exposure increased renal lipid peroxidation in diabetic mice and oxidative DNA damage in normal mice, meaning different effects of iAs exposure on normal and diabetic individuals. Nuclear magnetic resonance (NMR)-based metabolome analyses found that diabetes significantly changed urinary metabolic profiles of mice. Oxidative stress-related metabolites, such as arginine, glutamine, methionine, and β-hydroxybutyrate, were found to be changed in diabetic mice. The iAs exposure altered amino acid metabolism, lipid metabolism, carbohydrate metabolism, and energy metabolism in normal and diabetic mice, but had higher influence on metabolic profiles of diabetic mice than normal mice, especially for oxidative stress-related metabolites and metabolisms. Above results indicate that diabetes increased susceptibility to iAs exposure. This study provides basic information on differential toxicity of iAs on renal toxicity and urinary metabolic profiles in normal and diabetic mice and suggests that diabetic individuals should be considered as susceptible population in toxicity assessment of arsenic.

Selective toxicity of the mesoionic insecticide, triflumezopyrim, to rice planthoppers and beneficial arthropods.

PubMed

Zhu, Jun; Li, Yao; Jiang, Hua; Liu, Chen; Lu, Weiwei; Dai, Wei; Xu, Jianxiang; Liu, Fang

2018-05-01

The novel mesoionic insecticide triflumezopyrim was highly effective in controlling both imidacloprid-susceptible and resistant planthopper populations in Malaysia. However, the toxicity of triflumezopyrim to planthopper populations and their natural enemies has been under-investigated in China. In this study, the median lethal concentrations (LC 50 ) of triflumezopyrim were determined in eight field populations of Nilaparvata lugens and one population of Sogatella furcifera from China under laboratory conditions. Triflumezopyrim showed higher toxicity to planthopper populations than the commonly-used insecticide, imidacloprid. Furthermore, the lethal effect of triflumezopyrim on eight beneficial arthropods of planthoppers was investigated in the laboratory and compared with three commonly-used insecticides, thiamethoxam, chlorpyrifos and abamectin. Triflumezopyrim was harmless to Anagrus nilaparvatae, Cyrtorhinus lividipennis and Paederus fuscipes, while thiamethoxam, chlorpyrifos and abamectin were moderately harmful or harmful to the insect parasitoid and predators. Triflumezopyrim and thiamethoxam were harmless to the predatory spiders Pirata subpiraticus, Ummeliata insecticeps, Hylyphantes graminicola and Pardosa pseudoannulata, and slightly harmful to Theridion octomaculatum. Chlorpyrifos caused slight to high toxicity to four spider species except U. insecticeps. Abamectin was moderately to highly toxic to all five spider species. Our results indicate that triflumezopyrim has high efficacy for rice planthoppers populations and is compatibile with their natural enemies in China.

Spatial variability of intake fractions for Canadian emission scenarios: a comparison between three resolution scales.

PubMed

Manneh, Rima; Margni, Manuele; Deschênes, Louise

2010-06-01

Spatially differentiated intake fractions (iFs) linked to Canadian emissions of toxic organic chemicals were developed using the multimedia and multipathways fate and exposure model IMPACT 2002. The fate and exposure of chemicals released to the Canadian environment were modeled with a single regional mass-balance model and three models that provided multiple mass-balance regions within Canada. These three models were based on the Canadian subwatersheds (172 zones), ecozones (15 zones), and provinces (13 zones). Releases of 32 organic chemicals into water and air were considered. This was done in order to (i) assess and compare the spatial variability of iFs within and across the three levels of regionalization and (ii) compare the spatial iFs to nonspatial ones. Results showed that iFs calculated using the subwatershed resolution presented a higher spatial variability (up to 10 orders of magnitude for emissions into water) than the ones based on the ecozones and provinces, implying that higher spatial resolution could potentially reduce uncertainty in iFs and, therefore, increase the discriminating power when assessing and comparing toxic releases for known emission locations. Results also indicated that, for an unknown emission location, a model with high spatial resolution such as the subwatershed model could significantly improve the accuracy of a generic iF. Population weighted iFs span up to 3 orders of magnitude compared to nonspatial iFs calculated by the one-box model. Less significant differences were observed when comparing spatial versus nonspatial iFs from the ecozones and provinces, respectively.

Associations of arsenic metabolites, methylation capacity, and skin lesions caused by chronic exposure to high arsenic in tube well water.

PubMed

Yang, Linsheng; Chai, Yuanqing; Yu, Jiangping; Wei, Binggan; Xia, Yajuan; Wu, Kegong; Gao, Jianwei; Guo, Zhiwei; Cui, Na

2017-01-01

To investigate the interaction between skin lesion status and arsenic methylation profiles, the concentrations and proportions of arsenic metabolites in urine and arsenic methylation capacities of study subjects were determined. The results showed that the mean urinary concentrations of iAs (inorganic arsenic), MMA (monomethylarsonic acid), DMA (dimethylarsinic acid), and TAs (total arsenic) were 75.65, 68.78, 265.81, and 410.24 μg/L, respectively, in the skin lesions subjects. The highest values were observed in the multiple skin lesions subjects. Higher %iAs and %MMA, and lower %DMA, PMI (primary methylation index), and SMI (secondary methylation index) were found in skin lesions subjects. The multiple skin lesions subjects had highest %iAs and %MMA, and lowest %DMA, PMI, and SMI. The prevalence of skin lesions strongly, positively correlated with arsenic levels in drinking water. The elder persons also had higher frequency of skin lesions compared with younger persons. It can be concluded that arsenic levels in drinking water significantly affected the prevalence of skin lesions. Male subjects usually had higher proportions of skin lesions when compared with female subjects. Moreover, it may be concluded that MMA was significantly related to single skin lesion, whereas DMA and iAs were associated with multiple skin lesions. It seemed that MMA had greater toxicity to hyperkeratosis, whereas DMA and iAs had higher toxicity to depigmentation or pigmentation. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 28-36, 2017. © 2015 Wiley Periodicals, Inc.

Acute and sub-acute oral toxicity of Dracaena cinnabari resin methanol extract in rats.

PubMed

Al-Afifi, Nashwan Abdullah; Alabsi, Aied Mohammed; Bakri, Marina Mohd; Ramanathan, Anand

2018-02-05

Dracaena cinnabari (DC) is a perennial tree that located on the Southern coast of Yemen native to the Socotra Island. This tree produces a deep red resin known as the Dragon's blood, the Twobrother's Blood or Damm Alakhwain. The current study performed to evaluate the safety of the DC resin methanol extract after a single or 28 consecutive daily oral administrations. In assessing the safety of DC resin methanol extract, acute and sub-acute oral toxicity tests performed following OECD guidelines 423 and 407, respectively, with slight modifications. In acute oral toxicity test, DC resin methanol extract administered to female Sprague Dawley rats by oral gavage at a single dose of 300 and 2000 mg/kg body weight. Rats observed for toxic signs for 14 days. In sub-acute oral toxicity test, DC resin methanol extract administered to the rats by oral gavage at 500, 1000, and 1500 mg/kg body weight daily up to 28 days to male and female Spradgue Dawley rats. The control and high dose in satellite groups were also maintained and handled as the previous groups to determine the late onset toxicity of DC resin methanol extract. At the end of each test, hematological and biochemical analysis of the collected blood were performed as well as gross and microscopic pathology. In acute oral toxicity, no treatment-related death or toxic signs were observed. It revealed that the DC resin methanol extract could be well tolerated up to the dose 2000 mg/kg body weight and could be classified as Category 5. The sub-acute test observations indicated that there are no treatment-related changes up to the high dose level compared to the control. Food consumption, body weight, organ weight, hematological parameters, biochemical parameters and histopathological examination (liver, kidney, heart, spleen and lung) revealed no abnormalities. Water intake was significantly higher in the DC resin methanol extract treated groups compared to the control. This study demonstrates tolerability of DC resin methanol extract administered daily for 28 days up to 1500 mg/kg dose.

In vivo exposure of Dreissena polymorpha mussels to the quinones menadione and lawsone: menadione is more toxic to mussels than lawsone.

PubMed

Osman, A M; Rotteveel, S; den Besten, P J; van Noort, P C M

2004-01-01

The principal aim of this study was to assess whether the two quinones, menadione (2-methyl-1,4-naphthoquinone) and lawsone (2-hydroxy-1,4-naphthoquinone), elicit differential toxicity in mussels as has been reported for higher organisms. Therefore, the effects of short-term (48 h) and long-term (20 days) exposure of the two quinones at concentrations of 0.56 and 1 mg l(-1) to zebra mussels, Dreissena polymorpha, under laboratory conditions were studied. After the short-term exposure, the specific activities of the two-electron quinone oxidoreductase (DT-diaphorase) and the one-electron catalysing quinone reductases NADPH-cytochrome c reductase and NADH-cytochrome c reductase were determined in the gills and the rest of the soft tissues (soft mussel tissues minus the gills) of both treated and control mussels. At the higher concentrations of menadione and lawsone used, a significant reduction of the activity of NADPH-cytochrome c reductase in the gills and in the rest of the soft mussel tissues (by 33-34% and 31-43%, respectively) was observed. The activities of DT-diaphorase and NADH-cytochrome c reductase were not significantly affected. Interestingly, DT-diaphorase was observed in the gills, an organ requiring protection against antioxidants. Furthermore, a single-cell electrophoretic assay (comet assay) performed with gill cells to assess DNA damage by the quinones did not show any significant difference between the treated and the control organisms. This indicates that the formation of reactive species by the quinone metabolism in vivo in the mussels was possibly suppressed through the concerted action of DT-diaphorase and antioxidant enzymes. The results of in vitro experiments with gill extracts confirmed the protective role of DT-diaphorase. The rate of the two-electron quinone reduction was found to be five times that of the one-electron quinone reduction. The results of the long-term exposure unambiguously demonstrated that in mussels menadione, unlike in higher organisms, is more toxic than lawsone. The lack of detectability of xanthine oxidase in the mussel tissues could explain the comparatively lower toxicity of lawsone in the invertebtrate, lending support to a previous suggestion that xanthine oxidase might be responsible for the mechanism of toxicity of lawsone in higher organisms in vivo. Copyright 2004 John Wiley & Sons, Ltd.

Body burdens, sources and interrelations of selected toxic and essential elements among the nine Cree First Nations of Eeyou Istchee, James Bay region of northern Quebec, Canada.

PubMed

Nieboer, Evert; Martin, Ian D; Liberda, Eric N; Dewailly, Eric; Robinson, Elizabeth; Tsuji, Leonard J S

2017-05-24

this article constitutes a report on the comprehensive Nituuchischaayihtitaau Aschii multi-community environment-and-health study conducted among the Cree peoples (Eeyouch) of northern Quebec, Canada. to interpret observed concentrations of a suite of chemical elements in a multi-media biological monitoring study in terms of sources and predictors. the concentrations of 5 essential and 6 toxic chemical elements were measured in whole blood, and/or in urine or hair by ICP-MS. Concentrations of essential elements are compared to those considered normal (i.e., required for good health) and, when toxic, deemed acceptable at specified concentrations in public health guidelines. Their dependence on age, sex, the specific community lived-in and diet were explored employing multivariate analysis of variance (MANOVA) involving new variables generated by principle component analysis (PCA) and correspondence analysis (CA). the 5 most prominent PCA axes explained 67.7% of the variation, compared to 93.0% by 6 main CA factors. Concentrations of the essential elements in whole blood (WB) and iodine(i) and arsenic (As) in urine were comparable to those reported in the recent Canadian Health Measures survey and are assigned to dietary sources. By contrast, WB cadmium (Cd) was elevated even when smoking was considered. Mercury (Hg) concentrations in WB and hair were also higher in adults, although comparable to those observed for other indigenous populations living at northern latitudes. Fish consumption was identified as the prominent source. Of the 5 coastal communities, all but one had lower Hg exposures than the four inland communities, presumably reflecting the type of fish consumed. Use of firearms and smoking were correlated with WB-lead (Pb). The concentrations of both Hg and Pb increased with age and were higher in men, while WB-Cd and smoking prevalence were higher in women when considering all communities. Hg and Pb were low in children and women of reproductive age, with few exceedances of health guidelines. Although individuals with T2D had somewhat lower WB-Cd, there is some indication that Cd may potentiate renal dysfunction in this subgroup. Plots of selected CA axes grouped those elements expected to be in a normal diet and distinguished them from those with well-known unique sources (especially Hg and As in hair; and Hg, Pb and Cd in WB). the use of multiple biological media in conjunction with the complementary PCA and CA approaches for constructing composite variables allowed a more detailed understanding of both the sources of the essential and toxic elements in body fluids and the dependencies of their observed concentrations on age, sex, community and diet.

Uptake and partitioning of zinc in Lemnaceae.

PubMed

Lahive, Elma; O'Callaghan, Michael J A; Jansen, Marcel A K; O'Halloran, John

2011-11-01

Macrophytes provide food and shelter for aquatic invertebrates and fish, while also acting as reservoirs for nutrients and trace elements. Zinc accumulation has been reported for various Lemnaceae species. However, comparative accumulation across species and the link between zinc accumulation and toxicity are poorly understood. Morphological distribution and cellular storage, in either bound or soluble form, are important for zinc tolerance. This study shows differences in the uptake and accumulation of zinc by three duckweed species. Landoltia punctata and Lemna minor generally accumulated more zinc than Lemna gibba. L. minor, but not L. gibba or L. punctata, accumulated greater concentrations of zinc in roots compared to fronds when exposed to high levels of zinc. The proportion of zinc stored in the bound form relative to the soluble-form was higher in L. minor. L. punctata accumulated greater concentrations of zinc in fronds compared to roots and increased the proportion of zinc it stored in the soluble form, when exposed to high zinc levels. L. gibba is the only species that significantly accumulated zinc at low concentrations, and was zinc-sensitive. Overall, internal zinc concentrations showed no consistent correlation with toxic effect. We conclude that relationships between zinc toxicity and uptake and accumulation are species specific reflecting, among others, zinc distribution and storage. Differences in zinc distribution and storage are also likely to have implications for zinc bioavailability and trophic mobility.

The effect of methylmercury exposure on behavior and cerebellar granule cell physiology in aged mice.

PubMed

Bellum, Sairam; Thuett, Kerry A; Bawa, Bhupinder; Abbott, Louise C

2013-09-01

Epidemiology studies have clearly documented that the central nervous system is highly susceptible to methylmercury toxicity, and exposure to this neurotoxicant in humans primarily results from consumption of contaminated fish. While the effects of methylmercury exposure have been studied in great detail, comparatively little is known about the effects of moderate to low dose methylmercury toxicity in the aging central nervous system. We examined the toxic effects of a moderate dose of methylmercury on the aging mouse cerebellum. Male and female C57BL/6 mice at 16-20 months of age were exposed to methylmercury by feeding a total dose of 5.0 mg kg(-1) body weight and assessed using four behavioral tests. Methylmercury-treated aged mice performed significantly worse in open field, footprint analysis and the vertical pole test compared with age-matched control mice. Isolated cerebellar granule cells from methylmercury-treated aged mice exhibited higher levels of reactive oxygen species and reduced mitochondrial membrane potentials, but no differences in basal intracellular calcium ion levels compared with age-matched control mice. When aged mice were exposed to a moderate dose of methylmercury, they exhibited a similar degree of impairment when compared with young adult mice exposed to the same moderate dose of methylmercury, as reported in earlier studies from this laboratory. Thus, at least in mice, exposure of the aged brain to moderate concentrations methylmercury does not pose greater risk compared with the young adult brain exposed to similar concentrations of methylmercury. Copyright © 2012 John Wiley & Sons, Ltd.

Using Spider-Web Patterns To Determine Toxicity

NASA Technical Reports Server (NTRS)

Noever, David A.; Cronise, Raymond J.; Relwani, Rachna A.

1995-01-01

Method of determining toxicities of chemicals involves recording and analysis of spider-web patterns. Based on observation spiders exposed to various chemicals spin webs that differ, in various ways, from normal webs. Potential alternative to toxicity testing on higher animals.

Renal cysteine conjugate C-S lyase mediated toxicity of halogenated alkenes in primary cultures of human and rat proximal tubular cells.

PubMed

McGoldrick, Trevor A; Lock, Edward A; Rodilla, Vicente; Hawksworth, Gabrielle M

2003-07-01

Proximal tubular cells from human (HPT) and rat (RPT) kidneys were isolated, grown to confluence and incubated with S-(1,2-dichlorovinyl)- l-cysteine (DCVC), S-(1,2,2-trichlorovinyl)- l-cysteine (TCVC), S-(1,1,2,2-tetrafluoroethyl)- l-cysteine (TFEC) and S-(2-chloro-1,1-difluorethyl)- l-cysteine (CDFEC), the cysteine conjugates of nephrotoxicants. The cultures were exposed to the conjugates for 12, 24 and 48 h and the toxicity determined using the MTT assay. All four conjugates caused dose-dependent toxicity to RPT cells over the range 50-1,000 microM, the order of toxicity being DCVC>TCVC>TFEC=CDFEC. The inclusion of aminooxyacetic acid (AOAA; 250 microM), an inhibitor of pyridoxal phosphate-dependent enzymes such as C-S lyase, afforded protection, indicating that C-S lyase has a role in the bioactivation of these conjugates. In HPT cultures only DCVC caused significant time- and dose-dependent toxicity. Exposure to DCVC (500 microM) for 48 h decreased cell viability to 7% of control cell values, whereas co-incubation of DCVC (500 microM) with AOAA (250 microM) resulted in cell viability of 71%. Human cultures were also exposed to S-(1,2-dichlorovinyl)-glutathione (DCVG). DCVG was toxic to HPT cells, but the onset of toxicity was delayed compared with the corresponding cysteine conjugate. AOAA afforded almost complete protection from DCVG toxicity. Acivicin (250 microM), an inhibitor of gamma-glutamyl transferase (gamma-GT), partially protected against DCVG (500 microM)-induced toxicity at 48 h (5% viability and 53% viability in the absence and presence of acivicin, respectively). These results suggest that DCVG requires processing by gamma-GT prior to bioactivation by C-S lyase in HPT cells. The activity of C-S lyase, using TFEC as a substrate, and glutamine transaminase K (GTK) was measured in rat and human cells with time in culture. C-S lyase activity in RPT and HPT cells decreased to approximately 30% of fresh cell values by the time the cells reached confluence (120 h), whereas the decline in GTK activity was less marked (50% of the fresh cell values at confluence). Rat cells had threefold higher activity than human cells at each time point. This higher activity may partly explain the differences in toxicity between rat and human proximal tubular cells in culture.

Cost-Effectiveness Analysis of Intensity Modulated Radiation Therapy Versus 3-Dimensional Conformal Radiation Therapy for Preoperative Treatment of Extremity Soft Tissue Sarcomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Richard, Patrick, E-mail: patrjr@uw.edu; Phillips, Mark; Smith, Wade

Purpose: Create a cost-effectiveness model comparing preoperative intensity modulated radiation therapy (IMRT) versus 3-dimensional conformal radiation therapy (3DCRT) for extremity soft tissue sarcomas. Methods and Materials: Input parameters included 5-year local recurrence rates, rates of acute wound adverse events, and chronic toxicities (edema, fracture, joint stiffness, and fibrosis). Health-state utilities were used to calculate quality-adjusted life years (QALYs). Overall treatment costs per QALY or incremental cost-effectiveness ratio (ICER) were calculated. Roll-back analysis was performed using average costs and utilities to determine the baseline preferred radiation technique. One-way, 2-way, and probabilistic sensitivity analyses (PSA) were performed for input parameters with themore » largest impact on the ICER. Results: Overall treatment costs were $17,515.58 for 3DCRT compared with $22,920.51 for IMRT. The effectiveness was higher for IMRT (3.68 QALYs) than for 3DCRT (3.35 QALYs). The baseline ICER for IMRT was $16,842.75/QALY, making it the preferable treatment. The ICER was most sensitive to the probability of local recurrence, upfront radiation costs, local recurrence costs, certain utilities (no toxicity/no recurrence, grade 1 toxicity/no local recurrence, grade 4 toxicity/no local recurrence), and life expectancy. Dominance patterns emerged when the cost of 3DCRT exceeded $15,532.05 (IMRT dominates) or the life expectancy was under 1.68 years (3DCRT dominates). Furthermore, preference patterns changed based on the rate of local recurrence (threshold: 13%). The PSA results demonstrated that IMRT was the preferred cost-effective technique for 64% of trials compared with 36% for 3DCRT. Conclusions: Based on our model, IMRT is the preferred technique by lowering rates of local recurrence, severe toxicities, and improving QALYs. From a third-party payer perspective, IMRT should be a supported approach for extremity soft tissue sarcomas.« less

Interactive toxicity of chlorpyrifos and parathion in neonatal rats: Role of esterases in exposure sequence-dependent toxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kacham, R.; Karanth, S.; Baireddy, P.

2006-01-15

We previously reported that sequence of exposure to chlorpyrifos and parathion in adult rats can markedly influence toxic outcome. In the present study, we evaluated the interactive toxicity of chlorpyrifos (8 mg/kg, po) and parathion (0.5 mg/kg, po) in neonatal (7 days old) rats. Rats were exposed to the insecticides either concurrently or sequentially (separated by 4 h) and sacrificed at 4, 8, and 24 h after the first exposure for biochemical measurements (cholinesterase activity in brain, plasma, and diaphragm and carboxylesterase activity in plasma and liver). The concurrently-exposed group showed more cumulative lethality (15/24) than either of the sequentialmore » dosing groups. With sequential dosing, rats treated initially with chlorpyrifos prior to parathion (C/P) exhibited higher lethality (7/23) compared to those treated with parathion before chlorpyrifos (P/C; 1/24). At 8 h after initial dosing, brain cholinesterase inhibition was significantly greater in the C/P group (59%) compared to the P/C group (28%). Diaphragm and plasma cholinesterase activity also followed a relatively similar pattern of inhibition. Carboxylesterase inhibition in plasma and liver was relatively similar among the treatment groups across time-points. Similar sequence-dependent differences in brain cholinesterase inhibition were also noted with lower binary exposures to chlorpyrifos (2 mg/kg) and parathion (0.35 mg/kg). In vitro and ex vivo studies compared relative oxon detoxification of carboxylesterases (calcium-insensitive) and A-esterases (calcium-sensitive) in liver homogenates from untreated and insecticide pretreated rats. Using tissues from untreated rats, carboxylesterases detoxified both chlorpyrifos oxon and paraoxon, while A-esterases only detoxified chlorpyrifos oxon. With parathion pretreatment, A-esterases still detoxified chlorpyrifos oxon while liver from chlorpyrifos pretreated rats had little apparent effect on paraoxon. We conclude that while neonatal rats are less capable than adults at detoxifying many organophosphorus insecticides including chlorpyrifos and parathion, toxicant-selective differences in detoxification play a role in sequence-dependent toxicity in both neonatal and adult rats with these two insecticides.« less

Comparison of distribution and toxicity following repeated oral dosing of different vanadium oxide nanoparticles in mice.

PubMed

Park, Eun-Jung; Lee, Gwang-Hee; Yoon, Cheolho; Kim, Dong-Wan

2016-10-01

Vanadium is an important ultra-trace element derived from fuel product combustion. With the development of nanotechnology, vanadium oxide nanoparticles (VO NPs) have been considered for application in various fields, thus the possibility of release into the environment and human exposure is also increasing. Considering that verification of bioaccumulation and relevant biological responses are essential for safe application of products, in this study, we aimed to identify the physicochemical properties that determine their health effects by comparing the biological effects and tissue distribution of different types of VO NPs in mice. For this, we prepared five types of VO NPs, commercial (C)-VO2 and -V2O5 NPs and synthetic (S)-VO2, -V2O3, and -V2O5 NPs. While the hydrodynamic diameter of the two types of C-VO NPs was irregular and impossible to measure, those of the three types of S-VO NPs was in the range of 125-170nm. The S- and C-V2O5 NPs showed higher dissolution rates compared to other VO NPs. We orally dosed the five types of VO NPs (70 and 210μg/mouse, approximately 2 and 6mg/kg) to mice for 28 days and compared their biodistribution and toxic effects. We found that S-V2O5 and S-V2O3 NPs more accumulated in tissues compared to other three types of VO NPs, and the accumulated level was in order of heart>liver>kidney>spleen. Additionally, tissue levels of redox reaction-related elements and electrolytes (Na(+), K(+), and Ca(2+)) were most clearly altered in the heart of treated mice. Notably, all S- and C-VO NPs decreased the number of WBCs at the higher dose, while total protein and albumin levels were reduced at the higher dose of S-V2O5 and S-V2O3 NPs. Taken together, we conclude that the biodistribution and toxic effects of VO NPs depend on their dissolution rates and size (surface area). Additionally, we suggest that further studies are needed to clarify effects of VO NPs on functions of the heart and the immune system. Copyright © 2016 Elsevier Inc. All rights reserved.

Multi-walled Carbon Nanotubes Reduce Toxicity of Diphenhydramine to Ceriodaphnia dubia in Water and Sediment Exposures.

PubMed

Myer, Mark H; Black, Marsha C

2017-09-01

Multi-walled carbon nanotubes are adsorptive materials that have potential for remediation of organic contaminants in water. Sediment elutriate exposures were undertaken with Ceriodaphnia dubia to compare the toxic effects of diphenhydramine in the presence and absence of sediment and multi-walled carbon nanotubes. In both sediment and solution-only treatments, addition of 0.318 mg/g of carbon nanotubes significantly decreased 48-h mortality relative to control, with a 78.7%-90.1% reduction in treatments with nanotube-amended sediment and 40.7%-53.3% reduction in nanotube-amended water exposures. The greatest degree of relative mortality reduction occurred in sediments containing higher levels of natural organic matter, indicating a potential additive effect.

Final report on low-dose estramustine phosphate (EMP) monotherapy and very low-dose EMP therapy combined with LH-RH agonist for previously untreated advanced prostate cancer.

PubMed

Kitamura, T; Suzuki, M; Nishimatsu, H; Kurosaki, T; Enomoto, Y; Fukuhara, H; Kume, H; Takeuchi, T; Miao, L; Jiangang, H; Xiaoqiang, L

2010-01-01

In order to assess the efficacy and toxicity of oral estramustine phosphate (EMP) administration, low-dose EMP monotherapy (study 1) and very low-dose EMP therapy with luteinizing hormone-releasing hormone (LH-RH) agonist (study 2) were conducted in previously untreated prostate cancer and long-term outcomes were compared between the 2 study groups. Studies 1 and 2 were independently performed beginning in June 1999 and November 2001, respectively. Study 1 was composed of 87 patients including 85 assessable patients. All 108 patients recruited for study 2 were assessable. Low-dose EMP monotherapy (2 capsules/day or 280 mg/day) was used in study 1 and very low-dose EMP (1 capsule/day or 140 mg/day) combined with LH-RH agonist was adopted in study 2. Overall prostate specific antigen (PSA) -response rates in studies 1 and 2 were 92.3% and 94.2%, respectively, and overall toxicity rates were 54.1% and 38.9%, respectively. EMP discontinuation due to side effects was encountered more often in study 1 (45.9%) than in study 2 (27.8%). Among the adverse side effects gastrointestinal toxicity was most prevalent in both studies. One patient died of acute pulmonary embolism in study 1, but no one died in study 2. There were 6 cancer deaths in the gastrointestinal tract in study 1 but only 2 cancer deaths in study 2. Our data indicate that the overall PSA response rate was comparable between both studies. However, rates in overall toxicity and drug discontinuation were higher in study 1 than in study 2. We consider that study 2 is more promising for the treatment of previously untreated advanced prostate cancer, although the rate of adverse side effects is still high as compared with other hormonal therapies. In order to overcome the high toxicity rate, especially the gastrointestinal toxicity, we recently elaborated a method employing tailor-made medicine using SNPs of 1A1 gene in cytochrome P-450 for decreasing the rate of gastrointestinal toxicity. Using this method of patient selection, study 3 has been successfully launched on September 2005 with high drug compliance. Better clinical results are being accumulated.

Aluminum Toxicity-Induced Alterations of Leaf Proteome in Two Citrus Species Differing in Aluminum Tolerance.

PubMed

Li, Huan; Yang, Lin-Tong; Qi, Yi-Ping; Guo, Peng; Lu, Yi-Bin; Chen, Li-Song

2016-07-21

Seedlings of aluminum-tolerant 'Xuegan' (Citrus sinensis) and Al-intolerant 'sour pummelo' (Citrus grandis) were fertigated for 18 weeks with nutrient solution containing 0 and 1.2 mM AlCl₃·6H₂O. Al toxicity-induced inhibition of photosynthesis and the decrease of total soluble protein only occurred in C. grandis leaves, demonstrating that C. sinensis had higher Al tolerance than C. grandis. Using isobaric tags for relative and absolute quantification (iTRAQ), we obtained more Al toxicity-responsive proteins from C. sinensis than from C. grandis leaves, which might be responsible for the higher Al tolerance of C. sinensis. The following aspects might contribute to the Al tolerance of C. sinensis: (a) better maintenance of photosynthesis and energy balance via inducing photosynthesis and energy-related proteins; (b) less increased requirement for the detoxification of reactive oxygen species and other toxic compounds, such as aldehydes, and great improvement of the total ability of detoxification; and (c) upregulation of low-phosphorus-responsive proteins. Al toxicity-responsive proteins related to RNA regulation, protein metabolism, cellular transport and signal transduction might also play key roles in the higher Al tolerance of C. sinensis. We present the global picture of Al toxicity-induced alterations of protein profiles in citrus leaves, and identify some new Al toxicity-responsive proteins related to various biological processes. Our results provide some novel clues about plant Al tolerance.

A comparison of toxicities in acute myeloid leukemia patients with and without renal impairment treated with decitabine.

PubMed

Levine, Lauren B; Roddy, Julianna Vf; Kim, Miryoung; Li, Junan; Phillips, Gary; Walker, Alison R

2018-06-01

Purpose There are limited data regarding the clinical use of decitabine for the treatment of acute myeloid leukemia in patients with a serum creatinine of 2 mg/dL or greater. Methods We retrospectively evaluated 111 patients with acute myeloid leukemia who had been treated with decitabine and compared the development of toxicities during cycle 1 in those with normal renal function (creatinine clearance greater than or equal to 60 mL/min) to those with renal dysfunction (creatinine clearance less than 60 mL/min). Results Notable differences in the incidence of grade ≥3 cardiotoxicity (33% of renal dysfunction patients vs. 16% of normal renal function patients, p = 0.042) and respiratory toxicity (40% of renal dysfunction patients vs. 14% of normal renal function patients, p = 0.0037) were observed. The majority of heart failure, myocardial infarction, and atrial fibrillation cases occurred in the renal dysfunction group. The odds of developing grade ≥3 cardiotoxicity did not differ significantly between patients with and without baseline cardiac comorbidities (OR 1.43, p = 0.43). Conclusions This study noted a higher incidence of grade ≥3 cardiac and respiratory toxicities in decitabine-treated acute myeloid leukemia patients with renal dysfunction compared to normal renal function. This may prompt closer monitoring, regardless of baseline cardiac comorbidities. Further evaluation of decitabine in patients with renal dysfunction is needed.

A field and laboratory investigation of acid effects on largemouth bass, rock bass, black crappie, and yellow perch

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eaton, J.G.; McCormick, J.H.; Swenson, W.A.

1992-09-01

One-half of Little Rock Lake, a small seepage lake in north-central Wisconsin, was gradually acidified by additions of sulfuric acid between August 1983 and November 1990. The ambient pH (6.1) of the lake was reduced at successive 2-year intervals to pH 5.6, 5.1, and 4.7. Responses of largemouth bass Micropterus salmoides, rock bass Ambloplites rupestris, black crappie Pomoxis nigromaculatus, and yellow perch Perca flavescens populations to the pH reductions were recorded and compared to the responses of these species during in situ bioassays and laboratory toxicity tests on embryos and larvae. Laboratory results obtained for largemouth bass and rock bassmore » underestimated, black crappie results overestimated, and yellow perch results were similar to effects observed in field studies. In situ bioassays predicted field responses better than did laboratory toxicity tests. Laboratory results showed that monomeric Al concentrations of approximately 50 [mu]g/L, which were comparable to Al concentrations in the acidified half of the lake, altered low-pH toxicity. Reduced recruitment was observed in field populations at higher pH than that at which adult mortality was observed. The results indicate that laboratory toxicity tests with early life stages may not accurately predict field population responses and that results from laboratory tests should be field-validated whenever possible. 42 refs., 2 figs., 7 tabs.« less

Characterization of Size-Fractionated Airborne Particles Inside an Electronic Waste Recycling Facility and Acute Toxicity Testing in Mice.

PubMed

Kim, Yong Ho; Wyrzykowska-Ceradini, Barbara; Touati, Abderrahmane; Krantz, Q Todd; Dye, Janice A; Linak, William P; Gullett, Brian; Gilmour, M Ian

2015-10-06

Disposal of electronic waste (e-waste) in landfills, incinerators, or at rudimentary recycling sites can lead to the release of toxic chemicals into the environment and increased health risks. Developing e-waste recycling technologies at commercial facilities can reduce the release of toxic chemicals and efficiently recover valuable materials. While these e-waste operations represent a vast improvement over previous approaches, little is known about environmental releases, workplace exposures, and potential health impacts. In this study, airborne particulate matter (PM) was measured at various locations within a modern U.S.-based e-waste recycling facility that utilized mechanical processing. In addition, composite size fractionated PM (coarse, fine and ultrafine) samples were collected, extracted, chemically analyzed, and given by oropharyngeal aspiration to mice or cultured with lung slices for lung toxicity tests. Indoor total PM concentrations measured during the study ranged from 220 to 1200 μg/m(3). In general, the coarse PM (2.5-10 μm) was 3-4 times more abundant than fine/ultrafine PM (<2.5 μm). The coarse PM contained higher levels of Ni, Pb, and Zn (up to 6.8 times) compared to the fine (0.1-2.5 μm) and ultrafine (<0.1 μm) PM. Compared to coarse PM measurements from a regional near-roadway study, Pb and Ni were enriched 170 and 20 times, respectively, in the indoor PM, with other significant enrichments (>10 times) observed for Zn and Sb, modest enrichments (>5 times) for Cu and Sr, and minor enrichments (>2 times) for Cr, Cd, Mn, Ca, Fe, and Ba. Negligible enrichment (<2 times) or depletion (<1 time) were observed for Al, Mg, Ti, Si, and V. The coarse PM fraction elicited significant pro-inflammatory responses in the mouse lung at 24 h postexposure compared to the fine and ultrafine PM, and similar toxicity outcomes were observed in the lung slice model. We conclude that exposure to coarse PM from the facility caused substantial inflammation in the mouse lung and enrichment of these metals compared to levels normally present in the ambient PM could be of potential health concern.

Degradation of carbendazim in water via photo-Fenton in Raceway Pond Reactor: assessment of acute toxicity and transformation products.

PubMed

da Costa, Elizângela Pinheiro; Bottrel, Sue Ellen C; Starling, Maria Clara V M; Leão, Mônica M D; Amorim, Camila Costa

2018-05-08

This study aimed at investigating the degradation of fungicide carbendazim (CBZ) via photo-Fenton reactions in artificially and solar irradiated photoreactors at laboratory scale and in a semi-pilot scale Raceway Pond Reactor (RPR), respectively. Acute toxicity was monitored by assessing the sensibility of bioluminescent bacteria (Aliivibrio fischeri) to samples taken during reactions. In addition, by-products formed during solar photo-Fenton were identified by liquid chromatography coupled to mass spectrometry (UFLC-MS). For tests performed in lab-scale, two artificial irradiation sources were compared (UV λ > 254nm and UV-Vis λ > 320nm ). A complete design of experiments was performed in the semi-pilot scale RPR in order to optimize reaction conditions (Fe 2+ and H 2 O 2 concentrations, and water depth). Efficient degradation of carbendazim (> 96%) and toxicity removal were achieved via artificially irradiated photo-Fenton under both irradiation sources. Control experiments (UV photolysis and UV-Vis peroxidation) were also efficient but led to increased acute toxicity. In addition, H 2 O 2 /UV λ > 254nm required longer reaction time (60 minutes) when compared to the photo-Fenton process (less than 1 min). While Fenton's reagent achieved high CBZ and acute toxicity removal, its efficiency demands higher concentration of reagents in comparison to irradiated processes. Solar photo-Fenton removed carbendazim within 15 min of reaction (96%, 0.75 kJ L -1 ), and monocarbomethoxyguanidine, benzimidazole isocyanate, and 2-aminobenzimidazole were identified as transformation products. Results suggest that both solar photo-Fenton and artificially irradiated systems are promising routes for carbendazim degradation.

Flow cytometric assay for analysis of cytotoxic effects of potential drugs on human peripheral blood leukocytes

NASA Astrophysics Data System (ADS)

Nieschke, Kathleen; Mittag, Anja; Golab, Karolina; Bocsi, Jozsef; Pierzchalski, Arkadiusz; Kamysz, Wojciech; Tarnok, Attila

2014-03-01

Toxicity test of new chemicals belongs to the first steps in the drug screening, using different cultured cell lines. However, primary human cells represent the human organism better than cultured tumor derived cell lines. We developed a very gentle toxicity assay for isolation and incubation of human peripheral blood leukocytes (PBL) and tested it using different bioactive oligopeptides (OP). Effects of different PBL isolation methods (red blood cell lysis; Histopaque isolation among others), different incubation tubes (e.g. FACS tubes), anticoagulants and blood sources on PBL viability were tested using propidium iodide-exclusion as viability measure (incubation time: 60 min, 36°C) and flow cytometry. Toxicity concentration and time-depended effects (10-60 min, 36 °C, 0-100 μg /ml of OP) on human PBL were analyzed. Erythrocyte lysis by hypotonic shock (dH2O) was the fastest PBL isolation method with highest viability (>85%) compared to NH4Cl-Lysis (49%). Density gradient centrifugation led to neutrophil granulocyte cell loss. Heparin anticoagulation resulted in higher viability than EDTA. Conical 1.5 mL and 2 mL micro-reaction tubes (both polypropylene (PP)) had the highest viability (99% and 97%) compared to other tubes, i.e. three types of 5.0 mL round-bottom tubes PP (opaque-60%), PP (blue-62%), Polystyrene (PS-64%). Viability of PBL did not differ between venous and capillary blood. A gentle reproducible preparation and analytical toxicity-assay for human PBL was developed and evaluated. Using our assay toxicity, time-course, dose-dependence and aggregate formation by OP could be clearly differentiated and quantified. This novel assay enables for rapid and cost effective multiparametric toxicological screening and pharmacological testing on primary human PBL and can be adapted to high-throughput-screening.°z

Transition from LDR to HDR brachytherapy for cervical cancer: Evaluation of tumor control, survival, and toxicity.

PubMed

Romano, K D; Pugh, K J; Trifiletti, D M; Libby, B; Showalter, T N

In 2012, our institution transitioned from low-dose-rate (LDR) brachytherapy to high dose-rate (HDR) brachytherapy. We report clinical outcomes after brachytherapy for cervical cancer at our institution over a continuous 10-year period. From 2004 to 2014, 258 women (184 LDR and 74 HDR) were treated with tandem and ovoid brachytherapy in the multidisciplinary management of International Federation of Gynecology and Obstetrics Stages IA-IVB cervical cancer. Clinical and treatment-related prognostic factors including age, stage, smoking status, relevant doses, and toxicity data were recorded. Median followup for the LDR and HDR groups was 46 months and 12 months, respectively. The majority of patients (92%) received external beam radiotherapy as well as concurrent chemotherapy (83%) before the start of brachytherapy. For all stages, the 1-year local control and overall survival (OS) rates were comparable between the LDR and HDR groups (87% vs. 81%, p = 0.12; and 75% vs. 85%, p = 0.16), respectively. Factors associated with OS on multivariate analysis include age, stage, and nodal involvement. On multivariate analysis, severe toxicity (acute or chronic) was higher with HDR than LDR (24% vs. 10%, p = 0.04). Additional prognostic factors associated with increased severe toxicity include former/current smokers and total dose to lymph nodes. This comparative retrospective analysis of a large cohort of women treated with brachytherapy demonstrates no significant difference in OS or local control between the LDR and HDR. Acute and chronic toxicity increased shortly after the implementation of HDR, highlighting the importance of continued refinement of HDR methods, including integrating advanced imaging. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

New polymer of lactic-co-glycolic acid-modified polyethylenimine for nucleic acid delivery

PubMed Central

Lü, Jian-Ming; Liang, Zhengdong; Wang, Xiaoxiao; Gu, Jianhua; Yao, Qizhi; Chen, Changyi

2016-01-01

Aim: To develop an improved delivery system for nucleic acids. Materials & methods: We designed, synthesized and characterized a new polymer of lactic-co-glycolic acid-modified polyethylenimine (LGA-PEI). Functions of LGA-PEI polymer were determined. Results: The new LGA-PEI polymer spontaneously formed nanoparticles (NPs) with DNA or RNA, and showed higher DNA or RNA loading efficiency, higher or comparable transfection efficacy, and lower cytotoxicity in several cell types including PANC-1, Jurkat and HEK293 cells, when compared with lipofectamine 2000, branched or linear PEI (25 kDa). In nude mouse models, LGA-PEI showed higher delivery efficiency of plasmid DNA or miRNA mimic into pancreatic and ovarian xenograft tumors. LGA-PEI/DNA NPs showed much lower toxicity than control PEI NPs in mouse models. Conclusion: The new LGA-PEI polymer is a safer and more effective system to deliver DNA or RNA than PEI. PMID:27456396

Toxicity and accumulation of mercury in three species of crabs with different osmoregulatory capacities

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bianchini, A.; Gilles, R.

1996-07-01

Synergism between mercury and salinity has been shown in invertebrates. Two authors have tied to correlate salinity effects with a higher or lower accumulation of mercury. Zauke, demonstrated lower mercury levels in several benthic invertebrates from limnic regions of the Elbe estuary when compared to those from Marine regions. On the other hand, Kendall did not report any significant difference in mercury concentrations in benthic macroinvertebrates throughout a salinity gradient in two estuaries from Georgia. In species hyperosmoregulating in diluted media, it could, however, be considered that the high water turnover would favor mercury accumulation. In this context, one couldmore » also expect a relationship between environmental salinity and mercury toxicity in different euryhaline species depending on their osmoregulatory capacities. We have tested this hypothesis analyzing the toxic effects and accumulation of mercury in three euryhaline crabs presenting different osmoregulatory capacities: Eriocheir sinensis (strong hyperosmoregulator), Carcinus maenas (weak hyperosmoregulator) and Cancer pagurus (osmoconformer). 16 refs., 4 figs., 1 tab.« less

Ecotoxicological assessment of bluegill sunfish inhabiting a selenium-enriched fly ash stream

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reash, R.J.; Lohner, T.W.; Wood, K.V.

1999-07-01

Little Scary Creek (LSC), a 2nd-order tributary of the Kanawha River in West Virginia, receives treated fly ash produced during coal combustion. Selenium and other trace metals were determined in water column and sediment samples, caddisflies, and bluegill sunfish liver and gonads during 1995--96 to estimate pathways of selenium exposure and assess the likelihood of toxic effects. Selenium levels in LSC water and sediment samples, and in caddisflies were elevated compared to reference sites. Mean dry weight selenium concentrations in bluegill liver, ovary, and tested tissue equaled or exceeded published toxic thresholds. Other trace metals were significantly higher in LSCmore » bluegill. Leukopenia, elevated serum salts, and lowered liver weight were found in LSC bluegill. Fewer older bluegill were found in LSC. Sunfish in LSC are experiencing various kinds of sublethal stress, presumably due to metals exposure. However, major toxic effects that would be predicted to occur based on tissue selenium levels (complete reproductive failure or mortality) have not been observed in this population.« less

Toxicity of polyunsaturated aldehydes of diatoms to Indo-Pacific bioindicator organism Echinometra mathaei.

PubMed

Sartori, Davide; Gaion, Andrea

2016-01-01

Although it is well known suitability of early developmental stages of sea urchin as recommended model for pollutant toxicity testing, little is known about the sensitivity of Indo-Pacific species Echinometra mathaei to polyunsaturated aldehydes. In this study, the effect of three short chain aldehydes, 2,4-decadienal (DD), 2,4-octadienal (OD) and 2,4-heptadienal (HD), normally found in many diatoms, such as Skeletonema costatum, Skeletonema marinoi and Thalassiosira rotula, was evaluated on larval development of E. mathaei embryos. Aldehydes affected larval development in a dose-dependent manner, in particular HD>OD>DD; the results of this study highlighted the higher sensitivity of this species toward aldehydes compared with data registered for other sea urchin species. In comparison with studies reported in the literature, contrasting results were observed during our tests; therefore, an increasing toxic effect was registered with decreasing the chain length of aldehydes. This work could provide new insights in the development of new toxicological assays toward most sensitive species.

Three dimensional quantitative structure-toxicity relationship modeling and prediction of acute toxicity for organic contaminants to algae.

PubMed

Jin, Xiangqin; Jin, Minghao; Sheng, Lianxi

2014-08-01

Although numerous chemicals have been identified to have significant toxicological effect on aquatic organisms, there is still lack of a reliable, high-throughput approach to evaluate, screen and monitor the presence of organic contaminants in aquatic system. In the current study, we proposed a synthetic pipeline to automatically model and predict the acute toxicity of chemicals to algae. In the procedure, a new alignment-free three dimensional (3D) structure characterization method was described and, with this method, several 3D-quantitative structure-toxicity relationship (3D-QSTR) models were developed, from which two were found to exhibit strong internal fitting ability and high external predictive power. The best model was established by Gaussian process (GP), which was further employed to perform extrapolation on a random compound library consisting of 1014 virtually generated substituted benzenes. It was found that (i) substitution number can only exert slight influence on chemical׳s toxicity, but low-substituted benzenes seem to have higher toxicity than those of high-substituted entities, and (ii) benzenes substituted by nitro group and halogens exhibit high acute toxicity as compared to other substituents such as methyl and carboxyl groups. Subsequently, several promising candidates suggested by computational prediction were assayed by using a standard algal growth inhibition test. Consequently, four substituted benzenes, namely 2,3-dinitrophenol, 2-chloro-4-nitroaniline, 1,2,3-trinitrobenzene and 3-bromophenol, were determined to have high acute toxicity to Scenedesmus obliquus, with their EC50 values of 2.5±0.8, 10.5±2.1, 1.4±0.2 and 42.7±5.4μmol/L, respectively. Copyright © 2014 Elsevier Ltd. All rights reserved.

UGT1A1*6 and UGT1A1*28 polymorphisms are correlated with irinotecan-induced toxicity: A meta-analysis.

PubMed

Yang, Yuwei; Zhou, MengMeng; Hu, Mingjun; Cui, Yanjie; Zhong, Qi; Liang, Ling; Huang, Fen

2018-06-22

Previous articles explored the role of UGT1A1 polymorphism on predicting irinotecan-induced toxicity, but the conclusions were still inconsistent and not comprehensive. We performed this meta-analysis to investigate the association between UGT1A1 polymorphism and irinotecan-induced toxicity. PubMed and Web of Science were searched for articles before July 2017. Inclusion and exclusion criteria were set to select eligible articles, and corresponding data were extracted from those articles. Subgroup analyses based on different cancer categories, doses and races were carried out to achieve comprehensive results. Statistical analyses were conducted using STATA 11.0. A total of 38 studies with 6742 cases were included after reading full text. Both UGT1A1*6 and UGT1A1*28 polymorphism are significantly associated with severe irinotecan-induced toxicity. Both Asian and Caucasian cancer patients with UGT1A1*28 variant had an increased risk. Compared with heterozygous variant, patients with homozygous variant suffered from a higher risk of toxicity. The effect of UGT1A1*28 polymorphism on diarrhea was less than on neutropenia. Subgroup analysis exhibited that for UGT1A1*6 polymorphism, patients treated with low-dose irinotecan were at a notable risk of toxicity. Moreover, the association between UGT1A1*6 polymorphism and irinotecan-induced toxicity was found in patients suffering from respiratory system cancers. Both UGT1A1*6 and UGT1A1*28 polymorphisms can be considered as predictors of irinotecan-induced toxicity, with effect varying by race, cancer type and irinotecan dose. © 2018 John Wiley & Sons Australia, Ltd.

Reirradiation for recurrent head and neck cancers using charged particle or photon radiotherapy.

PubMed

Yamazaki, Hideya; Demizu, Yusuke; Okimoto, Tomoaki; Ogita, Mikio; Himei, Kengo; Nakamura, Satoaki; Suzuki, Gen; Yoshida, Ken; Kotsuma, Tadayuki; Yoshioka, Yasuo; Oh, Ryoongjin

2017-07-01

To examine the outcomes of reirradiation for recurrent head and neck cancers using different modalities. This retrospective study included 26 patients who received charged particle radiotherapy (CP) and 150 who received photon radiotherapy (117 CyberKnife radiotherapy [CK] and 36 intensity-modulated radiotherapy [IMRT]). Inverse probability of treatment weighting (IPTW) involving propensity scores was used to reduce background selection bias. Higher prescribed doses were used in CP than photon radiotherapy. The 1‑year overall survival (OS) rates were 67.9% for CP and 54.1% for photon radiotherapy (p = 0.15; 55% for CK and 51% for IMRT). In multivariate Cox regression, the significant prognostic factors for better survival were nasopharyngeal cancer, higher prescribed dose, and lower tumor volume. IPTW showed a statistically significant difference between CP and photon radiotherapy (p = 0.04). The local control rates for patients treated with CP and photon radiotherapy at 1 year were 66.9% (range 46.3-87.5%) and 67.1% (range 58.3-75.9%), respectively. A total of 48 patients (27%) experienced toxicity grade ≥3 (24% in the photon radiotherapy group and 46% in the CP group), including 17 patients with grade 5 toxicity. Multivariate analysis revealed that younger age and a larger planning target volume (PTV) were significant risk factors for grade 3 or worse toxicity. CP provided superior survival outcome compared to photon radiotherapy. Tumor volume, primary site (nasopharyngeal), and prescribed dose were identified as survival factors. Younger patients with a larger PTV experienced toxicity grade ≥3.

Enhancing productivity for cascade biotransformation of styrene to (S)-vicinal diol with biphasic system in hollow fiber membrane bioreactor.

PubMed

Gao, Pengfei; Wu, Shuke; Praveen, Prashant; Loh, Kai-Chee; Li, Zhi

2017-03-01

Biotransformation is a green and useful tool for sustainable and selective chemical synthesis. However, it often suffers from the toxicity and inhibition from organic substrates or products. Here, we established a hollow fiber membrane bioreactor (HFMB)-based aqueous/organic biphasic system, for the first time, to enhance the productivity of a cascade biotransformation with strong substrate toxicity and inhibition. The enantioselective trans-dihydroxylation of styrene to (S)-1-phenyl-1,2-ethanediol, catalyzed by Escherichia coli (SSP1) coexpressing styrene monooxygenase and an epoxide hydrolase, was performed in HFMB with organic solvent in the shell side and aqueous cell suspension in the lumen side. Various organic solvents were investigated, and n-hexadecane was found as the best for the HFMB-based biphasic system. Comparing to other reported biphasic systems assisted by HFMB, our system not only shield much of the substrate toxicity but also deflate the product recovery burden in downstream processing as the majority of styrene stayed in organic phase while the diol product mostly remained in the aqueous phase. The established HFMB-based biphasic system enhanced the production titer to 143 mM, being 16-fold higher than the aqueous system and 1.6-fold higher than the traditional dispersive partitioning biphase system. Furthermore, the combination of biphasic system with HFMB prevents the foaming and emulsification, thus reducing the burden in downstream purification. HFMB-based biphasic system could serve as a suitable platform for enhancing the productivity of single-step or cascade biotransformation with toxic substrates to produce useful and valuable chemicals.

Mechanisms of the Testis Toxicity Induced by Chronic Exposure to Mequindox.

PubMed

Liu, Qianying; Lei, Zhixin; Huang, Anxiong; Lu, Qirong; Wang, Xu; Ahmed, Saeed; Awais, Ihsan; Yuan, Zonghui

2017-01-01

Mequindox (MEQ) is a synthetic antimicrobial agent widely used in China since the 1980s. Although the toxicity of MEQ is well recognized, its testis toxicity has not been adequately investigated. In the present study, we provide evidence that MEQ triggers oxidative stress, mitochondrion dysfunction and spermatogenesis deficiency in mice after exposure to MEQ (0, 25, 55, and 110 mg/kg in the diet) for up to 18 months. The genotoxicity and adrenal toxicity may contribute to sperm abnormalities caused by MEQ. Moreover, using LC/MS-IT-TOF analysis, two metabolites, 3-methyl-2-(1-hydroxyethyl) quinoxaline- N 4-monoxide (M4) and 3-methyl-2-(1-hydroxyethyl) quinoxaline- N 1-monoxide (M8), were detected in the serum of mice, which directly confirms the relationship between the N →O group reduction metabolism of MEQ and oxidative stress. Interestingly, only M4 was detected in the testes, suggesting that the higher reproductive toxicity of M4 than M8 might be due to the increased stability of M4-radical (M4-R) compared to M8-radical (M8-R). Furthermore, the expression of the blood-testis barrier (BTB)-associated junctions such as tight junctions, gap junctions and basal ectoplasmic specializations were also examined. The present study demonstrated for the first time the role of the M4 in testis toxicity, and illustrated that the oxidative stress, mitochondrion dysfunction and interference in spermatogenesis, as well as the altered expression of BTB related junctions, were involved in the reproductive toxicity mediated by MEQ in vivo .

Mechanisms of the Testis Toxicity Induced by Chronic Exposure to Mequindox

PubMed Central

Liu, Qianying; Lei, Zhixin; Huang, Anxiong; Lu, Qirong; Wang, Xu; Ahmed, Saeed; Awais, Ihsan; Yuan, Zonghui

2017-01-01

Mequindox (MEQ) is a synthetic antimicrobial agent widely used in China since the 1980s. Although the toxicity of MEQ is well recognized, its testis toxicity has not been adequately investigated. In the present study, we provide evidence that MEQ triggers oxidative stress, mitochondrion dysfunction and spermatogenesis deficiency in mice after exposure to MEQ (0, 25, 55, and 110 mg/kg in the diet) for up to 18 months. The genotoxicity and adrenal toxicity may contribute to sperm abnormalities caused by MEQ. Moreover, using LC/MS-IT-TOF analysis, two metabolites, 3-methyl-2-(1-hydroxyethyl) quinoxaline-N4-monoxide (M4) and 3-methyl-2-(1-hydroxyethyl) quinoxaline-N1-monoxide (M8), were detected in the serum of mice, which directly confirms the relationship between the N→O group reduction metabolism of MEQ and oxidative stress. Interestingly, only M4 was detected in the testes, suggesting that the higher reproductive toxicity of M4 than M8 might be due to the increased stability of M4-radical (M4-R) compared to M8-radical (M8-R). Furthermore, the expression of the blood-testis barrier (BTB)-associated junctions such as tight junctions, gap junctions and basal ectoplasmic specializations were also examined. The present study demonstrated for the first time the role of the M4 in testis toxicity, and illustrated that the oxidative stress, mitochondrion dysfunction and interference in spermatogenesis, as well as the altered expression of BTB related junctions, were involved in the reproductive toxicity mediated by MEQ in vivo. PMID:29018347

Comparing the Toxicity of Water-Soluble Fractions of Biodiesel, Diesel and 5% Biodiesel/Diesel Blend on Oreochromis niloticus Using Histological Biomarkers.

PubMed

Leite, Maria Bernadete Neiva Lemos; da Cruz, André Luís; Rodrigues, Luiz Erlon Araújo; Yamashita, Sayuri Rocha; Carqueija, César Roberto Goes; Nascimento, Iracema Andrade

2015-11-01

This study estimated end compared the potential toxic effects of the water-soluble fractions (WSF) of biodiesel (B100), diesel and the commercial biodiesel (B5) on Oreochromis niloticus. After a 24 h-exposition to WSF-0% (control) and WSF-serial concentrations of 4.6%, 10%, 22%, 46% and 100%, samples of gill and liver of the exposed fishes were fixed in Bouin's solution, processed, stained using hematoxylin/eosin and analyzed by light-microscopy. WSF-hydrocarbons and methanol contents, analyzed by gas chromatography, were checked against the occurrence of abnormal histopathological alterations. These were not found in the control and WSF-4.6% exposed fishes, while exposures to or above 10%-WSF resulted in histopathological alterations whose severity increased in a dose-dependent manner, being higher in fishes exposed to WSF-diesel, or WSF-B5 when compared to biodiesel. These results, which were corroborated by the chemical analyses, highlighted the histological technique as an appropriate diagnostic tool that can be used for the preservation of water bodies' quality.

Host thiopurine methyltransferase status affects mercaptopurine antileukemic effectiveness in a murine model.

PubMed

Ramsey, Laura B; Janke, Laura J; Edick, Mathew J; Cheng, Cheng; Williams, Richard T; Sherr, Charles J; Evans, William E; Relling, Mary V

2014-05-01

Thiopurines are used for many cancers, including acute lymphoblastic leukemia (ALL). Patients with an inherited host defect in thiopurine methyltransferase (TPMT) are at high risk for life-threatening toxicity if treated with conventional dosages, but the impact on antileukemic efficacy is less clear. We treated thiopurine-sensitive BCR-ABL+Arf-null Tpmt+/+ ALL in Tpmt+/+, +/-, or -/- recipient mice to test the impact of the host polymorphism on antileukemic efficacy. Median survival was similar in untreated mice of different Tpmt genotypes (16-18 days). However, in mice treated with low-dose mercaptopurine (such as tolerated by TPMT-/- patients), the difference in 30-day leukemia-free survival by Tpmt genotype was profound: 5% (±9%) for Tpmt+/+ mice, 47% (±26%) for Tpmt+/- mice, and 85% (±14%) for Tpmt-/- mice (P=5×10), indicating a substantial impact of host Tpmt status on thiopurine effectiveness. Among Tpmt+/+ recipient mice, leukemia-free survival improved with higher doses of mercaptopurine (similar to doses tolerated by wild-type patients) compared with lower doses, and at higher doses was comparable (P=0.6) to the survival of Tpmt-/- mice treated with the lower dose. These findings support the notion that germline polymorphisms in Tpmt affect not only host tissue toxicity but also antitumor effectiveness.

Biodiesel versus Diesel: A Pilot Study Comparing Exhaust Exposures for Employees at a Rural Municipal Facility

PubMed Central

Traviss, Nora; Thelen, Brett Amy; Ingalls, Jaime Kathryn; Treadwell, Melinda Dawn

2016-01-01

Many organizations interested in renewable, domestic energy have switched from petroleum diesel to biodiesel blends for use in transportation and heavy-duty equipment. Although considerable evidence exists on the negative health effects of petroleum diesel exhaust exposures in occupational settings, there has been little research examining biodiesel exposures. Working collaboratively with a local municipality, concentrations of particulate matter (PM) and other air toxics were measured at a recycling facility in southwestern New Hampshire while heavy equipment operated first on petroleum diesel and then on a B20 blend (20% soy-based biodiesel/80% petroleum diesel). This pilot study used a combination of established industrial hygiene and environmental air monitoring methods to estimate occupational exposure profiles to PM and air toxics from combustion of petroleum diesel and biodiesel. Results indicate that B20 use dramatically reduces work area respirable particle, PM2.5 (PM ≤2.5 µm in aerodynamic diameter), and formaldehyde levels compared with petroleum diesel. Some volatile organic compound concentrations were higher for petroleum diesel and others were higher for the B20 blend. Overall, this study suggests that biodiesel blends reduce worker exposure to and health risk from petroleum diesel exhaust, but additional exposure research is recommended. PMID:20863048

The role of mycorrhizal symbiosis in aluminum and phosphorus interactions in relation to aluminum tolerance in soybean.

PubMed

Zhang, Shuang; Zhou, Jia; Wang, Guihua; Wang, Xiurong; Liao, Hong

2015-12-01

Arbuscular mycorrhizal (AM) fungi protect plants against aluminum (Al) toxicity, but the mechanisms of Al and phosphorus (P) interactions in relation to Al tolerance in mycorrhizal plants are only poorly understood. In this study, varying Al and P treatments were applied to soybean plants cultivated in the presence or absence of three different AM fungi. The results showed that plants in symbiotic association with Gigaspora margarita displayed higher Al tolerance than Rhizophagus irregularis or Glomus claroideum. The effectiveness of G. margarita appeared to be associated with more abundant arbuscules and less affected intraradical hyphae compared to no Al controls. The highest levels of Al toxicity mitigation were observed with the combination of high P availability and AM fungal inoculation, which was associated with a concomitant increase in the expression of the AM-inducible phosphate (Pi) transporter gene GmPT9 in soybean. Taken together, these results suggest that AM symbiosis can alleviate Al toxicity in soybean through enhanced P nutrition, as well as, the alteration of the abundance of mycorrhizal infection structures. These findings highlight the importance of P nutrition status in ameliorating Al toxicity in mycorrhizal plants.

Nursing protects honeybee larvae from secondary metabolites of pollen

PubMed Central

Lucchetti, Matteo A.; Kilchenmann, Verena; Glauser, Gaetan; Praz, Christophe

2018-01-01

The pollen of many plants contains toxic secondary compounds, sometimes in concentrations higher than those found in the flowers or leaves. The ecological significance of these compounds remains unclear, and their impact on bees is largely unexplored. Here, we studied the impact of pyrrolizidine alkaloids (PAs) found in the pollen of Echium vulgare on honeybee adults and larvae. Echimidine, a PA present in E. vulgare pollen, was isolated and added to the honeybee diets in order to perform toxicity bioassays. While adult bees showed relatively high tolerance to PAs, larvae were much more sensitive. In contrast to other bees, the honeybee larval diet typically contains only traces of pollen and consists predominantly of hypopharyngeal and mandibular secretions produced by nurse bees, which feed on large quantities of pollen-containing bee bread. We quantified the transfer of PAs to nursing secretions produced by bees that had previously consumed bee bread supplemented with PAs. The PA concentration in these secretions was reduced by three orders of magnitude as compared to the PA content in the nurse diet and was well below the toxicity threshold for larvae. Our results suggest that larval nursing protects honeybee larvae from the toxic effect of secondary metabolites of pollen. PMID:29563265

Effects of the filamentous cyanobacterium Nodularia on fitness and feeding behavior of young-of-the-year (YOY) Eurasian perch (Perca fluviatilis).

PubMed

Persson, Karl-Johan; Stenroth, Patrik; Legrand, Catherine

2011-06-01

This study reveals that both cyanobacterial toxicity and turbidity have the potential to reduce the growth and energy storage of young-of-the-year (YOY) perch and thereby influence survival rates. During the 1990's a reduction in recruitment of YOY perch (Perca fluviatilis) occurred along the Swedish East coast. Concurrently, large blooms of filamentous cyanobacteria have increased in the Baltic Proper and in coastal waters. This study examined whether extended exposure to toxic and non-toxic filamentous cyanobacterium Nodularia affect YOY perch growth and feeding behavior under simulated bloom conditions (30 days at 50 μg Chl a L(-1)). Specific growth rate (SGR), the somatic condition index (SCI) and the lipid content of YOY perch (10-12 weeks old) were significantly lower in perch exposed to Nodularia compared to fed controls (no Nodularia). YOY perch exposed to non-toxic Nodularia displayed a higher attack rate than perch living in Nodularia free controls in 2 out of 3 trials. Reductions in growth and energy storage, mediated by cyanobacteria, increase the risk of starvation and predation and could locally influence recruitment of YOY perch. Copyright © 2011 Elsevier Ltd. All rights reserved.

Pemetrexed degradation by photocatalytic process: Kinetics, identification of transformation products and estimation of toxicity.

PubMed

Secrétan, Philippe-Henri; Karoui, Maher; Levi, Yves; Sadou-Yayé, Hassane; Tortolano, Lionel; Solgadi, Audrey; Yagoubi, Najet; Do, Bernard

2018-05-15

This study employed a UV-A/visible/TiO 2 system to investigate the degradation of pemetrexed, an antifolate agent used in chemotherapy. The laboratory-scale method employed a photostability chamber that could be used to study multiple samples. Reversed-phase HPLC coupled with high-resolution ESI-LTQ-Orbitrap mass spectrometry was used to determine the transformation products (TPs) of PEME. Based on the identified TPs and existing chemical knowledge, the mechanism of degradation of the target compound was proposed. Concentrations were monitored as a function of time, and the degradation kinetics were compared. The structures of seven TPs, four of which have not been described to date, were proposed. Most of the TPs stemmed from OH radical additions to the dihydropyrrole moiety and oxidative decarboxylation of the glutamate residue. Based on the elucidated structures, a computational toxicity assessment was performed, showing that the TPs with higher log D values than the parent compound are more toxic than the PEME itself. To support these findings, the toxicities of irradiated samples on Vibrio fischeri were monitored over time. The experimental results corresponded well with the results of previous computational studies. Copyright © 2017 Elsevier B.V. All rights reserved.

Nursing protects honeybee larvae from secondary metabolites of pollen.

PubMed

Lucchetti, Matteo A; Kilchenmann, Verena; Glauser, Gaetan; Praz, Christophe; Kast, Christina

2018-03-28

The pollen of many plants contains toxic secondary compounds, sometimes in concentrations higher than those found in the flowers or leaves. The ecological significance of these compounds remains unclear, and their impact on bees is largely unexplored. Here, we studied the impact of pyrrolizidine alkaloids (PAs) found in the pollen of Echium vulgare on honeybee adults and larvae. Echimidine, a PA present in E. vulgare pollen, was isolated and added to the honeybee diets in order to perform toxicity bioassays. While adult bees showed relatively high tolerance to PAs, larvae were much more sensitive. In contrast to other bees, the honeybee larval diet typically contains only traces of pollen and consists predominantly of hypopharyngeal and mandibular secretions produced by nurse bees, which feed on large quantities of pollen-containing bee bread. We quantified the transfer of PAs to nursing secretions produced by bees that had previously consumed bee bread supplemented with PAs. The PA concentration in these secretions was reduced by three orders of magnitude as compared to the PA content in the nurse diet and was well below the toxicity threshold for larvae. Our results suggest that larval nursing protects honeybee larvae from the toxic effect of secondary metabolites of pollen. © 2018 The Authors.

Toxicophore exploration as a screening technology for drug design and discovery: techniques, scope and limitations.

PubMed

Singh, Pankaj Kumar; Negi, Arvind; Gupta, Pawan Kumar; Chauhan, Monika; Kumar, Raj

2016-08-01

Toxicity is a common drawback of newly designed chemotherapeutic agents. With the exception of pharmacophore-induced toxicity (lack of selectivity at higher concentrations of a drug), the toxicity due to chemotherapeutic agents is based on the toxicophore moiety present in the drug. To date, methodologies implemented to determine toxicophores may be broadly classified into biological, bioanalytical and computational approaches. The biological approach involves analysis of bioactivated metabolites, whereas the computational approach involves a QSAR-based method, mapping techniques, an inverse docking technique and a few toxicophore identification/estimation tools. Being one of the major steps in drug discovery process, toxicophore identification has proven to be an essential screening step in drug design and development. The paper is first of its kind, attempting to cover and compare different methodologies employed in predicting and determining toxicophores with an emphasis on their scope and limitations. Such information may prove vital in the appropriate selection of methodology and can be used as screening technology by researchers to discover the toxicophoric potentials of their designed and synthesized moieties. Additionally, it can be utilized in the manipulation of molecules containing toxicophores in such a manner that their toxicities might be eliminated or removed.

Cardiovascular involvement in patients with different causes of hyperthyroidism.

PubMed

Biondi, Bernadette; Kahaly, George J

2010-08-01

Various clinical disorders can cause hyperthyroidism, the effects of which vary according to the patient's age, severity of clinical presentation and association with other comorbidities. Hyperthyroidism is associated with increased morbidity and mortality from cardiovascular disease, although whether the risk of specific cardiovascular complications is related to the etiology of hyperthyroidism is unknown. This article will focus on patients with Graves disease, toxic adenoma and toxic multinodular goiter, and will compare the cardiovascular risks associated with these diseases. Patients with toxic multinodular goiter have a higher cardiovascular risk than do patients with Graves disease, although cardiovascular complications in both groups are differentially influenced by the patient's age and the cause of hyperthyroidism. Atrial fibrillation, atrial enlargement and congestive heart failure are important cardiac complications of hyperthyroidism and are prevalent in patients aged > or = 60 years with toxic multinodular goiter, particularly in those with underlying cardiac disease. An increased risk of stroke is common in patients > 65 years of age with atrial fibrillation. Graves disease is linked with autoimmune complications, such as cardiac valve involvement, pulmonary arterial hypertension and specific cardiomyopathy. Consequently, the etiology of hyperthyroidism must be established to enable correct treatment of the disease and the cardiovascular complications.

Comparison of the clinical efficacy between single-agent and dual-agent concurrent chemoradiotherapy in the treatment of unresectable esophageal squamous cell carcinoma: a multicenter retrospective analysis.

PubMed

Li, Jie; Gong, Youling; Diao, Peng; Huang, Qingmei; Wen, Yixue; Lin, Binwei; Cai, Hongwei; Tian, Honggang; He, Bing; Ji, Lanlan; Guo, Ping; Miao, Jidong; Du, Xiaobo

2018-01-22

Some Chinese patients with esophageal squamous cell carcinomaare often treated with single-agent concurrent chemoradiotherapy. However, no results have been reported from randomized controlled clinical trials comparing single-agent with double-agent concurrent chemoradiotherapy. It therefore remains unclear whether these regimens are equally clinically effective. In this study, we retrospectively analyzed and compared the therapeutic effects of single-agent and double-agent concurrent chemoradiotherapy in patients with unresectable esophageal squamous cell carcinoma. This study enrolled 168 patients who received definitive concurrent chemoradiotherapy for locally advanced unresectable esophageal squamous carcinoma at 10 hospitals between 2010 and 2015. We evaluated survival time and toxicity. The Kaplan-Meier method was used to estimate survival data. The log-rank test was used in univariate analysis A Cox proportional hazards regression model was used to conduct a multivariate analysis of the effects of prognostic factors on survival. In this study, 100 (59.5%) and 68 patients (40.5%) received single-agent and dual-agent combination chemoradiotherapy, respectively. The estimate 5-year progression-free survival (PFS) rate and overall survival (OS) rate of dual-agent therapy was higher than that of single-agent therapy (52.5% and 40.9%, 78.2% and 60.7%, respectively), but there were no significant differences (P = 0.367 and 0.161, respectively). Multivariate analysis showed that sex, age,and radiotherapy dose had no significant effects on OS or PFS. Only disease stage was associated with OS and PFS in the multivariable analysis (P = 0.006 and 0.003, respectively). In dual-agent group, the incidence of acute toxicity and the incidence of 3 and4 grade toxicity were higher than single-agent group. The 5-year PFS and OS rates of dual-agent therapy were higher than those of single-agent concurrent chemoradiotherapy for patients with unresectable esophageal squamous cell carcinoma; however, there were no significant differences in univariate analysis and multivariable analysis. Single-agent concurrent chemotherapy had less toxicity than a double-drug regimen. Therefore, we suggest that single therapis not inferior to dual therapy y. In the future, we aim to confirm our hypothesis through a prospective randomized study.

Elevation of blood lead levels in emergency department patients with extra-articular retained missiles.

PubMed

Nguyen, Ann; Schaider, Jeffrey J; Manzanares, Mariah; Hanaki, Roy; Rydman, Robert J; Bokhari, Faran

2005-02-01

Patients who survive gunshot wounds often have retained missiles. Unlike intra-articular retained missiles, extra-articular retained missiles (EARMs) are not routinely removed. Cases of lead toxicity from EARMs have been described. This study seeks to determine whether blood lead levels are elevated in emergency department patients with EARMs compared with matched controls, whether clinical symptoms of lead toxicity are more prevalent in patients with EARMs than in controls, and whether longer missile retention times or recent hypermetabolic conditions are associated with higher blood lead levels. One hundred twenty adults with EARMs and 120 age- and gender-matched controls with no history of gunshot wound were prospectively enrolled on presentation to a large urban emergency department. Whole blood lead (WBL), zinc protoporphyrin, and hemoglobin levels were obtained. Patients completed a questionnaire regarding time since gunshot injury; symptoms of lead toxicity; and occurrence within 30 days of any surgery, alcohol abuse, illicit drug abuse, diabetic ketoacidosis, hyperthyroidism, infection, fracture, pregnancy, or lactation. Five EARM patients (4%) and no control patients (0%) had WBL greater than our threshold for medical follow-up (20 microg/dL). Mean WBL was 6.71 microg/dL (95% confidence interval [CI], 5.68-7.74 microg/dL) in EARM patients and 3.16 mug/dL (95% CI, 2.79-3.53 microg/dL) in controls. This difference was statistically significant when analyzed by matched pairs t test (p = 0.0001). There was no difference in the number of symptoms associated with lead toxicity that were noted by EARM patients versus controls (p = 0.377). Longer duration of missile retention was not associated with higher blood lead levels (r = 0.125, p = 0.172). Of the five hypermetabolic conditions analyzed, only fractures were associated with elevated blood lead levels (9.95 microg/dL [95% CI, 5.77-14.13 microg/dL] in EARM patients with fractures vs. 6.23 microg/dL [95% CI, 5.23-7.23 microg/dL] in EARM patients without fractures). Patients with EARMs have significantly elevated blood lead levels compared with matched controls. The occurrence of a bony fracture within the past 30 days is associated with a higher lead level. In 96% of patients with EARMs, elevated lead levels were not clinically significant and did not change patient management.

Ecotoxicological characterization of polyoxyethylene glycerol ester non-ionic surfactants and their mixtures with anionic and non-ionic surfactants.

PubMed

Ríos, Francisco; Fernández-Arteaga, Alejandro; Lechuga, Manuela; Fernández-Serrano, Mercedes

2017-04-01

This paper reports on a study that investigated the aquatic toxicity of new non-ionic surfactants derived from renewable raw materials, polyoxyethylene glycerol ester (PGE), and their binary mixtures with anionic and non-ionic surfactants. Toxicity of pure PGEs was determined using representative organisms from different trophic levels: luminescent bacteria (Vibrio fischeri), microalgae (Pseudokirchneriella subcapitata), and freshwater crustaceans (Daphnia magna). Relationships between toxicity and the structural parameters such as unit of ethylene oxide (EO) and hydrophilic-lipophilic balance (HLB) were evaluated. Critical micellar concentration (CMC) in the conditions of the toxicity test was also determined. It was found that the toxicity of the aqueous solutions of PGE decreased when the number of EO units in the molecule, HLB, and CMC increased. PGEs showed lower CMC in marine medium, and the toxicity to V. ficheri is lower when the CMC was higher. Given their non-polar nature, narcosis was expected to be the primary mode of toxic action of PGEs. For the mixture of surfactants, we observed that the mixtures with PGE that had the higher numbers of EO units were more toxic than the aqueous solutions of pure surfactants. Moreover, we found that concentration addition was the type of action more likely to occur for mixtures of PGE with lower numbers of EO units with non-ionic surfactants (alkylpolyglucoside and fatty alcohol ethoxylate), whereas for the mixture of PGE with lower EO units and anionic surfactant (ether carboxylic derivative), the most common response type was response addition. In case of mixtures involving amphoteric surfactants and PGEs with the higher numbers of EO units, no clear pattern with regard to the mixture toxicity response type could be observed.

Long-term cosmetic outcomes and toxicities of proton beam therapy compared with photon-based 3-dimensional conformal accelerated partial-breast irradiation: a phase 1 trial.

PubMed

Galland-Girodet, Sigolène; Pashtan, Itai; MacDonald, Shannon M; Ancukiewicz, Marek; Hirsch, Ariel E; Kachnic, Lisa A; Specht, Michelle; Gadd, Michele; Smith, Barbara L; Powell, Simon N; Recht, Abram; Taghian, Alphonse G

2014-11-01

To present long-term outcomes of a prospective feasibility trial using either protons or 3-dimensional conformal photon-based (accelerated partial-breast irradiation [APBI]) techniques. From October 2003 to April 2006, 98 evaluable patients with stage I breast cancer were treated with APBI (32 Gy in 8 fractions given twice daily) on a prospective clinical trial: 19 with proton beam therapy (PBT) and 79 with photons or mixed photons/electrons. Median follow-up was 82.5 months (range, 2-104 months). Toxicity and patient satisfaction evaluations were performed at each visit. At 7 years, the physician rating of overall cosmesis was good or excellent for 62% of PBT patients, compared with 94% for photon patients (P=.03). Skin toxicities were more common for the PBT group: telangiectasia, 69% and 16% (P=.0013); pigmentation changes, 54% and 22% (P=.02); and other late skin toxicities, 62% and 18% (P=.029) for PBT and photons, respectively. There were no significant differences between the groups in the incidences of breast pain, edema, fibrosis, fat necrosis, skin desquamation, and rib pain or fracture. Patient-reported cosmetic outcomes at 7 years were good or excellent for 92% and 96% of PBT and photon patients, respectively (P=.95). Overall patient satisfaction was 93% for the entire cohort. The 7-year local failure rate for all patients was 6%, with 3 local recurrences in the PBT group (7-year rate, 11%) and 2 in photon-treated patients (4%) (P=.22). Local failure rates of 3-dimensional APBI and PBT were similar in this study. However, PBT, as delivered in this study, led to higher rates of long-term telangiectasia, skin color changes, and skin toxicities. We recommend the use of multiple fields and treatment of all fields per treatment session or the use of scanning techniques to minimize skin toxicity. Copyright © 2014 Elsevier Inc. All rights reserved.

Acute toxicity of 353-nonylphenol and its metabolites for zebrafish embryos.

PubMed

Kammann, Ulrike; Vobach, Michael; Wosniok, Werner; Schäffer, Andreas; Telscher, Andreas

2009-03-01

Nonylphenol (NP) can be detected in the aquatic environment all over the world. It is applied as a technical mixture of isomers of which 353-NP is the most relevant both in terms of abundance (about 20% of total mass) and endocrine potential. 353-NP is metabolised in sewage sludge. The aims of the present study were to determine and to compare the acute toxicity of t-NP, 353-NP and its metabolites as well as to discuss if the toxicity of 353-NP changes during degradation. 353-NP and two of its metabolites were synthesised. The zebrafish embryo test was performed according to standard protocols. Several lethal and non-lethal endpoints during embryonal development were reported. NOEL, LOEL and EC50 were calculated. All tested compounds caused lethal as well as non-lethal malformations during embryo development. 353-NP showed a higher toxicity (EC50 for lethal endpoints 6.7 mg/L) compared to its metabolites 4-(3.5-dimethyl-3-heptyl)-2-nitrophenol (EC50 13.3 mg/L) and 4-(3,5-dimethyl-3-heptyl)-2-bromophenol (EC50 27.1 mg/L). In surface water, concentrations of NP are far below the NOEC identified by the zebrafish embryo test. However, in soils and sewage sludge, concentrations may reach or even exceed these concentrations. Therefore, sludge-treated sites close to surface waters should be analysed for NP and its metabolites in order to detect an unduly high contamination due to runoff events. The results of the present study point out that the toxicity of 353-NP probably declines during metabolisation in water, sediment and soil, but does not vanish since the major metabolites exhibit a clear toxic potential for zebrafish embryos. Metabolites of environmental pollutants should be included in the ecotoxicological test strategy for a proper risk assessment.

Comparison of adverse effects of proton and X-ray chemoradiotherapy for esophageal cancer using an adaptive dose-volume histogram analysis.

PubMed

Makishima, Hirokazu; Ishikawa, Hitoshi; Terunuma, Toshiyuki; Hashimoto, Takayuki; Yamanashi, Koichi; Sekiguchi, Takao; Mizumoto, Masashi; Okumura, Toshiyuki; Sakae, Takeji; Sakurai, Hideyuki

2015-05-01

Cardiopulmonary late toxicity is of concern in concurrent chemoradiotherapy (CCRT) for esophageal cancer. The aim of this study was to examine the benefit of proton beam therapy (PBT) using clinical data and adaptive dose-volume histogram (DVH) analysis. The subjects were 44 patients with esophageal cancer who underwent definitive CCRT using X-rays (n = 19) or protons (n = 25). Experimental recalculation using protons was performed for the patient actually treated with X-rays, and vice versa. Target coverage and dose constraints of normal tissues were conserved. Lung V5-V20, mean lung dose (MLD), and heart V30-V50 were compared for risk organ doses between experimental plans and actual treatment plans. Potential toxicity was estimated using protons in patients actually treated with X-rays, and vice versa. Pulmonary events of Grade ≥2 occurred in 8/44 cases (18%), and cardiac events were seen in 11 cases (25%). Risk organ doses in patients with events of Grade ≥2 were significantly higher than for those with events of Grade ≤1. Risk organ doses were lower in proton plans compared with X-ray plans. All patients suffering toxicity who were treated with X-rays (n = 13) had reduced predicted doses in lung and heart using protons, while doses in all patients treated with protons (n = 24) with toxicity of Grade ≤1 had worsened predicted toxicity with X-rays. Analysis of normal tissue complication probability showed a potential reduction in toxicity by using proton beams. Irradiation dose, volume and adverse effects on the heart and lung can be reduced using protons. Thus, PBT is a promising treatment modality for the management of esophageal cancer. © The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Screen of Bacillus thuringiensis toxins for transgenic rice to control Sesamia inferens and Chilo suppressalis.

PubMed

Gao, Yulin; Hu, Yang; Fu, Qiang; Zhang, Jie; Oppert, Brenda; Lai, Fengxiang; Peng, Yufa; Zhang, Zhitao

2010-09-01

Transgenic rice to control stem borer damage is under development in China. To assess the potential of Bacillus thuringiensis (Bt) transgenes in stem borer control, the toxicity of five Bt protoxins (Cry1Aa, Cry1Ab, Cry1Ac, Cry1Ba and Cry1Ca) against two rice stem borers, Sesamia inferens (pink stem borer) and Chilo suppressalis (striped stem borer), was evaluated in the laboratory by feeding neonate larvae on artificial diets containing Bt protoxins. The results indicated that Cry1Ca exhibited the highest level of toxicity to both stem borers, with an LC(50) of 0.24 and 0.30 microg/g for C. suppressalis and S. inferens, respectively. However, S. inferens was 4-fold lower in susceptibility to Cry1Aa, and 6- and 47-fold less susceptible to Cry1Ab and Cry1Ba, respectively, compared to C. suppressalis. To evaluate interactions among Bt protoxins in stem borer larvae, toxicity assays were performed with mixtures of Cry1Aa/Cry1Ab, Cry1Aa/Cry1Ca, Cry1Ac/Cry1Ca, Cry1Ac/Cry1Ba, Cry1Ab/Cry1Ac, Cry1Ab/Cry1Ba, and Cry1Ab/Cry1Ca at 1:1 (w/w) ratios. All protoxin mixtures demonstrated significant synergistic toxicity activity against C. suppressalis, with values of 1.6- to 11-fold higher toxicity than the theoretical additive effect. Surprisingly, all but one of the Bt protoxin mixtures were antagonistic in toxicity to S. inferens. In mortality-time response experiments, S. inferens demonstrated increased tolerance to Cry1Ab and Cry1Ac compared to C. suppressalis when treated with low or high protoxin concentrations. The data indicate the utility of Cry1Ca protoxin and a Cry1Ac/Cry1Ca mixture to control both stem borer populations. Copyright 2010 Elsevier Inc. All rights reserved.

Influence of flow-through and renewal exposures on the toxicity of copper to rainbow trout

USGS Publications Warehouse

Welsh, P.G.; Lipton, J.; Mebane, C.A.; Marr, J.C.A.

2008-01-01

We examined changes in water chemistry and copper (Cu) toxicity in three paired renewal and flow-through acute bioassays with rainbow trout (Oncorhynchus mykiss). Test exposure methodology influenced both exposure water chemistry and measured Cu toxicity. Ammonia and organic carbon concentrations were higher and the fraction of dissolved Cu lower in renewal tests than in paired flow-through tests. Cu toxicity was also lower in renewal tests; 96 h dissolved Cu LC50 values were 7-60% higher than LC50s from matching flow-through tests. LC50 values in both types of tests were related to dissolved organic carbon (DOC) concentrations in exposure tanks. Increases in organic carbon concentrations in renewal tests were associated with reduced Cu toxicity, likely as a result of the lower bioavailability of Cu-organic carbon complexes. The biotic ligand model of acute Cu toxicity tended to underpredict toxicity in the presence of DOC. Model fits between predicted and observed toxicity were improved by assuming that only 50% of the measured DOC was reactive, and that this reactive fraction was present as fulvic acid. ?? 2007 Elsevier Inc. All rights reserved.

Honeybee (Apis cerana) foraging responses to the toxic honey of Tripterygium hypoglaucum (Celastraceae): changing threshold of nectar acceptability.

PubMed

Tan, K; Guo, Y H; Nicolson, S W; Radloff, S E; Song, Q S; Hepburn, H R

2007-12-01

To investigate honeybee foraging responses to toxic nectar, honey was collected from Apis cerana colonies in the Yaoan county of Yunnan Province, China, during June, when flowers of Tripterygium hypoglaucum were the main nectar source available. Pollen analysis confirmed the origin of the honey, and high-performance liquid chromatography showed the prominent component triptolide to be present at a concentration of 0.61 mug/g +/- 0.11 SD. In cage tests that used young adult worker bees, significantly more of those provided with a diet of T. hypoglaucum honey mixed with sugar powder (1:1) died within 6 d (68.3%) compared to control groups provided with normal honey mixed with sugar powder (15.8%). Honeybees were trained to visit feeders that contained honey of T. hypoglaucum (toxic honey) as the test group and honey of Vicia sativa or Elsholtzia ciliata as control groups (all honeys diluted 1:3 with water). Bees preferred the feeders with normal honey to those with toxic honey, as shown by significantly higher visiting frequencies and longer imbibition times. However, when the feeder of normal honey was removed, leaving only honey of T. hypoglaucum, the foraging bees returned to the toxic honey after a few seconds of hesitation, and both visiting frequency and imbibition time increased to values previously recorded for normal honey. Toxic honey thus became acceptable to the bees in the absence of other nectar sources.

Comparative Toxicities of Newer and Conventional Insecticides: Against Four Generalist Predator Species.

PubMed

Prabhaker, Nilima; Naranjo, Steven; Perring, Thomas; Castle, Steven

2017-12-05

Generalist insect predators play an essential role in regulating the populations of Bemisia tabaci and other pests in agricultural systems, but may be affected negatively by insecticides applied for pest management. Evaluation of insecticide compatibility with specific predator species can provide a basis for making treatment decisions with the aim of conserving natural enemies. Eleven insecticides representing six modes of action groups were evaluated for toxicity against four predator species and at different developmental stages. Full-concentration series bioassays were conducted on laboratory-reared or insectary-supplied predators using Petri dish and systemic uptake bioassay techniques. Highest toxicities were observed with imidacloprid and clothianidin against first and second instar nymphs of Geocoris punctipes (Say) (Hemiptera: Geocoridae). Later instar nymphs were less susceptible to neonicotinoid treatments based on higher LC50s observed with imidacloprid, thiamethoxam, and dinotefuran against third or fourth instar nymphs. The pyrethroid insecticide bifenthrin was highly toxic against adults of G. punctipes and Orius insidiosus (Say) (Hemiptera: Anthocoridae). Standard concentration/mortality evaluation of nonacute toxicity insecticides, including buprofezin, pyriproxyfen, spirotetramat, and spiromesifen, was inconclusive in terms of generating probit statistics. However, low mortality levels of insects exposed for up to 120 h suggested minimal lethality with the exception of pyriproxyfen that was mildly toxic to Chrysoperla rufilabris (Burmeister) (Neuroptera: Chrysopidae). Published by Oxford University Press on behalf of Entomological Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Stability of citrate-capped silver nanoparticles in exposure media and their effects on the development of embryonic zebrafish (Danio rerio)

PubMed Central

Park, Kwangsik; Tuttle, George; Sinche, Federico; Harper, Stace L.

2014-01-01

The stability of citrate-capped silver nanoparticles (AgNPs) and the embryonic developmental toxicity were evaluated in the fish test water. Serious aggregation of AgNPs was observed in undiluted fish water (DM-100) in which high concentration of ionic salts exist. However, AgNPs were found to be stable for 7 days in DM-10, prepared by diluting the original fish water (DM-100) with deionized water to 10%. The normal physiology of zebrafish embryos were evaluated in DM-10 to see if DM-10 can be used as a control vehicle for the embryonic fish toxicity test. As results, DM-10 without AgNPs did not induce any significant adverse effects on embryonic development of zebrafish determined by mortality, hatching, malformations and heart rate. When embryonic toxicity of AgNPs was tested in both DM-10 and in DM-100, AgNPs showed higher toxicity in DM-10 than in DM-100. This means that the big-sized aggregates of AgNPs were low toxic compared to the nano-sized AgNPs. AgNPs induced delayed hatching, decreased heart rate, pericardial edema, and embryo death. Accumulation of AgNPs in the embryo bodies was also observed. Based on this study, citrate-capped AgNPs are not aggregated in DM-10 and it can be used as a control vehicle in the toxicity test of fish embryonic development. PMID:23325492

Comparative In Vitro Biological Toxicity of Four Kinds of Air Pollution Particles.

PubMed

Shin, Han-Jae; Cho, Hyun Gi; Park, Chang Kyun; Park, Ki Hong; Lim, Heung Bin

2017-10-01

Accumulating epidemiological evidence indicates that exposure to fine air pollution particles (APPs) is associated with a variety of adverse health effects. However, the exact physiochemical properties and biological toxicities of fine APPs are still not well characterized. We collected four types of fine particle (FP) (diesel exhaust particles [DEPs], natural organic combustion [NOC] ash, synthetic organic combustion [SOC] ash, and yellow sand dust [YSD]) and investigated their physicochemical properties and in vitro biological toxicity. DEPs were almost entirely composed of ultrafine particles (UFPs), while the NOC, SOC, and YSD particles were a mixture of UFPs and FPs. The main elements in the DEPs, NOC ash, SOC ash, and YSD were black carbon, silicon, black carbon, and silicon, respectively. DEPs exhibited dose-dependent mutagenicity even at a low dose in Salmonella typhimurium TA 98 and 100 strains in an Ames test for genotoxicity. However, NOC, SOC, and YSD particles did not show any mutagenicity at high doses. The neutral red uptake assay to test cell viability revealed that DEPs showed dose-dependent potent cytotoxicity even at a low concentration. The toxicity of DEPs was relatively higher than that of NOC, SOC, and YSD particles. Therefore, these results indicate that among the four FPs, DEPs showed the highest in vitro biological toxicity. Additional comprehensive research studies such as chemical analysis and in vivo acute and chronic inhalation toxicity tests are necessary to determine and clarify the effects of this air contaminant on human health.

Intravascular hemolysis induced by phospholipases A2 from the venom of the Eastern coral snake, Micrurus fulvius: Functional profiles of hemolytic and non-hemolytic isoforms.

PubMed

Fernández, María Laura; Quartino, Pablo Yunes; Arce-Bejarano, Ruth; Fernández, Julián; Camacho, Luis F; Gutiérrez, José María; Kuemmel, Daniel; Fidelio, Gerardo; Lomonte, Bruno

2018-04-01

A unique feature of the venom of Micrurus fulvius (Eastern coral snake) is its ability to induce severe intravascular hemolysis in particular species, such as dogs or mice. This effect was previously shown to be induced by distinct phospholipase A 2 (PLA 2 ) isoforms which cause direct hemolysis in vitro, an uncommon finding for such enzymes. The functional profiles of PLA 2 -17, a direct hemolytic enzyme, and PLA 2 -12, a co-existing venom isoform lacking such effect, were compared. The enzymes differed not only in their ability to cause intravascular hemolysis: PLA 2 -17 additionally displayed lethal, myotoxic, and anticoagulant actions, whereas PLA 2 -12 lacked these effects. PLA 2 -12 was much more active in hydrolyzing a monodisperse synthetic substrate than PLA 2 -17, but the catalytic activity of latter was notably higher on a micellar substrate, or towards pure phospholipid artificial monolayers under controlled lateral pressures. Interestingly, PLA 2 -17 could hydrolyze substrate at a pressure of 20 mN m -1 , in contrast to PLA 2 -12 or the non-toxic pancreatic PLA 2 . This suggests important differences in the monolayer penetrating power, which could be related to differences in toxicity. Comparative examination of primary structures and predicted three-dimensional folding of PLA 2 -12 and PLA 2 -17, revealed that differences concentrate in their N-terminal and central regions, leading to variations of the surface properties at the membrane interacting interface. PLA 2 -17 presents a less basic interfacial surface than PLA 2 -12, but more bulky aromatic residues, which could be associated to its higher membrane-penetrating strength. Altogether, these structural and functional comparative observations suggest that the ability of PLA 2 s to penetrate substrate interfaces could be a major determinant of toxicity, perhaps more important than protein surface charge. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparison of non-toxic methods for creating beta-carotene encapsulated in PMMA nanoparticles

NASA Astrophysics Data System (ADS)

Dobrzanski, Christopher D.

Nano/microcapsules are becoming more prevalent in various industries such as drug delivery, cosmetics, etc. Current methods of particle formation often use toxic or carcinogenic/mutagenic/reprotoxic (CMR) chemicals. This study intends to improve upon existing methods of particle formation and compare their effectiveness in terms of entrapment efficiency, mean particle size, and yield utilizing only non-toxic chemicals. In this study, the solvent evaporation (SE), spontaneous emulsification, and spontaneous emulsion solvent diffusion (SESD) methods were compared in systems containing green solvents ethyl acetate, dimethyl carbonate or acetone. PMMA particles containing encapsulated beta carotene, an ultraviolet sensitive substance, were synthesized. It was desired to produce particles with minimum mean size and maximum yield and entrapment of beta carotene. The mass of the water phase, the mass of the polymer and the pumping or blending rate were varied for each synthesis method. The smallest particle sizes for SE and SESD both were obtained from the middle water phase sizes, 200 g and 100 g respectively. The particles obtained from the larger water phase in SESD were much bigger, about 5 microns in diameter, even larger than the ones obtained from SE. When varying the mass of PMMA used in each synthesis method, as expected, more PMMA led to larger particles. Increasing the blending rate in SE from 6,500 to 13,500 rpm had a minimal effect on average particle size, but the higher shear resulted in highly polydisperse particles (PDI = 0.87). By decreasing the pump rate in SESD, particles became smaller and had lower entrapment efficiency. The entrapment efficiencies of the particles were generally higher for the larger particles within a mode. Therefore, we found that minimizing the particle size while maximizing entrapment were somewhat contradictory goals. The solvent evaporation method was very consistent in terms of the values of mean particle size, yield, and entrapment efficiency. Comparing the synthesis methods, the smallest particles with the highest yield and entrapment efficiency were generated by the spontaneous emulsification method.

Occurrence, profiles, and toxic equivalents of chlorinated and brominated polycyclic aromatic hydrocarbons in E-waste open burning soils.

PubMed

Nishimura, Chiya; Horii, Yuichi; Tanaka, Shuhei; Asante, Kwadwo Ansong; Ballesteros, Florencio; Viet, Pham Hung; Itai, Takaaki; Takigami, Hidetaka; Tanabe, Shinsuke; Fujimori, Takashi

2017-06-01

We conducted this study to assess the occurrence, profiles, and toxicity of chlorinated polycyclic aromatic hydrocarbons (Cl-PAHs) and brominated polycyclic aromatic hydrocarbons (Br-PAHs) in e-waste open burning soils (EOBS). In this study, concentrations of 15 PAHs, 26 Cl-PAHs and 14 Br-PAHs were analyzed in EOBS samples. We found that e-waste open burning is an important emission source of Cl-PAHs and Br-PAHs as well as PAHs. Concentrations of total Cl-PAHs and Br-PAHs in e-waste open burning soil samples ranged from 21 to 2800 ng/g and from 5.8 to 520 ng/g, respectively. Compared with previous studies, the mean of total Cl-PAH concentrations of the EOBS samples in this study was higher than that of electronic shredder waste, that of bottom ash, and comparable to fly ash from waste incinerators in Korea and Japan. The mean of total Br-PAH concentrations of the EOBS samples was generally three to four orders of magnitude higher than those in incinerator bottom ash and comparable to incinerator fly ash, although the number of Br-PAH congeners measured differed among studies. We also found that the Cl-PAH and Br-PAH profiles were similar among all e-waste open burning soil samples but differed from those in waste incinerator fly ash. The profiles and principal component analysis results suggested a unique mechanism of Cl-PAH and Br-PAH formation in EOBS. In addition, the Cl-PAHs and Br-PAHs showed high toxicities equivalent to PCDD/Fs measured in same EOBS samples when calculated based on their relative potencies to benzo[a]pyrene. Along with chlorinated and brominated dioxins and PAHs, Cl-PAHs and Br-PAHs are important environmental pollutants to investigate in EOBS. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effect of genetic strain and gender on age-related changes in body composition of the laboratory rat.

PubMed

Gordon, C J; Jarema, K; Johnstone, A F M; Phillips, P M

2016-01-01

Body fat serves as a storage compartment for lipophilic pollutants and affects the pharmacokinetics of many toxic chemicals. Understanding how body fat varies with gender, strain, and age may be essential for development of experimental models to study mechanisms of toxicity. Nuclear magnetic resonance (NMR)-based analysis serves as a noninvasive means of assessing proportions of fat, lean, and fluid in rodents over their lifetime. The aim of this study was to track changes in body composition of male and female Long-Evans (LE), Sprague-Dawley (SD), Fischer (F334), and Brown Norway (BN) rats from postweaning over a >2-yr period. Percent fat of preweaned LE and SD rats was markedly higher compared to the other strains. LE and SD strains displayed marked increases in body fat from weaning to 8 mo of age. Postweaned F344 male and females showed relatively low levels of percent fat; however, at 2 yr of age percent fat of females was equal to that of SD and LE in females. BN rats showed the highest levels of lean tissue and lowest levels of fat. Percent fat of the BN strain rose at the slowest rate as they aged. Percent fluid was consistently higher in males for all strains. Females tended to have higher percent fat than males in LE, SD, and F344 strains. Assessing changes in body fat as well as lean and fluid of various strains of male and female rats over their lifetime may prove useful in many research endeavors, including pharmacokinetics of lipophilic toxicants, mechanisms underlying obesity, and metabolic disorders.

Diallyl Polysulfides from Allium sativum as Immunomodulators, Hepatoprotectors, and Antimycobacterial Agents.

PubMed

Oosthuizen, Carel; Arbach, Miriam; Meyer, Debra; Hamilton, Chris; Lall, Namrita

2017-07-01

Mycobacterium tuberculosis remains one of the world's deadliest killers, with an annual death rate of ∼1.5 million. The medicinal effects of garlic have been well documented, and natural products have been shown to have antimycobacterial activity. The current study evaluated the efficacy of six Allium sativum L. polysulfide mixtures as antimycobacterial agents together with their cytotoxic, immunomodulatory, and hepatoprotective activities. The microtitre PrestoBlue assay was used to determine the minimum inhibitory concentrations (MIC). Cytotoxicity was evaluated by using peripheral blood mononuclear cells (PBMC). Excreted cytokine levels were determined by utilizing an enzyme-linked immunosorbent assay (ELISA), by exposing isolated PBMCs to varying concentrations of polysulfide mixtures. Human C3A liver cells were utilized in the hepatoprotective study, to assess the protective effect against the toxicity induced by acetaminophen. Samples with higher amounts of diallyl trisulfide (Sample G4) showed the highest antimycobacterial activity, exhibiting an MIC of 2.5 μg/mL against M. tuberculosis H37Rv. Five samples showed moderate toxicity in PBMC, with G1 showing no toxicity. The selective index of G4 was the highest, with a selectivity index close to one. Two samples, G3 and G6 containing higher amounts of diallyl tetrasulfide and lower amounts of diallyl trisulfide, showed >50% hepatoprotection. This is comparable to a hepatoprotective agent, Silymarin, which showed a hepatoprotective effect of 30% at the tested concentration. Diallyl tetrasulfide showed significant antimycobacterial activity. A combination of higher diallyl tetrasulfide and lower diallyl trisulfide was indicative of hepatoprotective activity.

In vitro antioxidant and anti-lipoperoxidative activities of bark extracts of Xylopia aethiopica against ion-mediated toxicity on liver homogenates.

PubMed

Moukette Moukette, Bruno; Pieme, Constant Anatole; Nya Biapa, Prosper Cabral; Ngogang, Jeanne Yonkeu

2015-09-01

Reactive oxygen species (ROS), products of normal cell metabolism may cause damage to biological macromolecules leading to severe health threats when they are present in high concentrations. Aromatic plants contain phytochemicals rich of antioxidants that prevent oxidant formation or scavenge oxidants produced under oxidative stress conditions. In the present study, we investigated the free radical scavenging effects, the antioxidant and ion toxicity preventive effect of Xylopia aethiopica (X. aethiopica), a plant of the family of Annonaceae used as spice in Cameroon. The scavenging properties of extracts of X. aethiopica were tested on 2, 2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO), hydroxyl (OH), 2,2'-azinobis(3-ethylbenzthiazoline)-6-sulfonic acid (ABTS) radicals. The total antioxidant capacity was assayed by ferric reducing ability of plasma (FRAP), phosphomolybdenum antioxidant power (PAP), reduction assays. The protective potential was carried on superoxide dismutase (SOD), catalase and peroxidases. The results showed that both the ethanolic (BEE) and the hydroethanolic (BEH) extracts from the barks of X. aethiopica scavenged all the tested radicals. The sample BEH showed the highest total antioxidant capacity both in the FRAP and the PAP. This result was positively correlated to its higher phenolic content (30.74±0.44 CAE/g dried extract). The higher protective capacity of BEH on SOD, catalase and peroxidase activities was comparable to that of the vitamin C used as standard. In conclusion, X. aethiopica has a higher antioxidant and protective potential against ion-mediated oxidative damage and may be considered as a potential drug against metal-mediated toxicity.

Urethral toxicity after LDR brachytherapy: experience in Japan.

PubMed

Tanaka, Nobumichi; Asakawa, Isao; Hasegawa, Masatoshi; Fujimoto, Kiyohide

2015-01-01

Urinary toxicity is common after low-dose-rate (LDR) brachytherapy, and the resolution of urinary toxicity is a concern. In particular, urinary frequency is the most common adverse event among the urinary toxicities. We have previously reported that approximately 70% of patients experience urinary frequency during the first 6 months after seed implantation. Most urinary adverse events were classified as Grade 1, and Grade 2 or higher adverse events were rare. The incidence of urinary retention was approximately 2-4%. A high International Prostate Symptom Score before seed implantation was an independent predictor of acute urinary toxicity of Grade 2 or higher. Several previous reports from the United States also supported this trend. In Japan, LDR brachytherapy was legally approved in 2003. A nationwide prospective cohort study entitled Japanese Prostate Cancer Outcome Study of Permanent Iodine-125 Seed Implantation was initiated in July 2005. It is an important issue to limit urinary toxicities in patients who undergo LDR brachytherapy. Copyright © 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Toxicity evaluation of β-diketone antibiotics on the development of embryo-larval zebrafish (Danio rerio).

PubMed

Wang, Huili; Che, Baoguang; Duan, Ailian; Mao, Jingwen; Dahlgren, Randy A; Zhang, Minghua; Zhang, Hongqin; Zeng, Aibing; Wang, Xuedong

2014-10-01

This study evaluated the effects of β-diketone antibiotics (DKAs) on the development of embryo-larval zebrafish (Danio rerio). When exposure to DKAs, developmental malformations, such as hatching delay, curved body axis, pericardial edema, uninflated swim bladder and yolk sac edema, were observed at 120 h postfertilization (hpf). The estimated 120 hpf nominal concentrations of no observed effect concentration and lowest observed effect concentration for DKAs were 18.75 and 37.50 mg/L, respectively, suggesting that DKAs have much lower toxicity than other persistent pollutants. Following DKA exposure, embryonic heart rates were significantly reduced as compared to the controls at 48 and 60 hpf. The peak bending motion frequency appeared 1 h earlier than in control embryos. The 2.34 and 9.38-mg/L treatment groups had a higher basal swim rate than control groups at 120 hpf in both light and light-to-dark photoperiod experiments. The occurrence of high speed swim rates was enhanced approximately threefold to sevenfold in the 2.34 and 9.38 mg/L treatments compared to the control. Glutathione (GSH) concentrations in the 2.34 and 9.38-mg/L treatments were significantly higher than the control at 72 hpf, suggesting that GSH production was induced at the end of the hatching period. When exposed to DKAs, zebrafish superoxide dismutase enzyme (SOD) activities were significantly inhibited in the early embryonic period, demonstrating that the clearing ability in zebrafish was lower than the generation rate of free radicals. In summary, the combined DKAs were developmentally toxic to zebrafish in their early life stages and had the ability to impair individual behaviors that are of great importance in the assessment of their ecological fitness. Copyright © 2013 Wiley Periodicals, Inc., a Wiley company.

Rituximab, methotrexate, procarbazine, vincristine and intensified cytarabine consolidation for primary central nervous system lymphoma (PCNSL) in the elderly: a LOC network study.

PubMed

Houillier, Caroline; Ghesquières, Hervé; Chabrot, Cécile; Soussain, Carole; Ahle, Guido; Choquet, Sylvain; Nicolas-Virelizier, Emmanuelle; Bay, Jacques-Olivier; Vargaftig, Jacques; Gaultier, Claude; Touitou, Valérie; Martin-Duverneuil, Nadine; Cassoux, Nathalie; Le Garff-Tavernier, Magali; Costopoulos, Myrto; Faurie, Pierre; Hoang-Xuan, Khê

2017-06-01

Primary CNS lymphoma (PCNSL) is chemosensitive to high-dose methotrexate-based chemotherapy. However, responses in the elderly are short-lasting and outcome is poor. Given that radiotherapy and intensive chemotherapy expose elderly to severe toxicities, alternative consolidation approaches need to be evaluated. In this multicenter study, we retrospectively analyzed consecutive patients with newly-diagnosed PCNSL, aged >60, treated with a (R)-MPV-AAA regimen. The regimen consisted of three 28-day cycles of methotrexate (3.5 g/m 2 D1, D15), procarbazine, vincristine, followed by three 28-day cycles of cytarabine consolidation (3 g/m 2 D1-2). Addition of rituximab (375 mg/m 2 D1) was optional. The results were compared with the historical MPV-A regimen. Ninety patients received the (R)-MPV-AAA regimen with (n = 39) or without (n = 51) rituximab. Median age was 68 and median KPS 60. 55% of patients achieved a complete response, 8% a partial response and 37% progressed. The median PFS was 10 months, the median OS 28.1 months. Toxicity was mainly hematological, with 54 and 51% of grade III-IV neutropenia and thrombopenia. The response rate was higher in patients receiving rituximab (77 vs. 53%; p = 0.03), whereas no difference was observed in terms of PFS or OS. When comparing the results to the historical MPV-A, there was no difference in terms of response rate, PFS or OS, but a higher rate of hematotoxicity. This study suggests that extending cytarabine consolidation after methotrexate-based chemotherapy does not improve the MPV-A efficacy but increases toxicity in the elderly. The addition of rituximab may improve the response rate, but its impact on final outcome remains unclear.

Different patterns of nuclear and mitochondrial penetration by the G3 PAMAM dendrimer and its biotin–pyridoxal bioconjugate BC-PAMAM in normal and cancer cells in vitro

PubMed Central

Uram, Łukasz; Szuster, Magdalena; Filipowicz, Aleksandra; Gargasz, Krzysztof; Wołowiec, Stanisław; Wałajtys-Rode, Elżbieta

2015-01-01

The intracellular localization and colocalization of a fluorescently labeled G3 amine-terminated cationic polyamidoamine (PAMAM) dendrimer and its biotin–pyridoxal (BC-PAMAM) bioconjugate were investigated in a concentration-dependent manner in normal human fibroblast (BJ) and squamous epithelial carcinoma (SCC-15) cell lines. After 24 hours treatment, both cell lines revealed different patterns of intracellular dendrimer accumulation depending on their cytotoxic effects. Cancer cells exhibited much higher (20-fold) tolerance for native PAMAM treatment than fibroblasts, whereas BC-PAMAM was significantly toxic only for fibroblasts at 50 µM concentration. Fibroblasts accumulated the native and bioconjugated dendrimers in a concentration-dependent manner at nontoxic range of concentration, with significantly lower bioconjugate loading. After reaching the cytotoxicity level, fluorescein isothiocyanate-PAMAM accumulation remains at high, comparable level. In cancer cells, native PAMAM loading at higher, but not cytotoxic concentrations, was kept at constant level with a sharp increase at toxic concentration. Mander’s coefficient calculated for fibroblasts and cancer cells confirmed more efficient native PAMAM penetration as compared to BC-PAMAM. Significant differences in nuclear dendrimer penetration were observed for both cell lines. In cancer cells, PAMAM signals amounted to ~25%–35% of the total nuclei area at all investigated concentrations, with lower level (15%–25%) observed for BC-PAMAM. In fibroblasts, the dendrimer nuclear signal amounted to 15% at nontoxic and up to 70% at toxic concentrations, whereas BC-PAMAM remained at a lower concentration-dependent level (0.3%–20%). Mitochondrial localization of PAMAM and BC-PAMAM revealed similar patterns in both cell lines, depending on the extracellular dendrimer concentration, and presented significantly lower signals from BC-PAMAM, which correlated well with the cytotoxicity. PMID:26379435

Antibiotics and sweeteners in the aquatic environment: biodegradability, formation of phototransformation products, and in vitro toxicity.

PubMed

Bergheim, Marlies; Gminski, Richard; Spangenberg, Bernd; Debiak, Malgorzata; Bürkle, Alexander; Mersch-Sundermann, Volker; Kümmerer, Klaus; Gieré, Reto

2015-11-01

In the present study, in vitro toxicity as well as biopersistence and photopersistence of four artificial sweeteners (acesulfame, cyclamate, saccharine, and sucralose) and five antibiotics (levofloxacin, lincomycin, linezolid, marbofloxacin, and sarafloxacin) and of their phototransformation products (PTPs) were investigated. Furthermore, antibiotic activity was evaluated after UV irradiation and after exposure to inocula of a sewage treatment plant. The study reveals that most of the tested compounds and their PTPs were neither readily nor inherently biodegradable in the Organisation for Economic Co-operation and Development (OECD)-biodegradability tests. The study further demonstrates that PTPs are formed upon irradiation with an Hg lamp (UV light) and, to a lesser extent, upon irradiation with a Xe lamp (mimics sunlight). Comparing the nonirradiated with the corresponding irradiated solutions, a higher chronic toxicity against bacteria was found for the irradiated solutions of linezolid. Neither cytotoxicity nor genotoxicity was found in human cervical (HeLa) and liver (Hep-G2) cells for any of the investigated compounds or their PTPs. Antimicrobial activity of the tested fluoroquinolones was reduced after UV treatment, but it was not reduced after a 28-day exposure to inocula of a sewage treatment plant. This comparative study shows that PTPs can be formed as a result of UV treatment. The study further demonstrated that UV irradiation can be effective in reducing the antimicrobial activity of antibiotics, and consequently may help to reduce antimicrobial resistance in wastewaters. Nevertheless, the study also highlights that some PTPs may exhibit a higher ecotoxicity than the respective parent compounds. Consequently, UV treatment does not transform all micropollutants into harmless compounds and may not be a large-scale effluent treatment option.

Optimizing bevacizumab dosing in glioblastoma: less is more.

PubMed

Ajlan, Abdulrazag; Thomas, Piia; Albakr, Abdulrahman; Nagpal, Seema; Recht, Lawrence

2017-10-01

Compared to traditional chemotherapies, where dose limiting toxicities represent the maximum possible dose, monoclonal antibody therapies are used at doses well below maximum tolerated dose. However, there has been little effort to ascertain whether there is a submaximal dose at which the efficacy/complication ratio is maximized. Thus, despite the general practice of using Bevacizumab (BEV) at dosages of 10 mg/kg every other week for glioma patients, there has not been much prior work examining whether the relatively high complication rates reported with this agent can be decreased by lowering the dose without impairing efficacy. We assessed charts from 80 patients who received BEV for glioblastoma to survey the incidence of complications relative to BEV dose. All patients were treated with standard upfront chemoradiation. The toxicity was graded based on the NCI CTCAE, version 4.03. The rate of BEV serious related adverse events was 12.5% (n = 10/80). There were no serious adverse events (≥grade 3) when the administered dose was (<3 mg/kg/week), compared to a 21% incidence in those who received higher doses (≥3 mg/kg/week) (P < 0.01). Importantly, the three patient deaths attributable to BEV administration occurred in patients receiving higher doses. Patients who received lower doses also had a better survival rate, although this did not reach statistical significance [median OS 39 for low dose group vs. 17.3 for high dose group (P = 0.07)]. Lower rates of serious BEV related toxicities are noted when lower dosages are used without diminishing positive clinical impact. Further work aimed at optimizing BEV dosage is justified.

Alteration of Blood Parameters and Histoarchitecture of Liver and Kidney of Silver Barb after Chronic Exposure to Quinalphos

PubMed Central

Mohammod Mostakim, Golam; Zahangir, Md. Mahiuddin; Monir Mishu, Mahbuba; Rahman, Md. Khalilur; Islam, M. Sadiqul

2015-01-01

Quinalphos (QP) is commonly used for pest control in the agricultural fields surrounding freshwater reservoirs. This study was conducted to evaluate the chronic toxicity of this pesticide on blood parameters and some organs of silver barb, Barbonymus gonionotus. Fish were exposed to two sublethal concentrations, 0.47 ppm and 0.94 ppm, of QP for a period of 28 days. All the blood parameters (red blood cell, hematocrit, and hemoglobin) and blood glucose except for white blood cells decreased with increasing concentration of toxicant and become significantly lower (p < 0.05) at higher concentration when compared with control. The derived hematological indices of mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration were equally altered compared to control. Histoarchitectural changes of liver and kidney were observed after exposure to the QP. Hypertrophy of hepatocytes, mild to severe necrosis, ruptured central vein, and vacuolation were observed in the liver of treated groups. Highly degenerated kidney tubules and hematopoietic tissue, degeneration of renal corpuscle, vacuolization, and necrosis were evident in the kidney of treated groups. In conclusion, chronic exposure to QP at sublethal concentrations induced hematological and histological alterations in silver barb and offers a simple tool to evaluate toxicity derived alterations. PMID:26635877

Engineering a functional three-dimensional human cardiac tissue model for drug toxicity screening.

PubMed

Lu, Hong Fang; Leong, Meng Fatt; Lim, Tze Chiun; Chua, Ying Ping; Lim, Jia Kai; Du, Chan; Wan, Andrew C A

2017-05-11

Cardiotoxicity is one of the major reasons for clinical drug attrition. In vitro tissue models that can provide efficient and accurate drug toxicity screening are highly desired for preclinical drug development and personalized therapy. Here, we report the fabrication and characterization of a human cardiac tissue model for high throughput drug toxicity studies. Cardiac tissues were fabricated via cellular self-assembly of human transgene-free induced pluripotent stem cells-derived cardiomyocytes in pre-fabricated polydimethylsiloxane molds. The formed tissue constructs expressed cardiomyocyte-specific proteins, exhibited robust production of extracellular matrix components such as laminin, collagen and fibronectin, aligned sarcomeric organization, and stable spontaneous contractions for up to 2 months. Functional characterization revealed that the cardiac cells cultured in 3D tissues exhibited higher contraction speed and rate, and displayed a significantly different drug response compared to cells cultured in age-matched 2D monolayer. A panel of clinically relevant compounds including antibiotic, antidiabetic and anticancer drugs were tested in this study. Compared to conventional viability assays, our functional contractility-based assays were more sensitive in predicting drug-induced cardiotoxic effects, demonstrating good concordance with clinical observations. Thus, our 3D cardiac tissue model shows great potential to be used for early safety evaluation in drug development and drug efficiency testing for personalized therapy.

Relative sensitivity of developmental and immune parameters in juvenile versus adult male rats after exposure to di(2-ethylhexyl) phthalate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tonk, Elisa C.M., E-mail: ilse.tonk@rivm.nl; Laboratory for Health Protection Research, National Institute for Public Health and the Environment; Verhoef, Aart

The developing immune system displays a relatively high sensitivity as compared to both general toxicity parameters and to the adult immune system. In this study we have performed such comparisons using di(2-ethylhexyl) phthalate (DEHP) as a model compound. DEHP is the most abundant phthalate in the environment and perinatal exposure to DEHP has been shown to disrupt male sexual differentiation. In addition, phthalate exposure has been associated with immune dysfunction as evidenced by effects on the expression of allergy. Male wistar rats were dosed with corn oil or DEHP by gavage from postnatal day (PND) 10–50 or PND 50–90 atmore » doses between 1 and 1000 mg/kg/day. Androgen-dependent organ weights showed effects at lower dose levels in juvenile versus adult animals. Immune parameters affected included TDAR parameters in both age groups, NK activity in juvenile animals and TNF-α production by adherent splenocytes in adult animals. Immune parameters were affected at lower dose levels compared to developmental parameters. Overall, more immune parameters were affected in juvenile animals compared to adult animals and effects were observed at lower dose levels. The results of this study show a relatively higher sensitivity of juvenile versus adult rats. Furthermore, they illustrate the relative sensitivity of the developing immune system in juvenile animals as compared to general toxicity and developmental parameters. This study therefore provides further argumentation for performing dedicated developmental immune toxicity testing as a default in regulatory toxicology. -- Highlights: ► In this study we evaluate the relative sensitivities for DEHP induced effects. ► Results of this study demonstrate the age-dependency of DEHP toxicity. ► Functional immune parameters were more sensitive than structural immune parameters. ► Immune parameters were affected at lower dose levels than developmental parameters. ► Findings demonstrate the susceptibility of the developing immune system for DEHP.« less

Aluminum Toxicity-Induced Alterations of Leaf Proteome in Two Citrus Species Differing in Aluminum Tolerance

PubMed Central

Li, Huan; Yang, Lin-Tong; Qi, Yi-Ping; Guo, Peng; Lu, Yi-Bin; Chen, Li-Song

2016-01-01

Seedlings of aluminum-tolerant ‘Xuegan’ (Citrus sinensis) and Al-intolerant ‘sour pummelo’ (Citrus grandis) were fertigated for 18 weeks with nutrient solution containing 0 and 1.2 mM AlCl3·6H2O. Al toxicity-induced inhibition of photosynthesis and the decrease of total soluble protein only occurred in C. grandis leaves, demonstrating that C. sinensis had higher Al tolerance than C. grandis. Using isobaric tags for relative and absolute quantification (iTRAQ), we obtained more Al toxicity-responsive proteins from C. sinensis than from C. grandis leaves, which might be responsible for the higher Al tolerance of C. sinensis. The following aspects might contribute to the Al tolerance of C. sinensis: (a) better maintenance of photosynthesis and energy balance via inducing photosynthesis and energy-related proteins; (b) less increased requirement for the detoxification of reactive oxygen species and other toxic compounds, such as aldehydes, and great improvement of the total ability of detoxification; and (c) upregulation of low-phosphorus-responsive proteins. Al toxicity-responsive proteins related to RNA regulation, protein metabolism, cellular transport and signal transduction might also play key roles in the higher Al tolerance of C. sinensis. We present the global picture of Al toxicity-induced alterations of protein profiles in citrus leaves, and identify some new Al toxicity-responsive proteins related to various biological processes. Our results provide some novel clues about plant Al tolerance. PMID:27455238

Comparison of Biomarkers of Tobacco Exposure between Premium and Discount Brand Cigarette Smokers in the NHANES 2011-2012 Special Sample.

PubMed

Wasserman, Emily J; Reilly, Samantha M; Goel, Reema; Foulds, Jonathan; Richie, John P; Muscat, Joshua E

2018-05-01

Background: Increased cigarette costs have inadvertently strengthened the appeal of discounted brands to price-sensitive smokers. Although smokers perceive discounted brands as having poorer quality, little is known about their delivery of toxic tobacco smoke constituents compared with premium-branded tobacco products. Methods: We investigated the differences between discount and premium brand smokers using the National Health and Nutrition Examination Survey 2011-2012 Special Smoker Sample. Our analyses focused on demographic differences and 27 biomarkers of harmful and potentially harmful constituents (HPHC) listed by the FDA, including volatile organic compounds, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronide [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol glucuronide; reported as total NNAL (tNNAL)], metals, and polycyclic aromatic hydrocarbons (PAHs). Data were analyzed using linear regression models adjusting for potential confounders. Results: A total of 976 non-tobacco users and 578 recent cigarette smokers were eligible for analysis, of which 141 (26.0% weighted) smoked discount brand cigarettes and 437 (74.0% weighted) smoked premium. Discount brand smokers were older, predominantly non-Hispanic white, and had higher serum cotinine. Discount brand smokers had significantly higher levels of 13 smoking-related biomarkers, including tNNAL, uranium, styrene, xylene, and biomarkers of exposure to PAHs (naphthalene, fluorene, and phenanthrene), compared with premium brand smokers. Conclusions: These findings suggest that discount cigarette use is associated with higher exposure to several carcinogenic and toxic HPHCs. Impact: These results may have important regulatory implications for product standards, as higher exposures could lead to a greater degree of harm. Cancer Epidemiol Biomarkers Prev; 27(5); 601-9. ©2018 AACR . ©2018 American Association for Cancer Research.

Late Radiation and Cardiovascular Adverse Effects After Androgen Deprivation and High-Dose Radiation Therapy in Prostate Cancer: Results From the DART 01/05 Randomized Phase 3 Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zapatero, Almudena, E-mail: almudena.zapatero@salud.madrid.org; Guerrero, Araceli; Maldonado, Xavier

Purpose: To present data on the late toxicity endpoints of a randomized trial (DART 01/05) conducted to determine whether long-term androgen deprivation (LTAD) was superior to short-term AD (STAD) when combined with high-dose radiation therapy (HDRT) in patients with prostate cancer (PCa). Patients and Methods: Between November 2005 and December 2010, 355 eligible men with cT1c-T3aN0M0 PCa and intermediate-risk and high-risk factors (2005 National Comprehensive Cancer Network criteria) were randomized to 4 months of AD combined with HDRT (median dose, 78 Gy) (STAD) or the same treatment followed by 24 months of AD (LTAD). Treatment-related complications were assessed using European Organization for Research andmore » Treatment of Cancer–Radiation Therapy Oncology Group and Common Terminology Criteria for Adverse Events v3.0 scoring schemes. Multivariate analyses for late toxicity were done using the Fine-Gray method. Results: The 5-year incidence of grade ≥2 rectal and urinary toxicity was 11.1% and 8.2% for LTAD and 7.6% and 7.3% for STAD, respectively. Compared with STAD, LTAD was not significantly associated with a higher risk of late grade ≥2 rectal toxicity (hazard ratio [HR] 1.360, 95% confidence interval [CI] 0.660-2.790, P=.410) or urinary toxicity (HR 1.028, 95% CI 0.495-2.130, P=.940). The multivariate analysis showed that a baseline history of intestinal comorbidity (HR 3.510, 95% CI 1.560-7.930, P=.025) and the rectal volume receiving >60 Gy (Vr60) (HR 1.030, 95% CI 1.001-1.060, P=.043) were the only factors significantly correlated with the risk of late grade ≥2 rectal complications. A history of previous surgical prostate manipulations was significantly associated with a higher risk of grade ≥2 urinary complications (HR 2.427, 95% CI 1.051-5.600, P=.038). Long-term AD (HR 2.090; 95% CI 1.170-3.720, P=.012) and a history of myocardial infarction (HR 2.080; 95% CI 1.130-3.810, P=.018) were significantly correlated with a higher probability of cardiovascular events. Conclusion: Long-term AD did not significantly impact urinary or rectal radiation-induced toxicity, although it was associated with a higher risk of cardiovascular events. Longer follow-up is needed to measure the impact of AD on late morbidity and non-PCa mortality.« less

A polymeric colchicinoid prodrug with reduced toxicity and improved efficacy for vascular disruption in cancer therapy

PubMed Central

Crielaard, Bart J; van der Wal, Steffen; Lammers, Twan; Le, Huong Thu; Hennink, Wim E; Schiffelers, Raymond M; Storm, Gert; Fens, Marcel HAM

2011-01-01

Colchicinoids are very potent tubulin-binding compounds, which interfere with microtubule formation, giving them strong cytotoxic properties, such as cell mitosis inhibition and induction of microcytoskeleton depolymerization. While this makes them promising vascular disrupting agents (VDAs) in cancer therapy, their dose-limiting toxicity has prevented any clinical application for this purpose. Therefore, colchicinoids are considered attractive lead molecules for the development of novel vascular disrupting nanomedicine. In a previous study, a polymeric colchicinoid prodrug that showed favorable hydrolysis characteristics at physiological conditions was developed. In the current study, this polymeric colchicinoid prodrug was evaluated in vitro and in vivo for its toxicity and vascular disrupting potential. Cell viability studies with human umbilical vein endothelial cells, as an in vitro measure for colchicine activity, reflected the degradation kinetics of the prodrug accordingly. Upon intravenous treatment, in vivo, of B16F10 melanoma-bearing mice with colchicine or with the polymeric colchicinoid prodrug, apparent vascular disruption and consequent tumor necrosis was observed for the prodrug but not for free colchicine at an equivalent dose. Moreover, a five-times-higher dose of the prodrug was well tolerated, indicating reduced toxicity. These findings demonstrate that the polymeric colchicinoid prodrug has a substantially improved efficacy/toxicity ratio compared with that of colchicine, making it a promising VDA for cancer therapy. PMID:22114500

Carvacrol as a potent natural acaricide against Dermanyssus gallinae.

PubMed

Tabari, Mohaddeseh Abouhosseini; Youssefi, Mohammad Reza; Barimani, Alireza; Araghi, Atefeh

2015-10-01

Resistance to conventional synthetic pesticides has been widely reported in Dermanyssus gallinae in poultry production systems. Introducing novel acaricides to poultry industry today is more urgent than ever. Research in this field recently focused on plants and plant-derived compounds as acaricides. In the present study, acaricidal activity of three plant bioactive components, carvacrol, thymol, and farnesol, was assessed against D. gallinae and compared with synthetic pesticide permethrin. Mode of acaricidal action was determined by contact toxicity and fumigant toxicity bioassays. Except farnesol which did not cause any mortality, carvacrol and thymol were found to be toxic to D. gallinae with LD50 values of 1 and 3.15 μg/cm(3), respectively. Permethrin gave the LD50 value of 31.95 μg/cm(3) which was less efficient than carvacrol and thymol. In fumigant toxicity bioassay, mortality rate in carvacrol- and thymol-treated groups in closed method was significantly higher than the open one. On the other hand, permethrin exhibited poor fumigant toxicity as there was no statistically significant difference between mortality rate in open and closed methods. These findings revealed that mechanism of acaricidal activity of carvacrol and thymol but not permethrin was mainly due to fumigant action. Results of the present study suggested that carvacrol and thymol, especially carvacrol, can be developed as a novel potent bioacaricide against D. gallinae.

Biological impact of cigarette smoke compared to an aerosol produced from a prototypic modified risk tobacco product on normal human bronchial epithelial cells.

PubMed

Kogel, U; Gonzalez Suarez, I; Xiang, Y; Dossin, E; Guy, P A; Mathis, C; Marescotti, D; Goedertier, D; Martin, F; Peitsch, M C; Hoeng, J

2015-12-01

Cigarette smoking causes serious and fatal diseases. The best way for smokers to avoid health risks is to quit smoking. Using modified risk tobacco products (MRTPs) may be an alternative to reduce the harm caused for those who are unwilling to quit smoking, but little is known about the toxic effects of MRTPs, nor were the molecular mechanisms of toxicity investigated in detail. The toxicity of an MRTP and the potential molecular mechanisms involved were investigated in high-content screening tests and whole genome transcriptomics analyses using human bronchial epithelial cells. The prototypic (p)MRTP that was tested had less impact than reference cigarette 3R4F on the cellular oxidative stress response and cell death pathways. Higher pMRTP aerosol extract concentrations had impact on pathways associated with the detoxification of xenobiotics and the reduction of oxidative damage. A pMRTP aerosol concentration up to 18 times higher than the 3R4F caused similar perturbation effects in biological networks and led to the perturbation of networks related to cell stress, and proliferation biology. These results may further facilitate the development of a systems toxicology-based impact assessment for use in future risk assessments in line with the 21st century toxicology paradigm, as shown here for an MRTP. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Functional differences in epigenetic modulators-superiority of mercaptoacetamide-based histone deacetylase inhibitors relative to hydroxamates in cortical neuron neuroprotection studies.

PubMed

Kozikowski, Alan P; Chen, Yufeng; Gaysin, Arsen; Chen, Bin; D'Annibale, Melissa A; Suto, Carla M; Langley, Brett C

2007-06-28

We compare the ability of two structurally different classes of epigenetic modulators, namely, histone deacetylase (HDAC) inhibitors containing either a hydroxamate or a mercaptoacetamide as the zinc binding group, to protect cortical neurons in culture from oxidative stress-induced death. This study reveals that some of the mercaptoacetamide-based HDAC inhibitors are fully protective, whereas the hydroxamates show toxicity at higher concentrations. Our present results appear to be consistent with the possibility that the mercaptoacetamide-based HDAC inhibitors interact with a different subset of the HDAC isozymes [less activity at HDAC1 and 2 correlates with less inhibitor toxicity], or alternatively, are interacting selectively with only the cytoplasmic HDACs that are crucial for protection from oxidative stress.

[Significance of hydrocyanic acid formation during fires].

PubMed

von Meyer, L; Drasch, G; Kauert, G

1979-01-01

Cyanide concentrations of blood samples from fire victims autopsied in the Institute of Legal Medicine, Munich, have been determined. In 25% of 48 analyzed cases cyanide concentrations from 0.52 microgram to 6.24 microgram Cyanide/ml blood have been detected. These results are compared to former studies and the higher mean level in our collective is emphasized. The importance of hydrocyanid acid in the toxicity of fire gases is evidently greater, than assumed. Hydrocyanic acid may be produced from nitrogen continaing polymers during combustion. The quote of these polymers in clothing, furniture, and also in equipment of cars is increasing. Therefore, it is necessary to take more notice of the formation of hydrocyanic acid during combustion, even though carbon monoxide is in general the main toxic agent in fire gases.

Photodynamic Therapy for Gynecological Diseases and Breast Cancer

PubMed Central

Shishkova, Natashis; Kuznetsova, Olga; Berezov, Temirbolat

2012-01-01

Photodynamic therapy (PDT) is a minimally invasive and promising new method in cancer treatment. Cytotoxic reactive oxygen species (ROS) are generated by the tissue-localized non-toxic sensitizer upon illumination and in the presence of oxygen. Thus, selective destruction of a targeted tumor may be achieved. Compared with traditional cancer treatment, PDI has advantages including higher selectivity and lower rate of toxicity. The high degree of selectivity of the proposed method was applied to cancer diagnosis using fluorescence. This article reviews previous studies done on PDT treatment and photodetection of cervical intraepithelial neoplasia, vulvar intraepithelial neoplasia, ovarian and breast cancer, and PDT application in treating non-cancer lesions. The article also highlights the clinical responses to PDT, and discusses the possibility of enhancing treatment efficacy by combination with immunotherapy and targeted therapy. PMID:23691448

Evaluation of Glider Coatings Against Biofouling for Improved Flight Performance

DTIC Science & Technology

2011-08-17

and used to conduct assays of survivorship with approximately 100 nauplii larvae ofArtemia sp. (brine shrimp ). The larvae were exposed to the...seal (D). These coatings showed higher mortality of brine shrimp as well as 100% mortality of cypris larvae during the settlement assay which...brine shrimp compared to the glass control; however these did not inhibit settlement and were evidently not toxic to the cypris larvae . All other

Reed beds receiving industrial sludge containing nitroaromatic compounds. Effects of outgoing water and bed material extracts in the umu-c genotoxicity assay, DR-CALUX assay and on early life stage development in zebrafish (Danio rerio).

PubMed

Gustavsson, Lillemor; Hollert, Henner; Jonsson, Sofie; van Bavel, Bert; Engwall, Magnus

2007-05-01

Sweden has prohibited the deposition of organic waste since January, 2005. Since 1 million tons of sludge is produced every year in Sweden and the capacity for incineration does not fill the demands, other methods of sludge management have to be introduced to a larger degree. One common method in the USA and parts of Europe is the use of wetlands to treat wastewater and sewage sludge. The capacity of reed beds to affect the toxicity of a complex mixture of nitroaromatics in sludge, however, is not fully elucidated. In this study, an industrial sludge containing explosives and pharmaceutical residues was therefore treated in artificial reed beds and the change in toxicity was studied. Nitroaromatic compounds, which are the main ingredients of many pharmaceuticals and explosives, are well known to cause cytotoxicity and genotoxicity. Recently performed studies have also showed that embryos of zebrafish (Danio rerio) are sensitive to nitroaromatic compounds. Therefore, we tested the sludge passing through constructed wetlands in order to detect any changes in levels of embryotoxicity, genotoxicity and dioxin-like activity (AhR-agonists). We also compared unplanted and planted systems in order to examine the impact of the root system on the fate of the toxicants. An industrial sludge containing a complex mixture of nitroaromatics was added daily to small-scale constructed wetlands (vertical flow), both unplanted and planted with Phragmites australis. Sludge with an average dry weight of 1.25%, was added with an average hydraulic loading rate of 1.2 L/day. Outgoing water was collected daily and stored at -20 degrees C. The artificial wetland sediment was Soxhlet extracted, followed by clean-up with multi-layer silica, or extracted by ultrasonic treatment, yielding one organic extract and one water extract of the same sample. Genotoxicity of the extracts was measured according to the ISO protocol for the umu-C genotoxicity assay (ISO/TC 147/SC 5/ WG9 N8), using Salmonella typhimurium TA1535/pSK1002 as test organism. Embryotoxicity and teratogenicity were studied using the fish egg assay with zebrafish (Danio rerio) and the dioxin-like activity was measured using the DR-CALUX assay. Chemical analyses of nitroaromatic compounds were performed using Solid Phase Micro Extraction (SPME) and GC-MS. Organic extracts of the bed material showed toxic potential in all three toxicity tests after two years of sludge loading. There was a difference between the planted and the unplanted beds, where the toxicity of organic extracts overall was higher in the bed material from the planted beds. The higher toxicity of the planted beds could have been caused by the higher levels of total carbon in the planted beds, which binds organic toxicants, and by enrichment caused by lower volumes of outgoing water from the planted beds. Developmental disorders were observed in zebrafish exposed directly in contact to bed material from unplanted beds, but not in fish exposed to bed material from planted beds. Hatching rates were slightly lower in zebrafish exposed to outgoing water from unplanted beds than in embryos exposed to outgoing water from planted beds. Genotoxicity in the outgoing water was below detection limit for both planted and unplanted beds. Most of the added toxicants via the sludge were unaccounted for in the outgoing water, suggesting that the beds had toxicant removal potential, although the mechanisms behind this remain unknown. During the experimental period, the beds received a sludge volume (dry weight) of around three times their own volume. In spite of this, the toxicity in the bed material was lower than in the sludge. Thus, the beds were probably able to actually decrease the toxicity of the added, sludge-associated toxicants. When testing the acetone extracts of the bed material, the planted bed showed a higher toxicity than the unplanted beds in all three toxicity tests. The toxicity of water extracts from the unplanted beds, detected by the fish egg assay, were higher than the water extracts from the planted beds. No genotoxicity was detected in outgoing water from either planted or unplanted beds. All this together indicates that the planted reed beds retained semi-lipophilic acetone-soluble toxic compounds from the sludge better than the unplanted beds, which tended to leak out more of the water soluble toxic compounds in the outgoing water. The compounds identified by SPME/GC in the outgoing water were not in sufficient concentrations to have caused induction in the genotoxicity test. This study has pointed out the benefits of using constructed wetlands receiving an industrial sludge containing a complex mixture of nitroaromatics to reduce toxicity in the outgoing water. The water from planted, constructed wetlands could therefore be directed to a recipient without further cleaning. The bed material should be investigated over a longer period of time in order to evaluate potential accumulation and leakage prior to proper usage or storage. The plants should be investigated in order to examine uptake and possible release when the plant biomass is degraded.

Molecular-receptor-specific, non-toxic, near-infrared-emitting Au cluster-protein nanoconjugates for targeted cancer imaging

NASA Astrophysics Data System (ADS)

Retnakumari, Archana; Setua, Sonali; Menon, Deepthy; Ravindran, Prasanth; Muhammed, Habeeb; Pradeep, Thalappil; Nair, Shantikumar; Koyakutty, Manzoor

2010-02-01

Molecular-receptor-targeted imaging of folate receptor positive oral carcinoma cells using folic-acid-conjugated fluorescent Au25 nanoclusters (Au NCs) is reported. Highly fluorescent Au25 clusters were synthesized by controlled reduction of Au+ ions, stabilized in bovine serum albumin (BSA), using a green-chemical reducing agent, ascorbic acid (vitamin-C). For targeted-imaging-based detection of cancer cells, the clusters were conjugated with folic acid (FA) through amide linkage with the BSA shell. The bioconjugated clusters show excellent stability over a wide range of pH from 4 to 14 and fluorescence efficiency of ~5.7% at pH 7.4 in phosphate buffer saline (PBS), indicating effective protection of nanoclusters by serum albumin during the bioconjugation reaction and cell-cluster interaction. The nanoclusters were characterized for their physico-chemical properties, toxicity and cancer targeting efficacy in vitro. X-ray photoelectron spectroscopy (XPS) suggests binding energies correlating to metal Au 4f7/2~83.97 eV and Au 4f5/2~87.768 eV. Transmission electron microscopy and atomic force microscopy revealed the formation of individual nanoclusters of size ~1 nm and protein cluster aggregates of size ~8 nm. Photoluminescence studies show bright fluorescence with peak maximum at ~674 nm with the spectral profile covering the near-infrared (NIR) region, making it possible to image clusters at the 700-800 nm emission window where the tissue absorption of light is minimum. The cell viability and reactive oxygen toxicity studies indicate the non-toxic nature of the Au clusters up to relatively higher concentrations of 500 µg ml-1. Receptor-targeted cancer detection using Au clusters is demonstrated on FR+ve oral squamous cell carcinoma (KB) and breast adenocarcinoma cell MCF-7, where the FA-conjugated Au25 clusters were found internalized in significantly higher concentrations compared to the negative control cell lines. This study demonstrates the potential of using non-toxic fluorescent Au nanoclusters for the targeted imaging of cancer.

Combined biocidal action of silver nanoparticles and ions against Chlorococcales (Scenedesmus quadricauda, Chlorella vulgaris) and filamentous algae (Klebsormidium sp.).

PubMed

Zouzelka, Radek; Cihakova, Pavlina; Rihova Ambrozova, Jana; Rathousky, Jiri

2016-05-01

Despite the extensive research, the mechanism of the antimicrobial and biocidal performance of silver nanoparticles has not been unequivocally elucidated yet. Our study was aimed at the investigation of the ability of silver nanoparticles to suppress the growth of three types of algae colonizing the wetted surfaces or submerged objects and the mechanism of their action. Silver nanoparticles exhibited a substantial toxicity towards Chlorococcales Scenedesmus quadricauda, Chlorella vulgaris, and filamentous algae Klebsormidium sp., which correlated with their particle size. The particles had very good stability against agglomeration even in the presence of multivalent cations. The concentration of silver ions in equilibrium with nanoparticles markedly depended on the particle size, achieving about 6 % and as low as about 0.1 % or even less for the particles 5 nm in size and for larger ones (40-70 nm), respectively. Even very limited proportion of small particles together with larger ones could substantially increase concentration of Ag ions in solution. The highest toxicity was found for the 5-nm-sized particles, being the smallest ones in this study. Their toxicity was even higher than that of silver ions at the same silver concentration. When compared as a function of the Ag(+) concentration in equilibrium with 5-nm particles, the toxicity of ions was at least 17 times higher than that obtained by dissolving silver nitrite (if not taking into account the effect of nanoparticles themselves). The mechanism of the toxicity of silver nanoparticles was found complex with an important role played by the adsorption of silver nanoparticles and the ions released from the particles on the cell surface. This mechanism could be described as some sort of synergy between nanoparticles and ions. While our study clearly showed the presence of this synergy, its detailed explanation is experimentally highly demanding, requiring a close cooperation between materials scientists, physical chemists, and biologists.

Validation of a biotic ligand model on site-specific copper toxicity to Daphnia magna in the Yeongsan River, Korea.

PubMed

Park, Jinhee; Ra, Jin-Sung; Rho, Hojung; Cho, Jaeweon; Kim, Sang Don

2018-03-01

The objective of this study was to determine whether the water effect ratio (WER) or biotic ligand model (BLM) could be applied to efficiently develop water quality criteria (WQC) in Korea. Samples were collected from 12 specific sites along the Yeongsan River (YSR), Korea, including two sewage treatment plants and one estuary lake. A copper toxicity test using Daphnia magna was performed to determine the WER and to compare to the BLM prediction. The results of the WER from YSR samples also indicated significantly different copper toxicities in all sites. The model-based predictions showed that effluent and estuary waters had significantly different properties in regard to their ability to be used to investigate water characteristics and copper toxicity. It was supposed that the slight water characteristics changes, such as pH, DOC, hardness, conductivity, among others, influence copper toxicity, and these variable effects on copper toxicity interacted with the water composition. The 38% prediction was outside of the validation range by a factor of two in all sites, showing a poor predictive ability, especially in STPs and streams adjacent to the estuary, while the measured toxicity was more stable. The samples that ranged from pH 7.3-7.7 generated stable predictions, while other samples, including those with lower and the higher pH values, led to more unstable predictions. The results also showed that the toxicity of Cu in sample waters to D. magna was closely proportional to the amounts of acidity, including the carboxylic and phenolic groups, as well as the DOC concentrations. Consequently, the acceptable prediction of metal toxicity in various water samples needs the site-specific results considering the water characteristics such as pH and DOC properties particularly in STPs and estuary regions. Copyright © 2017 Elsevier Inc. All rights reserved.

A study on toxic and essential elements in wheat grain from the Republic of Kazakhstan.

PubMed

Tattibayeva, Damira; Nebot, Carolina; Miranda, Jose M; Abuova, Altynai B; Baibatyrov, Torebek A; Kizatova, Maigul Z; Cepeda, Alberto; Franco, Carlos M

2016-03-01

Little information is currently available about the content of different elements in wheat samples from the Republic of Kazakhstan. The concentrations of toxic (As, Cd, Cr, Hg, Pb, and U) and essential (Co, Cu, Fe, Mn, Ni, Se, and Zn) elements in 117 sampled wheat grains from the Republic of Kazakhstan were measured. The results indicated that the mean and maximum concentrations of most investigated elements (As, Cd, Co, Cr, Mn, Se, Pb, and U) were higher in samples collected from southern Kazakhstan. The mean and maximum concentrations of toxic elements such as As, Cd, Hg, and Pb did not exceed levels specified by European, FAO, or Kazakh legislation, although the hazard quotient (HQ) values for Co, Cu, Mn, and Zn were higher than 1 and the hazard index (HI) was higher than 1 for samples collected from all areas of Kazakhstan. This indicates that there should be concern about the potential hazards of the combination of toxic elements in Kazakh wheat.

Systemic treatments for metastatic cutaneous melanoma.

PubMed

Pasquali, Sandro; Hadjinicolaou, Andreas V; Chiarion Sileni, Vanna; Rossi, Carlo Riccardo; Mocellin, Simone

2018-02-06

The prognosis of people with metastatic cutaneous melanoma, a skin cancer, is generally poor. Recently, new classes of drugs (e.g. immune checkpoint inhibitors and small-molecule targeted drugs) have significantly improved patient prognosis, which has drastically changed the landscape of melanoma therapeutic management. This is an update of a Cochrane Review published in 2000. To assess the beneficial and harmful effects of systemic treatments for metastatic cutaneous melanoma. We searched the following databases up to October 2017: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase and LILACS. We also searched five trials registers and the ASCO database in February 2017, and checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs). We considered RCTs of systemic therapies for people with unresectable lymph node metastasis and distant metastatic cutaneous melanoma compared to any other treatment. We checked the reference lists of selected articles to identify further references to relevant trials. Two review authors extracted data, and a third review author independently verified extracted data. We implemented a network meta-analysis approach to make indirect comparisons and rank treatments according to their effectiveness (as measured by the impact on survival) and harm (as measured by occurrence of high-grade toxicity). The same two review authors independently assessed the risk of bias of eligible studies according to Cochrane standards and assessed evidence quality based on the GRADE criteria. We included 122 RCTs (28,561 participants). Of these, 83 RCTs, encompassing 21 different comparisons, were included in meta-analyses. Included participants were men and women with a mean age of 57.5 years who were recruited from hospital settings. Twenty-nine studies included people whose cancer had spread to their brains. Interventions were categorised into five groups: conventional chemotherapy (including single agent and polychemotherapy), biochemotherapy (combining chemotherapy with cytokines such as interleukin-2 and interferon-alpha), immune checkpoint inhibitors (such as anti-CTLA4 and anti-PD1 monoclonal antibodies), small-molecule targeted drugs used for melanomas with specific gene changes (such as BRAF inhibitors and MEK inhibitors), and other agents (such as anti-angiogenic drugs). Most interventions were compared with chemotherapy. In many cases, trials were sponsored by pharmaceutical companies producing the tested drug: this was especially true for new classes of drugs, such as immune checkpoint inhibitors and small-molecule targeted drugs.When compared to single agent chemotherapy, the combination of multiple chemotherapeutic agents (polychemotherapy) did not translate into significantly better survival (overall survival: HR 0.99, 95% CI 0.85 to 1.16, 6 studies, 594 participants; high-quality evidence; progression-free survival: HR 1.07, 95% CI 0.91 to 1.25, 5 studies, 398 participants; high-quality evidence. Those who received combined treatment are probably burdened by higher toxicity rates (RR 1.97, 95% CI 1.44 to 2.71, 3 studies, 390 participants; moderate-quality evidence). (We defined toxicity as the occurrence of grade 3 (G3) or higher adverse events according to the World Health Organization scale.)Compared to chemotherapy, biochemotherapy (chemotherapy combined with both interferon-alpha and interleukin-2) improved progression-free survival (HR 0.90, 95% CI 0.83 to 0.99, 6 studies, 964 participants; high-quality evidence), but did not significantly improve overall survival (HR 0.94, 95% CI 0.84 to 1.06, 7 studies, 1317 participants; high-quality evidence). Biochemotherapy had higher toxicity rates (RR 1.35, 95% CI 1.14 to 1.61, 2 studies, 631 participants; high-quality evidence).With regard to immune checkpoint inhibitors, anti-CTLA4 monoclonal antibodies plus chemotherapy probably increased the chance of progression-free survival compared to chemotherapy alone (HR 0.76, 95% CI 0.63 to 0.92, 1 study, 502 participants; moderate-quality evidence), but may not significantly improve overall survival (HR 0.81, 95% CI 0.65 to 1.01, 2 studies, 1157 participants; low-quality evidence). Compared to chemotherapy alone, anti-CTLA4 monoclonal antibodies is likely to be associated with higher toxicity rates (RR 1.69, 95% CI 1.19 to 2.42, 2 studies, 1142 participants; moderate-quality evidence).Compared to chemotherapy, anti-PD1 monoclonal antibodies (immune checkpoint inhibitors) improved overall survival (HR 0.42, 95% CI 0.37 to 0.48, 1 study, 418 participants; high-quality evidence) and probably improved progression-free survival (HR 0.49, 95% CI 0.39 to 0.61, 2 studies, 957 participants; moderate-quality evidence). Anti-PD1 monoclonal antibodies may also result in less toxicity than chemotherapy (RR 0.55, 95% CI 0.31 to 0.97, 3 studies, 1360 participants; low-quality evidence).Anti-PD1 monoclonal antibodies performed better than anti-CTLA4 monoclonal antibodies in terms of overall survival (HR 0.63, 95% CI 0.60 to 0.66, 1 study, 764 participants; high-quality evidence) and progression-free survival (HR 0.54, 95% CI 0.50 to 0.60, 2 studies, 1465 participants; high-quality evidence). Anti-PD1 monoclonal antibodies may result in better toxicity outcomes than anti-CTLA4 monoclonal antibodies (RR 0.70, 95% CI 0.54 to 0.91, 2 studies, 1465 participants; low-quality evidence).Compared to anti-CTLA4 monoclonal antibodies alone, the combination of anti-CTLA4 plus anti-PD1 monoclonal antibodies was associated with better progression-free survival (HR 0.40, 95% CI 0.35 to 0.46, 2 studies, 738 participants; high-quality evidence). There may be no significant difference in toxicity outcomes (RR 1.57, 95% CI 0.85 to 2.92, 2 studies, 764 participants; low-quality evidence) (no data for overall survival were available).The class of small-molecule targeted drugs, BRAF inhibitors (which are active exclusively against BRAF-mutated melanoma), performed better than chemotherapy in terms of overall survival (HR 0.40, 95% CI 0.28 to 0.57, 2 studies, 925 participants; high-quality evidence) and progression-free survival (HR 0.27, 95% CI 0.21 to 0.34, 2 studies, 925 participants; high-quality evidence), and there may be no significant difference in toxicity (RR 1.27, 95% CI 0.48 to 3.33, 2 studies, 408 participants; low-quality evidence).Compared to chemotherapy, MEK inhibitors (which are active exclusively against BRAF-mutated melanoma) may not significantly improve overall survival (HR 0.85, 95% CI 0.58 to 1.25, 3 studies, 496 participants; low-quality evidence), but they probably lead to better progression-free survival (HR 0.58, 95% CI 0.42 to 0.80, 3 studies, 496 participants; moderate-quality evidence). However, MEK inhibitors probably have higher toxicity rates (RR 1.61, 95% CI 1.08 to 2.41, 1 study, 91 participants; moderate-quality evidence).Compared to BRAF inhibitors, the combination of BRAF plus MEK inhibitors was associated with better overall survival (HR 0.70, 95% CI 0.59 to 0.82, 4 studies, 1784 participants; high-quality evidence). BRAF plus MEK inhibitors was also probably better in terms of progression-free survival (HR 0.56, 95% CI 0.44 to 0.71, 4 studies, 1784 participants; moderate-quality evidence), and there appears likely to be no significant difference in toxicity (RR 1.01, 95% CI 0.85 to 1.20, 4 studies, 1774 participants; moderate-quality evidence).Compared to chemotherapy, the combination of chemotherapy plus anti-angiogenic drugs was probably associated with better overall survival (HR 0.60, 95% CI 0.45 to 0.81; moderate-quality evidence) and progression-free survival (HR 0.69, 95% CI 0.52 to 0.92; moderate-quality evidence). There may be no difference in terms of toxicity (RR 0.68, 95% CI 0.09 to 5.32; low-quality evidence). All results for this comparison were based on 324 participants from 2 studies.Network meta-analysis focused on chemotherapy as the common comparator and currently approved treatments for which high- to moderate-quality evidence of efficacy (as represented by treatment effect on progression-free survival) was available (based on the above results) for: biochemotherapy (with both interferon-alpha and interleukin-2); anti-CTLA4 monoclonal antibodies; anti-PD1 monoclonal antibodies; anti-CTLA4 plus anti-PD1 monoclonal antibodies; BRAF inhibitors; MEK inhibitors, and BRAF plus MEK inhibitors. Analysis (which included 19 RCTs and 7632 participants) generated 21 indirect comparisons.The best evidence (moderate-quality evidence) for progression-free survival was found for the following indirect comparisons:• both combinations of immune checkpoint inhibitors (HR 0.30, 95% CI 0.17 to 0.51) and small-molecule targeted drugs (HR 0.17, 95% CI 0.11 to 0.26) probably improved progression-free survival compared to chemotherapy;• both BRAF inhibitors (HR 0.40, 95% CI 0.23 to 0.68) and combinations of small-molecule targeted drugs (HR 0.22, 95% CI 0.12 to 0.39) were probably associated with better progression-free survival compared to anti-CTLA4 monoclonal antibodies;• biochemotherapy (HR 2.81, 95% CI 1.76 to 4.51) probably lead to worse progression-free survival compared to BRAF inhibitors;• the combination of small-molecule targeted drugs probably improved progression-free survival (HR 0.38, 95% CI 0.21 to 0.68) compared to anti-PD1 monoclonal antibodies;• both biochemotherapy (HR 5.05, 95% CI 3.01 to 8.45) and MEK inhibitors (HR 3.16, 95% CI 1.77 to 5.65) were probably associated with worse progression-free survival compared to the combination of small-molecule targeted drugs; and• biochemotherapy was probably associated with worse progression-free survival (HR 2.81, 95% CI 1.54 to 5.11) compared to the combination of immune checkpoint inhibitors.The best evidence (moderate-quality evidence) for toxicity was found for the following indirect comparisons:• combination of immune checkpoint inhibitors (RR 3.49, 95% CI 2.12 to 5.77) probably increased toxicity compared to chemotherapy;• combination of immune checkpoint inhibitors probably increased toxicity (RR 2.50, 95% CI 1.20 to 5.20) compared to BRAF inhibitors;• the combination of immune checkpoint inhibitors probably increased toxicity (RR 3.83, 95% CI 2.59 to 5.68) compared to anti-PD1 monoclonal antibodies; and• biochemotherapy was probably associated with lower toxicity (RR 0.41, 95% CI 0.24 to 0.71) compared to the combination of immune checkpoint inhibitors.Network meta-analysis-based ranking suggested that the combination of BRAF plus MEK inhibitors is the most effective strategy in terms of progression-free survival, whereas anti-PD1 monoclonal antibodies are associated with the lowest toxicity.Overall, the risk of bias of the included trials can be considered as limited. When considering the 122 trials included in this review and the seven types of bias we assessed, we performed 854 evaluations only seven of which (< 1%) assigned high risk to six trials. We found high-quality evidence that many treatments offer better efficacy than chemotherapy, especially recently implemented treatments, such as small-molecule targeted drugs, which are used to treat melanoma with specific gene mutations. Compared with chemotherapy, biochemotherapy (in this case, chemotherapy combined with both interferon-alpha and interleukin-2) and BRAF inhibitors improved progression-free survival; BRAF inhibitors (for BRAF-mutated melanoma) and anti-PD1 monoclonal antibodies improved overall survival. However, there was no difference between polychemotherapy and monochemotherapy in terms of achieving progression-free survival and overall survival. Biochemotherapy did not significantly improve overall survival and has higher toxicity rates compared with chemotherapy.There was some evidence that combined treatments worked better than single treatments: anti-PD1 monoclonal antibodies, alone or with anti-CTLA4, improved progression-free survival compared with anti-CTLA4 monoclonal antibodies alone. Anti-PD1 monoclonal antibodies performed better than anti-CTLA4 monoclonal antibodies in terms of overall survival, and a combination of BRAF plus MEK inhibitors was associated with better overall survival for BRAF-mutated melanoma, compared to BRAF inhibitors alone.The combination of BRAF plus MEK inhibitors (which can only be administered to people with BRAF-mutated melanoma) appeared to be the most effective treatment (based on results for progression-free survival), whereas anti-PD1 monoclonal antibodies appeared to be the least toxic, and most acceptable, treatment.Evidence quality was reduced due to imprecision, between-study heterogeneity, and substandard reporting of trials. Future research should ensure that those diminishing influences are addressed. Clinical areas of future investigation should include the longer-term effect of new therapeutic agents (i.e. immune checkpoint inhibitors and targeted therapies) on overall survival, as well as the combination of drugs used in melanoma treatment; research should also investigate the potential influence of biomarkers.

Eco-friendly control of the poultry red mite, Dermanyssus gallinae (Dermanyssidae), using the α-thujone-rich essential oil of Artemisia sieberi (Asteraceae): toxic and repellent potential.

PubMed

Tabari, Mohaddeseh Abouhosseini; Youssefi, Mohammad Reza; Benelli, Giovanni

2017-05-01

The poultry red mite, Dermanyssus gallinae, represents a key threat for the poultry industry worldwide. The control of D. gallinae is mainly achieved by continuous applications of acaricides. However, the fast-growing development of resistance, and the strict laws concerning chemicals admitted for treatments on food animals, highlighted the importance of alternative control tools. Here, we explored the potential of Artemisia sieberi essential oil against D. gallinae. In this study, the A. sieberi essential oil was analyzed using GC and GC-MS. The oil toxicity through contact and fumigant assays on adult mites was evaluated. The oil repellent activity was assessed on adult mites over different time intervals. Lastly, the residual toxicity of various doses of the oil was evaluated on D. gallinae until 14 days post treatment. GC and GC-MS showed that the oil was rich in α-thujone (31.5%), β-thujone (11.92%), camphor (12.3%), and 1,8-cineole (10.09%). Contact toxicity on adult mites showed 50% lethal concentration (LC 50 ), LC 90 , and LC 99 of 15.85, 26.63, and 35.42 μg/cm 3 , respectively. In fumigant assays, the oil was toxic on D. gallinae, and mortality was significantly higher in open containers over closed ones, underlining the key role of highly volatile constituents. Repellent assays showed that after 24 h from the treatment, all doses of the A. sieberi essential oil led to significant repellent activity over the control, except for 2 μg/cm 3 . After 48 h, A. sieberi essential oil tested at all doses led to significant repellent activity, if compared to the control. Residual toxicity assays showed that time exposure and concentration tested had a significant impact on mite mortality after 1, 2, 5, and 7 days from the treatment. Notably, mortality remained significantly higher over the control for 7 days after spraying with oil at 2%. Further field assays with selected molecules from the A. sieberi essential oil are ongoing, testing them in synergistic blends, as well as in microencapsulated formulations.

Chemical and toxicological characteristics of conventional and low-TSNA moist snuff tobacco products.

PubMed

Song, Min-Ae; Marian, Catalin; Brasky, Theodore M; Reisinger, Sarah; Djordjevic, Mirjana; Shields, Peter G

2016-03-14

Use of smokeless tobacco products (STPs) is associated with oral cavity cancer and other health risks. Comprehensive analysis for chemical composition and toxicity is needed to compare conventional and newer STPs with lower tobacco-specific nitrosamines (TSNAs) yields. Seven conventional and 12 low-TSNA moist snuff products purchased in the U.S., Sweden, and South Africa were analyzed for 18 chemical constituents (International Agency for Research on Cancer classified carcinogens), pH, nicotine, and free nicotine. Chemicals were compared in each product using Wilcoxon rank-sum test and principle component analysis (PCA). Conventional compared to low-TSNA moist snuff products had higher ammonia, benzo[a]pyrene, cadmium, nickel, nicotine, nitrate, and TSNAs and had lower arsenic in dry weight content and per mg nicotine. Lead and chromium were significantly higher in low-TSNA moist snuff products. PCA showed a clear difference for constituents between conventional and low-TSNA moist snuff products. Differences among products were reduced when considered on a per mg nicotine basis. As one way to contextualize differences in constituent levels, probabilistic lifetime cancer risk was estimated for chemicals included in The University of California's carcinogenic potency database (CPDB). Estimated probabilistic cancer risks were 3.77-fold or 3-fold higher in conventional compared to low-TSNA moist snuff products under dry weight or under per mg nicotine content, respectively. In vitro testing for the STPs indicated low level toxicity and no substantial differences. The comprehensive chemical characterization of both conventional and low-TSNA moist snuff products from this study provides a broader assessment of understanding differences in carcinogenic potential of the products. In addition, the high levels and probabilistic cancer risk estimates for certain chemical constituents of smokeless tobacco products will further inform regulatory decision makers and aid them in their efforts to reduce carcinogen exposure in smokeless tobacco products. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Repeated-dose toxicological studies of Tithonia diversifolia (Hemsl.) A. gray and identification of the toxic compounds.

PubMed

Passoni, Flávia Donaire; Oliveira, Rejane Barbosa; Chagas-Paula, Daniela Aparecida; Gobbo-Neto, Leonardo; Da Costa, Fernando Batista

2013-05-20

Tithonia diversifolia (Hemsl.) A. Gray has been commonly used in folk medicine to treat abscesses, microbiological infections, snake bites, malaria and diabetes. Both anti-inflammatory and anti-malarial properties have been identified using appropriate assays, but the effective doses have demonstrated toxic effects for the experimental animals. Most of the pharmacological activities have been attributed to sesquiterpene lactones (STLs) and some chlorogenic acid derivatives (CAs) in the leaves of this species. This work aimed to evaluate the repeated-dose toxicity of an aqueous extract (AE) from Tithonia diversifolia leaves and to compare the results with an extract rich in STLs (LRE) and a polar extract (PE) without STLs but rich in CAs. The purpose of this work was to provide insights into the identity of the compounds responsible for the toxic effects of Tithonia diversifolia. The major classes of compounds were confirmed in each extract by IR spectra and HPLC-UV-DAD profiling using previously isolated or standard compounds. The toxicity of each extract was evaluated in a repeated-dose toxicity study in Wistar rats for 90 days. The AE is composed of both STLs and CAs, the LRE is rich in STLs, and the PE is rich in CAs. The AE caused alterations in haematological parameters but few alterations in biochemical parameters and was relatively safe at doses lower than 100mg/kg. However, the PE and LRE demonstrated several adverse effects by damaging the liver and kidneys, respectively. STLs and CAs can be toxic in prolonged use at higher doses in extracts prepared from Tithonia diversifolia by affecting the kidneys and liver. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Comparative Analysis of the Relationship between Trichloroethylene Metabolism and Tissue-Specific Toxicity among Inbred Mouse Strains: Kidney Effects

PubMed Central

Yoo, Hong Sik; Bradford, Blair U.; Kosyk, Oksana; Uehara, Takeki; Shymonyak, Svitlana; Collins, Leonard B.; Bodnar, Wanda M.; Ball, Louise M.; Gold, Avram; Rusyn, Ivan

2014-01-01

Trichloroethylene (TCE) is a well-known environmental and occupational toxicant that is classified as carcinogenic to humans based on the epidemiological evidence of an association with higher risk of renal cell carcinoma. A number of scientific issues critical for assessing human health risks from TCE remain unresolved, such as the amount of kidney-toxic glutathione conjugation metabolites formed, inter-species and -individual differences, and the mode of action for kidney carcinogenicity. We hypothesized that TCE metabolite levels in the kidney are associated with kidney-specific toxicity. Oral dosing with TCE was conducted in sub-acute (600 mg/kg/d; 5 days; 7 inbred mouse strains) and sub-chronic (100 or 400 mg/kg/d; 1, 2, or 4 weeks; 2 inbred mouse strains) designs. We evaluated the quantitative relationship between strain-, dose-, and time-dependent formation of TCE metabolites from cytochrome P450-mediated oxidation [trichloroacetic acid (TCA), dichloroacetic acid (DCA), and trichloroethanol] and glutathione conjugation [S-(1,2-dichlorovinyl)-L-cysteine and S-(1,2-dichlorovinyl)glutathione], and various kidney toxicity phenotypes. In sub-acute study, we observed inter-strain differences in TCE metabolite levels in the kidney. In addition, we found that in several strains kidney-specific effects of TCE included induction of peroxisome proliferator-marker genes Cyp4a10 and Acox1, increased cell proliferation, and expression of KIM-1, a marker of tubular damage and regeneration. In sub-chronic study, peroxisome proliferator-marker gene induction and kidney toxicity diminished while cell proliferative response was elevated in a dose-dependent manner in NZW/LacJ, but not C57BL/6J mice. Overall, we show that TCE metabolite levels in the kidney are associated with kidney-specific toxicity and that these effects are strain-dependent. PMID:25424545

Effects of the pharmaceuticals gemfibrozil and diclofenac on biomarker expression in the zebra mussel (Dreissena polymorpha) and their comparison with standardised toxicity tests.

PubMed

Quinn, Brian; Schmidt, Wiebke; O'Rourke, Kathleen; Hernan, Robert

2011-07-01

Pharmaceuticals, including the lipid regulator gemfibrozil and the non-steroidal anti-inflammatory drug diclofenac have been identified in waste water treatment plant effluents and receiving waters throughout the western world. The acute and chronic toxicity of these compounds was assessed for three freshwater species (Daphnia magna, Pseudokirchneriella subcapitata, Lemna minor) using standardised toxicity tests with toxicity found in the non-environmentally relevant mid mg L(-1) concentration range. For the acute endpoints (IC(50) and EC(50)) gemfibrozil showed higher toxicity ranging from 29 to 59 mg L(-1) (diclofenac 47-67 mg L(-1)), while diclofenac was more toxic for the chronic D. magna 21 d endpoints ranging from 10 to 56 mg L(-1) (gemfibrozil 32-100 mg L(-1)). These results were compared with the expression of several biomarkers in the zebra mussel (Dreissena polymorpha) 24 and 96 h after exposure by injection to concentrations of 21 and 21,000 μg L(-1) corresponding to nominal concentrations of 1 and 1000 μg L(-1). Exposure to gemfibrozil and diclofenac at both concentrations significantly increased the level of lipid peroxidation, a biomarker of damage. At the elevated nominal concentration of 1000 μg L(-1) the biomarkers of defence glutathione transferase and metallothionein were significantly elevated for gemfibrozil and diclofenac respectively, as was DNA damage after 96 h exposure to gemfibrozil. No evidence of endocrine disruption was observed using the alkali-labile phosphate technique. Results from this suite of biomarkers indicate these compounds can cause significant stress at environmentally relevant concentrations acting primarily through oxidation pathways with significant destabilization of the lysosomal membrane and that biomarker expression is a more sensitive endpoint than standardised toxicity tests. Copyright © 2011 Elsevier Ltd. All rights reserved.

Fluvial biofilms: A pertinent tool to assess beta-blockers toxicity.

PubMed

Bonnineau, Chloé; Guasch, Helena; Proia, Lorenzo; Ricart, Marta; Geiszinger, Anita; Romaní, Anna M; Sabater, Sergi

2010-02-18

Among increasingly used pharmaceutical products, beta-blockers have been commonly reported at low concentrations in rivers and littoral waters of Europe and North America. Little is known about the toxicity of these chemicals in freshwater ecosystems while their presence may lead to chronic pollution. Hence, in this study the acute toxicity of 3 beta-blockers: metoprolol, propranolol and atenolol on fluvial biofilms was assessed by using several biomarkers. Some were indicative of potential alterations in biofilm algae (photosynthetic efficiency), and others in biofilm bacteria (peptidase activity, bacterial mortality). Propranolol was the most toxic beta-blocker, mostly affecting the algal photosynthetic process. The exposure to 531microg/L of propranolol caused 85% of inhibition of photosynthesis after 24h. Metoprolol was particularly toxic for bacteria. Though estimated No-Effect Concentrations (NEC) were similar to environmental concentrations, higher concentrations of the toxic (503microg/L metoprolol) caused an increase of 50% in bacterial mortality. Atenolol was the least toxic of the three tested beta-blockers. Effects superior to 50% were only observed at very high concentration (707mg/L). Higher toxicity of metoprolol and propranolol might be due to better absorption within biofilms of these two chemicals. Since beta-blockers are mainly found in mixtures in rivers, their differential toxicity could have potential relevant consequences on the interactions between algae and bacteria within river biofilms. 2009 Elsevier B.V. All rights reserved.

One in five mortality in non-menstrual toxic shock syndrome versus no mortality in menstrual cases in a balanced French series of 55 cases.

PubMed

Descloux, E; Perpoint, T; Ferry, T; Lina, G; Bes, M; Vandenesch, F; Mohammedi, I; Etienne, J

2008-01-01

Staphylococcus aureus superantigenic toxins are responsible for menstrual and non-menstrual toxic shock syndrome (TSS). We compared the clinical and biological characteristics of 21 cases of menstrual TSS (MTSS) with 34 cases of non-menstrual TSS (NMTSS) diagnosed in France from December 2003 to June 2006. All 55 S. aureus isolates had been spontaneously referred to the French National Staphylococcal Reference Center, where they were screened for superantigenic toxin gene sequences. Most of the patients had previously been in good health. The most striking differences between MTSS and NMTSS were the higher frequency in NMTSS of neurological disorders (p=0.028), of S. aureus isolation by blood culture (50% versus 0% in MTSS), and the higher mortality rate in NMTSS (22% versus 0% in MTSS). The tst and sea genes were less frequent in isolates causing NMTSS than in those causing MTSS (p<0.001 and 0.051, respectively). Higher mortality was significantly associated with the presence of the sed gene (p=0.041), but when considering NMTSS survivors and non-survivors, no clinical or bacteriological factors predictive of vital outcome were identified. Specific antitoxinic therapy was rarely prescribed, and never in fatal cases. Higher mortality was observed in NMTSS than in MTSS, and no definite factors could explain the higher severity of NMTSS. NMTSS would require more aggressive therapy, comprising systematic rapid wound debridement, antistaphylococcal agents, including an antitoxin antibiotics, and intravenous immunoglobulin.

Evaluation of copper toxicity using site specific algae and water chemistry: Field validation of laboratory bioassays.

PubMed

Fawaz, Elyssa G; Salam, Darine A; Kamareddine, Lina

2018-07-15

Studies of metal toxicity to microalgae have predominantly been conducted using single non-target algae species and without due regard for the chemistry of the treated waters, leading to ineffective or excessive algaecide treatments. In this study, indigenous multi-algal species (Scenedesmus quadricauda, and Scenedesmus subspicatus and Oscillatoria agardhii) were used in laboratory toxicity bioassays under simulated field water chemistry (pH = 7.2, hardness = 196 mg L -1 as CaCO 3 , and alkalinity = 222 mg L -1 as CaCO 3 ) to determine the optimum copper sulfate treatment dose to control algae growth in an irrigation canal. Toxicity bioassays were conducted using copper sulfate in chelated (with EDTA) and non-chelated (without EDTA) forms to assess the influence of the use of synthetic chelators in toxicity studies. Also, copper toxicity to the indigenous algae species was measured in the non-modified EPA test medium (pH = 7.5, hardness = 92 mg L -1 as CaCO 3 , alkalinity = 10 mg L -1 as CaCO 3 and EDTA= 300 µg L -1 ) to assess the impact of the water chemistry on algae inhibitory algal dosages. Under simulated water chemistry conditions, lower toxicity was measured in the test flasks with the chelated form of copper (96 h- EC 50 = 386.67 µg L -1 as Cu) as compared to those with the non-chelated metal (96 h-EC 50 = 217.17 µg L -1 as Cu). In addition, higher copper toxicity was measured in the test flasks prepared with the non-modified EPA medium using chelated copper (96 h-EC 50 = 65.93 µg L -1 as Cu) as compared to their analogous microcosms with modified water chemistry (96 h-EC 50 = 386.67 µg L -1 as Cu), the increased water hardness and alkalinity in the latter case contributing to the decrease of the metal bioavailability. Results from laboratory experiments showed good correlation with copper dosages used in a small scale field testing to control algae growth, increasing confidence in laboratory bioassays. Copyright © 2018 Elsevier Inc. All rights reserved.

Reduction of quaternary ammonium-induced ocular surface toxicity by emulsions: an in vivo study in rabbits

PubMed Central

Liang, H.; Brignole-Baudouin, F.; Rabinovich-Guilatt, L.; Mao, Z.; Riancho, L.; Faure, M.O.; Warnet, J.M.; Lambert, G.

2008-01-01

Purpose To evaluate and compare the toxicological profiles of two quaternary ammonium compounds (QAC), benzalkonium chloride (BAK), and cetalkonium chloride (CKC), in standard solution or cationic emulsion formulations in rabbit eyes using newly developed in vivo and ex vivo experimental approaches. Methods Seventy eyes of 35 adult male New Zealand albino rabbits were used in this study. They were randomly divided into five groups: 50 µl of phosphate-buffered saline (PBS), PBS containing 0.02% BAK or 0.002% CKC (BAK Sol and CKC Sol, respectively), and emulsion containing 0.02% BAK or 0.002% CKC (BAK Em and CKC Em, respectively) were applied to rabbit eyes 15 times at 5-min intervals. The ocular surface changes induced by these eye drops were investigated using slit-lamp examination, flow cytometry (FCM), impression cytology (IC) on conjunctiva, and corneal in vivo confocal microscopy (IVCM). Standard immunohistology in cryosections was also examined for cluster of differentiation (CD) 45+ infiltrating and terminal deoxynucleotidyl transferase-mediated dUTP-nick end labeling (TUNEL)+ apoptotic cells. Results Clinical observations and IVCM showed that the highest toxicity was induced by BAK Sol, characterized by damaged corneal epithelium and a high level of inflammatory infiltration. BAK Em and CKC Sol presented moderate effects, and CKC Em showed the lowest toxicity with results similar to those of PBS. Conjunctival imprints analyzed by FCM showed a higher expression of RLA-DR and TNFR1 markers in BAK Sol-instilled eyes than in all other groups, especially at 4 h. Immunohistology was correlated with in vivo and ex vivo findings and confirmed this toxicity profile. A high level of infiltration of CD45+ inflammatory cells and TUNEL+ apoptotic cells was observed in limbus and conjunctiva, especially in QAC solution-receiving eyes compared to QAC emulsion-instilled eyes. Conclusions The acute administration of 15 instillations at 5 min intervals was a rapid and efficient model to assess quaternary ammonium toxicity profiles. This model showed the highest toxicity, induced by the BAK solution, and the lowest level of toxicity, induced by the CKC emulsion. These in vivo and ex vivo experimental approaches demonstrated that ocular surface toxicity was reduced by using an emulsion instead of a traditional solution and that a CKC emulsion was safe for future ocular administration. PMID:18347566

Reduction of quaternary ammonium-induced ocular surface toxicity by emulsions: an in vivo study in rabbits.

PubMed

Liang, H; Brignole-Baudouin, F; Rabinovich-Guilatt, L; Mao, Z; Riancho, L; Faure, M O; Warnet, J M; Lambert, G; Baudouin, C

2008-01-31

To evaluate and compare the toxicological profiles of two quaternary ammonium compounds (QAC), benzalkonium chloride (BAK), and cetalkonium chloride (CKC), in standard solution or cationic emulsion formulations in rabbit eyes using newly developed in vivo and ex vivo experimental approaches. Seventy eyes of 35 adult male New Zealand albino rabbits were used in this study. They were randomly divided into five groups: 50 microl of phosphate-buffered saline (PBS), PBS containing 0.02% BAK or 0.002% CKC (BAK Sol and CKC Sol, respectively), and emulsion containing 0.02% BAK or 0.002% CKC (BAK Em and CKC Em, respectively) were applied to rabbit eyes 15 times at 5-min intervals. The ocular surface changes induced by these eye drops were investigated using slit-lamp examination, flow cytometry (FCM), impression cytology (IC) on conjunctiva, and corneal in vivo confocal microscopy (IVCM). Standard immunohistology in cryosections was also examined for cluster of differentiation (CD) 45+ infiltrating and terminal deoxynucleotidyl transferase-mediated dUTP-nick end labeling (TUNEL)+ apoptotic cells. Clinical observations and IVCM showed that the highest toxicity was induced by BAK Sol, characterized by damaged corneal epithelium and a high level of inflammatory infiltration. BAK Em and CKC Sol presented moderate effects, and CKC Em showed the lowest toxicity with results similar to those of PBS. Conjunctival imprints analyzed by FCM showed a higher expression of RLA-DR and TNFR1 markers in BAK Sol-instilled eyes than in all other groups, especially at 4 h. Immunohistology was correlated with in vivo and ex vivo findings and confirmed this toxicity profile. A high level of infiltration of CD45+ inflammatory cells and TUNEL+ apoptotic cells was observed in limbus and conjunctiva, especially in QAC solution-receiving eyes compared to QAC emulsion-instilled eyes. The acute administration of 15 instillations at 5 min intervals was a rapid and efficient model to assess quaternary ammonium toxicity profiles. This model showed the highest toxicity, induced by the BAK solution, and the lowest level of toxicity, induced by the CKC emulsion. These in vivo and ex vivo experimental approaches demonstrated that ocular surface toxicity was reduced by using an emulsion instead of a traditional solution and that a CKC emulsion was safe for future ocular administration.

Vaccination with nontoxic mutant toxic shock syndrome toxin 1 protects against Staphylococcus aureus infection.

PubMed

Hu, Dong-Liang; Omoe, Katsuhiko; Sasaki, Sanae; Sashinami, Hiroshi; Sakuraba, Hirotake; Yokomizo, Yuichi; Shinagawa, Kunihiro; Nakane, Akio

2003-09-01

To investigate whether vaccination with nontoxic mutant toxic shock syndrome toxin 1 (mTSST-1) can protect against Staphylococcus aureus infection, mice were vaccinated with mTSST-1 and challenged with viable S. aureus. Survival in the mTSST-1-vaccinated group was higher, and bacterial counts in organs were significantly lower than those of control mice. Passive transfer of mTSST-1-specific antibodies also provided protection against S. aureus-induced septic death. Interferon (IFN)-gamma production in the serum samples and spleens from vaccinated mice was significantly decreased compared with that in controls, whereas interleukin-10 titers were significantly higher in vaccinated mice. IFN-gamma and tumor necrosis factor-alpha production in vitro were significantly inhibited by serum samples from mTSST-1-immunized mice but not from control mice. These results suggest that vaccination with mTSST-1 devoid of superantigenic properties provides protection against S. aureus infection and that the protection might be mediated by TSST-1-neutralizing antibodies as well as by the down-regulation of IFN-gamma production.

Preliminary research on 1-(4-bromo-2-nitroimidazol-1-yl)-3-[(18)F]fluoropropan-2-ol as a novel brain hypoxia PET tracer in a rodent model of stroke.

PubMed

Nieto, Elena; Delgado, Mercedes; Sobrado, Mónica; de Ceballos, María L; Alajarín, Ramón; García-García, Luis; Kelly, James; Lizasoain, Ignacio; Pozo, Miguel A; Álvarez-Builla, Julio

2015-08-28

The synthesis of the new radiotracer precursor 4-Br-NITTP and the radiolabeling of the new tracer 1-(4-bromo-2-nitroimidazol-1-yl)-3-[(18)F]fluoropropan-2-ol (4-Br-[(18)F]FMISO) is reported. The cyclic voltammetry behaviour, neuronal cell toxicity, transport through the brain endothelial cell monolayer, in vivo PET imaging and preliminary calculations of the tracer uptake for a rodent model of stroke were studied for the new compound and the results were compared to those obtained with [(18)F]FMISO, the current gold standard PET hypoxia tracer. The new PET brain hypoxia tracer is more easily reduced, has higher CLogP than [(18)F]FMISO and it diffuses more rapidly through brain endothelial cells. The new compound is non-toxic to neuronal cells and it allows the in vivo mapping of stroke in mice with higher sensitivity. 4-Br-[(18)F]FMISO is a good candidate for further development in ischemic stroke. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Toxicity of AMPA to the earthworm Eisenia andrei Bouché, 1972 in tropical artificial soil

NASA Astrophysics Data System (ADS)

Domínguez, Anahí; Brown, George Gardner; Sautter, Klaus Dieter; Ribas de Oliveira, Cintia Mara; de Vasconcelos, Eliane Carvalho; Niva, Cintia Carla; Bartz, Marie Luise Carolina; Bedano, José Camilo

2016-01-01

Aminomethylphosphonic acid (AMPA) - one of glyphosate’s main metabolites - has been classified as persistent in soils, raising concern regarding the widespread use of glyphosate in agriculture and forestry. Glyphosate may have negative or neutral effects on soil biota, but no information is available on the toxicity of AMPA to soil invertebrates. Therefore our aim was to study the effect of AMPA on mortality and reproduction of the earthworm species Eisenia andrei using standard soil ecotoxicological methods (ISO). Field-relevant concentrations of AMPA had no significant effects on mortality in acute or chronic assays. Except at the highest concentration tested, a significant biomass loss was observed compared to controls in the chronic assay. The number of juveniles and cocoons increased with higher concentrations of AMPA applied, but their mean weights decreased. This mass loss indicates higher sensitivity of juveniles than adults to AMPA. Our results suggest that earthworms coming from parents grown in contaminated soils may have reduced growth, limiting their beneficial roles in key soil ecosystem functions. Nevertheless, further research is needed to better understand the mechanisms underlying the sublethal effects observed here.

Application of carbon foam for heavy metal removal from industrial plating wastewater and toxicity evaluation of the adsorbent.

PubMed

Lee, Chang-Gu; Song, Mi-Kyung; Ryu, Jae-Chun; Park, Chanhyuk; Choi, Jae-Woo; Lee, Sang-Hyup

2016-06-01

Electroplating wastewater contains various types of toxic substances, such as heavy metals, solvents, and cleaning agents. Carbon foam was used as an adsorbent for the removal of heavy metals from real industrial plating wastewater. Its sorption capacity was compared with those of a commercial ion-exchange resin (BC258) and a heavy metal adsorbent (CupriSorb™) in a batch system. The experimental carbon foam has a considerably higher sorption capacity for Cr and Cu than commercial adsorbents for acid/alkali wastewater and cyanide wastewater. Additionally, cytotoxicity test showed that the newly developed adsorbent has low cytotoxic effects on three kinds of human cells. In a pilot plant, the carbon foam had higher sorption capacity for Cr (73.64 g kg(-1)) than for Cu (14.86 g kg(-1)) and Ni (7.74 g kg(-1)) during 350 h of operation time. Oxidation pretreatments using UV/hydrogen peroxide enhance heavy metal removal from plating wastewater containing cyanide compounds. Copyright © 2016 Elsevier Ltd. All rights reserved.

Retrospective analysis of bendamustine and rituximab use in indolent and mantle cell non-Hodgkin lymphoma based on initial starting dose.

PubMed

Bond, David A; Huang, Ying; Ruppert, Amy S; Walker, Alison R; Dotson, Emily K; Roddy, Julianna; Blum, Kristie A; Christian, Beth A

2017-07-01

The initial dose of bendamustine, an alkylating agent used in treating indolent lymphoma (iNHL) and mantle cell lymphoma, is variable in clinical practice. 134 patients treated with bendamustine and rituximab were evaluated for starting dosage, patient characteristics, toxicities, and clinical outcome. The starting dosage ranged from 50 to 90 mg/m 2 . Lower starting dosage (<90 mg/m 2 ) was associated with relapsed disease, increased age and worse performance status (PS), histologic subtype other than follicular lymphoma, baseline renal impairment, and cytopenias. No significant difference was observed in toxicities between patients treated with 90 mg/m 2 compared with lower doses. The starting dose of 90 mg/m 2 was associated with a higher complete response rate (56% vs. 29%) and longer progression free survival (PFS) (39.5 months vs. 19.7 months). However, in a multivariable model, the higher starting dose was not associated with longer PFS in those with similar age, histology, PS, and number of prior therapies.

Advances in radiotherapy for esophageal cancer

PubMed Central

Deng, Wei

2018-01-01

Esophageal cancer is a common type of malignancy worldwide and usually requires multidisciplinary care. Radiotherapy plays an important part in management of the disease. During the past few years, researchers have made much progress about radiotherapy for esophageal cancer, which was revealed in every aspect of clinical practice. Neoadjuvant chemoradiotherapy remains the standard treatment for locally advanced esophageal cancer, whereas neoadjuvant chemotherapy appears to show less toxicities and non-inferior prognosis. What’s more, definitive chemoradiotherapy could be an option for non-surgical candidates and good responders to chemoradiotherapy. Advances in radiation techniques result in higher conformity, homogeneity, more normal tissue sparing and less treatment time. Promising prognoses and less toxicities were also seen in advanced techniques. As radiation dose higher than 50 Gy obtains better local control and survival, simultaneously integrated boost is designed to increase primary tumor dosage and keep prophylactic dose to subclinical areas. Elective nodal irradiation brings about better local control but do not show advantages in survival compared with involved field irradiation (IFI). As a trend, more tolerable chemoradiotherapy regimen would be taken into account in dealing with elderly patients. PMID:29666802

Mercury concentration on Enhalus acoroides and Thalassia hemprichii at Seribu Islands

NASA Astrophysics Data System (ADS)

Suratno; Irawan, Andri

2018-02-01

Mercury is a toxic heavy metal element that can damage embryo development. Although this element is highly toxic, some human activities such as mining and industries are still using it. The uncontrolled usage of this element leads to pollution problem in the environment, which includes the seagrass ecosystem in the coastal area of Seribu Islands. For that, to gather more information about mercury pollution in the seagrass beds of these islands, the concentration of mercury (Hg) was measured in sediment, rhizomes, roots and leaves of two species of seagrass (Enhalus acoroides and Thalassia hemprichii) from Lancang Island, Pari Island and Panggang Island at Seribu Islands, Indonesia in April-May 2017. The highest concentration of mercury was found in sediment on Lancang Island. The concentration of mercury was significantly higher on leaves compare to on roots or rhizomes in E. acoroides on Lancang Island and Panggang Island. T. hemprichii accumulate mercury higher than E. acoroides on Lancang Island. Overall, mercury accumulation on both species ranges at 7.12 - 87.41 ug/kg dw and this shows that they have the potential as bio-indicator of mercury bio accumulation.

Threshold of toxicological concern values for non-genotoxic effects in industrial chemicals: re-evaluation of the Cramer classification.

PubMed

Kalkhof, H; Herzler, M; Stahlmann, R; Gundert-Remy, U

2012-01-01

The TTC concept employs available data from animal testing to derive a distribution of NOAELs. Taking a probabilistic view, the 5th percentile of the distribution is taken as a threshold value for toxicity. In this paper, we use 824 NOAELs from repeated dose toxicity studies of industrial chemicals to re-evaluate the currently employed TTC values, which have been derived for substances grouped according to the Cramer scheme (Cramer et al. in Food Cosm Toxicol 16:255-276, 1978) by Munro et al. (Food Chem Toxicol 34:829-867, 1996) and refined by Kroes and Kozianowski (Toxicol Lett 127:43-46, 2002), Kroes et al. 2000. In our data set, consisting of 756 NOAELs from 28-day repeated dose testing and 57 NOAELs from 90-days repeated dose testing, the experimental NOAEL had to be extrapolated to chronic TTC using regulatory accepted extrapolation factors. The TTC values derived from our data set were higher than the currently used TTC values confirming the safety of the latter. We analysed the prediction of the Cramer classification by comparing the classification by this tool with the guidance values for classification according to the Globally Harmonised System of classification and labelling of the United Nations (GHS). Nearly 90% of the chemicals were in Cramer class 3 and assumed as highly toxic compared to 22% according to the GHS. The Cramer classification does underestimate the toxicity of chemicals only in 4.6% of the cases. Hence, from a regulatory perspective, the Cramer classification scheme might be applied as it overestimates hazard of a chemical.

Effects of methylenetetrahydrofolate reductase gene polymorphisms on toxicities during consolidation therapy in pediatric acute lymphoblastic leukemia in a Chinese population.

PubMed

Liu, Shu-Guang; Li, Zhi-Gang; Cui, Lei; Gao, Chao; Li, Wei-Jing; Zhao, Xiao-Xi

2011-06-01

This study aimed to investigate whether there was a correlation between the genotype or haplotype of the methylenetetrahydrofolate reductase gene (MTHFR) and toxicities during consolidation therapy or plasma methotrexate (MTX) levels at 48 h after the first dose of MTX infusion. We retrospectively genotyped 181 children with newly diagnosed acute lymphoblastic leukemia (ALL) who were treated with the Chinese Children's Leukemia Group protocol. In standard- and medium-risk treatment branches, the 677T carriers (CT + TT) had a higher risk of developing thrombocytopenia when compared with carriers of the CC genotype (odds ratio [OR] 5.21, 95% confidence interval [CI] 1.18-23.01, p = 0.017). The 1298AC/CC genotypes were associated with a decrease in skin toxicity, as compared with the common AA genotype (p = 0.037). An estimation of haplotype frequencies showed that there was no 677T-1298C haplotype in the population. A lower frequency of anemia (OR 0.44, 95% CI 0.21-0.90, p = 0.025) and lower MTX level (p = 0.044) were observed in patients with the 677C-1298C haplotype than in those without. High plasma MTX level was correlated with anemia (p = 0.011) and neutropenia (p = 0.044). In the high-risk group, the polymorphisms or plasma MTX levels were not correlated with any toxicity. Taken together, our data demonstrate that genotyping of MTHFR and measurement of plasma MTX levels might be useful to optimize MTX therapy.

Effects of Cylindrospermopsis raciborskii strains (Woloszynska, 1912) Senayya & Subba Raju on the mobility of Daphnia laevis (Cladocera, Daphniidae).

PubMed

Restani, G C; Fonseca, A L

2014-02-01

Cylindrospermopsis raciborskii is a cyanobacterium distributed worldwide that is known to produce cyanotoxins. Some of the Brazilian strains can produce saxitoxins (STXs), which are classified as neurotoxins and can paralyze cladocerans .Daphnia laevis is a cladoceran with a wide distribution in the Americas and has been studied as a possible test-organism in toxicity bioassays. The present work tested the acute effect on D laevis mobility when fed a saxitoxin-producing (STX and neoSTX) C. raciborskii strain, CYRF-01, and compared the results with the effects of a non-toxic strain (NPCS-1). Neonates (6-24 hours after birth) were exposed to concentrations of C. raciborskii varying from 102 to 106 cells·mL-1 of each strain for up to three hours. The cladocerans were then transferred to a medium without toxic filaments for 24 hours. Only the organisms exposed to the STX-producing strain showed signs of the immobilization of swimming movements, confirming the effects of the toxins. There was a linear correlation between the time required to induce stopping the swimming movement, with a shorter time to needed to induce immobilization at a higher the concentration; this correlation was inverse to the time required to recover the swimming movements (longer at higher concentrations, p < 0.1). D. laevis is a tropical and subtropical species with great potential for use in toxicity tests for the detection of STXs, despite being native to and found in a great array of freshwater bodies. This is the first assay testing STX-producing and non-producing C. raciborskii strains on D. laevis, species that are both found in Brazilian ecosystems.

Side Chain Degradable Cationic-Amphiphilic Polymers with Tunable Hydrophobicity Show in Vivo Activity.

PubMed

Uppu, Divakara S S M; Samaddar, Sandip; Hoque, Jiaul; Konai, Mohini M; Krishnamoorthy, Paramanandham; Shome, Bibek R; Haldar, Jayanta

2016-09-12

Cationic-amphiphilic antibacterial polymers with optimal amphiphilicity generally target the bacterial membranes instead of mammalian membranes. To date, this balance has been achieved by varying the cationic charge or side chain hydrophobicity in a variety of cationic-amphiphilic polymers. Optimal hydrophobicity of cationic-amphiphilic polymers has been considered as the governing factor for potent antibacterial activity yet minimal mammalian cell toxicity. However, the concomitant role of hydrogen bonding and hydrophobicity with constant cationic charge in the interactions of antibacterial polymers with bacterial membranes is not understood. Also, degradable polymers that result in nontoxic degradation byproducts offer promise as safe antibacterial agents. Here we show that amide- and ester (degradable)-bearing cationic-amphiphilic polymers with tunable side chain hydrophobicity can modulate antibacterial activity and cytotoxicity. Our results suggest that an amide polymer can be a potent antibacterial agent with lower hydrophobicity whereas the corresponding ester polymer needs a relatively higher hydrophobicity to be as effective as its amide counterpart. Our studies reveal that at higher hydrophobicities both amide and ester polymers have similar profiles of membrane-active antibacterial activity and mammalian cell toxicity. On the contrary, at lower hydrophobicities, amide and ester polymers are less cytotoxic, but the former have potent antibacterial and membrane activity compared to the latter. Incorporation of amide and ester moieties made these polymers side chain degradable, with amide polymers being more stable than the ester polymers. Further, the polymers are less toxic, and their degradation byproducts are nontoxic to mice. More importantly, the optimized amide polymer reduces the bacterial burden of burn wound infections in mice models. Our design introduces a new strategy of interplay between the hydrophobic and hydrogen bonding interactions keeping constant cationic charge density for developing potent membrane-active antibacterial polymers with minimal toxicity to mammalian cells.

Developmental and reproductive toxicity of PVP/PEI-coated silver nanoparticles to zebrafish.

PubMed

Orbea, Amaia; González-Soto, Nagore; Lacave, José María; Barrio, Irantzu; Cajaraville, Miren P

2017-09-01

Cellular and molecular mechanisms of toxicity of silver nanoparticles (NPs) and their toxicity to fish embryos after waterborne exposure have been widely investigated, but much less information is available regarding the effect of Ag NPs on physiological functions such as growth or reproduction. In this work, the effects of waterborne exposure of adult zebrafish (Danio rerio) to PVP/PEI coated Ag NPs (~5nm) on reproduction (fecundity) were investigated. Moreover, the development of the embryos after parental exposure was compared with the development of embryos after direct waterborne exposure to the NPs. For this, two experiments were run: 1) embryos from unexposed parents were treated for 5days with Ag NPs (10μgAgL -1 -10mgAgL -1 ) and development was monitored, and 2) selected breeding zebrafish were exposed for 3weeks to 100ngAgL -1 (environmentally relevant concentration) or to 10μgAgL -1 of Ag NPs, fecundity was scored and development of resulting embryos was monitored up to 5days. Waterborne exposure of embryos to Ag NPs resulted in being highly toxic (LC50 at 120h=50μgAgL -1 ), causing 100% mortality during the first 24h of exposure at 0.1mgAgL -1 . Exposure of adults, even at the environmentally relevant silver concentration, caused a significant reduction of fecundity by the second week of treatment and resulting embryos showed a higher prevalence of malformations than control embryos. Exposed adult females presented higher prevalence of vacuolization in the liver. These results show that Ag NPs at an environmentally relevant concentration are able to affect population level parameters in zebrafish. Copyright © 2017 Elsevier Inc. All rights reserved.

Equity and Information: Information Regulation, Environmental Justice, and Risks from Toxic Chemicals

ERIC Educational Resources Information Center

Shapiro, Marc D.

2005-01-01

Decreases over time in pounds of industrial chemical emissions have led to concerns that nonminority, higher-income communities have benefited disproportionately in reductions in risk. Toxic chemical release data, modeled for toxicity and dispersion in square kilometer units across 45 states, are used to test six sets of hypotheses of potential…

Haloactamides versus halomethanes formation and toxicity in chloraminated drinking water.

PubMed

Yang, Fan; Zhang, Jing; Chu, Wenhai; Yin, Daqiang; Templeton, Michael R

2014-06-15

In this study we quantified the concentrations of nine haloacetamides (HAcAms) and nine halomethanes (HMs) in the final waters of five drinking water treatment plants (DWTPs) that use either chlorination or chloramination for disinfection and evaluated the toxicity of dichloroacetamide (DCAcAm) and dichloromethane (DCM) in normal rat kidney (NRK) cells using four in vitro toxicity assays. All the DWTPs final waters contained primarily di-HAcAms, followed by tri- and mono-HAcAms, and DCAcAm was the most abundant species of the 9 HAcAms, regardless of chlorination or chloramination being applied. In the final waters of DWTPs using chlorination, tri-HMs (trihalomethanes, THMs) accounted for the majority of HMs, whereas chloramination resulted in more di-HMs (especially DCM) than THMs. All four in vitro toxicity assays indicated that the NRK cell chronic cytotoxicity and acute genotoxicity of DCAcAm were substantially higher than that of DCM. In view of observed occurrence concentrations and quantified toxicity levels, the findings of this study suggest that DCAcAm represents a higher toxicity risk than DCM in chloraminated drinking waters. Copyright © 2014 Elsevier B.V. All rights reserved.

Insecticidal, repellent and fungicidal properties of novel trifluoromethylphenyl amides.

PubMed

Tsikolia, Maia; Bernier, Ulrich R; Coy, Monique R; Chalaire, Katelyn C; Becnel, James J; Agramonte, Natasha M; Tabanca, Nurhayat; Wedge, David E; Clark, Gary G; Linthicum, Kenneth J; Swale, Daniel R; Bloomquist, Jeffrey R

2013-09-01

Twenty trifluoromethylphenyl amides were synthesized and evaluated as fungicides and as mosquito toxicants and repellents. Against Aedes aegypti larvae, N-(2,6-dichloro-4-(trifluoromethyl)phenyl)-3,5-dinitrobenzamide (1e) was the most toxic compound (24 h LC50 1940 nM), while against adults N-(2,6-dichloro-4-(trifluoromethyl)phenyl)-2,2,2-trifluoroacetamide (1c) was most active (24 h LD50 19.182 nM, 0.5 μL/insect). However, the 24 h LC50 and LD50 values of fipronil against Ae. aegypti larvae and adults were significantly lower: 13.55 nM and 0.787 × 10(-4) nM, respectively. Compound 1c was also active against Drosophila melanogaster adults with 24 h LC50 values of 5.6 and 4.9 μg/cm(2) for the Oregon-R and 1675 strains, respectively. Fipronil had LC50 values of 0.004 and 0.017 μg/cm(2) against the two strains of D. melanogaster, respectively. In repellency bioassays against female Ae. aegypti, 2,2,2-trifluoro-N-(2-(trifluoromethyl)phenyl)acetamide (4c) had the highest repellent potency with a minimum effective dosage (MED) of 0.039 μmol/cm(2) compared to DEET (MED of 0.091 μmol/cm(2)). Compound N-(2-(trifluoromethyl)phenyl)hexanamide (4a) had an MED of 0.091 μmol/cm(2) which was comparable to DEET. Compound 4c was the most potent fungicide against Phomopsis obscurans. Several trends were discerned between the structural configuration of these molecules and the effect of structural changes on toxicity and repellency. Para- or meta- trifluoromethylphenyl amides with an aromatic ring attached to the carbonyl carbon showed higher toxicity against Ae. aegypti larvae, than ortho- trifluoromethylphenyl amides. Ortho- trifluoromethylphenyl amides with trifluoromethyl or alkyl group attached to the carbonyl carbon produced higher repellent activity against female Ae. aegypti and Anopheles albimanus than meta- or para- trifluoromethylphenyl amides. The presence of 2,6-dichloro- substitution on the phenyl ring of the amide had an influence on larvicidal and repellent activity of para- trifluoromethylphenyl amides. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Sarcopenic obesity: A probable risk factor for dose limiting toxicity during neo-adjuvant chemotherapy in oesophageal cancer patients.

PubMed

Anandavadivelan, Poorna; Brismar, Torkel B; Nilsson, Magnus; Johar, Asif M; Martin, Lena

2016-06-01

Profound weight loss and malnutrition subsequent to severe dysphagia and cancer cachexia are cardinal symptoms in oesophageal cancer (OC). Low muscle mass/sarcopenia has been linked to toxicity during neo-adjuvant therapy in other cancers, with worser effects in sarcopenic obesity. In this study the association between sarcopenia and/or sarcopenic obesity and dose limiting toxicity (DLT) during cycle one chemotherapy in resectable OC patients was evaluated. Body composition was assessed from computed tomography scans of 72 consecutively diagnosed OC patients. Lean body mass and body fat mass were estimated. Patients were grouped as sarcopenic or non-sarcopenic based on pre-defined gender-specific cut-offs for sarcopenia, and as underweight/normal (BMI < 25) or overweight/obese (BMI ≥ 25). Sarcopenic obesity was defined as sarcopenia combined with overweight and obesity. DLT was defined as temporary reduction/delay or permanent discontinuation of drugs due to adverse effects. Odds ratios for developing toxicity were ascertained using multiple logistic regression. Of 72 patients, 85% (n = 61) were males. Sarcopenia and sarcopenic obesity were present in 31 (43%) and 10 (14%), respectively, prior to chemotherapy. Sarcopenic patients had significantly lower adipose tissue index (p = 0.02) compared to non-sarcopenic patients. Patients with DLT (n = 24) had lower skeletal muscle mass (p = 0.04) than those without DLT. Sarcopenic patients (OR = 2.47; 95% CI: 0.88-6.93) showed a trend towards increased DLT risk (p < 0.10). Logistic regression with BMI as an interaction term indicated higher DLT risk in sarcopenic patients with normal BMI (OR = 1.60; 95% CI 0.30-8.40), but was non-significant. In the sarcopenic obese, risk of DLT increased significantly (OR = 5.54; 95% CI 1.12-27.44). Sarcopenic and sarcopenic obese OC patients may be at a higher risk for developing DLT during chemotherapy compared to non-sarcopenic OC patients. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Ecotoxicological assessment of flocculant modified soil for lake restoration using an integrated biotic toxicity index.

PubMed

Wang, Zhibin; Zhang, Honggang; Pan, Gang

2016-06-15

Flocculant modified soils/clays are being increasingly studied as geo-engineering materials for lake restoration and harmful algal bloom control. However, the potential impacts of adding these materials in aquatic ecological systems remain unclear. This study investigated the potential effects of chitosan, cationic starch, chitosan modified soils (MS-C) and cationic starch modified soils (MS-S) on the aquatic organisms by using a bioassay battery. The toxicity potential of these four flocculants was quantitatively assessed using an integrated biotic toxicity index (BTI). The test system includes four aquatic species, namely Chlorella vulgaris, Daphnia magna, Cyprinus carpio and Limnodrilus hoffmeisteri, which represent four trophic levels in the freshwater ecosystem. Results showed that median effect concentrations (EC50) of the MS-C and MS-S were 31-124 times higher than chitosan and cationic starch, respectively. D. magna was the most sensitive species to the four flocculants. Histological examination of C. carpio showed that significant pathological changes were found in gills. Different from chitosan and cationic starch, MS-C and MS-S significantly alleviated the acute toxicities of chitosan and cationic starch. The toxicity order of the four flocculants based on BTI were cationic starch > chitosan > MS-S > MS-C. The results suggested that BTI can be used as a quantitative and comparable indicator to assess biotic toxicity for aquatic geo-engineering materials. Chitosan or cationic starch modified soil/clay materials can be used at their optimal dosage without causing substantial adverse effects to the bioassay battery in aquatic ecosystem. Copyright © 2015 Elsevier Ltd. All rights reserved.

Thermal treatment of toxic metals of industrial hazardous wastes with fly ash and clay.

PubMed

Singh, I B; Chaturvedi, K; Morchhale, R K; Yegneswaran, A H

2007-03-06

Waste generated from galvanizing and metal finishing processes is considered to be a hazardous due to the presence of toxic metals like Pb, Cu, Cr, Zn, etc. Thermal treatment of such types of wastes in the presence of clay and fly ash can immobilizes their toxic metals to a maximum level. After treatment solidified mass can be utilized in construction or disposed off through land fillings without susceptibility of re-mobilization of toxic metals. In the present investigation locally available clay and fly ash of particular thermal power plant were used as additives for thermal treatment of both of the wastes in their different proportions at 850, 900 and 950 degrees C. Observed results indicated that heating temperature to be a key factor in the immobilization of toxic metals of the waste. It was noticed that the leachability of metals of the waste reduces to a negligible level after heating at 950 degrees C. Thermally treated solidified specimen of 10% waste and remaining clay have shown comparatively a higher compressive strength than clay fired bricks used in building construction. Though, thermally heated specimens made of galvanizing waste have shown much better strength than specimen made of metal finishing waste. The lechability of toxic metals like Cr, Cu, Pb and Zn became far below from their regulatory threshold after heating at 950 degrees C. Addition of fly ash did not show any improvement either in engineering property or in leachability of metals from the solidified mass. X-ray diffraction (XRD) analysis of the solidified product confirmed the presence of mixed phases of oxides of metals.

Bioavailability and Toxicity of Copper, Manganese, and Nickel in Paronychiurus kimi (Collembola), and Biomarker Discovery for Their Exposure.

PubMed

Son, Jino; Lee, Yun-Sik; Lee, Sung-Eun; Shin, Key-Il; Cho, Kijong

2017-01-01

Bioavailability and toxicity of Cu, Mn, and Ni in Paronychiurus kimi were investigated after 28 days of exposure to OECD artificial soil spiked with these metals. Uptake and effect of Cu, Mn, and Ni on the reproduction of P. kimi were related to different metal fractions (water-soluble, 0.01 M CaCl 2 -extractable or porewater metal concentrations). Cu and Mn concentrations in P. kimi increased with increasing Cu and Mn concentrations in the soil, while Ni contents in P. kimi reached a plateau at a concentration higher than 200 mg/kg in soil. Both uptake and juvenile production related well to different metal fractions, suggesting that these metal fractions are suitable for assessing bioavailability and toxicity of metals in P. kimi. When toxicity for reproduction was compared, as reflected by EC 50 values, the order of metal toxicity varied depending upon how exposure concentration was expressed. Moreover, the results of proteomic analysis showed that several proteins involved in the immune system, neuronal outgrowth, and metal ion binding were up-regulated in P. kimi following short-term (7 days) exposure to sublethal level (corresponding to 50% of the EC 50 ) of Cu, Mn, or Ni, respectively. This suggests that the ecotoxicoproteomic approach seems to be a promising tool for early exposure warnings below which significant adverse effects are unlikely to occur. This study demonstrated that a combination of chemical and biological measures can provide information about metal bioavailability and toxicity to which P. kimi has been exposed.

Mercury in traditional medicines: Is cinnabar toxicologically similar to common mercurials?

PubMed Central

Liu, Jie; Shi, Jing-Zheng; Yu, Li-Mei; Goyer, Robert A.; Waalkes, Michael P.

2009-01-01

Mercury is a major toxic metal ranking top in the Toxic Substances List. Cinnabar (contains mercury sulfide) has been used in traditional medicines for thousands years as an ingredient in various remedies, and 40 cinnabar-containing traditional medicines are still used today. Little is known about toxicology profiles or toxicokinetics of cinnabar and cinnabar-containing traditional medicines, and the high mercury content in these Chinese medicines raises justifiably escalations of public concern. This minireview searched the available database of cinnabar, compared cinnabar with common mercurials, such as mercury vapor, inorganic mercury, and organic mercury, and discusses differences in their bioavailability, disposition, and toxicity. The analysis showed that cinnabar is insoluble and poorly absorbed from the gastrointestinal tract. Absorbed mercury from cinnabar is mainly accumulated in kidney, resembling the disposition pattern of inorganic mercury. Heating cinnabar results in release of mercury vapor, which in turn can produce toxicity similar to inhalation of these vapors. The doses of cinnabar required to produce neurotoxicity are thousands 1000 times higher than methyl mercury. Following long-term use of cinnabar, renal dysfunction may occur. Dimercaprol and succimer are effective chelation therapies for general mercury intoxication including cinnabar. Pharmacology studies of cinnabar suggest sedative and hypnotic effects, but the therapeutic basis of cinnabar is still not clear. In summary, cinnabar is chemically inert with a relatively low toxic potential when taken orally. In risk assessment, cinnabar is less toxic than many other forms of mercury, but the rationale for its inclusion in traditional Chinese medicines remains to be fully justified. PMID:18445765

Esophageal Dose Tolerance in Patients Treated With Stereotactic Body Radiation Therapy.

PubMed

Nuyttens, Joost J; Moiseenko, Vitali; McLaughlin, Mark; Jain, Sheena; Herbert, Scott; Grimm, Jimm

2016-04-01

Mediastinal critical structures such as trachea, bronchus, esophagus, and heart are among the dose-limiting factors for stereotactic body radiation therapy (SBRT) to central lung lesions. The purpose of this study was to characterize the risk of esophagitis for patients treated with SBRT and to develop a statistical dose-response model to assess the equivalent uniform dose, D10%, D5cc, D1cc, and Dmax, to the esophagus and the risk of toxicity. Toxicity outcomes of a dose-escalation study of 56 patients who had taken CyberKnife treatment from 45-60Gy in 3-7 fractions at the Erasmus MC-Daniel den Hoed Cancer Center were utilized to create the dose-response model for esophagus. A total of 5 grade 2 esophageal complications were reported (Common Terminology Criteria for Adverse Events version 3.0); 4 complications were early effects and 1 complication was a late effect. All analyses were performed in terms of 5-fraction equivalent dosing. According to our study, D1cc at a dose of 32.9Gy and Dmax dose of 43.4Gy corresponded to a complication probability of 50% for grade 2 toxicity. In this series of 58 CyberKnife mediastinal lung cases, no grade 3 or higher esophageal toxicity occurred. Our estimates of esophageal toxicity are compared with the data in the literature. Further research needs to be performed to establish more reliable dose limits as longer follow-up and toxicity outcomes are reported in patients treated with SBRT for central lung lesions. Copyright © 2016 Elsevier Inc. All rights reserved.

Toxicity of irradiated advanced heavy water reactor fuels.

PubMed

Priest, N D; Richardson, R B; Edwards, G W R

2013-02-01

The good neutron economy and online refueling capability of the CANDU® heavy water moderated reactor (HWR) enable it to use many different fuels such as low enriched uranium (LEU), plutonium, or thorium, in addition to its traditional natural uranium (NU) fuel. The toxicity and radiological protection methods for these proposed fuels, unlike those for NU, are not well established. This study uses software to compare the fuel composition and toxicity of irradiated NU fuel against those of two irradiated advanced HWR fuel bundles as a function of post-irradiation time. The first bundle investigated is a CANFLEX® low void reactor fuel (LVRF), of which only the dysprosium-poisoned central element, and not the outer 42 LEU elements, is specifically analyzed. The second bundle investigated is a heterogeneous high-burnup (LEU,Th)O(2) fuelled bundle, whose two components (LEU in the outer 35 elements and thorium in the central eight elements) are analyzed separately. The LVRF central element was estimated to have a much lower toxicity than that of NU at all times after shutdown. Both the high burnup LEU and the thorium fuel had similar toxicity to NU at shutdown, but due to the creation of such inhalation hazards as (238)Pu, (240)Pu, (242)Am, (242)Cm, and (244)Cm (in high burnup LEU), and (232)U and (228)Th (in irradiated thorium), the toxicity of these fuels was almost double that of irradiated NU after 2,700 d of cooling. New urine bioassay methods for higher actinoids and the analysis of thorium in fecal samples are recommended to assess the internal dose from these two fuels.

Preventing and Managing Toxicities of High-Dose Methotrexate.

PubMed

Howard, Scott C; McCormick, John; Pui, Ching-Hon; Buddington, Randall K; Harvey, R Donald

2016-12-01

: High-dose methotrexate (HDMTX), defined as a dose higher than 500 mg/m 2 , is used to treat a range of adult and childhood cancers. Although HDMTX is safely administered to most patients, it can cause significant toxicity, including acute kidney injury (AKI) in 2%-12% of patients. Nephrotoxicity results from crystallization of methotrexate in the renal tubular lumen, leading to tubular toxicity. AKI and other toxicities of high-dose methotrexate can lead to significant morbidity, treatment delays, and diminished renal function. Risk factors for methotrexate-associated toxicity include a history of renal dysfunction, volume depletion, acidic urine, and drug interactions. Renal toxicity leads to impaired methotrexate clearance and prolonged exposure to toxic concentrations, which further worsen renal function and exacerbate nonrenal adverse events, including myelosuppression, mucositis, dermatologic toxicity, and hepatotoxicity. Serum creatinine, urine output, and serum methotrexate concentration are monitored to assess renal clearance, with concurrent hydration, urinary alkalinization, and leucovorin rescue to prevent and mitigate AKI and subsequent toxicity. When delayed methotrexate excretion or AKI occurs despite preventive strategies, increased hydration, high-dose leucovorin, and glucarpidase are usually sufficient to allow renal recovery without the need for dialysis. Prompt recognition and effective treatment of AKI and associated toxicities mitigate further toxicity, facilitate renal recovery, and permit patients to receive other chemotherapy or resume HDMTX therapy when additional courses are indicated. High-dose methotrexate (HDMTX), defined as a dose higher than 500 mg/m 2 , is used for a range of cancers. Although HDMTX is safely administered to most patients, it can cause significant toxicity, including acute kidney injury (AKI), attributable to crystallization of methotrexate in the renal tubular lumen, leading to tubular toxicity. When AKI occurs despite preventive strategies, increased hydration, high-dose leucovorin, and glucarpidase allow renal recovery without the need for dialysis. This article, based on a review of the current associated literature, provides comprehensive recommendations for prevention of toxicity and, when necessary, detailed treatment guidance to mitigate AKI and subsequent toxicity. ©AlphaMed Press.

Preventing and Managing Toxicities of High-Dose Methotrexate

PubMed Central

McCormick, John; Pui, Ching-Hon; Buddington, Randall K.; Harvey, R. Donald

2016-01-01

High-dose methotrexate (HDMTX), defined as a dose higher than 500 mg/m2, is used to treat a range of adult and childhood cancers. Although HDMTX is safely administered to most patients, it can cause significant toxicity, including acute kidney injury (AKI) in 2%–12% of patients. Nephrotoxicity results from crystallization of methotrexate in the renal tubular lumen, leading to tubular toxicity. AKI and other toxicities of high-dose methotrexate can lead to significant morbidity, treatment delays, and diminished renal function. Risk factors for methotrexate-associated toxicity include a history of renal dysfunction, volume depletion, acidic urine, and drug interactions. Renal toxicity leads to impaired methotrexate clearance and prolonged exposure to toxic concentrations, which further worsen renal function and exacerbate nonrenal adverse events, including myelosuppression, mucositis, dermatologic toxicity, and hepatotoxicity. Serum creatinine, urine output, and serum methotrexate concentration are monitored to assess renal clearance, with concurrent hydration, urinary alkalinization, and leucovorin rescue to prevent and mitigate AKI and subsequent toxicity. When delayed methotrexate excretion or AKI occurs despite preventive strategies, increased hydration, high-dose leucovorin, and glucarpidase are usually sufficient to allow renal recovery without the need for dialysis. Prompt recognition and effective treatment of AKI and associated toxicities mitigate further toxicity, facilitate renal recovery, and permit patients to receive other chemotherapy or resume HDMTX therapy when additional courses are indicated. Implications for Practice: High-dose methotrexate (HDMTX), defined as a dose higher than 500 mg/m2, is used for a range of cancers. Although HDMTX is safely administered to most patients, it can cause significant toxicity, including acute kidney injury (AKI), attributable to crystallization of methotrexate in the renal tubular lumen, leading to tubular toxicity. When AKI occurs despite preventive strategies, increased hydration, high-dose leucovorin, and glucarpidase allow renal recovery without the need for dialysis. This article, based on a review of the current associated literature, provides comprehensive recommendations for prevention of toxicity and, when necessary, detailed treatment guidance to mitigate AKI and subsequent toxicity. PMID:27496039

A Comparative Analysis of Drug-Induced Hepatotoxicity in Clinically Relevant Situations

PubMed Central

Thiel, Christoph; Cordes, Henrik; Fabbri, Lorenzo; Aschmann, Hélène Eloise; Baier, Vanessa; Atkinson, Francis; Blank, Lars Mathias; Kuepfer, Lars

2017-01-01

Drug-induced toxicity is a significant problem in clinical care. A key problem here is a general understanding of the molecular mechanisms accompanying the transition from desired drug effects to adverse events following administration of either therapeutic or toxic doses, in particular within a patient context. Here, a comparative toxicity analysis was performed for fifteen hepatotoxic drugs by evaluating toxic changes reflecting the transition from therapeutic drug responses to toxic reactions at the cellular level. By use of physiologically-based pharmacokinetic modeling, in vitro toxicity data were first contextualized to quantitatively describe time-resolved drug responses within a patient context. Comparatively studying toxic changes across the considered hepatotoxicants allowed the identification of subsets of drugs sharing similar perturbations on key cellular processes, functional classes of genes, and individual genes. The identified subsets of drugs were next analyzed with regard to drug-related characteristics and their physicochemical properties. Toxic changes were finally evaluated to predict both molecular biomarkers and potential drug-drug interactions. The results may facilitate the early diagnosis of adverse drug events in clinical application. PMID:28151932

Central nervous system toxicity of mefenamic acid overdose compared with other NSAIDs: an analysis of cases reported to the United Kingdom National Poisons Information Service

PubMed Central

Crichton, Siobhan; Cooper, Gill; Lupton, David J.; Eddleston, Michael; Vale, J. Allister; Thompson, John P.; Thomas, Simon H. L.

2016-01-01

Aims Case reports and small case series suggest increased central nervous system (CNS) toxicity, especially convulsions, after overdose of mefenamic acid, compared with other nonsteroidal anti‐inflammatory drugs (NSAIDs), although comparative epidemiological studies have not been conducted. The current study compared rates of CNS toxicity after overdose between mefenamic acid, ibuprofen, diclofenac and naproxen, as reported in telephone enquiries to the UK National Poisons Information Service (NPIS). Methods NPIS telephone enquiries related to the four NSAIDs, received between January 2007 and December 2013, were analysed, comparing the frequency of reported CNS toxicity (convulsions, altered conscious level, agitation or aggression, confusion or disorientation) using multivariable logistic regression. Results Of 22 937 patient‐specific telephone enquiries, 10 398 did not involve co‐ingestion of other substances (mefenamic acid 461, ibuprofen 8090, diclofenac 1300, naproxen 547). Patients taking mefenamic acid were younger and more commonly female than those using other NSAIDs. Those ingesting mefenamic acid were more likely to experience CNS toxicity than those ingesting the other NSAIDs combined [adjusted odds ratio (OR) 7.77, 95% confidence interval (CI) 5.68, 10.62], especially convulsions (adjusted OR 81.5, 95% CI 27.8, 238.8). Predictors of CNS toxicity included reported dose and age, but not gender. Conclusions Mefenamic acid overdose is associated with a much larger and dose‐related risk of CNS toxicity, especially convulsions, compared with overdose of other NSAIDs. The benefit–risk profile of mefenamic acid should now be re‐evaluated in light of effective and less toxic alternatives. PMID:27785820

Central nervous system toxicity of mefenamic acid overdose compared with other NSAIDs: an analysis of cases reported to the United Kingdom National Poisons Information Service.

PubMed

Kamour, Ashraf; Crichton, Siobhan; Cooper, Gill; Lupton, David J; Eddleston, Michael; Vale, J Allister; Thompson, John P; Thomas, Simon H L

2017-04-01

Case reports and small case series suggest increased central nervous system (CNS) toxicity, especially convulsions, after overdose of mefenamic acid, compared with other nonsteroidal anti-inflammatory drugs (NSAIDs), although comparative epidemiological studies have not been conducted. The current study compared rates of CNS toxicity after overdose between mefenamic acid, ibuprofen, diclofenac and naproxen, as reported in telephone enquiries to the UK National Poisons Information Service (NPIS). NPIS telephone enquiries related to the four NSAIDs, received between January 2007 and December 2013, were analysed, comparing the frequency of reported CNS toxicity (convulsions, altered conscious level, agitation or aggression, confusion or disorientation) using multivariable logistic regression. Of 22 937 patient-specific telephone enquiries, 10 398 did not involve co-ingestion of other substances (mefenamic acid 461, ibuprofen 8090, diclofenac 1300, naproxen 547). Patients taking mefenamic acid were younger and more commonly female than those using other NSAIDs. Those ingesting mefenamic acid were more likely to experience CNS toxicity than those ingesting the other NSAIDs combined [adjusted odds ratio (OR) 7.77, 95% confidence interval (CI) 5.68, 10.62], especially convulsions (adjusted OR 81.5, 95% CI 27.8, 238.8). Predictors of CNS toxicity included reported dose and age, but not gender. Mefenamic acid overdose is associated with a much larger and dose-related risk of CNS toxicity, especially convulsions, compared with overdose of other NSAIDs. The benefit-risk profile of mefenamic acid should now be re-evaluated in light of effective and less toxic alternatives. © 2016 The British Pharmacological Society.

Cytotoxicity of seven bisphenol analogues compared to bisphenol A and relationships with membrane affinity data.

PubMed

Russo, Giacomo; Capuozzo, Antonella; Barbato, Francesco; Irace, Carlo; Santamaria, Rita; Grumetto, Lucia

2018-06-01

Bisphenol A (BPA) is a chemical used in numerous industrial applications. Due to its well ascertained toxicity as endocrine disruptor, industries have started to replace it with other bisphenols whose alleged greater safety is scarcely supported by literature studies. In this study, the toxicity of seven BPA analogues was evaluated using both in silico and in vitro techniques, as compared to BPA toxicity. Furthermore, their affinity indexes for phospholipids (i.e. phospholipophilicity) were determined by immobilized artificial membrane liquid chromatography (IAM-LC) and possible relationships with in vitro toxic activity were also investigated. The results on four different cell cultures yielded similar ranking of toxicity for the bisphenols considered, with IC 50 values confirming their poor acute toxicity. As compared to BPA, bisphenol AF, bisphenol B, bisphenol M, and bisphenol A diglycidyl ether resulted more toxic, while bisphenol S, bisphenol F and bisphenol E were found as the less toxic congeners. These results are partly consistent with the scale of phospholipid affinity showing that toxicity increases at increasing membrane affinity. Therefore, phospholipophilicity determination can be assumed as a useful preliminary tool to select less toxic congeners to surrogate BPA in industrial applications. Copyright © 2018 Elsevier Ltd. All rights reserved.

Commuter exposure to particulate matter and particle-bound PAHs in three transportation modes in Beijing, China.

PubMed

Yan, Caiqing; Zheng, Mei; Yang, Qiaoyun; Zhang, Qunfang; Qiu, Xinghua; Zhang, Yanjun; Fu, Huaiyu; Li, Xiaoying; Zhu, Tong; Zhu, Yifang

2015-09-01

Exposure to fine and ultrafine particles as well as particulate polycyclic aromatic hydrocarbons (PAHs) by commuters in three transportation modes (walking, subway and bus) were examined in December 2011 in Beijing, China. During the study period, real-time measured median PM2.5 mass concentration (PMC) for walking, riding buses and taking the subway were 26.7, 32.9 and 56.9 μg m(-3), respectively, and particle number concentrations (PNC) were 1.1 × 10(4), 1.0 × 10(4) and 2.2 × 10(4) cm(-3). Commuters were exposed to higher PNC in air-conditioned buses and aboveground-railway, but higher PMC in underground-subway compared to aboveground-railway. PNC in roadway modes (bus and walking) peaked at noon, but was lower during traffic rush hours, negatively correlated with PMC. Toxic potential of particulate-PAHs estimated based on benzo(a)pyrene toxic equivalents (BaP TEQs) showed that walking pedestrians were subjected to higher BaP TEQs than bus (2.7-fold) and subway (3.6-fold) commuters, though the highest PMC and PNC were observed in subway. Copyright © 2015 Elsevier Ltd. All rights reserved.

“Rational” Management of Dichlorophenols Biodegradation by the Microalga Scenedesmus obliquus

PubMed Central

Papazi, Aikaterini; Kotzabasis, Kiriakos

2013-01-01

The microalga Scenedesmus obliquus exhibited the ability to biodegrade dichlorophenols (dcps) under specific autotrophic and mixotrophic conditions. According to their biodegradability, the dichlorophenols used can be separated into three distinct groups. Group I (2,4-dcp and 2,6 dcp – no meta-substitution) consisted of quite easily degraded dichlorophenols, since both chloride substituents are in less energetically demanding positions. Group II (2,3-dcp, 2,5-dcp and 3,4-dcp – one meta-chloride) was less susceptible to biodegradation, since one of the two substituents, the meta one, required higher energy for C-Cl-bond cleavage. Group III (3,5-dcp – two meta-chlorides) could not be biodegraded, since both chlorides possessed the most energy demanding positions. In general, when the dcp-toxicity exceeded a certain threshold, the microalga increased the energy offered for biodegradation and decreased the energy invested for biomass production. As a result, the biodegradation per cell volume of group II (higher toxicity) was higher, than group I (lower toxicity) and the biodegradation of dichlorophenols (higher toxicity) was higher than the corresponding monochlorophenols (lower toxicity). The participation of the photosynthetic apparatus and the respiratory mechanism of microalga to biodegrade the group I and the group II, highlighted different bioenergetic strategies for optimal management of the balance between dcp-toxicity, dcp-biodegradability and culture growth. Additionally, we took into consideration the possibility that the intermediates of each dcp-biodegradation pathway could influence differently the whole biodegradation procedures. For this reason, we tested all possible combinations of phenolic intermediates to check cometabolic interactions. The present contribution bring out the possibility of microalgae to operate as “smart” bioenergetic “machines”, that have the ability to continuously “calculate” the energy reserves and “use” the most energetically advantageous dcp-biodegradation strategy. We tried to manipulate the above fact, changing the energy reserves and as a result the chosen strategy, in order to take advantage of their abilities in detoxifying the environment. PMID:23613903

"Rational" management of dichlorophenols biodegradation by the microalga Scenedesmus obliquus.

PubMed

Papazi, Aikaterini; Kotzabasis, Kiriakos

2013-01-01

The microalga Scenedesmus obliquus exhibited the ability to biodegrade dichlorophenols (dcps) under specific autotrophic and mixotrophic conditions. According to their biodegradability, the dichlorophenols used can be separated into three distinct groups. Group I (2,4-dcp and 2,6 dcp - no meta-substitution) consisted of quite easily degraded dichlorophenols, since both chloride substituents are in less energetically demanding positions. Group II (2,3-dcp, 2,5-dcp and 3,4-dcp - one meta-chloride) was less susceptible to biodegradation, since one of the two substituents, the meta one, required higher energy for C-Cl-bond cleavage. Group III (3,5-dcp - two meta-chlorides) could not be biodegraded, since both chlorides possessed the most energy demanding positions. In general, when the dcp-toxicity exceeded a certain threshold, the microalga increased the energy offered for biodegradation and decreased the energy invested for biomass production. As a result, the biodegradation per cell volume of group II (higher toxicity) was higher, than group I (lower toxicity) and the biodegradation of dichlorophenols (higher toxicity) was higher than the corresponding monochlorophenols (lower toxicity). The participation of the photosynthetic apparatus and the respiratory mechanism of microalga to biodegrade the group I and the group II, highlighted different bioenergetic strategies for optimal management of the balance between dcp-toxicity, dcp-biodegradability and culture growth. Additionally, we took into consideration the possibility that the intermediates of each dcp-biodegradation pathway could influence differently the whole biodegradation procedures. For this reason, we tested all possible combinations of phenolic intermediates to check cometabolic interactions. The present contribution bring out the possibility of microalgae to operate as "smart" bioenergetic "machines", that have the ability to continuously "calculate" the energy reserves and "use" the most energetically advantageous dcp-biodegradation strategy. We tried to manipulate the above fact, changing the energy reserves and as a result the chosen strategy, in order to take advantage of their abilities in detoxifying the environment.

Polymeric films loaded with cisplatin for malignant pleural mesothelioma: a pharmacokinetic study in an ovine model

PubMed Central

Barocelli, Elisabetta; Cavazzoni, Andrea; Petronini, Piergiorgio; Mucchino, Claudio; Cantoni, Anna Maria; Leonardi, Fabio; Ventura, Luigi; Barbieri, Stefano; Colombo, Paolo; Fusari, Antonella; Carbognani, Paolo; Rusca, Michele; Sonvico, Fabio

2018-01-01

Background Malignant pleural mesothelioma (MPM) continues to be a distressing tumor due to its aggressive biologic behavior and scanty prognosis. Several therapeutic approaches have been tested both in clinical and preclinical settings, being intrapleural chemotherapy one of the most promising. Some years ago, our interest focused on polymeric films loaded with cisplatin for the adjuvant intrapleural treatment of surgical patients. After in vitro and in vivo studies in a rat recurrence model of MPM, the aim of this study was to evaluate the pharmacokinetics of the polymeric films in a sheep model in view of further studies in a clinical setting. Methods An ovine model was used. Animals were divided into four groups according to pharmacologic treatment: control group (three animals undergoing left pneumonectomy and saline-NaCl solution); intrapleural hyaluronate cisplatin films (HYALCIS) group (six animals undergoing left pneumonectomy and intrapleural application of polymeric films loaded with cisplatin); intrapleural cisplatin solution (six animals undergoing left pneumonectomy and intrapleural application of cisplatin solution); intravenous cisplatin (five animals undergoing left pneumonectomy and intravenous administration of cisplatin solution). The primary objective was the plasmatic and pleural concentration of cisplatin in the treatment groups. The secondary objective was the treatment-related toxicity evaluated by plasmatic analysis performed at prearranged time intervals and histological examinations of tissue samples collected during animal autopsy. Analysis of variance (ANOVA) was used for statistical analysis. Bonferroni correction was applied for comparison between all groups. Results Twenty female Sardinian sheep with a mean weight of 45.1 kg were studied. All animals survived the surgical procedures. The whole surgical procedure had a mean duration of 113 minutes. Cisplatin blood levels obtained from polymeric films application were low during the first 24 hours after the application; then, the cisplatin blood level increased gradually and progressively until it reached significantly higher plasmatic concentrations after 120 hours compared to intrapleural cisplatin solution (P=0.004) and intravenous administration (P=0.001), respectively. Considering cisplatin concentration at 168 hours after the application, animals treated with polymeric films had higher plasmatic values than animals treated with intrapleural cisplatin solution and intravenous cisplatin (P=0.001). Despite the high cisplatin plasmatic concentrations, treatment related-toxicity towards kidneys and liver was comparatively lower compared to the intravenous and intrapleural cisplatin administration and closer to the control levels. Conclusions Polymeric films loaded with cisplatin allowed to reach significantly higher intrapleural and plasmatic cisplatin concentrations compared to intrapleural and intravenous cisplatin solution, providing at the same time, a significant reduction of treatment related toxicity. PMID:29507788

Polymeric films loaded with cisplatin for malignant pleural mesothelioma: a pharmacokinetic study in an ovine model.

PubMed

Ampollini, Luca; Barocelli, Elisabetta; Cavazzoni, Andrea; Petronini, Piergiorgio; Mucchino, Claudio; Cantoni, Anna Maria; Leonardi, Fabio; Ventura, Luigi; Barbieri, Stefano; Colombo, Paolo; Fusari, Antonella; Carbognani, Paolo; Rusca, Michele; Sonvico, Fabio

2018-01-01

Malignant pleural mesothelioma (MPM) continues to be a distressing tumor due to its aggressive biologic behavior and scanty prognosis. Several therapeutic approaches have been tested both in clinical and preclinical settings, being intrapleural chemotherapy one of the most promising. Some years ago, our interest focused on polymeric films loaded with cisplatin for the adjuvant intrapleural treatment of surgical patients. After in vitro and in vivo studies in a rat recurrence model of MPM, the aim of this study was to evaluate the pharmacokinetics of the polymeric films in a sheep model in view of further studies in a clinical setting. An ovine model was used. Animals were divided into four groups according to pharmacologic treatment: control group (three animals undergoing left pneumonectomy and saline-NaCl solution); intrapleural hyaluronate cisplatin films (HYALCIS) group (six animals undergoing left pneumonectomy and intrapleural application of polymeric films loaded with cisplatin); intrapleural cisplatin solution (six animals undergoing left pneumonectomy and intrapleural application of cisplatin solution); intravenous cisplatin (five animals undergoing left pneumonectomy and intravenous administration of cisplatin solution). The primary objective was the plasmatic and pleural concentration of cisplatin in the treatment groups. The secondary objective was the treatment-related toxicity evaluated by plasmatic analysis performed at prearranged time intervals and histological examinations of tissue samples collected during animal autopsy. Analysis of variance (ANOVA) was used for statistical analysis. Bonferroni correction was applied for comparison between all groups. Twenty female Sardinian sheep with a mean weight of 45.1 kg were studied. All animals survived the surgical procedures. The whole surgical procedure had a mean duration of 113 minutes. Cisplatin blood levels obtained from polymeric films application were low during the first 24 hours after the application; then, the cisplatin blood level increased gradually and progressively until it reached significantly higher plasmatic concentrations after 120 hours compared to intrapleural cisplatin solution (P=0.004) and intravenous administration (P=0.001), respectively. Considering cisplatin concentration at 168 hours after the application, animals treated with polymeric films had higher plasmatic values than animals treated with intrapleural cisplatin solution and intravenous cisplatin (P=0.001). Despite the high cisplatin plasmatic concentrations, treatment related-toxicity towards kidneys and liver was comparatively lower compared to the intravenous and intrapleural cisplatin administration and closer to the control levels. Polymeric films loaded with cisplatin allowed to reach significantly higher intrapleural and plasmatic cisplatin concentrations compared to intrapleural and intravenous cisplatin solution, providing at the same time, a significant reduction of treatment related toxicity.

Acute and chronic toxicity assessment of benzylpenicillin G residue in heat-treated animal food products.

PubMed

Cui, Cheng; Zhang, Xiang; Wang, Yang; Lu, Shiying; Lu, Huijun; Hui, Qi; Ahmad, Waqas; Cai, Yan; Liu, Xilin; Liu, Lingjiu; Shi, Fengfeng; Liu, Yanyan; Zhao, Ke; Zhai, FeiFei; Xiang, Yangzhen; Hu, Pan; Li, Yansong; Ren, Honglin; Jin, Ningyi; Liu, Zengshan

2018-07-01

The current level of penicillin use and its persisting residue in livestock is potentially concerning; the toxicity of penicillin residue in heat-treated animal food products (HAFP) is yet to be elucidated. In this study, the acute and chronic toxicity of benzylpenicillin G (BPG) residue in HAFP was investigated in a mouse model. The calculated LD 50 of BPG heated to cooking temperature (BPHCT) was 933.04 mg kg -1 [b.w.] intraperitoneally corresponding to 3.75 times lower than its prototype. Mice fed on the experimental diet containing heat-treated beef with high BPG levels for 6 months displayed a reduction in body weight and altered serum values indicating for liver and renal function. Further, the organ ratios of intestinal and spleen were increased. Histopathological changes were observed in the liver, lung and parenchyma testis tissue. BPHCT residue induced sperm aberration and micronucleated polychromatic erythrocytes formation. Present results indicate that prolonged exposure of BPHCT at higher residue levels might have an impact on public health. Importantly the toxic concentrations of BPHCT are relatively high compared with levels that would result from the degradation of antibiotic residues in meat from animals that have received a therapeutic dose of BPG. Copyright © 2018 Elsevier Ltd. All rights reserved.

Influence of salinity on the toxicity of silver nanoparticles (AgNPs) and silver nitrate (AgNO3) in halophilic microalgae, Dunaliella salina.

PubMed

Johari, Seyed Ali; Sarkheil, Mehrdad; Behzadi Tayemeh, Mohammad; Veisi, Shakila

2018-06-13

This study aim to evaluate the potential toxic effects of citrate coated silver nanoparticles (AgNPs) and ionic silver (AgNO 3 ) on marine microalgae Dunaliella salina under three different salinities (35, 70, and 140 g/L). The toxicity was investigated according to modified OECD guideline (No. 201) by 72 h exposure of microalgae to various concentrations of each of the chemicals in Walne's saline media. According to the results, the growth inhibitory effects of AgNPs and AgNO 3 increased significantly coincidence with increasing time and concentration compared to control (P < 0.05). The values of median inhibitory concentrations (IC 50 ) of AgNPs and AgNO 3 based on average specific growth rate and yield for D. salina increased significantly with elevation of water salinity from 35 to 140 g/L (P < 0.05). Toxicity of AgNO 3 based on IC 50 to D. salina was significantly higher than AgNPs at all salinities (P < 0.05). In conclusion, both AgNPs and AgNO 3 inhibited the growth of D. salina at different saltwater medium. Copyright © 2018 Elsevier Ltd. All rights reserved.

Modified Whole Effluent Toxicity Test to Assess and Decouple Wastewater Effects from Environmental Gradients

PubMed Central

Sauco, Sebastián; Gómez, Julio; Barboza, Francisco R.; Lercari, Diego; Defeo, Omar

2013-01-01

Environmental gradients and wastewater discharges produce aggregated effects on marine populations, obscuring the detection of human impact. Classical assessment methods do not include environmental effects in toxicity tests designs, which could lead to incorrect conclusions. We proposed a modified Whole Effluent Toxicity test (mWET) that includes environmental gradients in addition to effluent dilutions, together with the application of Generalized Linear Mixed Models (GLMM) to assess and decouple those effects. We tested this approach, analyzing the lethal effects of wastewater on a marine sandy beach bivalve affected by an artificial canal freshwater discharge used for rice crops irrigation. To this end, we compared bivalve mortality between canal water dilutions (CWd) and salinity controls (SC: without canal water). CWd were prepared by diluting the water effluent (sampled during the pesticide application period) with artificial marine water. The salinity gradient was included in the design by achieving the same final salinities in both CWd and SC, allowing us to account for the effects of salinity by including this variable as a random factor in the GLMM. Our approach detected significantly higher mortalities in CWd, indicating potential toxic effects of the effluent discharge. mWET represents an improvement over the internationally standardized WET tests, since it considers environmental variability and uses appropriate statistical analyses. PMID:23755304

Mitochondrial oxidative stress and dysfunction induced by isoniazid: study on isolated rat liver and brain mitochondria.

PubMed

Ahadpour, Morteza; Eskandari, Mohammad Reza; Mashayekhi, Vida; Haj Mohammad Ebrahim Tehrani, Kamaleddin; Jafarian, Iman; Naserzadeh, Parvaneh; Hosseini, Mir-Jamal

2016-01-01

Isoniazid (INH or isonicotinic hydrazide) is used for the treatment and prophylaxis of tuberculosis. Liver and brain are two important target organs in INH toxicity. However, the exact mechanisms behind the INH hepatotoxicity or neurotoxicity have not yet been completely understood. Considering the mitochondria as one of the possible molecular targets for INH toxicity, the aim of this study was to evaluate the mechanisms of INH mitochondrial toxicity on isolated mitochondria. Mitochondria were isolated by differential ultracentrifugation from male Sprague-Dawley rats and incubated with different concentrations of INH (25-2000 μM) for the investigation of mitochondrial parameters. The results indicated that INH could interact with mitochondrial respiratory chain and inhibit its activity. Our results showed an elevation in mitochondrial reactive oxygen species (ROS) formation, lipid peroxidation and mitochondrial membrane potential collapse after exposure of isolated liver mitochondria in INH. However, different results were obtained in brain mitochondria. Noteworthy, significant glutathione oxidation, adenosine triphosphate (ATP) depletion and lipid peroxidation were observed in higher concentration of INH, as compared to liver mitochondria. In conclusion, our results suggest that INH may initiate its toxicity in liver mitochondria through interaction with electron transfer chain, lipid peroxidation, mitochondrial membrane potential decline and cytochrome c expulsion which ultimately lead to cell death signaling.

Effects of phosphate and thiosulphate on arsenic accumulation in the species Brassica juncea.

PubMed

Grifoni, Martina; Schiavon, Michela; Pezzarossa, Beatrice; Petruzzelli, Gianniantonio; Malagoli, Mario

2015-02-01

Arsenic (As) is recognized as a toxic pollutant in soils of many countries. Since phosphorus (P) and sulphur (S) can influence arsenic mobility and bioavailability, as well as the plant tolerance to As, phytoremediation techniques employed to clean-up As-contaminated areas should consider the interaction between As and these two nutrients. In this study, the bioavailability and accumulation of arsenate in the species Brassica juncea were compared between soil system and hydroponics in relation to P and S concentration of the growth substrate. In one case, plants were grown in pots filled with soil containing 878 mg As kg(-1). The addition of P to soil resulted in increased As desorption and significantly higher As accumulation in plants, with no effect on growth. The absence of toxic effects on plants was likely due to high S in soil, which could efficiently mitigate metal toxicity. In the hydroponic experiment, plants were grown with different combinations of As (0 or 100 μM) and P (56 or 112 μM). S at 400 μM was also added to the nutrient solution of control (-As) and As-treated plants, either individually or in combination with P. The addition of P reduced As uptake by plants, while high S resulted in higher As accumulation and lower P content. These results suggest that S can influence the interaction between P and As for the uptake by plants. The combined increase of P and S in the nutrient solution did not lead to higher accumulation of As, but enhanced As translocation from the root to the shoot. This aspect is of relevance for the phytoremediation of As-contaminated sites.

Comparison of Re-irradiation Outcomes for Charged Particle Radiotherapy and Robotic Stereotactic Radiotherapy Using CyberKnife for Recurrent Head and Neck Cancers: A Multi-institutional Matched-cohort Analysis.

PubMed

Yamazaki, Hideya; Demizu, Yusuke; Okimoto, Tomoaki; Ogita, Mikio; Himei, Kengo; Nakamura, Satoaki; Suzuki, Gen; Yoshida, Ken; Kotsuma, Tadayuki; Yoshioka, Yasuo

2016-10-01

To compare survival outcomes for charged particle radiotherapy (CP) and stereotactic body radiotherapy using CyberKnife (CK) in patients who had undergone re-irradiation for head and neck cancers. We conducted a retrospective multi-institutional matched-cohort analysis on 25 patients treated with CP and 25 matched patients treated with CK according to three prognostic factors (nasopharyngeal cancer or not, interval between initial radiotherapy and re-irradiation, and planning target volume). CP was used more often to treat non-squamous cell cancer ((non-SCC): 52% vs. 0%) with a higher prescribed dose (median=57.6 Gy(RBE)/16 fractions) than CK (32 Gy/5 fractions). The local control rate (LC) for patients treated with CP was 71.2% at 1 year and that for patients treated with CK was 63.8% (p=0.24). The 1-year overall survival (OS) rates were 67.1% for CP and 36.3% for CK (p=0.0002), respectively. Non-SCC patients showed better OS rates at 1 year than SCC patients. In the SCC sub-group analysis, the 1-year LC, OS rates were 65%, 58.3% in the CP group and 64%, 36.3% in the CK group (p=0.81, p=0.02), respectively. A total of 16 patients (32%) experienced grade 3 or worse toxicities (24% in CK and 40% in CP, p=0.36), including six grade 5 toxicities. CP produced higher survival rates than CK, treated more non-SCC patients and used a higher prescribed dose. On the other hand, severe toxicities occurred in both groups, which, however, require further investigation. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jabbari, Siavash; Weinberg, Vivian K.; Kaprealian, Tania

Purpose: High dose rate (HDR) brachytherapy has been established as an excellent monotherapy or after external-beam radiotherapy (EBRT) boost treatment for prostate cancer (PCa). Recently, dosimetric studies have demonstrated the potential for achieving similar dosimetry with stereotactic body radiotherapy (SBRT) compared with HDR brachytherapy. Here, we report our technique, PSA nadir, and acute and late toxicity with SBRT as monotherapy and post-EBRT boost for PCa using HDR brachytherapy fractionation. Patients and Methods: To date, 38 patients have been treated with SBRT at University of California-San Francisco with a minimum follow-up of 12 months. Twenty of 38 patients were treated withmore » SBRT monotherapy (9.5 Gy Multiplication-Sign 4 fractions), and 18 were treated with SBRT boost (9.5 Gy Multiplication-Sign 2 fractions) post-EBRT and androgen deprivation therapy. PSA nadir to date for 44 HDR brachytherapy boost patients with disease characteristics similar to the SBRT boost cohort was also analyzed as a descriptive comparison. Results: SBRT was well tolerated. With a median follow-up of 18.3 months (range, 12.6-43.5), 42% and 11% of patients had acute Grade 2 gastrourinary and gastrointestinal toxicity, respectively, with no Grade 3 or higher acute toxicity to date. Two patients experienced late Grade 3 GU toxicity. All patients are without evidence of biochemical or clinical progression to date, and favorably low PSA nadirs have been observed with a current median PSA nadir of 0.35 ng/mL (range, <0.01-2.1) for all patients (0.47 ng/mL, range, 0.2-2.1 for the monotherapy cohort; 0.10 ng/mL, range, 0.01-0.5 for the boost cohort). With a median follow-up of 48.6 months (range, 16.4-87.8), the comparable HDR brachytherapy boost cohort has achieved a median PSA nadir of 0.09 ng/mL (range, 0.0-3.3). Conclusions: Early results with SBRT monotherapy and post-EBRT boost for PCa demonstrate acceptable PSA response and minimal toxicity. PSA nadir with SBRT boost appears comparable to those achieved with HDR brachytherapy boost.« less

Direct Push Optical Screening Tool for High-Resolution, Real-Time Mapping of Chlorinated Solvent DNAPL Architecture

DTIC Science & Technology

2016-04-01

due to higher densities, lower viscosities , and increased weathering (mass depletion) of residual chlorinated solvent DNAPL compared to those other...demonstration area can be generally classified as stratified layers of fine sand and silt with few clay layers. A silt layer was penetrated consistently at...toxic and carcinogenic. Another potential issue evaluated was that in plastic soils (stiff clays for example) there is potential for the thickness of

Host Thiopurine Methyltransferase Status Affects Mercaptopurine Antileukemic Effectiveness in a Murine Model

PubMed Central

Ramsey, Laura B.; Janke, Laura J.; Edick, Mathew J.; Cheng, Cheng; Williams, Richard T.; Sherr, Charles J.; Evans, William E.; Relling, Mary V.

2014-01-01

Thiopurines are used for many cancers, including acute lymphoblastic leukemia (ALL). Patients with an inherited host defect in thiopurine methyltransferase (TPMT) are at high risk for life-threatening toxicity if treated with conventional dosages, but the impact on antileukemic efficacy is less clear. Herein, we treated thiopurine-sensitive BCR-ABL+ Arf-null Tpmt+/+ ALL in Tpmt+/+, +/−, or −/− recipient mice to test the impact of the host polymorphism on antileukemic efficacy. Median survival was similar in untreated mice of different Tpmt genotypes (16–18 days). However, in mice treated with low-dose mercaptopurine (such as tolerated by TPMT−/− patients), the difference in 30-day leukemia-free survival by Tpmt genotype was profound: 5% (± 9%) for Tpmt+/+ mice, 47% (± 26%) for Tpmt+/− mice, and 85% (± 14%) for Tpmt−/− mice (p = 5×10−8), indicating a substantial impact of host Tpmt status on thiopurine effectiveness. Among Tpmt+/+ recipient mice, leukemia-free survival improved with higher doses of mercaptopurine (similar to doses tolerated by wild-type patients) compared to lower doses, and at higher doses was comparable (p =0.6) to the survival of Tpmt−/− mice treated with the lower dose. These findings support the notion that germline polymorphisms in Tpmt affect not only host tissue toxicity, but also antitumor effectiveness. PMID:24710003

Sequestosome1/p62 protects mouse embryonic fibroblasts against low-dose methylercury-induced cytotoxicity and is involved in clearance of ubiquitinated proteins.

PubMed

Takanezawa, Yasukazu; Nakamura, Ryosuke; Harada, Ryohei; Sone, Yuka; Uraguchi, Shimpei; Kiyono, Masako

2017-12-01

Methylmercury (MeHg) is a widely distributed environmental pollutant that causes a series of cytotoxic effects. However, molecular mechanisms underlying MeHg toxicity are not fully understood. Here, we report that sequestosome1/p62 protects mouse embryonic fibroblasts (MEFs) against low-dose MeHg cytotoxicity via clearance of MeHg-induced ubiquitinated proteins. p62 mRNA and protein expression in MEFs were temporally induced by MeHg exposure p62-deficient MEFs exhibited higher sensitivity to MeHg exposure compared to their wild-type (WT) counterparts. An earlier and higher level of accumulation of ubiquitinated proteins was detected in p62-deficient cells compared with WT MEFs. Confocal microscopy revealed that p62 and ubiquitinated proteins co-localized in the perinuclear region of MEFs following MeHg treatment. Further analysis of MEFs revealed that ubiquitinated proteins co-localized with LC3-positive puncta upon co-treatment with MeHg and chloroquine, an autophagy inhibitor. In contrast, there was minimal co-localization in p62-deficient MEFs. The present study, for the first time, examined the expression and distribution of p62 and ubiquitinated proteins in cells exposed to low-dose MeHg. Our findings suggest that p62 is crucial for cytoprotection against MeHg-induced toxicity and is required for MeHg-induced ubiquitinated protein clearance.

Functionalized graphene oxide-based thermosensitive hydrogel for near-infrared chemo-photothermal therapy on tumor.

PubMed

Zhu, Xiali; Zhang, Yingjie; Huang, Heqing; Zhang, Huijuan; Hou, Lin; Zhang, Zhenzhong

2016-03-01

A functionalized graphene oxide-based thermosensitive hydrogel loaded with docetaxel for intratumoral delivery was designed to enhance therapeutic efficacy and alleviate system toxicity. First, graphene oxide was functionalized with chitosan to acquire high stability in physiological solutions. And then docetaxel-graphene oxide/chitosan gel was formed by mixed docetaxel-graphene oxide/chitosan suspension with hydrogel which was made from Poloxamer 407 and Poloxamer 188. Cellular uptake, antitumor effect in vitro and in vivo, cell apoptosis, and biodistribution of docetaxel-graphene oxide/chitosan gel were investigated, compared with the docetaxel solution. Graphene oxide/chitosan was stable in physiological solution, and docetaxel released much slower from docetaxel-graphene oxide/chitosan gel with a pH-responsive feature. Compared with free docetaxel, docetaxel-graphene oxide/chitosan could afford higher antitumor efficacy in Michigan Cancer Foundation-7 (MCF-7) cells in vitro. Furthermore, docetaxel-grapheme oxide/chitosan gel which was injected within tumor could afford higher concentration and longer resident time in tumor tissues of mice in vivo, without obvious toxic effects to normal organs. Meanwhile, the combination of near-infrared laser irradiation at 808 nm significantly enhanced tumor inhibition in vitro and in vivo. Docetaxel-graphene oxide/chitosan gel in combination with 808 nm near-infrared laser irradiation had great potential for cancer chemo-photothermal therapy. © The Author(s) 2016.

Comparative study of cyanotoxins affecting cytoskeletal and chromatin structures in CHO-K1 cells.

PubMed

Gácsi, Mariann; Antal, Otilia; Vasas, Gábor; Máthé, Csaba; Borbély, György; Saker, Martin L; Gyori, János; Farkas, Anna; Vehovszky, Agnes; Bánfalvi, Gáspár

2009-06-01

In this study we compared the effects of the two frequently occuring and most dangerous cyanobacterial toxins on the cellular organization of microfilaments, microtubules and on the chromatin structure in Chinese hamster ovary (CHO-K1) cells. These compounds are the widely known microcystin-LR (MC-LR) and cylindrospermopsin (CYN) classified as the highest-priority cyanotoxin. Toxic effects were tested in a concentration and time dependent manner. The hepatotoxic MC-LR did not cause significant cytotoxicity on CHO-K1 cells under 20 microM, but caused apoptotic changes at higher concentrations. Apoptotic shrinkage was associated with the shortening and loss of actin filaments and with a concentration dependent depolymerization of microtubules. No necrosis was observed over the concentration range (1-50 microM MC-LR) tested. Cylindrospermopsin did cause apoptosis at low concentrations (1-2 microM) and over short exposure periods (12h). Necrosis was observed at higher concentrations (5-10 microM) and following longer exposure periods (24 or 48h). Cyanotoxins also affected the chromatin structure. The condensation process was inhibited by MC-LR at a later stage and manifested as broken elongated prechromosomes. CYN inhibited chromatin condensation at the early fibrillary stage leading to blurred fluorescent images of apoptotic bodies and preventing the formation of metaphase chromosomes. Cylindrospermopsin exhibited a more pronounced toxic effect causing cytoskeletal and nuclear changes as well as apoptotic and necrotic alterations.

A comparative study of health risk of potentially toxic metals in urban and suburban road dust in the most populated city of China

NASA Astrophysics Data System (ADS)

Shi, Guitao; Chen, Zhenlou; Bi, Chunjuan; Wang, Li; Teng, Jiyan; Li, Yuansheng; Xu, Shiyuan

2011-01-01

Urban and suburban road dust samples were collected in the most populated city of China, Shanghai. Size fractions of dust particles were analyzed; metal levels of the dust were also measured. Human exposure to individual toxic metals through road dust was assessed for both children and adults. The results showed that dust particles from urban and suburban road were presented similar size distribution pattern, with most particles in the range of 100-400 μm. Urban road dust consisted of higher proportions of inhalable, thoracic and respirable particles with increased risk of adverse effects to human. In general, mean grain sizes of urban road dust were smaller than suburban dust. Total organic carbon contents and levels of Pb, Cd, Cu, Zn, Ni, Cr in urban dust were higher than those of suburban dust. But the concentrations of As and Hg from suburban dust were higher, indicting a different main source. The exposure pathway which resulted in the highest level of risk for human exposed to road dust was ingestion of this material, which was followed by dermal contact. Except for some locations, risk values of both cancer and non-cancer obtained in this study were in the receivable range on the whole. Children had greater health risks than adults. The overall risks of non-cancer in urban area were higher than those in suburban area, but the values of cancer in the two areas were comparable. As for the aggregate noncarcinogenic risk, Pb was of most concern regarding the potential occurrence of health impacts. Of the three carcinogenic metals As, Cr and Cd, the only mean risk higher than 10 -6 was Cr, accounting for a great percentage (95%) of the overall risk of cancer. Hence, potentially adverse health effects arising from Pb and Cr in road dust should arouse wide concern.

Small heat shock proteins protect against {alpha}-synuclein-induced toxicity and aggregation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Outeiro, Tiago Fleming; Klucken, Jochen; Strathearn, Katherine E.

Protein misfolding and inclusion formation are common events in neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD) or Huntington's disease (HD). {alpha}-Synuclein (aSyn) is the main protein component of inclusions called Lewy bodies (LB) which are pathognomic of PD, Dementia with Lewy bodies (DLB), and other diseases collectively known as LB diseases. Heat shock proteins (HSPs) are one class of the cellular quality control system that mediate protein folding, remodeling, and even disaggregation. Here, we investigated the role of the small heat shock proteins Hsp27 and {alpha}B-crystallin, in LB diseases. We demonstrate, via quantitative PCR, that Hsp27 messengermore » RNA levels are {approx}2-3-fold higher in DLB cases compared to control. We also show a corresponding increase in Hsp27 protein levels. Furthermore, we found that Hsp27 reduces aSyn-induced toxicity by {approx}80% in a culture model while {alpha}B-crystallin reduces toxicity by {approx}20%. In addition, intracellular inclusions were immunopositive for endogenous Hsp27, and overexpression of this protein reduced aSyn aggregation in a cell culture model.« less

Toxicity Assessment of Expired Pesticides to Green Algae Pseudokirchneriella subcapitata

PubMed Central

Satyavani, G.; Chandrasehar, G.; Varma, K. Krishna; Goparaju, A.; Ayyappan, S.; Reddy, P. Neelakanta; Murthy, P. Balakrishna

2012-01-01

In order to investigate the effect of expired pesticides on the yield and growth rate of green algae Pseudokirchneriella subcapitata, a study was conducted as per the Organisation for Economic Cooperation and Development (OECD) guideline number 201. Fifteen expired pesticide formulations, most commonly used in Indian agriculture, were tested in comparison with their unexpired counterparts. The expired pesticide formulations studied belonged to various class and functional groups: organophosphate, pyrethroid-based insecticides; azole-based fungicides; acetamide, propionate, acetic acid-based herbicides; fungicides mixtures containing two actives—azole and dithiocarbamate. The toxicity endpoints of yield (EyC50: 0–72 h) and growth rate (ErC50: 0–72 h) of Pseudokirchneriella subcapitata for each pesticide formulation (both expired and unexpired pesticides) were determined statistically using TOXSTAT 3.5 version software. The results pointed out that some expired pesticide formulations exhibited higher toxicity to tested algal species, as compared to the corresponding unexpired pesticides. These data thus stress the need for greater care to dispose expired pesticides to water bodies, to avoid the effects on aquatic ecospecies tested. PMID:23762633

[Analgesic efficacy and clinical safety of intraperitoneal instillation combined with rectus sheath block using ropivacaine for pain relief after laparoscopic gynecological surgery].

PubMed

Yakoshi, Chihiro; Hashimoto, Hiroshi; Niwa, Hidetomo; Kitayama, Masatou; Kudo, Tsuyoshi; Kudo, Mihoko; Hirota, Kazuyoshi

2014-03-01

The aim of this study was to evaluate the analgesic efficacy and safety of rectus sheath block combined with intraperitoneal instillation using two doses of ropivacaine in patients undergoing laparoscopic gynecological surgery. Altogether 53 consenting women were randomized to receive intraperitoneal infiltration with 0.25% ropivacaine or 0.5% ropivacaine followed by rectus sheath block with 0.375% ropivacaine. The outcomes of clinical safety were measured using plasma concentration of local anesthetics and occurrence of toxic symptoms. The analgesic efficacy was assessed using numerical rating scales for pain and morphine consumption up to 24 hours after surgery. Patients' baseline characteristics, surgical factors, and analgesic outcomes were comparable between the two groups. Although peak plasma concentration of ropivacaine was significantly higher in patients receiving 0.5% ropivacaine, none of analyzed concentrations was above the toxic ones. Besides, no patients showed any symptoms of local anesthetic toxicity. The present study showed that the combination of rectus sheath block with intraperitoneal instillation of ropivacaine was safe and potent enough to relieve pain after laparoscopic surgery.

Nanomedicine and epigenome. Possible health risks.

PubMed

Smolkova, Bozena; Dusinska, Maria; Gabelova, Alena

2017-11-01

Nanomedicine is an emerging field that combines knowledge of nanotechnology and material science with pharmaceutical and biomedical sciences, aiming to develop nanodrugs with increased efficacy and safety. Compared to conventional therapeutics, nanodrugs manifest higher stability and circulation time, reduced toxicity and improved targeted delivery. Despite the obvious benefit, the accumulation of imaging agents and nanocarriers in the body following their therapeutic or diagnostic application generates concerns about their safety for human health. Numerous toxicology studies have demonstrated that exposure to nanomaterials (NMs) might pose serious risks to humans. Epigenetic modifications, representing a non-genotoxic mechanism of toxicant-induced health effects, are becoming recognized as playing a potential causative role in the aetiology of many diseases including cancer. This review i) provides an overview of recent advances in medical applications of NMs and ii) summarizes current evidence on their possible epigenetic toxicity. To discern potential health risks of NMs, since current data are mostly based upon in vitro and animal models, a better understanding of functional relationships between NM exposure, epigenetic deregulation and phenotype is required. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cumulative effects of bamboo sawdust addition on pyrolysis of sewage sludge: Biochar properties and environmental risk from metals.

PubMed

Jin, Junwei; Wang, Minyan; Cao, Yucheng; Wu, Shengchun; Liang, Peng; Li, Yanan; Zhang, Jianyun; Zhang, Jin; Wong, Ming Hung; Shan, Shengdao; Christie, Peter

2017-03-01

A novel type of biochar was produced by mixing bamboo sawdust with sewage sludge (1:1, w/w) via a co-pyrolysis process at 400-600°C. Changes in physico-chemical properties and the intrinsic speciation of metals were investigated before and after pyrolysis. Co-pyrolysis resulted in a lower biochar yield but a higher C content in the end product compared with use of sludge alone as the raw material. FT-IR analysis indicates that phosphine derivatives containing PH bonds were formed in the co-pyrolyzed biochars. In addition, co-pyrolysis of sludge with bamboo sawdust transformed the potentially toxic metals in the sludge into more stable fractions, leading to a considerable decrease in their direct toxicity and bioavailability in the co-pyrolyzed biochar. In conclusion, the co-pyrolysis technology provides a feasible method for the safe disposal of metal-contaminated sewage sludge in an attempt to minimize the environmental risk from potentially toxic metals after land application. Copyright © 2016 Elsevier Ltd. All rights reserved.

Study of amyloid-β peptide functional brain networks in AD, MCI and HC.

PubMed

Jiang, Jiehui; Duan, Huoqiang; Huang, Zheming; Yu, Zhihua

2015-01-01

One medical challenge in studying the amyloid-β (Aβ) peptide mechanism for Alzheimer's disease (AD) is exploring the law of beta toxic oligomers' diffusion in human brains in vivo. One beneficial means of solving this problem is brain network analysis based on graph theory. In this study, the characteristics of Aβ functional brain networks of Healthy Control (HC), Mild Cognitive Impairment (MCI), and AD groups were compared by applying graph theoretical analyses to Carbon 11-labeled Pittsburgh compound B positron emission tomography (11C PiB-PET) data. 120 groups of PiB-PET images from the ADNI database were analyzed. The results showed that the small-world property of MCI and AD were lost as compared to HC. Furthermore, the local clustering of networks was higher in both MCI and AD as compared to HC, whereas the path length was similar among the three groups. The results also showed that there could be four potential Aβ toxic oligomer seeds: Frontal_Sup_Medial_L, Parietal_Inf_L, Frontal_Med_Orb_R, and Parietal_Inf_R. These four seeds are corresponding to Regions of Interests referred by physicians to clinically diagnose AD.

A mixture toxicity approach to predict the toxicity of Ag decorated ZnO nanomaterials.

PubMed

Azevedo, S L; Holz, T; Rodrigues, J; Monteiro, T; Costa, F M; Soares, A M V M; Loureiro, S

2017-02-01

Nanotechnology is a rising field and nanomaterials can now be found in a vast variety of products with different chemical compositions, sizes and shapes. New nanostructures combining different nanomaterials are being developed due to their enhancing characteristics when compared to nanomaterials alone. In the present study, the toxicity of a nanostructure composed by a ZnO nanomaterial with Ag nanomaterials on its surface (designated as ZnO/Ag nanostructure) was assessed using the model-organism Daphnia magna and its toxicity predicted based on the toxicity of the single components (Zn and Ag). For that ZnO and Ag nanomaterials as single components, along with its mixture prepared in the laboratory, were compared in terms of toxicity to ZnO/Ag nanostructures. Toxicity was assessed by immobilization and reproduction tests. A mixture toxicity approach was carried out using as starting point the conceptual model of Concentration Addition. The laboratory mixture of both nanomaterials showed that toxicity was dependent on the doses of ZnO and Ag used (immobilization) or presented a synergistic pattern (reproduction). The ZnO/Ag nanostructure toxicity prediction, based on the percentage of individual components, showed an increase in toxicity when compared to the expected (immobilization) and dependent on the concentration used (reproduction). This study demonstrates that the toxicity of the prepared mixture of ZnO and Ag and of the ZnO/Ag nanostructure cannot be predicted based on the toxicity of their components, highlighting the importance of taking into account the interaction between nanomaterials when assessing hazard and risk. Copyright © 2016 Elsevier B.V. All rights reserved.

Complex toxic effects of Cd2+, Zn2+, and acid rain on growth of kidney bean (Phaseolus vulgaris L).

PubMed

Liao, Bo-han; Liu, Hong-yu; Zeng, Qing-ru; Yu, Ping-zhong; Probst, Anne; Probst, Jean-Luc

2005-08-01

Complex toxic effects of Cd2+, Zn2+, and acid rain on growth of kidney bean (Phaseolus vulgaris L) were studied in a pot experiment by measurement of fresh weights of the plants, determination of surperoxide dismutase (SOD), peroxidase (POD), and lipid peroxidation (MDA) in the plant organs, and observation of injury symptoms. The experimental results demonstrated that all treatments of Cd2+, Zn2+, and/or acid rain significantly decreased fresh weights of kidney bean and caused toxic effects on growth of the plants, especially higher amounts of Cd2+ and Zn2+ and higher acidity of acid rain. Combination of these three pollutant factors resulted in more serious toxic effects than any single pollutant and than combinations of any two pollutants. SOD, POD, and MDA in the plant organs changed with different pollution levels, but MDA content in the leaves showed the best relationship between the pollution levels and toxic effects.

Environmental Inequality in Exposures to Airborne Particulate Matter Components in the United States

PubMed Central

Ebisu, Keita

2012-01-01

Background: Growing evidence indicates that toxicity of fine particulate matter ≤ 2.5 μm in diameter (PM2.5) differs by chemical component. Exposure to components may differ by population. Objectives: We investigated whether exposures to PM2.5 components differ by race/ethnicity, age, and socioeconomic status (SES). Methods: Long-term exposures (2000 through 2006) were estimated for 215 U.S. census tracts for PM2.5 and for 14 PM2.5 components. Population-weighted exposures were combined to generate overall estimated exposures by race/ethnicity, education, poverty status, employment, age, and earnings. We compared population characteristics for tracts with and without PM2.5 component monitors. Results: Larger disparities in estimated exposures were observed for components than for PM2.5 total mass. For race/ethnicity, whites generally had the lowest exposures. Non-Hispanic blacks had higher exposures than did whites for 13 of the 14 components. Hispanics generally had the highest exposures (e.g., 152% higher than whites for chlorine, 94% higher for aluminum). Young persons (0–19 years of age) had levels as high as or higher than other ages for all exposures except sulfate. Persons with lower SES had higher estimated exposures, with some exceptions. For example, a 10% increase in the proportion unemployed was associated with a 20.0% increase in vanadium and an 18.3% increase in elemental carbon. Census tracts with monitors had more non-Hispanic blacks, lower education and earnings, and higher unemployment and poverty than did tracts without monitors. Conclusions: Exposures to PM2.5 components differed by race/ethnicity, age, and SES. If some components are more toxic than others, certain populations are likely to suffer higher health burdens. Demographics differed between populations covered and not covered by monitors. PMID:22889745

Toxicity of zero-valent iron nanoparticles to a trichloroethylene-degrading groundwater microbial community.

PubMed

Zabetakis, Kara M; Niño de Guzmán, Gabriela T; Torrents, Alba; Yarwood, Stephanie

2015-01-01

The microbiological impact of zero-valent iron used in the remediation of groundwater was investigated by exposing a trichloroethylene-degrading anaerobic microbial community to two types of iron nanoparticles. Changes in total bacterial and archaeal population numbers were analyzed using qPCR and were compared to results from a blank and negative control to assess for microbial toxicity. Additionally, the results were compared to those of samples exposed to silver nanoparticles and iron filings in an attempt to discern the source of toxicity. Statistical analysis revealed that the three different iron treatments were equally toxic to the total bacteria and archaea populations, as compared with the controls. Conversely, the silver nanoparticles had a limited statistical impact when compared to the controls and increased the microbial populations in some instances. Therefore, the findings suggest that zero-valent iron toxicity does not result from a unique nanoparticle-based effect.

Acute lead toxicosis via ingestion of spent ammunition in a free-ranging cougar (Puma concolor)

USGS Publications Warehouse

Burco, Julia; Myers, Anne Mary; Schuler, Krysten; Gillin, Colin

2012-01-01

Lead toxicity has long been documented and acknowledged as a significant health issue of water birds and avian scavengers. However, few instances of toxic effects to higher mammalian carnivores have been documented. Here we present an acute case of lead toxicity in a free-ranging cougar (Puma concolor) in Oregon.

Acute lead toxicosis via ingestion of spent ammunition in a free-ranging cougar (Puma concolor).

PubMed

Burco, Julia; Myers, Anne Mary; Schuler, Krysten; Gillin, Colin

2012-01-01

Lead toxicity has long been documented and acknowledged as a significant health issue of water birds and avian scavengers. However, few instances of toxic effects to higher mammalian carnivores have been documented. Here we present an acute case of lead toxicity in a free-ranging cougar (Puma concolor) in Oregon.

In vivo pharmacological evaluation and efficacy study of methotrexate-encapsulated polymer-coated layered double hydroxide nanoparticles for possible application in the treatment of osteosarcoma.

PubMed

Ray, Sayantan; Saha, Suman; Sa, Biswanath; Chakraborty, Jui

2017-04-01

Considering the existing drawbacks of methotrexate (MTX) with respect to its solubility and toxicity, we incorporated it in a nanoceramic matrix, Mg-Al-layered double hydroxide (LDH) to form LDH-MTX nanoparticles, and the same was in turn encapsulated in a nontoxic and biodegradable polymer, poly (D,L-lactide-co-glycolide) (PLGA), to arrest the initial burst release and dose-dumping-related toxicity, already reported by our group. Our present study was designed to evaluate the pharmacokinetics, tissue distribution, survival rate of the test animals, and antitumor efficacy of the PLGA-LDH-MTX nanoparticles and its counterpart without LDH, PLGA-MTX nanoparticles compared with bare MTX. The median lethal dose (LD 50 ) of the former was higher, compared with bare MTX, using Balb/c nude mice, indicating it to be completely safe for use. Also, a comparative pharmacokinetic and antitumour efficacy study using MTX, PLGA-MTX, and PLGA-LDH-MTX nanoparticles in osteosarcoma-induced Balb/c nude mice in vivo demonstrated superiority of PLGA-LDH-MTX as compared to PLGA-MTX and bare MTX. The results suggest that PLGA-LDH-MTX nanoparticles might exhibit potential advantages over the present-day chemotherapy over bare MTX, for the possibility of treatment of osteosarcoma.

Determination of oxidative stress in wheat leaves as influenced by boron toxicity and NaCl stress.

PubMed

Masood, Sajid; Saleh, Livia; Witzel, Katja; Plieth, Christoph; Mühling, Karl H

2012-07-01

Boron (B) toxicity symptoms are visible in the form of necrotic spots and may worsen the oxidative stress caused by salinity. Hence, the interactive effects of combined salinity and B toxicity stress on antioxidative activities (TAC, LUPO, SOSA, CAT, and GR) were investigated by novel luminescence assays and standard photometric procedures. Wheat plants grown under hydroponic conditions were treated with 2.5 μM H₃BO₃ (control), 75 mM NaCl, 200 μM H₃BO₃, or 75 mM NaCl + 200 μM H₃BO₃, and analysed 6 weeks after germination. Shoot fresh weight (FW), shoot dry weight (DW), and relative water content (RWC) were significantly reduced, whereas the antioxidative activity of all enzymes was increased under salinity compared with the control. High B application led to necrotic leaf spots but did not influence growth parameters. Following NaCl + B treatment, shoot DW, RWC, SOSA, GR, and CAT activities remained the same compared with NaCl alone, whereas the TAC and LUPO activities were increased under the combined stress compared with NaCl alone. However, shoot FW was significantly reduced under NaCl + B compared with NaCl alone, as an additive effect of combined stress. Thus, we found an adjustment of antioxidative enzyme activity to the interactive effects of NaCl and high B. The stress factor "salt" mainly produced more oxidative stress than that of the factor "high B". Furthermore, addition of higher B in the presence of NaCl increases TAC and LUPO demonstrating that increased LUPO activity is an important physiological response in wheat plants against multiple stresses. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Radiation therapy in patients with inflammatory bowel disease and colorectal cancer: risks and benefits.

PubMed

Chang, Bianca W; Kumar, Aryavarta M S; Koyfman, Shlomo A; Kalady, Matthew; Lavery, Ian; Abdel-Wahab, May

2015-03-01

The effects of radiotherapy are debated in inflammatory bowel disease (IBD). We examined IBD patients with colorectal cancer (CRC) and compared those who underwent external beam radiation therapy (EBRT) to those who did not. We then compared those same patients treated with EBRT to similarly treated non-IBD patients to ascertain differences in toxicity and perioperative outcomes. Fifty-seven IBD patients with CRC received EBRT, of which 23 had perioperative follow-up and 15 had complete records. The 23 patients were compared to 229 IBD patients with CRC who did not receive EBRT. The 15 patients were matched, 1:2, to similarly treated non-IBD patients with CRC based on age (±5 years), treatment year (±1 year), BMI (±10 kg/m2), and clinical stage. There was significantly more postoperative bleeding (5.3 % vs. 0 %, p < 0.01), wound dehiscence (3.5 % vs. 0 %, p < 0.01), and perineal infection (8.8 % vs. 1.3 %, p < 0.01) in IBD patients with EBRT compared to those without EBRT. IBD patients were significantly more likely to have grade 3 or higher lower GI toxicity (40 % vs. 7 %, p = 0.02) and wound dehiscence (36 % vs. 7 %, p = 0.02) than non-IBD patients, however without significant difference in bleeding, infection, ileus, or survival. IBD patients with CRC who received EBRT were more likely than similar patients without EBRT to experience perioperative complications. These patients also experienced more lower GI toxicity than similarly treated non-IBD patients with CRC. The expected decrease in survival in IBD-associated CRC was not observed. Thus, EBRT may contribute to a survival benefit in this group.

Evaluation of Planned Treatment Breaks During Radiation Therapy for Anal Cancer: Update of RTOG 92-08

DOE Office of Scientific and Technical Information (OSTI.GOV)

Konski, Andre; Garcia, Miguel; John, Madhu

2008-09-01

Purpose: Radiation Therapy Oncology Group (RTOG) 92-08 began as a single arm, Phase II trial for patients with anal cancer consisting of radiation (RT) + 5-flourouracil + mitomycin-C with a mandatory 2-week break and was amended after completion to evaluate the same treatment regimen without a treatment break. Long-term efficacy and late toxicity reporting are the specific aims of this study. Methods and Materials: Survivals were estimated with the Kaplan-Meier method. Overall survival (OS) was compared with RTOG 87-04 with the log-rank test. Time to local failure, regional failure, locoregional failure (LRF), distant metastases, second primary, and colostomy failure weremore » estimated by the cumulative incidence method. LRF was compared with RTOG 87-04 using the Gray's test. Results: Forty-seven patients entered in the mandatory treatment break cohort. The study was reopened in 1995 to the no mandatory treatment break cohort completing accrual with 20 patients in 1996. Of 67 total patients, 1 patient in the mandatory treatment break portion of the study did not receive any protocol treatment and is excluded from analyses. After adjusting for tumor size, neither cohort showed a statistically significant difference in OS or LRF compared with the RTOG 87-04 mitomycin-C arm. No patient in either cohort experienced a Grade 3 or higher late toxicity. Conclusions: No statistically significant differences were seen in OS or LRF when compared to the mitomycin-C arm of RTOG 87-04, but the sample sizes for the mandatory break cohort and the no mandatory break cohort are small. Late toxicity was low and similar for the treatment cohorts.« less

High Time Resolution Measurements of VOCs from Vehicle Cold Starts: The Air Toxic Cold Start Pulse

NASA Astrophysics Data System (ADS)

Jobson, B. T.; Huangfu, Y.; Vanderschelden, G. S.

2017-12-01

Pollutants emitted during motor vehicle cold starts, especially in winter in some climates, is a significant source of winter time air pollution. While data exist for CO, NO, and total hydrocarbon emissions from federal testing procedures for vehicle emission certification, little is known about the emission rates of individual volatile organic compounds, in particular the air toxics benzene, formaldehyde, and acetaldehyde. Little is known about the VOC speciation and temperature dependence for cold starts. The US EPA vehicle emission model MOVES assumes that cold start emissions have the same speciation profile as running emissions. We examined this assumption by measuring cold start exhaust composition for 4 vehicles fueled with E10 gasoline over a temperature range of -4°C to 10°C in winter of 2015. The extra cold start emissions were determined by comparison with emissions during engine idling. In addition to CO and NOx measurements a proton transfer reaction mass spectrometer was used to measure formaldehyde, acetaldehyde, benzene, toluene, and C2-alkylbenzenes at high time resolution to compare with the cold start emission speciation profiles used in the EPA MOVES2014 model. The results show that after the vehicle was started, CO mixing ratios can reach a few percent of the exhaust and then drop to several ppmv within 2 minutes of idling, while NOx showed different temporal behaviors among the four vehicles. VOCs displayed elevated levels during cold start and the peak mixing ratios can be two orders higher than idling phase levels. Molar emission ratios relative to toluene were used to compare with the emission ratio used in MOVES2014 and we found the formaldehyde-to-toluene emission ratio was about 0.19, which is 5 times higher than the emission ratio used in MOVES2014 and the acetaldehyde-to-toluene emission ratios were 0.86-0.89, which is 8 times higher than the ones in MOVES2014. The C2-alkylbenzene-to-toluene ratio agreed well with moves. Our results suggest that for the air toxics acetaldehyde and formaldehyde, wintertime cold temperature vehicle start emissions are likely significantly underestimated in the MOVES 2014 model.

Tellurate enters Escherichia coli K-12 cells via the SulT-type sulfate transporter CysPUWA.

PubMed

Goff, Jennifer; Yee, Nathan

2017-12-29

Soluble forms of tellurium are environmental contaminants that are toxic to microorganisms. While tellurite [Te(IV)] is a well-characterized antimicrobial agent, little is known about the interactions of tellurate [Te(VI)] with bacterial cells. In this study, we investigated the role of sulfate transporters in the uptake of tellurate in Escherichia coli K-12. Mutant strains carrying a deletion of the cysW gene in the CysPUWA sulfate transporter system accumulated less cellular tellurium and exhibited higher resistance to tellurate compared with the wild-type strain. Complementation of the mutation restored tellurate sensitivity and uptake. These results indicate that tellurate enters E. coli cells to cause toxic effects via the CysPUWA sulfate transporter. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Efficacy and safety of native versus pegylated Escherichia coli asparaginase for treatment of adults with high-risk, Philadelphia chromosome-negative acute lymphoblastic leukemia.

PubMed

Ribera, Josep-Maria; Morgades, Mireia; Montesinos, Pau; Martino, Rodrigo; Barba, Pere; Soria, Beatriz; Bermúdez, Arancha; Moreno, María-José; González-Campos, José; Vives, Susana; Gil, Cristina; Abella, Eugenia; Guàrdia, Ramon; Martínez-Carballeira, Daniel; Martínez-Sánchez, Pilar; Amigo, María-Luz; Mercadal, Santiago; Serrano, Alfons; López-Martínez, Aurelio; Vall-Llovera, Ferran; Sánchez-Sánchez, María-José; Peñarrubia, María-Jesús; Calbacho, María; Méndez, Jose-Angel; Bergua, Juan; Cladera, Antonia; Tormo, Mar; García-Belmonte, Daniel; Feliu, Evarist; Ciudad, Juana; Orfao, Alberto

2017-11-22

Native or pegylated (PEG) asparaginase (ASP) are commonly used in treatment of acute lymphoblastic leukemia (ALL), but have been scarcely compared in the same trial in adult patients. Native vs. PEG-ASP administered according to availability in each center were prospectively evaluated in adults with high-risk ALL. Ninety-one patients received native ASP and 35 PEG-ASP in induction. No significant differences were observed in complete remission, minimal residual disease levels after induction and after consolidation, disease-free survival, and overall survival. No significant differences in grades 3-4 toxicity were observed in the induction period, although a trend for higher hepatic toxicity was observed in patients receiving PEG-ASP. In this trial the type of ASP did not influence patient response and outcome.

Zinc oxide nanoparticles affect carbon and nitrogen mineralization of Phoenix dactylifera leaf litter in a sandy soil.

PubMed

Rashid, Muhammad Imtiaz; Shahzad, Tanvir; Shahid, Muhammad; Ismail, Iqbal M I; Shah, Ghulam Mustafa; Almeelbi, Talal

2017-02-15

We investigated the impact of zinc oxide nanoparticles (ZnO NPs; 1000mgkg -1 soil) on soil microbes and their associated soil functions such as date palm (Phoenix dactylifera) leaf litter (5gkg -1 soil) carbon and nitrogen mineralization in mesocosms containing sandy soil. Nanoparticles application in litter-amended soil significantly decreased the cultivable heterotrophic bacterial and fungal colony forming units (cfu) compared to only litter-amended soil. The decrease in cfu could be related to lower microbial biomass carbon in nanoparticles-litter amended soil. Likewise, ZnO NPs also reduced CO 2 emission by 10% in aforementioned treatment but this was higher than control (soil only). Labile Zn was only detected in the microbial biomass of nanoparticles-litter applied soil indicating that microorganisms consumed this element from freely available nutrients in the soil. In this treatment, dissolved organic carbon and mineral nitrogen were 25 and 34% lower respectively compared to litter-amended soil. Such toxic effects of nanoparticles on litter decomposition resulted in 130 and 122% lower carbon and nitrogen mineralization efficiency respectively. Hence, our results entail that ZnO NPs are toxic to soil microbes and affect their function i.e., carbon and nitrogen mineralization of applied litter thus confirming their toxicity to microbial associated soil functions. Copyright © 2016 Elsevier B.V. All rights reserved.

Arsenic levels in immigrant children from countries at risk of consuming arsenic polluted water compared to children from Barcelona.

PubMed

Piñol, S; Sala, A; Guzman, C; Marcos, S; Joya, X; Puig, C; Velasco, M; Velez, D; Vall, O; Garcia-Algar, O

2015-11-01

Arsenic is a highly toxic element that pollutes groundwater, being a major environmental problem worldwide, especially in the Bengal Basin. About 40% of patients in our outpatient clinics come from those countries, and there is no published data about their arsenic exposure. This study compares arsenic exposure between immigrant and native children. A total of 114 children (57 natives, 57 immigrants), aged 2 months to 16 years, were recruited and sociodemographic and environmental exposure data were recorded. Total arsenic in urine, hair, and nails and arsenic-speciated compounds in urine were determined. We did not find significant differences in total and inorganic arsenic levels in urine and hair, but in organic arsenic monomethylarsenic acid (MMA) and dimethylarsinous acid (DMA) in urine and in total arsenic in nails. However, these values were not in the toxic range. There were significant differences between longer than 5 years exposure and less than 5 years exposure (consumption of water from tube wells), with respect to inorganic and organic MMA arsenic in urine and total arsenic in nails. There was partial correlation between the duration of exposure and inorganic arsenic levels in urine. Immigrant children have higher arsenic levels than native children, but they are not toxic. At present, there is no need for specific arsenic screening or follow-up in immigrant children recently arrived in Spain from exposure high-risk countries.

Comparison of essential and toxic elements in esophagus, lung, mouth and urinary bladder male cancer patients with related to controls.

PubMed

Kazi, Tasneem Gul; Wadhwa, Sham Kumar; Afridi, Hassan Imran; Talpur, Farah Naz; Tuzen, Mustafa; Baig, Jameel Ahmed

2015-05-01

There is a compelling evidence in support of negative associations between essential trace and toxic elements in different types of cancer. The aim of the present study was to investigate the relationship between carcinogenic (As, Cd, Ni) and anti-carcinogenic (Se, Zn) trace elements in scalp hair samples of different male cancerous patients (esophagus, lung, mouth, and urinary bladder). For comparative purposes, the scalp hair samples of healthy males of the same age group (ranged 35-65 years) as controls were analyzed. Both controls and patients have the same socioeconomic status, localities, dietary habits, and smoking locally made cigarette. The scalp hair samples were oxidized by 65% nitric acid: 30% hydrogen peroxide (2:1) ratio in microwave oven followed by atomic absorption spectrometry. The validity and accuracy of the methodology were checked using certified reference material of human hair BCR 397. The mean concentrations of As, Cd, and Ni were found to be significantly higher in scalp hair samples of patients having different cancers as compared to the controls, while reverse results were obtained in the case of Se and Zn levels (p < 0.01). The study revealed that the carcinogenic processes are significantly affecting the trace elements burden and mutual interaction of essential trace and toxic elements in the cancerous patients.

[Randomized clinical trial of IEP and EP regimens in the treatment of patients with small cell lung cancer].

PubMed

Zhou, Hui; Wang, Anlan; Huang, Zhihua; Zhou, Wenwei

2004-06-20

To observe and compare the efficacy and safety of IEP and EP regimens for small cell lung cancer (SCLC). Sixty-four patients with SCLC pathologically proved were randomly divided into IEP group ( n =32) and EP group ( n =32). All the 64 patients were evaluable for response and toxicity. In IEP group, the total responsive rate, responsive rates of limited-stage patients and extensive-stage patients were 84.4%(27/32), 100.0%(15/15) and 70.6%(12/17) respectively; while in EP group, those were 75.0%(24/32), 85.7%(12/14) and 66.7% (12/18) respectively. The median duration of remission was 6 months and 1-year survival rate was 62.5% in IEP group, and 5 months and 56.2% in EP group. There was no significant difference in response rate, median duration of remission and 1-year survival between the two groups ( P > 0.05). The main toxicity was myelosuppression. Incidences of leukopenia at grade III-IV, nausea, vomiting and alopecia were significantly higher in the IEP arm than those in the EP arm ( P < 0.01 ). High response rates and tolerable toxicities are attainable for small cell lung cancer treated with IEP and EP. IEP regimen shows a similar response rate compared with EP regimen. They might be considered as relevant regimens in initial patients with small cell lung cancer.

Multivariate analysis of survival, local control, and time to distant metastases in patients with unresectable non-small-cell lung carcinoma treated with 3-dimensional conformal radiation therapy with or without concurrent chemotherapy.

PubMed

Wolski, Michal J; Bhatnagar, Ajay; Flickinger, John C; Belani, Chandra P; Ramalingam, Suresh; Greenberger, Joel S

2005-09-01

Three-dimensional (3D) conformal radiation therapy (CRT) and chemotherapy have recently improved lung cancer management. We reviewed outcomes in 68 patients with unresectable stage I-III non-small-cell lung cancer. Treatment consisted of 3D CRT alone or with concurrent chemotherapy (CCR). Concurrent chemotherapy improved survival, to a median of 17 months +/- 4.9 months, compared with 8 months+/- 4.1 months for the radiation therapy (RT) alone group (P=0.0347). The 2- and 5-year survival rates were 40.3%+/-7.7% and 14.1%+/-6.4%, respectively, with CCR, compared with 19.6%+/- 9.6% and 0, respectively, for RT alone. In a subgroup analysis for age > 65, patients who received CCR (n=20) had significantly improved survival and local control (P=0.005 and P=0.0286, respectively). Acute esophageal toxicity Radiation Therapy Oncology Group grade >or= 3 was significantly higher in the CCR group and correlated with the RT dose (19% in CCR vs. 0 in RT, P=0.0234; P=0.050). The overall incidences of esophageal and pulmonary toxicity grade >or= 3 were 20.6% and 5.9%, respectively. Our study confirms that CCR is associated with improved survival over RT alone, with a tolerable increase in acute toxicity.

Effect of leaf extracts of Taraxacum officinale on CCl4 induced hepatotoxicity in rats, in vivo study.

PubMed

Gulfraz, Muhammad; Ahamd, Dawood; Ahmad, Muhammad Sheeraz; Qureshi, Rehmatullah; Mahmood, Raja Tahir; Jabeen, Nyla; Abbasi, Kashif Sarfraz

2014-07-01

Taraxacum officinale L is a medicinal plant, which has enormous medicinal values against various types of liver disorders and it has traditionally been used for the treatment of liver problems by people from the South East Asia. Previously we have screened the crude methanolic extract of T. officinale against cytotoxicity induced by CCl4. Present study was designed to compare the protective effect of ethanolic and n-hexane extract of leaves in carbon tetrachloride (CCl4) induced liver toxicity in rats. The extract (200 mg/kg and 400mg/kg body weight) along with silymarin (100 mg/kg) a standard drug was administered to experimental animals. It was observed that ethanolic plant extract has significantly reduced the negative effect of CCl4 as compared to n-hexane extract and effect of extract was increased with increasing dose level. Although both leaf extracts decreased the concentration of TBARS, H2O2 and nitrite contents which enhance due to CCl4 toxicity but effect was higher in ethanolic extract. The results clearly indicated that Taraxacum officinale ethanolic leaves extract has better protective effect against CCl4 induced liver tissues toxicity. This claim was also supported by histopathological results obtained during this study and this might be due to presence of various polar phytochemicals that might be more prevent in this extract.

Morpho-physiological analysis of tolerance to aluminum toxicity in rice varieties of North East India

PubMed Central

Awasthi, Jay Prakash; Saha, Bedabrata; Regon, Preetom; Sahoo, Smita; Chowra, Umakanta; Pradhan, Amit; Roy, Anupam; Panda, Sanjib Kumar

2017-01-01

Aluminum (Al) is the third most abundant metal in earth crust, whose chemical form is mainly dependent on soil pH. The most toxic form of Al with respect to plants is Al3+, which exists in soil pH <5. Acidic soil significantly limits crop production mainly due to Al3+ toxicity worldwide, impacting approximately 50% of the world’s arable land (in North-Eastern India 80% soil are acidic). Al3+ toxicity in plants ensues root growth inhibition leading to less nutrient and water uptake impacting crop productivity as a whole. Rice is one of the chief grains which constitutes the staple food of two-third of the world population including India and is not untouched by Al3+ toxicity. Al contamination is a critical constraint to plant production in agricultural soils of North East India. 24 indigenous Indica rice varieties (including Badshahbhog as tolerant check and Mashuri as sensitive check) were screened for Al stress tolerance in hydroponic plant growth system. Results show marked difference in growth parameters (relative growth rate, Root tolerance index, fresh and dry weight of root) of rice seedlings due to Al (100 μM) toxicity. Al3+ uptake and lipid peroxidation level also increased concomitantly under Al treatment. Histochemical assay were also performed to elucidate uptake of aluminum, loss of membrane integrity and lipid peroxidation, which were found to be more in sensitive genotypes at higher Al concentration. This study revealed that aluminum toxicity is a serious harmful problem for rice crop productivity in acid soil. Based on various parameters studied it’s concluded that Disang is a comparatively tolerant variety whereas Joymati a sensitive variety. Western blot hybridization further strengthened the claim, as it demonstrated more accumulation of Glutathione reductase (GR) protein in Disang rice variety than Joymati under stressed condition. This study also observed that the emergence of lethal toxic symptoms occurs only after 48h irrespective of the dose used in the study. PMID:28448589

Influence of Vancomycin Infusion Methods on Endothelial Cell Toxicity

PubMed Central

Drouet, Maryline; Chai, Feng; Barthélémy, Christine; Lebuffe, Gilles; Debaene, Bertrand; Odou, Pascal

2014-01-01

Peripheral intravenous therapy is frequently used in routine hospital practice and, due to various factors, its most common side effect is phlebitis. The infusion of vancomycin is particularly associated with phlebitis despite its widespread use. French guidelines recommend central intravenous infusion for high concentrations of vancomycin, but peripheral intravenous therapy is often preferred in intensive care units. Methods of vancomycin infusion are either intermittent infusion or continuous infusion. A comparison of these methods under in vitro conditions simulating clinical use could result in better infusion efficacy. Human umbilical vein endothelial cells (HUVECs) were therefore challenged with clinical doses of vancomycin over a 24- to 72-h period using these infusion methods. Cell death was measured with the alamarBlue test. Concentration-dependent and time-dependent vancomycin toxicity on HUVECs was noted with a 50% lethal dose at 5 mg/ml after 24 h, reaching 2.5 mg/ml after 72 h of infusion, simulating long-term infusion. This toxicity does not seem to be induced by acidic pH. In comparing infusion methods, we observed that continuous infusion induced greater cell toxicity than intermittent infusion at doses higher than 1 g/day. The increasing use of vancomycin means that new guidelines are required to avoid phlebitis. If peripheral intravenous therapy is used to reduce infusion time, along with intermittent infusion, vein irritation and localized phlebitis may be reduced. Further studies have to be carried out to explore the causes of vancomycin endothelial toxicity. PMID:25421476

High levels of heavy metal accumulation in dental calculus of smokers: a pilot inductively coupled plasma mass spectrometry study.

PubMed

Yaprak, E; Yolcubal, I; Sinanoğlu, A; Doğrul-Demiray, A; Guzeldemir-Akcakanat, E; Marakoğlu, I

2017-02-01

Various trace elements, including toxic heavy metals, may exist in dental calculus. However, the effect of environmental factors on heavy metal composition of dental calculus is unknown. Smoking is a major environmental source for chronic toxic heavy metal exposition. The aim of this study is to compare toxic heavy metal accumulation levels in supragingival dental calculus of smokers and non-smokers. A total of 29 supragingival dental calculus samples were obtained from non-smoker (n = 14) and smoker (n = 15) individuals. Subjects with a probability of occupational exposure were excluded from the study. Samples were analyzed by inductively coupled plasma mass spectrometry in terms of 26 metals and metalloids, including toxic heavy metals. Toxic heavy metals, arsenic (p < 0.05), cadmium (p < 0.05), lead (p < 0.01), manganese (p < 0.01) and vanadium (p < 0.01) levels were significantly higher in smokers than non-smokers. The levels of other examined elements were similar in both groups (p > 0.05). Within the limitations of this study, it can be concluded that the elementary composition of dental calculus may be affected by environmental factors such as tobacco smoke. Therefore, dental calculus may be utilized as a non-invasive diagnostic biological material for monitoring chronic oral heavy metal exposition. However, further studies are required to evaluate its diagnostic potential. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Synthesis of β-cyclodextrin hydrogel nanoparticles for improving the solubility of dexibuprofen: characterization and toxicity evaluation.

PubMed

Khalid, Qandeel; Ahmad, Mahmood; Minhas, Muhammad Usman

2017-11-01

This study was aimed to enhance aqueous solubility of dexibuprofen through designing β-cyclodextrin (βCD) hydrogel nanoparticles and to evaluate toxicological potential through acute toxicity studies in rats. Dexibuprofen is a non-steroidal analgesic and anti-inflammatory drug that is one of safest over the counter medications. However, its clinical effectiveness is hampered due to poor aqueous solubility. βCD hydrogel nanoparticles were prepared and characterized by percent yield, drug loading, solubilization efficiency, FTIR, XRD, DSC, FESEM and in-vitro dissolution studies. Acute oral toxicity study was conducted to assess safety of oral administration of prepared βCD hydrogel nanoparticles. βCD hydrogel nanoparticles dramatically enhanced the drug loading and solubilization efficiency of dexibuprofen in aqueous media. FTIR, TGA and DSC studies confirmed the formation of new and a stable nano-polymeric network and interactions of dexibuprofen with these nanoparticles. Resulting nanoparticles were highly porous with 287 nm in size. XRD analysis revealed pronounced reduction in crystalline nature of dexibuprofen within nanoparticles. Release of dexibuprofen in βCD hydrogel nanoparticles was significantly higher compared with dexibuprofen tablet at pH 1.2 and 6.8. In acute toxicity studies, no significant changes in behavioral, physiological, biochemical or histopathologic parameters of animals were observed. The efficient preparation, high solubility, excellent physicochemical characteristics, improved dissolution and non-toxic βCD hydrogel nanoparticles may be a promising approach for oral delivery of lipophilic drugs.

Loading and removal of PAHs, fragrance compounds, triclosan and toxicity by composting process from sewage sludge.

PubMed

Ozaki, Noriatsu; Nakazato, Akihiro; Nakashima, Kazuki; Kindaichi, Tomonori; Ohashi, Akiyoshi

2017-12-15

Although the production of compost from sewage sludge is well established in developed countries, the use of sludge-based compost may represent a source of pollutants. The present study assessed the levels of potentially harmful compounds in compost as well as their rates of decrease during composting. The concentrations of 16 polycyclic aromatic hydrocarbons (PAHs), three fragrance compounds (OTNE, HHCB and AHTN) and triclosan were determined in the initial sewage sludge and in compost over the span of 1year. Simultaneously, the toxicity to luminescent bacteria (Aliivibrio fischeri) and aryl hydrocarbon receptor reactivity of organic solvent extracts of sludge and compost samples were assessed. Higher PAH, fragrance compounds, and triclosan concentrations were found in sewage sludge from urban areas compared with rural regions, and the urban sludge was also more toxic than the rural sludge. The high pollutant concentrations in urban sludge raised the concentrations of these compounds in the raw materials for composting and in the resulting composts. The organic matter was decomposed by 65% during the composting process, and the measured toxic substances were decreased by a similar amount, with the exception of triclosan, which decreased by only 35%. The toxicity to A. fischeri decreased to a greater extent (90%) than did the organic matter, while the aryl hydrocarbon receptor reactivity decreased by only 35%. This lower decrease coincided with that of the aryl hydrocarbon receptor-reactive PAHs (37%). Copyright © 2017 Elsevier B.V. All rights reserved.

Acute and subacute oral toxicity of polychlorinated diphenyl sulfides in mice: determining LD50 and assessing the status of hepatic oxidative stress.

PubMed

Zhang, Xuesheng; Liu, Fu; Chen, Binyuan; Li, Ying; Wang, Zunyao

2012-07-01

Polychlorinated diphenyl sulfides (PCDPSs), a series of dioxin-like compounds, have been detected in various environmental samples. However, information on the toxicity of these compounds is limited. In the present study, the toxic effects of PCDPSs were assessed after acute and subacute exposure in mice. Relationships between acute toxicity, number, and position of substituted Cl atoms were assessed. In the acute study, 11 types of PCDPSs were administered to female Kunming mice by gavage, and median lethal doses (LD50s) were determined by the Karber method. Results indicated that the LD50s of lower substituted PCDPSs were smaller than higher substituted PCDPSs. Substituted positions also influenced the LD50 of PCDPSs. Terminal necropsy showed increased relative liver weights and decreased relative kidney weights. Histological examination of livers demonstrated swollen cells, inflammation, vacuolization, and necrosis. In the 28-d subacute exposure tests, 11 types of PCDPSs were dissolved in corn oil and administered to mice at doses of 1, 10, and 100 mg/kg. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels in mouse liver were determined after the exposure period. Results suggested that lower substituted PCDPSs decreased SOD activity in the high-dose groups compared with controls, and MDA level in the 100-mg/kg dose group was significantly increased. In addition, acute toxicity of PCDPSs partly corresponded to the hepatic oxidative damage observed. Copyright © 2012 SETAC.

NO3-/NH4+ ratios affect nutritional homeostasis and production of Tanzania guinea grass under Cu toxicity.

PubMed

de Souza Junior, João Cardoso; Nogueirol, Roberta Corrêa; Monteiro, Francisco Antonio

2018-05-01

Nitrogen (N) can alleviate metal toxicity. However, as of yet, there have been no studies showing the efficacy of NO 3 - /NH 4 + in mitigating Cu toxicity. The objective of this study was to evaluate the Cu toxicity on the nutritional and productive attributes of Panicum maximum cv. Tanzania as well as the role of NO 3 - and NH 4 + ratios in nutritional homeostasis. The experiment was conducted using 3 × 4 factorial treatments arranged in a randomized complete block design with three replicates. The treatments were three NO 3 - /NH 4 + ratios (100/0, 70/30, and 50/50) and four Cu rates (0.3, 250, 500, and 1000 μmol L -1 ) in nutrient solution. Copper concentrations in the diagnostic leaves (DL) were highest in plants grown under 70/30 NO 3 - /NH 4 + ratios and a Cu rate of 1000 μmol L -1 . In this combination, it was observed that DL had higher concentrations of NH 4 + , greater glutamine synthetase activity, lower chlorophyll concentration (SPAD value), and lower shoot dry mass, suggesting high disorders of nutritional homeostasis. Plants receiving N in the form of NO 3 - and 1000 Cu μmol L -1 showed that DL had lower concentrations of Cu, higher concentration of chlorophyll, higher NO 3 - concentration, higher nitrate reductase activity, and higher NO 3 - accumulation in the roots, suggesting a reduction in disorders of nutritional homeostasis. The disorders on mineral uptake, N assimilation, and biomass production caused by Cu toxicity are shown to be affected by NO 3 - /NH 4 + ratios, and N supply via NO 3 - allowed for better homeostasis of the forage grass.

Differential fipronil susceptibility and metabolism in two rice stem borers from China.

PubMed

Fang, Qi; Huang, Cheng-Hua; Ye, Gong-Yin; Yao, Hong-Wei; Cheng, Jia-An; Akhtar, Zunnu-Raen

2008-08-01

The susceptibilities of larvae of two rice stem borers, namely, Chilo suppressalis (Walker) (Lepidoptera: Crambidae) and Sesamia inferens (Walker) (Lepidoptera: Nocutidae) to fipronil and its metabolites were investigated, and then the activities of microsomal O-demethylase, and glutathione transferase (GST) in two species were measured. The metabolism of fipronil in both stem borers was determined in vivo and in vitro. The LD50 value of fipronil to S. inferens was 118.5-fold higher than that of C. suppressalis. The bioassay results offipronil metabolites showed that the toxicities of sulfone and sulfide were higher than fipronil for both species, and the differential toxicity between sulfone and fipronil was remarkable. Alternatively, the activities of microsomal O-demethylase and GST of C. suppressalis were 1.35- and 2.06-fold higher than S. inferens, respectively. The in vivo and in vitro studies on metabolism of fipronil showed that all of fipronil, sulfone, and sulfide were detected and the content of sulfone was higher than sulfide in both stem borers. The residue of sulfone in C. suppressalis was significantly higher than that in S. inferens. These results suggest that the higher activity of mixed function oxidases may cause the higher capacity of C. suppressalis to produce fipronil-sulfone, which is more toxic than fipronil leading to the higher susceptibility of this species.

Rapid bioassessment methods for assessing vegetation toxicity at the Savannah River Site - germination tests and root elongation trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Specht, W.L.; Klaine, S.J.; Hook, D.D.

1996-01-01

Plants form the basis of all ecosystems including wetlands. Although they are the most abundant life form and are the primary producers for all other organisms, they have received the least attention when it comes to environmental matters. Higher plants have rarely been used in ecotoxicity testing and may not respond in the same manner as algae, which have been used more frequently. The introduction of hazardous waste materials into wetland areas has the potential to alter and damage the ecological processes in these ecosystems. Measuring the impact of these contaminants on higher plants is therefore important and needs furthermore » research. Higher plants are useful for detecting both herbicidal toxicity and heavy metal toxicity. For phytotoxicity tests to be practical they must be simple, inexpensive, yet sensitive to a variety of contaminants. A difference between seed germination and root elongation tests is that seed germination tests measure toxicity associated with soils directly, while root elongation tests consider the indirect effects of water-soluble constituents that may be present in site samples.« less

Curcumin loaded chitin nanogels for skin cancer treatment via the transdermal route

NASA Astrophysics Data System (ADS)

Mangalathillam, Sabitha; Rejinold, N. Sanoj; Nair, Amrita; Lakshmanan, Vinoth-Kumar; Nair, Shantikumar V.; Jayakumar, Rangasamy

2011-12-01

In this study, curcumin loaded chitin nanogels (CCNGs) were developed using biocompatible and biodegradable chitin with an anticancer curcumin drug. Chitin, as well as curcumin, is insoluble in water. However, the developed CCNGs form a very good and stable dispersion in water. The CCNGs were analyzed by DLS, SEM and FTIR and showed spherical particles in a size range of 70-80 nm. The CCNGs showed higher release at acidic pH compared to neutral pH. The cytotoxicity of the nanogels were analyzed on human dermal fibroblast cells (HDF) and A375 (human melanoma) cell lines and the results show that CCNGs have specific toxicity on melanoma in a concentration range of 0.1-1.0 mg mL-1, but less toxicity towards HDF cells. The confocal analysis confirmed the uptake of CCNGs by A375. The apoptotic effect of CCNGs was analyzed by a flow-cytometric assay and the results indicate that CCNGs at the higher concentration of the cytotoxic range showed comparable apoptosis as the control curcumin, in which there was negligible apoptosis induced by the control chitin nanogels. The CCNGs showed a 4-fold increase in steady state transdermal flux of curcumin as compared to that of control curcumin solution. The histopathology studies of the porcine skin samples treated with the prepared materials showed loosening of the horny layer of the epidermis, facilitating penetration with no observed signs of inflammation. These results suggest that the formulated CCNGs offer specific advantage for the treatment of melanoma, the most common and serious type of skin cancer, by effective transdermal penetration.

Comparative Response of the Hepatic Transcriptomes of Domesticated and Wild Turkey to Aflatoxin B₁.

PubMed

Reed, Kent M; Mendoza, Kristelle M; Abrahante, Juan E; Coulombe, Roger A

2018-01-13

The food-borne mycotoxin aflatoxin B₁ (AFB₁) poses a significant risk to poultry, which are highly susceptible to its hepatotoxic effects. Domesticated turkeys ( Meleagris gallopavo ) are especially sensitive, whereas wild turkeys ( M. g. silvestris ) are more resistant. AFB₁ toxicity entails bioactivation by hepatic cytochrome P450s to the electrophilic exo-AFB₁-8,9-epoxide (AFBO). Domesticated turkeys lack functional hepatic GST-mediated detoxification of AFBO, and this is largely responsible for the differences in resistance between turkey types. This study was designed to characterize transcriptional changes induced in turkey livers by AFB₁, and to contrast the response of domesticated (susceptible) and wild (more resistant) birds. Gene expression responses to AFB₁ were examined using RNA-sequencing. Statistically significant differences in gene expression were observed among treatment groups and between turkey types. Expression analysis identified 4621 genes with significant differential expression (DE) in AFB₁-treated birds compared to controls. Characterization of DE transcripts revealed genes dis-regulated in response to toxic insult with significant association of Phase I and Phase II genes and others important in cellular regulation, modulation of apoptosis, and inflammatory responses. Constitutive expression of GSTA3 was significantly higher in wild birds and was significantly higher in AFB₁-treated birds when compared to controls for both genetic groups. This pattern was also observed by qRT-PCR in other wild and domesticated turkey strains. Results of this study emphasize the differential response of these genetically distinct birds, and identify genes and pathways that are differentially altered in aflatoxicosis.

Convection-enhancement delivery of platinum-based drugs and Lipoplatin™ to optimize the concomitant effect with radiotherapy in F98 glioma rat model

PubMed Central

Shi, Minghan; Fortin, David; Sanche, Léon; Paquette, Benoit

2015-01-01

The prognosis for patients with glioblastoma remains poor with current treatments. Although platinum based drugs are sometimes offered at relapse, their efficacy in this setting is still disputed. In this study, we use convection-enhanced delivery (CED) to deliver the platinum-based drugs (cisplatin, carboplatin, and Lipoplatin™-liposomal formulation of cisplatin) directly into the tumor of F98 glioma-bearing rats that were subsequently treated with γ radiation (15 Gy). CED increased by factors varying between 17 and 111, the concentration of these platinum-based drugs in the brain tumor compared to intra-venous (i.v.) administration, and by 9- to 34-fold, when compared to intra-arterial (i.a.) administration. Furthermore, CED resulted in a better systemic tolerance to platinum drugs compared to their i.a. injection. Among the drugs tested, carboplatin showed the highest maximum tolerated dose (MTD). Treatment with carboplatin resulted in the best median survival time (MeST) (38.5 days), which was further increased by the addition of radiotherapy (54.0 days). Although the DNA-bound platinum adduct were higher at 4 h after CED than 24 h for carboplatin group, combination with radiotherapy led to similar improvement of median survival time. However, less toxicity was observed in animals irradiated 24 h after CED-based chemotherapy. In conclusion, CED increased the accumulation of platinum drugs in tumor, reduced the toxicity, and resulted in a higher median survival time. The best treatment was obtained in animals treated with carboplatin and irradiated 24 h later. PMID:25784204

Convection-enhancement delivery of platinum-based drugs and Lipoplatin(TM) to optimize the concomitant effect with radiotherapy in F98 glioma rat model.

PubMed

Shi, Minghan; Fortin, David; Sanche, Léon; Paquette, Benoit

2015-06-01

The prognosis for patients with glioblastoma remains poor with current treatments. Although platinum-based drugs are sometimes offered at relapse, their efficacy in this setting is still disputed. In this study, we use convection-enhanced delivery (CED) to deliver the platinum-based drugs (cisplatin, carboplatin, and Lipoplatin(TM) - liposomal formulation of cisplatin) directly into the tumor of F98 glioma-bearing rats that were subsequently treated with γ radiation (15 Gy). CED increased by factors varying between 17 and 111, the concentration of these platinum-based drugs in the brain tumor compared to intra-venous (i.v.) administration, and by 9- to 34-fold, when compared to intra-arterial (i.a.) administration. Furthermore, CED resulted in a better systemic tolerance to platinum drugs compared to their i.a. injection. Among the drugs tested, carboplatin showed the highest maximum tolerated dose (MTD). Treatment with carboplatin resulted in the best median survival time (MeST) (38.5 days), which was further increased by the addition of radiotherapy (54.0 days). Although the DNA-bound platinum adduct were higher at 4 h after CED than 24 h for carboplatin group, combination with radiotherapy led to similar improvement of median survival time. However, less toxicity was observed in animals irradiated 24 h after CED-based chemotherapy. In conclusion, CED increased the accumulation of platinum drugs in tumor, reduced the toxicity, and resulted in a higher median survival time. The best treatment was obtained in animals treated with carboplatin and irradiated 24 h later.

Curcumin loaded chitin nanogels for skin cancer treatment via the transdermal route.

PubMed

Mangalathillam, Sabitha; Rejinold, N Sanoj; Nair, Amrita; Lakshmanan, Vinoth-Kumar; Nair, Shantikumar V; Jayakumar, Rangasamy

2012-01-07

In this study, curcumin loaded chitin nanogels (CCNGs) were developed using biocompatible and biodegradable chitin with an anticancer curcumin drug. Chitin, as well as curcumin, is insoluble in water. However, the developed CCNGs form a very good and stable dispersion in water. The CCNGs were analyzed by DLS, SEM and FTIR and showed spherical particles in a size range of 70-80 nm. The CCNGs showed higher release at acidic pH compared to neutral pH. The cytotoxicity of the nanogels were analyzed on human dermal fibroblast cells (HDF) and A375 (human melanoma) cell lines and the results show that CCNGs have specific toxicity on melanoma in a concentration range of 0.1-1.0 mg mL(-1), but less toxicity towards HDF cells. The confocal analysis confirmed the uptake of CCNGs by A375. The apoptotic effect of CCNGs was analyzed by a flow-cytometric assay and the results indicate that CCNGs at the higher concentration of the cytotoxic range showed comparable apoptosis as the control curcumin, in which there was negligible apoptosis induced by the control chitin nanogels. The CCNGs showed a 4-fold increase in steady state transdermal flux of curcumin as compared to that of control curcumin solution. The histopathology studies of the porcine skin samples treated with the prepared materials showed loosening of the horny layer of the epidermis, facilitating penetration with no observed signs of inflammation. These results suggest that the formulated CCNGs offer specific advantage for the treatment of melanoma, the most common and serious type of skin cancer, by effective transdermal penetration.

A subchronic toxicity study of elemental Nano-Se in Sprague-Dawley rats.

PubMed

Jia, X; Li, N; Chen, J

2005-03-11

The subchronic toxicity of Nano-Se was compared with selenite and high-selenium protein in rats. Groups of Sprague-Dawley rats (12 males and 12 females per group) were fed diets containing Nano-Se, selenite and high-selenium protein at concentrations of 0, 2, 3, 4 and 5 ppm Se, respectively, for 13 weeks. Clinical observations were made and body weight and food consumption were recorded weekly. At the end of the study, the rats were subjected to a full necropsy, blood samples were collected for hematology and clinical chemistry determination. Histopathological examination was performed on selected tissues. At the two higher doses (4 and 5 ppm Se), significant abnormal changes were found in body weight, hematology, clinical chemistry, relative organ weights and histopathology parameters. However, the toxicity was more pronounced in the selenite and high-selenium protein groups than the Nano-Se group. At the dose of 3 ppm Se, significant growth inhibition and degeneration of liver cells were found in the selenite and high-selenium protein groups. No changes attributable to administration of Nano-Se at the dose of 3 ppm Se were found. Taken together, the no-observed-adverse-effect level (NOAEL) of Nano-Se in male and female rats was considered to be 3 ppm Se, equivalent to 0.22 mg/kg bw/day for males and 0.33 mg/kg bw/day for females. On the other hand, the NOAELs of selenite and high-selenium protein in males and females were considered to be 2 ppm Se, equivalent to 0.14 mg/kg bw/day for males and 0.20 mg/kg bw/day for females. In addition, studies have shown that Nano-Se has a similar bioavailability in rat, and much less acute toxicity in mice compared with selenite. In conclusion, Nano-Se is less toxic than selenite and high-selenium protein in the 13-week rat study.

Convection-enhanced drug delivery of interleukin-4 Pseudomonas exotoxin (PRX321): increased distribution and magnetic resonance monitoring.

PubMed

Mardor, Y; Last, D; Daniels, D; Shneor, R; Maier, S E; Nass, D; Ram, Z

2009-08-01

Convection-enhanced drug delivery (CED) enables achieving a drug concentration within brain tissue and brain tumors that is orders of magnitude higher than by systemic administration. Previous phase I/II clinical trials using intratumoral convection of interleukin-4 Pseudomonas exotoxin (PRX321) have demonstrated an acceptable safety and toxicity profile with promising signs of therapeutic activity. The present study was designed to assess the distribution efficiency and toxicity of this PRX321 using magnetic resonance imaging (MRI) and to test whether reformulation with increased viscosity could enhance drug distribution. Convection of low- [0.02% human serum albumin (HSA)] and high-viscosity (3% HSA) infusates mixed with gadolinium-diethylenetriamine pentaacetic acid and PRX321 were compared with low- and high-viscosity infusates without the drug, in normal rat brains. MRI was used for assessment of drug distribution and detection of early and late toxicity. Representative brain samples were subjected to histological examination. Distribution volumes calculated from the magnetic resonance images showed that the average distribution of 0.02% HSA was larger than that of 0.02% HSA with PRX321 by a factor of 1.98 (p < 0.02). CED of 3.0% HSA, with or without PRX321, tripled the volume of distribution compared with 0.02% HSA with PRX321 (p < 0.015). No drug-related toxicity was detected. These results suggest that the impeded convection of the PRX321 infusate used in previous clinical trials can be reversed by increasing infusate viscosity and lead to tripling of the volume of distribution. This effect was not associated with any detectable toxicity. A similar capability to reverse impeded convection was also demonstrated in a CED model using acetic acid. These results will be implemented in an upcoming phase IIb PRX321 CED trial with a high-viscosity infusate.

Enhanced bio-concentration of tris(1,3-dichloro-2-propyl) phosphate in the presence of nano-TiO2 can lead to adverse reproductive outcomes in zebrafish.

PubMed

Ren, Xin; Zhao, Xuesong; Duan, Xiaoyue; Fang, Ziwei

2018-02-01

Interactions between organic toxicants and nano-particles in the aquatic environment may modify toxicant bioavailability and consequently the toxicant's fate and toxicity. To evaluate the potential impact of nano-titanium dioxide (TiO 2 ) on the bio-concentration and reproductive endocrine disruption of tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) in fish, a comparative bioaccumulation study was conducted on zebrafish (Danio rerio, AB strain) treated with 0, 5.74, 23.6, or 90.7 μg L -1 TDCIPP alone or co-exposed to TDCIPP and 0.09 mg L -1 nano-TiO 2 for 21 days. Nano-TiO 2 can absorb TDCIPP and nano-TiO 2 is taken up into zebrafish. Chemical measurements showed that TDCIPP was bio-concentrated in zebrafish, and the highest level was detected in the liver, followed by the brain and gonads. Compared with TDCIPP treatment, increased tissue burdens of both TDCIPP were observed in the liver, brain, and gonads suggesting that nano-TiO 2 adsorbed TDCIPP and acted as a carrier facilitating the uptake and translocation of TDCIPP in tissues. Higher bio-concentration in the presence of nano-TiO 2 resulted in a significant decrease in the hepatic-somatic index, gonad-somatic index and brain-somatic index in F0 females but not F0 males. Moreover, a further gender-dependent reduction in testosterone (T), estradiol (E2), follicle-stimulating hormone (FSH) and luteinizing hormone (LH), and induction of plasma vitellogenin (VTG) concentrations in adults were observed following co-exposure. Co-exposure also inhibited egg production and caused significant developmental toxicity in F1 larvae. The results obtained using this multi-marker approach suggested that nano-TiO 2 is a carrier of TDCIPP and accelerated its bio-concentration in adult zebrafish, resulting in adverse reproduction outcomes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cytotoxicity of cadmium-free quantum dots and their use in cell bioimaging.

PubMed

Soenen, Stefaan J; Manshian, Bella B; Aubert, Tangi; Himmelreich, Uwe; Demeester, Jo; De Smedt, Stefaan C; Hens, Zeger; Braeckmans, Kevin

2014-06-16

The use of quantum dots (QDots) as bright and photostable probes for long-term fluorescence imaging is gaining more interest. Thus far, (pre)clinical use of QDots remains limited, which is primarily caused by the potential toxicity of QDots. Most QDots consist of Cd2+ ions, which are known to cause high levels of toxicity. In order to overcome this problem, several strategies have been tested, such as the generation of cadmium-free QDots. In the present study, two types of cadmium-free QDots, composed of ZnSe/ZnS (QDotZnSe) and InP/ZnS (QDotInP), were studied with respect to their cytotoxicity and cellular uptake in a variety of cell types. A multiparametric cytotoxicity approach is used, where the QDots are studied with respect to cell viability, oxidative stress, cell morphology, stem cell differentiation, and neurite outgrowth. The data reveal slight differences in uptake levels for both types of QDots (maximal for QDotZnSe), but clear differences in cytotoxicity and cell functionality effects exist, with highest toxicity for QDotZnSe. Differences between cell types and between both types of QDots can be explained by the intrinsic sensitivity of certain cell types and chemical composition of the QDots. At concentrations at which no toxic effects can be observed, the functionality of the QDots for fluorescence cell visualization is evaluated, revealing that the higher brightness of QDotZnSe overcomes most of the toxicity issues compared to that of QDotInP. Comparing the results obtained with common Cd2+-containing QDots tested under identical conditions, the importance of particle functionality is demonstrated, revealing that cadmium-free QDots tested in this study are not significantly better than Cd2+-containing QDots for long-term cell imaging and that more work needs to be performed in optimizing the brightness and surface chemistry of cadmium-free QDots for them to replace currently used Cd2+-containing QDots.

Contaminant exposure of birds nesting in Green Bay, Wisconsin, USA

USGS Publications Warehouse

Custer, Thomas W.; Dummer, Paul M.; Custer, Christine M.; Franson, J. Christian; Jones, Michael

2014-01-01

In earlier studies, elevated concentrations of polychlorinated biphenyl (PCB) and p,p'-dichlorodiphenyldichloroethylene (DDE) were reported in double-crested cormorant (Phalacrocorax auritus) eggs and tree swallow (Tachycineta bicolor) eggs and nestlings collected from lower Green Bay (WI, USA) in 1994 and 1995 and black-crowned night-heron (Nycticorax nycticorax) eggs collected in 1991. Comparable samples collected in 2010 and 2011 indicated that concentrations of PCBs were 35%, 62%, 70%, and 88% lower than in the early 1990s in tree swallow eggs, tree swallow nestlings, double-crested cormorant eggs, and black-crowned night-heron eggs, respectively; concentrations of DDE were 47%, 43%, 51%, and 80% lower, respectively. These declines are consistent with regional contaminant trends in other species. Concentrations of PCBs were higher in herring gull (Larus argentatus) than in black-crowned night-heron eggs collected from Green Bay in 2010; PCB concentrations in double-crested cormorant and tree swallow eggs were intermediate. The estimated toxicity of the PCB mixture in eggs of the insectivorous tree swallow was the equal to or greater than toxicity in the 3 piscivorous bird species. A multivariate analysis indicated that the composition percentage of lower-numbered PCB congeners was greater in eggs of the insectivorous tree swallow than in eggs of the 3 piscivorous species nesting in Green Bay. Dioxin and furan concentrations and the toxicity of these chemicals were also higher in tree swallows than these other waterbird species nesting in Green Bay.

Effects of humic acid on the interactions between zinc oxide nanoparticles and bacterial biofilms

DOE PAGES

Ouyang, Kai; Yu, Xiao-Ying; Zhu, Yunlin; ...

2017-08-26

The effects of humic acid (HA) on interactions between ZnO nanoparticles (ZnO NPs) and Pseudomonas putida KT2440 biofilms at different maturity stages were investigated. Three stages of biofilm development were identified according to bacterial adenosine triphosphate (ATP) activity associated with biofilm development process. In the initial biofilm stage 1, the ATP content of bacteria was reduced by more than 90% when biofilms were exposed to ZnO NPs. But, in the mature biofilm stages 2 and 3, the ATP content was only slightly decreased. Biofilms at stage 3 exhibited less susceptibility to ZnO NPs than biofilms at stage 2. These resultsmore » suggest that more mature biofilms have a significantly higher tolerance to ZnO NPs compared to young biofilms. In addition, biofilms with intact extracellular polymeric substances (EPS) showed higher tolerance to ZnO NPs than those without EPS, indicating that EPS play a key role in alleviating the toxic effects of ZnO NPs. In both pure ZnO NPs and ZnO-HA mixtures, dissolved Zn 2+ originating from the NPs significantly contributed to the overall toxicity. The presence of HA dramatically decreased the toxicity of ZnO NPs due to the binding of Zn 2+ on HA. Furthermore, the combined results from this work suggest that the biofilm maturity stages and environmental constituents (such as humic acid) are important factors to consider when evaluating potential risks of NPs to ecological systems.« less

Toxicological effects of cationic nanobubbles on the liver and kidneys: biomarkers for predicting the risk.

PubMed

Pan, Tai-Long; Wang, Pei-Wen; Al-Suwayeh, Saleh A; Huang, Yi-Ju; Fang, Jia-You

2012-11-01

Nanobubbles with acoustical activity are used as both diagnostic and therapeutic carriers for detecting and treating diseases. We aimed to prepare nanobubbles and assess toxic responses to them in the liver and kidneys. The cytotoxicity of nanobubbles was determined by examining the viability of liver (HepG2) and kidney (293T) cell lines after a 24-h treatment at various concentrations (0.01-2%). Toxic effects of different formulations were compared by determining functional markers such as γ-glutamyl transferase (γ-GT) and blood urea nitrogen (BUN) after intravenous administration of nanobubbles. Cationic nanobubbles caused concentration-dependent cytotoxicity against cultured cells with a more significant effect in the liver than in the kidneys. A significant reduction of viability was revealed at a concentration as low as 0.1%. Cational systems with soyaethyl morpholinium ethosulfate (SME) exhibited the greatest γ-GT level at 6-fold higher than the control. Immunohistochemistry detected liver fibrosis and inflammation with nanobubbles treatment, especially SME-containing ones at higher doses. According to plasma proteomic profiles, gelsolin and fetuin-B were significantly downregulated 3-fold in the high-dose SME-treated group. Transthyretin decreased by 6-fold in this group. The fibrinogen gamma chain expression was highly elevated. The results suggest that these protein biomarkers are sensitive for assessing the risk of nanobubble exposure. This study is the first to systematically evaluate the possible toxicity of nanobubbles in the liver and kidneys. Copyright © 2012 Elsevier Ltd. All rights reserved.

Air toxics concentrations, source identification, and health risks: An air pollution hot spot in southwest Memphis, TN

NASA Astrophysics Data System (ADS)

Jia, Chunrong; Foran, Jeffery

2013-12-01

Southwest Memphis is a residential region surrounded by fossil fuel burning, steel, refining, and food processing industries, and considerable mobile sources whose emissions may pose adverse health risks to local residents. This study characterizes cancer and non-cancer risks resulting from exposure to ambient air toxics in southwest Memphis. Air toxics samples were collected at a central location every 6 days from June 5, 2008 to January 8, 2010. Volatile organic compounds (VOCs) were collected in evacuated stainless-steel canisters and aldehydes by DNPH cartridges, and samples were analyzed for 73 target compounds. A total of 60 compounds were detected and 39 were found in over 86% of the samples. Mean concentrations of many compounds were higher than those measured in many industrial communities throughout the U.S. The cumulative cancer risk associated with exposure to 13 carcinogens found in southwest Memphis air was 2.3 × 10-4, four times higher than the national average of 5.0 × 10-5. Three risk drivers were identified: benzene, formaldehyde, and acrylonitrile, which contributed 43%, 19%, and 14% to the cumulative risk, respectively. This is the first field study to confirm acrylonitrile as a potential risk driver. Mobile, secondary, industrial, and background sources contributed 57%, 24%, 14%, and 5% of the risk, respectively. The results of this study indicate that southwest Memphis, a region of significant income, racial, and social disparities, is also a region under significant environmental stress compared with surrounding areas and communities.

Different modes of TiO2 uptake by Ceriodaphnia dubia: relevance to toxicity and bioaccumulation.

PubMed

Dalai, Swayamprava; Iswarya, V; Bhuvaneshwari, M; Pakrashi, Sunandan; Chandrasekaran, N; Mukherjee, Amitava

2014-07-01

The extensive environmental exposure of engineered metal oxide nanoparticles (NPs) may result in their bioaccumulation in aquatic organisms leading to their biotransfer in a food chain through various routes in a freshwater ecosystem. The present study focuses on the possible modes of TiO2 NP trophic transfer to Ceriodaphnia dubia, in presence and/absence of its diet, Scenedesmus obliquus (primary producer). The acute exposure studies (48h) were designed to have daphnids exposed to (i) the free NPs, (ii) both the free and the algae-borne NPs; and (iii) only the algae-borne NPs in separate tests to understand the possible routes of NP transfer. The dietary uptake of TiO2 NPs (algae-borne) was found to be the primary route for NP biotransfer with ∼70% of total NP uptake. Interestingly, in a separate study it was noticed that the NPs coated with algal exudates were easily taken up by daphnids as compared to pristine NPs of same concentrations, leading to their higher bioaccumulation. A chronic toxicity study, where daphnids were exposed to both free and algae-borne NPs for 21 days was undertaken to comprehend the TiO2 NP effect on daphnia growth and reproduction upon chronic exposure and also the bioaccumulation potential. Both acute and chronic exposure studies suggested higher bioaccumulation of TiO2 in daphnids when the particles were less toxic to the diet (algae). Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of humic acid on the interactions between zinc oxide nanoparticles and bacterial biofilms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ouyang, Kai; Yu, Xiao-Ying; Zhu, Yunlin

The effects of humic acid (HA) on interactions between ZnO nanoparticles (ZnO NPs) and Pseudomonas putida KT2440 biofilms at different maturity stages were investigated. Three stages of biofilm development were identified according to bacterial adenosine triphosphate (ATP) activity associated with biofilm development process. In the initial biofilm stage 1, the ATP content of bacteria was reduced by more than 90% when biofilms were exposed to ZnO NPs. However, in the mature biofilm stages 2 and 3, the ATP content was only slightly decreased. Biofilms at stage 3 exhibited less susceptibility to ZnO NPs than biofilms at stage 2. These resultsmore » suggest that more mature biofilms have a significantly higher tolerance to ZnO NPs compared to young biofilms. In addition, biofilms with intact extracellular poly-meric substances (EPS) showed higher tolerance to ZnO NPs than those without EPS, indicating that EPS play a key role in alleviating the toxic effects of ZnO NPs. In both pure ZnO NPs and ZnO-HA mixtures, dissolved Zn 2+ originating from the NPs significantly contributed to the overall toxicity. The presence of HA dramatically decreased the toxicity of ZnO NPs due to the binding of Zn 2+ on HA. The combined results from this work suggest that the biofilm maturity stages and environmental constituents (such as humic acid) are important factors to consider when evaluating potential risks of NPs to ecological systems.« less

Effects of humic acid on the interactions between zinc oxide nanoparticles and bacterial biofilms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ouyang, Kai; Yu, Xiao-Ying; Zhu, Yunlin

The effects of humic acid (HA) on interactions between ZnO nanoparticles (ZnO NPs) and Pseudomonas putida KT2440 biofilms at different maturity stages were investigated. Three stages of biofilm development were identified according to bacterial adenosine triphosphate (ATP) activity associated with biofilm development process. In the initial biofilm stage 1, the ATP content of bacteria was reduced by more than 90% when biofilms were exposed to ZnO NPs. But, in the mature biofilm stages 2 and 3, the ATP content was only slightly decreased. Biofilms at stage 3 exhibited less susceptibility to ZnO NPs than biofilms at stage 2. These resultsmore » suggest that more mature biofilms have a significantly higher tolerance to ZnO NPs compared to young biofilms. In addition, biofilms with intact extracellular polymeric substances (EPS) showed higher tolerance to ZnO NPs than those without EPS, indicating that EPS play a key role in alleviating the toxic effects of ZnO NPs. In both pure ZnO NPs and ZnO-HA mixtures, dissolved Zn 2+ originating from the NPs significantly contributed to the overall toxicity. The presence of HA dramatically decreased the toxicity of ZnO NPs due to the binding of Zn 2+ on HA. Furthermore, the combined results from this work suggest that the biofilm maturity stages and environmental constituents (such as humic acid) are important factors to consider when evaluating potential risks of NPs to ecological systems.« less

Contaminant exposure of birds nesting in Green Bay, Wisconsin, USA.

PubMed

Custer, Thomas W; Dummer, Paul M; Custer, Christine M; Franson, J Christian; Jones, Michael

2014-08-01

In earlier studies, elevated concentrations of polychlorinated biphenyl (PCB) and p,p'-dichlorodiphenyldichloroethylene (DDE) were reported in double-crested cormorant (Phalacrocorax auritus) eggs and tree swallow (Tachycineta bicolor) eggs and nestlings collected from lower Green Bay (WI, USA) in 1994 and 1995 and black-crowned night-heron (Nycticorax nycticorax) eggs collected in 1991. Comparable samples collected in 2010 and 2011 indicated that concentrations of PCBs were 35%, 62%, 70%, and 88% lower than in the early 1990s in tree swallow eggs, tree swallow nestlings, double-crested cormorant eggs, and black-crowned night-heron eggs, respectively; concentrations of DDE were 47%, 43%, 51%, and 80% lower, respectively. These declines are consistent with regional contaminant trends in other species. Concentrations of PCBs were higher in herring gull (Larus argentatus) than in black-crowned night-heron eggs collected from Green Bay in 2010; PCB concentrations in double-crested cormorant and tree swallow eggs were intermediate. The estimated toxicity of the PCB mixture in eggs of the insectivorous tree swallow was the equal to or greater than toxicity in the 3 piscivorous bird species. A multivariate analysis indicated that the composition percentage of lower-numbered PCB congeners was greater in eggs of the insectivorous tree swallow than in eggs of the 3 piscivorous species nesting in Green Bay. Dioxin and furan concentrations and the toxicity of these chemicals were also higher in tree swallows than these other waterbird species nesting in Green Bay. Published 2014 Wiley Periodicals, Inc.

Effects of humic acid on the interactions between zinc oxide nanoparticles and bacterial biofilms.

PubMed

Ouyang, Kai; Yu, Xiao-Ying; Zhu, Yunlin; Gao, Chunhui; Huang, Qiaoyun; Cai, Peng

2017-12-01

The effects of humic acid (HA) on interactions between ZnO nanoparticles (ZnO NPs) and Pseudomonas putida KT2440 biofilms at different maturity stages were investigated. Three stages of biofilm development were identified according to bacterial adenosine triphosphate (ATP) activity associated with biofilm development process. In the initial biofilm stage 1, the ATP content of bacteria was reduced by more than 90% when biofilms were exposed to ZnO NPs. However, in the mature biofilm stages 2 and 3, the ATP content was only slightly decreased. Biofilms at stage 3 exhibited less susceptibility to ZnO NPs than biofilms at stage 2. These results suggest that more mature biofilms have a significantly higher tolerance to ZnO NPs compared to young biofilms. In addition, biofilms with intact extracellular polymeric substances (EPS) showed higher tolerance to ZnO NPs than those without EPS, indicating that EPS play a key role in alleviating the toxic effects of ZnO NPs. In both pure ZnO NPs and ZnO-HA mixtures, dissolved Zn 2+ originating from the NPs significantly contributed to the overall toxicity. The presence of HA dramatically decreased the toxicity of ZnO NPs due to the binding of Zn 2+ on HA. The combined results from this work suggest that the biofilm maturity stages and environmental constituents (such as humic acid) are important factors to consider when evaluating potential risks of NPs to ecological systems. Copyright © 2017 Elsevier Ltd. All rights reserved.

Methylboronic acid fertilization alleviates boron deficiency symptoms in Arabidopsis thaliana.

PubMed

Duran, Catherine; Arce-Johnson, Patricio; Aquea, Felipe

2018-07-01

Our results showed that methylboronic acid is capable of alleviating boron deficiency, enhancing plant growth, and is less toxic than boric acid at higher concentrations. Boron is an essential plant micronutrient and its deficiency occurs in several regions globally, resulting in impaired plant growth. Boron fertilization is a common agricultural practice, but the action range of boron is narrow, sharply transitioning from deficiency to toxicity. Boric acid (BA) is the most common chemical form used in agriculture. In this work, we describe that methylboronic acid (MBA) is capable of alleviating boron deficiency in Arabidopsis. MBA is a boronic acid, but does not naturally occur in soils, necessitating synthesis. Other boronic acids have been described as boron competitors in plants, inhibiting auxin biosynthesis and root development. MBA is more water-soluble than BA and delivers the same amount of boron per molecule. We observed that Arabidopsis seedlings grown in the presence of MBA presented higher numbers of lateral roots and greater main root length compared to plants grown in BA. In addition, root hair length and leaf surface area were increased using MBA as a boron fertilizer. Finally, MBA was less toxic than BA at high concentrations, producing a slight reduction in the main root length but no decrease in total chlorophyll. Our results open a new opportunity to explore the use of a synthetic form of boron in agriculture, providing a tool for future research for plant nutrition.

Toxicity profile and treatment delays in NOPHO ALL2008-comparing adults and children with Philadelphia chromosome-negative acute lymphoblastic leukemia.

PubMed

Toft, Nina; Birgens, Henrik; Abrahamsson, Jonas; Griškevičius, Laimonas; Hallböök, Helene; Heyman, Mats; Klausen, Tobias Wirenfeldt; Jónsson, Ólafur Gísli; Palk, Katrin; Pruunsild, Kaie; Quist-Paulsen, Petter; Vaitkeviciene, Goda; Vettenranta, Kim; Asberg, Ann; Helt, Louise Rold; Frandsen, Thomas; Schmiegelow, Kjeld

2016-02-01

Cure rates improve when adolescents and young adults with acute lymphoblastic leukemia (ALL) are treated according to pediatric protocols. Assumed risks of toxicities and associated delays in treatment have played a role in setting upper age limits. The aim of this study was to examine the toxicity profile and treatment delays in NOPHO ALL2008 comparing children and adults. We collected information on 19 treatment-related toxicities, systematically captured at 3-month intervals throughout therapy, and time intervals between 12 consecutive treatment phases for 1076 patients aged 1-45 yrs treated according to the Nordic/Baltic ALL2008 protocol. No adults died during induction. The duration of induction therapy and postinduction treatment phases did not differ between children and adults, except for patients 18-45 yrs being significantly delayed during two of nine high-risk blocks (median number of days for patients 1-9, 10-17, and 18-45 yrs; the glucocorticosteroid/antimetabolite-based block B1: 24, 26, and 29 d, respectively, P = 0.001, and Block 5 (in most cases also a B block): 29, 29, and 37 d, respectively, P = 0.02). A higher incidence of thrombosis with increasing age was found; highest odds ratio 5.4 (95% CI: (2.6;11.0)) for patients 15-17 yrs compared with children 1-9 yrs (P < 0.0001). Risk of avascular osteonecrosis was related to age with the highest OR for patients 10-14 yrs (OR = 10.4 (95% CI: (4.4;24.9)), P < 0.0001). Adults followed and tolerated the NOPHO ALL2008 protocol virtually as well as children, although thrombosis and avascular osteonecrosis was most common among adolescents. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Parental dietary seleno-L-methionine exposure and resultant offspring developmental toxicity

PubMed Central

Chernick, Melissa; Ware, Megan; Albright, Elizabeth; Kwok, Kevin W.H.; Dong, Wu; Zheng, Na; Hinton, David E.

2015-01-01

Selenium (Se) leaches into water from agricultural soils and from storage sites for coal fly ash. Se toxicity causes population and community level effects in fishes and birds. We used the laboratory aquarium model fish, Japanese medaka (Oryzias latipes), an asynchronous breeder, to determine aspects of uptake in adults and resultant developmental toxicity in their offspring. The superior imaging properties of the model enabled detailed descriptions of phenotypic alterations not commonly reported in the existing Se literature. Adult males and females in treatment groups were exposed, separately and together, to a dry diet spiked with 0, 12.5, 25, or 50 µg/g (dry weight) seleno-L-methionine (SeMet) for 6 days, and their embryo progeny collected for 5 days, maintained under controlled conditions and observed daily for hatchability, mortality and/or developmental toxicity. Sites of alteration included: craniofacial, pericardium and abdomen (Pc/Ab), notochord, gall bladder, spleen, blood, and swim bladder. Next, adult tissue Se concentrations (liver, skeletal muscle, ovary and testis) were determined and compared in treatment groups of bred and unbred individuals. No significant difference was found across treatment groups at the various SeMet concentrations; and, subsequent analysis compared exposed vs. control in each of the treatment groups at 10 dpf. Increased embryo mortality was observed in all treatment groups, compared to controls, and embryos had a decreased hatching rate when both parents were exposed. Exposure resulted in significantly more total altered phenotypes than controls. When altered phenotypes following exposure of both parents were higher than maternal only exposure, a male role was suggested. The comparisons between treatment groups revealed that particular types of phenotypic change may be driven by the sex of the exposed parent. Additionally, breeding reduced Se concentrations in some adult tissues, specifically the liver of exposed females and skeletal muscle of exposed males. Detailed phenotypic analysis of progeny from SeMet exposed parents should inform investigations of later life stages in an effort to determine consequences of early life exposure. PMID:26655662

Trace elements in blood of sea turtles Lepidochelys olivacea in the Gulf of California, Mexico.

PubMed

Zavala-Norzagaray, A A; Ley-Quiñónez, C P; Espinosa-Carreón, T L; Canizalez-Román, A; Hart, C E; Aguirre, A A

2014-11-01

This study determined the concentrations of heavy metals in blood collected from Pacific Ridley sea turtles (Lepidochelys olivacea) inhabiting the coast of Guasave, Mexico, in the Gulf of California. The highest reported metal concentration in blood was Zn, followed by Se. Of nonessential toxic metals, As was reported in higher percentage compared to Cd. The concentrations of metals detected were present as follows: Zn > Se > Mn > As > Ni > Cd > Cu. Cd concentration in blood is higher in our population in comparison with other populations of L. olivacea, and even higher in other species of sea turtles. Our study reinforces the usefulness of blood for the monitoring of the levels of contaminating elements, and is easily accessible and nonlethal for sea turtles.

Long-term Cosmetic Outcomes and Toxicities of Proton Beam Therapy Compared With Photon-Based 3-Dimensional Conformal Accelerated Partial-Breast Irradiation: A Phase 1 Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Galland-Girodet, Sigolène; Pashtan, Itai; MacDonald, Shannon M.

2014-11-01

Purpose: To present long-term outcomes of a prospective feasibility trial using either protons or 3-dimensional conformal photon-based (accelerated partial-breast irradiation [APBI]) techniques. Methods and Materials: From October 2003 to April 2006, 98 evaluable patients with stage I breast cancer were treated with APBI (32 Gy in 8 fractions given twice daily) on a prospective clinical trial: 19 with proton beam therapy (PBT) and 79 with photons or mixed photons/electrons. Median follow-up was 82.5 months (range, 2-104 months). Toxicity and patient satisfaction evaluations were performed at each visit. Results: At 7 years, the physician rating of overall cosmesis was good or excellent for 62% of PBTmore » patients, compared with 94% for photon patients (P=.03). Skin toxicities were more common for the PBT group: telangiectasia, 69% and 16% (P=.0013); pigmentation changes, 54% and 22% (P=.02); and other late skin toxicities, 62% and 18% (P=.029) for PBT and photons, respectively. There were no significant differences between the groups in the incidences of breast pain, edema, fibrosis, fat necrosis, skin desquamation, and rib pain or fracture. Patient-reported cosmetic outcomes at 7 years were good or excellent for 92% and 96% of PBT and photon patients, respectively (P=.95). Overall patient satisfaction was 93% for the entire cohort. The 7-year local failure rate for all patients was 6%, with 3 local recurrences in the PBT group (7-year rate, 11%) and 2 in photon-treated patients (4%) (P=.22). Conclusions: Local failure rates of 3-dimensional APBI and PBT were similar in this study. However, PBT, as delivered in this study, led to higher rates of long-term telangiectasia, skin color changes, and skin toxicities. We recommend the use of multiple fields and treatment of all fields per treatment session or the use of scanning techniques to minimize skin toxicity.« less

Shape-Related Toxicity of Titanium Dioxide Nanofibres

PubMed Central

Allegri, Manfredi; Bianchi, Massimiliano G.; Chiu, Martina; Varet, Julia; Costa, Anna L.; Ortelli, Simona; Blosi, Magda; Bussolati, Ovidio; Poland, Craig A.; Bergamaschi, Enrico

2016-01-01

Titanium dioxide (TiO2) nanofibres are a novel fibrous nanomaterial with increasing applications in a variety of fields. While the biological effects of TiO2 nanoparticles have been extensively studied, the toxicological characterization of TiO2 nanofibres is far from being complete. In this study, we evaluated the toxicity of commercially available anatase TiO2 nanofibres using TiO2 nanoparticles (NP) and crocidolite asbestos as non-fibrous or fibrous benchmark materials. The evaluated endpoints were cell viability, haemolysis, macrophage activation, trans-epithelial electrical resistance (an indicator of the epithelial barrier competence), ROS production and oxidative stress as well as the morphology of exposed cells. The results showed that TiO2 nanofibres caused a cell-specific, dose-dependent decrease of cell viability, with larger effects on alveolar epithelial cells than on macrophages. The observed effects were comparable to those of crocidolite, while TiO2 NP did not decrease cell viability. TiO2 nanofibres were also found endowed with a marked haemolytic activity, at levels significantly higher than those observed with TiO2 nanoparticles or crocidolite. Moreover, TiO2 nanofibres and crocidolite, but not TiO2 nanoparticles, caused a significant decrease of the trans-epithelial electrical resistance of airway cell monolayers. SEM images demonstrated that the interaction with nanofibres and crocidolite caused cell shape perturbation with the longest fibres incompletely or not phagocytosed. The expression of several pro-inflammatory markers, such as NO production and the induction of Nos2 and Ptgs2, was significantly increased by TiO2 nanofibres, as well as by TiO2 nanoparticles and crocidolite. This study indicates that TiO2 nanofibres had significant toxic effects and, for most endpoints with the exception of pro-inflammatory changes, are more bio-active than TiO2 nanoparticles, showing the relevance of shape in determining the toxicity of nanomaterials. Given that several toxic effects of TiO2 nanofibres appear comparable to those observed with crocidolite, the possibility that they exert length dependent toxicity in vivo seems worthy of further investigation. PMID:26999274

Risk of Severe Toxicity According to Site of Recurrence in Patients Treated With Stereotactic Body Radiation Therapy for Recurrent Head and Neck Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ling, Diane C.; Vargo, John A.; Ferris, Robert L.

Purpose: To report a 10-year update of our institutional experience with stereotactic body radiation therapy (SBRT) for reirradiation of locally recurrent head and neck cancer, focusing on predictors of toxicity. Methods and Materials: A retrospective review was performed on 291 patients treated with SBRT for recurrent, previously irradiated head and neck cancer between April 2002 and March 2013. Logistic regression analysis was performed to identify predictors of severe acute and late toxicity. Patients with <3 months of follow-up (n=43) or who died within 3 months of treatment (n=21) were excluded from late toxicity analysis. Results: Median time to death or last clinicalmore » follow-up was 9.8 months among the entire cohort and 53.1 months among surviving patients. Overall, 33 patients (11.3%) experienced grade ≥3 acute toxicity and 43 (18.9%) experienced grade ≥3 late toxicity. Compared with larynx/hypopharynx, treatment of nodal recurrence was associated with a lower risk of severe acute toxicity (P=.03), with no significant differences in severe acute toxicity among other sites. Patients treated for a recurrence in the larynx/hypopharynx experienced significantly more severe late toxicity compared with those with oropharyngeal, oral cavity, base of skull/paranasal sinus, salivary gland, or nodal site of recurrence (P<.05 for all). Sixteen patients (50%) with laryngeal/hypopharyngeal recurrence experienced severe late toxicity, compared with 6-20% for other sites. Conclusions: Salvage SBRT is a safe and effective option for most patients with previously irradiated head and neck cancer. However, patients treated to the larynx or hypopharynx experience significantly more late toxicity compared with others and should be carefully selected for treatment, with consideration given to patient performance status, pre-existing organ dysfunction, and goals of care. Treatment toxicity in these patients may be mitigated with more conformal plans to allow for increased sparing of adjacent normal tissues.« less

Toxicity of the pyrolysis products of spacecraft materials

NASA Technical Reports Server (NTRS)

Lawrence, W. H.

1974-01-01

A number of spacecraft construction materials are evaluated for the toxic effects of their thermodegradation products on rats. Pyrolysis toxicity testing of pyrolysate fumes establish carbon monoxide, carbon dioxide and hydrogen cyanide as the most common intoxicating agents. Generally, COHb levels of animals expiring in the test chamber suggest higher concentrations of CO are produced with larger samples of most materials.

Mixture toxicity of the anti-inflammatory drugs diclofenac, ibuprofen, naproxen, and acetylsalicylic acid.

PubMed

Cleuvers, Michael

2004-11-01

The ecotoxicity of the nonsteroidal anti-inflammatory drugs (NSAIDs) diclofenac, ibuprofen, naproxen, and acetylsalicylic acid (ASA) has been evaluated using acute Daphnia and algal tests. Toxicities were relatively low, with half-maximal effective concentration (EC50) values obtained using Daphnia in the range from 68 to 166 mg L(-1) and from 72 to 626 mg L(-1) in the algal test. Acute effects of these substances seem to be quite improbable. The quantitative structure-activity relationships (QSAR) approach showed that all substances act by nonpolar narcosis; thus, the higher the n-octanol/water partitioning coefficient (log Kow) of the substances, the higher is their toxicity. Mixture toxicity of the compounds could be accurately predicted using the concept of concentration addition. Toxicity of the mixture was considerable, even at concentrations at which the single substances showed no or only very slight effects, with some deviations in the Daphnia test, which could be explained by incompatibility of the very steep dose-response curves and the probit analysis of the data. Because pharmaceuticals in the aquatic environment occur usually as mixtures, an accurate prediction of the mixture toxicity is indispensable for environmental risk assessment.

Acute ecotoxicity bioassay using Dendrocephalus brasiliensis: alternative test species for monitoring of contaminants in tropical and subtropical freshwaters.

PubMed

Santos, Vanessa Santana Vieira; Campos, Carlos Fernando; de Campos Júnior, Edimar Olegário; Pereira, Boscolli Barbosa

2018-05-23

In International guidelines for standard ecotoxicological bioassays, Daphnia magna is the most applied microcrustacea for assessing toxicity of different pollutants. However, in research realized in tropical and subtropical areas, autochthonous species must be prioritized because they are adapted to the specificities of ecosystems. In this sense, the present study aimed to assess and compare (with D. magna) the sensitivity of the tropical species Dendrocephalus brasiliensis as alternative test species for monitoring of contaminants in tropical and subtropical freshwaters, by carrying out acute toxicity tests with different pollutants. According results, D. brasiliensis presented EC50-48 h values lower than D. magna for all substances tested, indicating higher sensitivity of the tropical organism in relation to the temperate organism. Furthermore, comparing the results obtained with data from other studies, D. brasiliensis is more sensitive to the chemicals tested than D. magna and has similar sensitivity to Pseudosida ramosa and Ceriodaphnia dubia, common species in tropical areas. In view of this, we suggest that D. brasiliensis can be used as alternative test species for monitoring of contaminants in tropical and subtropical freshwaters.

Time Course, Behavioral Safety, and Protective Efficacy of Centrally Active Reversible Acetylcholinesterase Inhibitors in Cynomolgus Macaques.

PubMed

Hamilton, Lindsey R; Schachter, Steven C; Myers, Todd M

2017-07-01

Galantamine hydrobromide and (-)huperzine A, centrally active reversible acetylcholinesterase inhibitors, are potentially superior to the current standard, pyridostigmine bromide, as a pretreatment for organophosphorus chemical warfare nerve agent intoxication. Galantamine, huperzine, and pyridostigmine were compared for time course of acetylcholinesterase inhibition in 12 cynomolgus macaques. Although both galantamine and huperzine shared a similar time course profile for acetylcholinesterase inhibition, huperzine was 88 times more potent than galantamine. The dose for 50% acetylcholinesterase inhibition (ID 50 ) was 4.1 ug/kg for huperzine, 362 ug/kg for galantamine, and 30.9 ug/kg for pyridostigmine. In a safety assessment, galantamine, huperzine, and pyridostigmine were examined using an operant time-estimation task. Huperzine and pyridostigmine were devoid of behavioral toxicity, whereas galantamine was behaviorally toxic at doses producing peak acetylcholinesterase inhibition of about 50% and higher. Following pretreatment with galantamine, huperzine or pyridostigmine, monkeys were challenged with the median lethal dose of soman at the time of peak acetylcholinesterase inhibition and evaluated for overt signs of soman toxicity (cholinergic crisis, convulsions). Both huperzine and galantamine were equally effective at preventing overt signs of soman toxicity, but neither drug was capable of preventing soman-induced neurobehavioral disruption. In contrast, three of four pyridostigmine-pretreated animals exposed to soman exhibited convulsions and required therapy. Full functional recovery required 3-16 days. The degree of acetylcholinesterase inhibition was lower for pyridostigmine, but rates of recovery of acetylcholinesterase activity following soman challenge were comparable for all drug pretreatments. Huperzine may be the more promising centrally active reversible acetylcholinesterase inhibitor due to its greater potency and superior safety profile.

Silver nanocrystallites: Facile biofabrication using Shewanella oneidensis, and an evaluation of their comparative toxicity on Gram-negative and Gram-positive bacteria

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suresh, Anil K; Wang, Wei; Pelletier, Dale A

Microorganisms have long been known to develop resistance to metal ions either by sequestering metals inside the cell or by effluxing them into the extracellular media. Here we report the biosynthesis of extracellular silver based single nanocrystallites of well-defined composition and homogeneous morphology utilizing the -proteobacterium, Shewanella oneidensis strain MR-1, upon incubation with an aqueous solution of silver nitrate. Further characterization of these particles revealed that the crystals consist of small, reasonably monodispersed spheres in the size range 2 11 nm (with an average of 4 1.5 nm). The bactericidal effect of these biologically synthesized silver nanoparticles (biogenic-Ag) are comparedmore » to similar chemically synthesized nanoparticles (colloidal silver [colloidal-Ag] and oleate capped silver [oleate-Ag]). The determination of the bactericidal effect of these different silver nanoparticles was assessed using both Gram-negative (E. coli) and Gram-positive (B. subtilis) bacteria and based on the diameter of the inhibition zone in disc diffusion tests, minimum inhibitory concentrations, Live/Dead staining assays, and atomic force microscopy. From a toxicity perspective, a clear synthesis procedure, and a surface coat- and strain-dependent inhibition were observed for silver nanoparticles. Biogenic-Ag was found to be of higher toxicity when compared to colloidal-Ag for both E. coli and B. subtilis. E. coli was found to be more resistant to either of these nanoparticles than B. subtilis. In contrast, Oleate-Ag was not toxic to either of the bacteria. These findings have important implications for the potential uses of Ag nanomaterials and for their fate in biological and environmental systems.« less

Differences between organophosphorus insecticides in human self-poisoning: a prospective cohort study.

PubMed

Eddleston, Michael; Eyer, Peter; Worek, Franz; Mohamed, Fahim; Senarathna, Lalith; von Meyer, Ludwig; Juszczak, Edmund; Hittarage, Ariyasena; Azhar, Shifa; Dissanayake, Wasantha; Sheriff, M H Rezvi; Szinicz, Ladislaus; Dawson, Andrew H; Buckley, Nick A

Although more than 100 organophosphorus insecticides exist, organophosphorus poisoning is usually regarded as a single entity, distinguished only by the compound's lethal dose in animals. We aimed to determine whether the three most common organophosphorus insecticides used for self-poisoning in Sri Lanka differ in the clinical features and severity of poisoning they cause. We prospectively studied 802 patients with chlorpyrifos, dimethoate, or fenthion self-poisoning admitted to three hospitals. Blood cholinesterase activity and insecticide concentration were measured to determine the compound and the patients' response to insecticide and therapy. We recorded clinical outcomes for each patient. Compared with chlorpyrifos (35 of 439, 8.0%), the proportion dying was significantly higher with dimethoate (61 of 264, 23.1%, odds ratio [OR] 3.5, 95% CI 2.2-5.4) or fenthion (16 of 99, 16.2%, OR 2.2, 1.2-4.2), as was the proportion requiring endotracheal intubation (66 of 439 for chlorpyrifos, 15.0%; 93 of 264 for dimethoate, 35.2%, OR 3.1, 2.1-4.4; 31 of 99 for fenthion, 31.3%, 2.6, 1.6-4.2). Dimethoate-poisoned patients died sooner than those ingesting other pesticides and often from hypotensive shock. Fenthion poisoning initially caused few symptoms but many patients subsequently required intubation. Acetylcholinesterase inhibited by fenthion or dimethoate responded poorly to pralidoxime treatment compared with chlorpyrifos-inhibited acetylcholinesterase. Organophosphorus insecticide poisoning is not a single entity, with substantial variability in clinical course, response to oximes, and outcome. Animal toxicity does not predict human toxicity since, although chlorpyrifos is generally the most toxic in rats, it is least toxic in people. Each organophosphorus insecticide should be considered as an individual poison and, consequently, patients might benefit from management protocols developed for particular organophosphorus insecticides.

The protective effect of royal jelly on chronic lambda-cyhalothrin toxicity: serum biochemical parameters, lipid peroxidation, and genotoxic and histopathological alterations in swiss albino mice.

PubMed

Cavuşoğlu, Kültiğin; Yapar, Kürşad; Oruç, Ertan; Yalçın, Emine

2011-10-01

The present study was undertaken to investigate the protective effect of royal jelly (RJ) against toxicity induced by a synthetic pyrethroid insecticide, lambda-cyhalothrin (LCT), in Swiss albino mice. Animals were randomly divided into six groups of six animals each. The control group received distilled water alone, whereas mice in the treatment groups received RJ alone (100 or 250 mg/kg of body weight), LCT alone (668 ppm), or RJ+LCT for 21 days. All mice (100%) survived until the end of experiment and were sacrificed at the end of 24 hours. Blood, bone marrow, and liver and kidney tissues were analyzed for aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), creatinine, malondialdehyde (MDA), and reduced glutathione (GSH) levels and micronucleus (MN) frequency, chromosomal aberrations (CAs), and pathological damages. Serum AST, ALT, BUN, and creatinine levels were elevated in mice treated with LCT alone compared with the other tested groups (P<.05). LCT-induced oxidative damage caused a significant decrease in GSH levels and a significant rise in MDA levels of liver and kidney tissues. LCT alone-treated mice presented higher frequencies (P<.05) of MNs, CAs, and abnormal metaphases compared with the controls; moreover, the mitotic index was lower than in controls (P<.05). Oral treatment with RJ significantly ameliorated the indices of hepatotoxicity, nephrotoxicity, lipid peroxidation, and genotoxicity induced by LCT. Both doses of RJ tested provided significant protection against LCT-induced toxicity, and its strongest effect was observed at the dose level of 250 mg/kg of body weight. In vivo results suggest that RJ is a potent antioxidant against LCT-induced toxicity, and its protective effect is dose dependent.

Magnitude of benefit for adjuvant radiotherapy following minimally invasive surgery in intermediate to high risk HPV-positive oropharyngeal squamous cell carcinoma.

PubMed

Pasalic, Dario; Funk, Ryan K; García, Joaquín J; Price, Daniel L; Price, Katharine A; Harmsen, William S; Patel, Samir H; Young, Geoffrey D; Foote, Robert L; Moore, Eric J; Ma, Daniel J

2018-07-01

To determine the outcomes and toxicities of minimally-invasive surgery with adjuvant intensity-modulated radiotherapy +/- chemotherapy (AT) compared to definitive surgical therapy (ST) in a contemporary cohort of HPV-positive oropharyngeal squamous cell carcinoma (OPSCC). From 2005 to 2013, a consecutive cohort of 190 HPV-positive OPSCC patients was retrospectively reviewed from multi-institutional databases maintained by the Departments of Otorhinolaryngology and Radiation Oncology. A total of 116 AT patients and 42 ST patients with intermediate or high risk pathologic features were included in the final analysis. All patients received minimally invasive surgery. Time to recurrence and time to death from the onset of surgery were evaluated. Toxicity data collected included dysphagia or xerostomia requiring feeding tube placement >6 months, or mandibular osteonecrosis requiring surgery or hyperbaric oxygen. All AT patients received IMRT to a median dose of 60 Gy. Chemotherapy delivered to 67.2% of AT patients. AT group included more high-risk patients given higher nodal classification (p = 0.005) and extracapsular extension (p = 0.0005). AT improved disease-free survival (HR 2.77, CI 1.22-6.28; p = 0.02) and local-regional control (HR 14.83, CI 3.240-67.839; p = 0.001). Disease-free survival with AT and tumor extracapsular extension was improved when compared to ST (HR of 4.34, CI 1.540-12.213; p = 0.006). Dysphagia or mandibular osteonecrosis toxicity after AT vs. ST of 19.0% vs. 2.4%. AT improved local-regional control and disease-free survival but was associated with greater toxicity. The recurrence benefit was most pronounced in tumors with extracapsular extension. Copyright © 2018 Elsevier Ltd. All rights reserved.

Chemoradionuclide Therapy with 186Re-Labeled Liposomal Doxorubicin: Toxicity, Dosimetry, and Therapeutic Response

PubMed Central

Soundararajan, Anuradha; Bao, Ande; Phillips, William T.; McManus, Linda M.

2011-01-01

Abstract This study was performed to determine the maximum tolerated dose (MTD) and therapeutic effects of rhenium-186 (186Re)-labeled liposomal doxorubicin (Doxil), investigate associated toxicities, and calculate radiation absorbed dose in head and neck tumor xenografts and normal organs. Doxil and control polyethylene glycol (PEG)-liposomes were labeled using 186Re-N,N-bis(2-mercaptoethyl)-N′,N′-diethylethylenediamine (BMEDA) method. Tumor-bearing rats received either no therapy (n=6), intravenous Doxil (n=4), or escalating radioactivity of 186Re-Doxil (185–925 MBq/kg) or 186Re-PEG-liposomes (1110–1665 MBq/kg) and were monitored for 28 days. Based on body weight loss and systemic toxicity, MTD for 186Re-Doxil and 186Re-PEG-liposomes were established at injected radioactivity/body weight of 740 and 1480 MBq/kg, respectively. 186Re-injected radioactivity/body weight for therapy studies was determined to be 555 MBq/kg for 186Re-Doxil and 1295 MBq/kg for 186Re-PEG-liposomes. All groups recovered from their body weight loss, leucopenia, and thrombocytopenia by 28 days postinjection. Normalized radiation absorbed dose to tumor was significantly higher for 186Re-Doxil (0.299±0.109 Gy/MBq) compared with 186Re-PEG-liposomes (0.096±0.120 Gy/MBq) (p<0.05). In a separate therapy study, tumor volumes were significantly smaller for 186Re-Doxil (555 MBq/kg) compared with 186Re-PEG-liposomes (1295 MBq/kg) (p<0.01) at 42 days postinjection. In conclusion, combination chemoradionuclide therapy with 186Re-Doxil has promising potential, because good tumor control was achieved with limited associated toxicity. PMID:21834653

Combined effects of warming and acidification on accumulation and elimination dynamics of paralytic shellfish toxins in mussels Mytilus galloprovincialis.

PubMed

Braga, Ana C; Camacho, Carolina; Marques, António; Gago-Martínez, Ana; Pacheco, Mário; Costa, Pedro R

2018-07-01

Harmful algal blooms (HAB) have been increasing in frequency and intensity most likely due to changes on global conditions, which constitute a significant threat to wild shellfish and its commercial farming. This study evaluated the impact of increasing seawater temperature and acidification on the accumulation/elimination dynamics of HAB-toxins in shellfish. Mytilus galloprovincialis were acclimated to four environmental conditions simulating different climate change scenarios: i) current conditions, ii) warming, iii) acidification and iv) interaction of warming with acidification. Once acclimated, mussels were exposed to the paralytic shellfish toxins (PSTs) producing dinoflagellate Gymnodinium catenatum for 5 days and to non-toxic diet during the subsequent 10 days. High toxicity levels (1493 µg STX eq. kg -1 ) exceeding the safety limits were determined under current conditions at the end of the uptake period. Significantly lower PSP toxicity levels were registered for warming- and acidification-acclimated mussels (661 and 761 µg STX eq. kg -1 ). The combined effect of both warming and acidification resulted in PSP toxicity values slightly higher (856 μg STX eq. kg -1 ). A rapid decrease of toxicity was observed in mussels at the current conditions after shifting to a non-toxic diet, which was not noticed under the predicted climate change scenarios. Variability of each PST analogue, measured throughout the experiment, highlighted different mechanisms are associated with changes of each environmental factor, although both resulting in lower toxicity. Warming-acclimated mussels showed lower accumulation/elimination rates, while acidification-acclimated mussels showed higher capability to accumulate toxins, but also a higher elimination rate preventing high toxicity levels. As different mechanisms are triggered by warming and acidification, their combined effect not leads to a synergism of their individual effects. The present work is the first assessing the combined effect of climate change drivers on accumulation/elimination of PSTs, in mussels, indicating that warming and acidification may lead to lower toxicity values but longer toxic episodes. PSTs are responsible for the food poisoning syndrome, paralytic shellfish poisoning (PSP) in humans. This study can be considered as the first step to build models for predicting shellfish toxicity under climate change scenarios. Copyright © 2018 Elsevier Inc. All rights reserved.

Late Urinary Side Effects 10 Years After Low-Dose-Rate Prostate Brachytherapy: Population-Based Results From a Multiphysician Practice Treating With a Standardized Protocol and Uniform Dosimetric Goals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keyes, Mira, E-mail: mkeyes@bccancer.bc.ca; Miller, Stacy; Pickles, Tom

2014-11-01

Purpose: To determine late urinary toxicity (>12 months) in a large cohort of uniformly treated low-dose-rate prostate brachytherapy patients. Methods and Materials: From 1998 to 2009, 2709 patients with National Comprehensive Cancer Network–defined low-risk and low-tier intermediate-risk prostate cancer were treated with Iodine 125 ({sup 125}I) low-dose-rate prostate brachytherapy; 2011 patients with a minimum of 25 months of follow-up were included in the study. Baseline patients, treatment, implant factors, and late urinary toxicity (Radiation Therapy Oncology Group [RTOG] grading system and International Prostate Symptom Score [IPSS]) were recorded prospectively. Time to IPSS resolution, late RTOG genitourinary toxicity was examined with Kaplan-Meier andmore » log-rank tests. Cox proportional hazards regression was done for individual covariates and multivariable models. Results: Median follow-up was 54.5 months (range, 2-13 years). Actuarial toxicity rates reached 27% and 10% (RTOG ≥2 and ≥3, respectively) at 9-13 years. Symptoms resolved quickly in the majority of patients (88% in 6-12 months). The prevalence of RTOG 0, 1, 2, 3, and 4 toxicity with a minimum of 7 years' follow-up was 70%, 21%, 6.4%, 2.3%, and 0.08%, respectively. Patients with a larger prostate volume, higher baseline IPSS, higher D90, acute toxicity, and age >70 years had more late RTOG ≥2 toxicity (all P≤.02). The IPSS resolved slower in patients with lower baseline IPSS and larger ultrasound prostate volume, those not receiving androgen deprivation therapy, and those with higher D90. The crude rate of RTOG 3 toxicity was 6%. Overall the rate of transurethral resection of the prostate was 1.9%; strictures, 2%; incontinence, 1.3%; severe symptoms, 1.8%; late catheterization, 1.3%; and hematuria, 0.8%. The majority (80%) resolved their symptoms in 6-12 months. Conclusion: Long-term urinary toxicity after brachytherapy is low. Although actuarial rates increase with longer follow-up (27% RTOG 2 and 10% RTOG 3 at 13 years), symptoms resolve relatively quickly; between 5 and 13 years' follow-up, >90% of patients have minimal urinary toxicity. Refining patient selection criteria, planning, and treatment delivery may further reduce toxicity.« less

Elemental selenium at nano size possesses lower toxicity without compromising the fundamental effect on selenoenzymes: comparison with selenomethionine in mice.

PubMed

Wang, Huali; Zhang, Jinsong; Yu, Hanqing

2007-05-15

Glutathione peroxidase and thioredoxin reductase are major selenoenzymes through which selenium exerts powerful antioxidant effects. Selenium also elicits pro-oxidant effects at toxic levels. The antioxidant and pro-oxidant effects, or bioavailability and toxicity, of selenium depend on its chemical form. Selenomethionine is considered to be the most appropriate supplemental form due to its excellent bioavailability and lower toxicity compared to various selenium compounds. The present studies reveal that, compared with selenomethionine, elemental selenium at nano size (Nano-Se) possesses equal efficacy in increasing the activities of glutathione peroxidase and thioredoxin reductase but has much lower toxicity as indicated by median lethal dose, acute liver injury, and short-term toxicity. Our results suggest that Nano-Se can serve as an antioxidant with reduced risk of selenium toxicity.

Assessment of potential toxicity of a smokeless tobacco product (naswar) available on the Pakistani market.

PubMed

Zakiullah; Saeed, Muhammad; Muhammad, Naveed; Khan, Saeed Ahmad; Gul, Farah; Khuda, Fazli; Humayun, Muhammad; Khan, Hamayun

2012-07-01

'Naswar' is a smokeless tobacco product (STP) widely used in Pakistan. It has been correlated with oral and oesophageal cancer in recent clinical studies. The toxic effects associated with STPs have been associated with trace level contaminants present in these products. The toxin levels of Pakistani naswar are reported for the first time in this study. A total of 30 Pakistani brands of naswar were tested for a variety of toxic constituents and carcinogens such as cadmium, arsenic, lead and other carcinogenic metals, nitrite and nitrate, and nicotine and pH. The average values of all the toxins studied were well above their allowable limits, making the product a health risk for consumers. Calculated lifetime cancer risk from cadmium and lead was 1 lac (100,000) to 10 lac (1,000,000) times higher than the minimum 10E-4 (0.00001) to 10E-6 (0.000001), which is the 'target range' for potentially hazardous substances, according to the US Environmental Protection Agency. Similarly, the level of arsenic was in the range of 0.15 to 14.04 μg/g, the average being 1.25 μg/g. The estimated average bioavailable concentration of arsenic is 0.125-0.25 μg/g, which is higher than the allowable standard of 0.01 μg/g. Similarly, the average minimum daily intake of chromium and nickel was 126.97 μg and 122.01 μg, as compared to allowable 30-35 μg and 35 μg, respectively; a 4-5 times higher exposure. However, beryllium was not detected in any of the brands studied. The pH was highly basic, averaging 8.56, which favours the formation of tobacco specific amines thus making the product potentially toxic. This study validates clinical studies correlating incidence of cancer with naswar use in Pakistan. This study shows that the production, packaging, sale and consumption of naswar should be regulated so as to protect the public from the health hazards associated with its consumption.

The neglected nano-specific toxicity of ZnO nanoparticles in the yeast Saccharomyces cerevisiae

PubMed Central

Zhang, Weicheng; Bao, Shaopan; Fang, Tao

2016-01-01

Nanoparticles (NPs) with unique physicochemical properties induce nano-specific (excess) toxicity in organisms compared with their bulk counterparts. Evaluation and consideration of nano-specific toxicity are meaningful for the safe design and environmental risk assessment of NPs. However, ZnO NPs have been reported to lack excess toxicity for diverse organisms. In the present study, the nano-specific toxicity of ZnO NPs was evaluated in the yeast Saccharomyces cerevisiae. Nano-specific toxicity of ZnO NPs was not observed in the wild type yeast. However, the ZnO NPs induced very similar nano-specific toxicities in the three mutants with comparable log Te (particle) values (0.64 vs 0.65 vs 0.62), suggesting that the mutants were more sensitive and specific for the NPs’ nano-specific toxicity. The toxic effects in the yeast were slightly attributable to dissolved zinc ions from the ZnO (nano or bulk) particles. Oxidative damage and mechanical damage contributed to the toxic effect of the ZnO particles. The mechanism of mechanical damage is proposed to be an inherent characteristic underlying the nano-specific toxicity in the mutants. The log Te (particle) was a useful parameter for evaluation of NPs nano-specific toxicity, whereas log Te (ion) efficiently determined the NPs toxicity associated with released ions. PMID:27094203

The neglected nano-specific toxicity of ZnO nanoparticles in the yeast Saccharomyces cerevisiae

NASA Astrophysics Data System (ADS)

Zhang, Weicheng; Bao, Shaopan; Fang, Tao

2016-04-01

Nanoparticles (NPs) with unique physicochemical properties induce nano-specific (excess) toxicity in organisms compared with their bulk counterparts. Evaluation and consideration of nano-specific toxicity are meaningful for the safe design and environmental risk assessment of NPs. However, ZnO NPs have been reported to lack excess toxicity for diverse organisms. In the present study, the nano-specific toxicity of ZnO NPs was evaluated in the yeast Saccharomyces cerevisiae. Nano-specific toxicity of ZnO NPs was not observed in the wild type yeast. However, the ZnO NPs induced very similar nano-specific toxicities in the three mutants with comparable log Te (particle) values (0.64 vs 0.65 vs 0.62), suggesting that the mutants were more sensitive and specific for the NPs’ nano-specific toxicity. The toxic effects in the yeast were slightly attributable to dissolved zinc ions from the ZnO (nano or bulk) particles. Oxidative damage and mechanical damage contributed to the toxic effect of the ZnO particles. The mechanism of mechanical damage is proposed to be an inherent characteristic underlying the nano-specific toxicity in the mutants. The log Te (particle) was a useful parameter for evaluation of NPs nano-specific toxicity, whereas log Te (ion) efficiently determined the NPs toxicity associated with released ions.

The neglected nano-specific toxicity of ZnO nanoparticles in the yeast Saccharomyces cerevisiae.

PubMed

Zhang, Weicheng; Bao, Shaopan; Fang, Tao

2016-04-20

Nanoparticles (NPs) with unique physicochemical properties induce nano-specific (excess) toxicity in organisms compared with their bulk counterparts. Evaluation and consideration of nano-specific toxicity are meaningful for the safe design and environmental risk assessment of NPs. However, ZnO NPs have been reported to lack excess toxicity for diverse organisms. In the present study, the nano-specific toxicity of ZnO NPs was evaluated in the yeast Saccharomyces cerevisiae. Nano-specific toxicity of ZnO NPs was not observed in the wild type yeast. However, the ZnO NPs induced very similar nano-specific toxicities in the three mutants with comparable log Te ((particle)) values (0.64 vs 0.65 vs 0.62), suggesting that the mutants were more sensitive and specific for the NPs' nano-specific toxicity. The toxic effects in the yeast were slightly attributable to dissolved zinc ions from the ZnO (nano or bulk) particles. Oxidative damage and mechanical damage contributed to the toxic effect of the ZnO particles. The mechanism of mechanical damage is proposed to be an inherent characteristic underlying the nano-specific toxicity in the mutants. The log Te ((particle)) was a useful parameter for evaluation of NPs nano-specific toxicity, whereas log Te ((ion)) efficiently determined the NPs toxicity associated with released ions.

Testing the toxicity of metals, phenol, effluents, and receiving waters by root elongation in Lactuca sativa L.

PubMed

Lyu, Jie; Park, Jihae; Kumar Pandey, Lalit; Choi, Soyeon; Lee, Hojun; De Saeger, Jonas; Depuydt, Stephen; Han, Taejun

2018-03-01

Phytotoxicity tests using higher plants are among the most simple, sensitive, and cost-effective of the methods available for ecotoxicity testing. In the present study, a hydroponic-based phytotoxicity test using seeds of Lactuca sativa was used to evaluate the water quality of receiving waters and effluents near two industrial sites (Soyo and Daejon) in Korea with respect to the toxicity of 10 metals (As, Cd, Cr, Cu, Fe, Pb, Mn, Hg, Ni, Zn) and phenol, and of the receiving waters and effluents themselves. First, the L. sativa hydroponic bioassay was used to determine whether the receiving water or effluents were toxic; then, the responsible toxicant was identified. The results obtained with the L. sativa bioassay ranked the EC 50 toxicities of the investigated metal ions and phenol as: Cd > Ni > Cu > Zn > Hg > phenol > As > Mn > Cr > Pb > Fe. We found that Zn was the toxicant principally responsible for toxicity in Daejeon effluents. The Daejeon field effluent had a higher Zn concentration than permitted by the effluent discharge criteria of the Ministry of Environment of Korea. Our conclusion on the importance of Zn toxicity was supported by the results of the L. sativa hydroponic assay, which showed that the concentration of Zn required to inhibit root elongation in L. sativa by 50% (EC 50 ) was higher in the Daejeon field effluent than that of pure Zn. More importantly, we proved that the L. sativa hydroponic test method can be applied not only as an alternative tool for determining whether a given waste is acceptable for discharge into public water bodies, but also as an alternative method for measuring the safety of aquatic environments using EC 20 values, with respect to the water pollutants investigated (i.e., Cd, Cr, Cu, Pb, Mn, Hg, Ni, Zn, and phenol). Copyright © 2017. Published by Elsevier Inc.

Photoenhanced Toxicity of Oil to Larval Fish

EPA Science Inventory

Photoenhanced toxicity is the increase in the toxicity of a chemical in the presence of ultraviolet light (UV), compared to toxicity elicited under conditions of minimal UV. Oil products, weathered oils, combusted oil products, and specific polycyclic aromatic compounds in oil ha...

Changing patterns in water toxicity associated with current use pesticides in three California agriculture regions.

PubMed

Anderson, Brian S; Phillips, Bryn M; Voorhees, Jennifer P; Deng, Xin; Geraci, Jeff; Worcester, Karen; Tjeerdema, Ron S

2018-03-01

Regulation of agriculture irrigation water discharges in California, USA, is assessed and controlled by its 9 Regional Water Quality Control Boards under the jurisdiction of the California State Water Resources Control Board. Each Regional Water Board has developed programs to control pesticides in runoff as part of the waste discharge requirements implemented through each region's Irrigated Lands Regulatory Program. The present study assessed how pesticide use patterns differ in the Imperial (Imperial County) and the Salinas and Santa Maria (Monterey County) valleys, which host 3 of California's prime agriculture areas. Surface-water toxicity associated with current use pesticides was monitored at several sites in these areas in 2014 and 2015, and results were linked to changes in pesticide use patterns in these areas. Pesticide use patterns appeared to coincide with differences in the way agriculture programs were implemented by the 2 respective Regional Water Quality Control Boards, and these programs differed in the 2 Water Board Regions. Different pesticide use patterns affected the occurrence of pesticides in agriculture runoff, and this influenced toxicity test results. Greater detection frequency and higher concentrations of the organophosphate pesticide chlorpyrifos were detected in agriculture runoff in Imperial County compared to Monterey County, likely due to more rigorous monitoring requirements for growers using this pesticide in Monterey County. Monterey County agriculture runoff contained toxic concentrations of pyrethroid and neonicotinoid pesticides, which impacted amphipods (Hyalella azteca) and midge larvae (Chironomus dilutus) in toxicity tests. Study results illustrate how monitoring strategies need to evolve as regulatory actions affect change in pesticide use and demonstrate the importance of using toxicity test indicator species appropriate for the suite of contaminants in runoff in order to accurately assess environmental risk. Integr Environ Assess Manag 2018;14:270-281. © 2017 SETAC. © 2017 SETAC.

Acute embryo toxicity and teratogenicity of three potential biofuels also used as flavor or solvent.

PubMed

Bluhm, Kerstin; Seiler, Thomas-Benjamin; Anders, Nico; Klankermayer, Jürgen; Schaeffer, Andreas; Hollert, Henner

2016-10-01

The demand for biofuels increases due to concerns regarding greenhouse gas emissions and depletion of fossil oil reserves. Many substances identified as potential biofuels are solvents or already used as flavors or fragrances. Although humans and the environment may be readily exposed little is known regarding their (eco)toxicological effects. In this study, the three potential biofuels ethyl levulinate (EL), 2-methyltetrahydrofuran (2-MTHF) and 2-methylfuran (2-MF) were investigated for their acute embryo toxicity and teratogenicity using the fish embryo toxicity (FET) test to identify unknown hazard potentials and to allow focusing further research on substances with low toxic potentials. In addition, two fossil fuels (diesel and gasoline) and an established biofuel (rapeseed oil methyl ester) were investigated as references. The FET test is widely accepted and used in (eco)toxicology. It was performed using the zebrafish Danio rerio, a model organism useful for the prediction of human teratogenicity. Testing revealed a higher acute toxicity for EL (LC50: 83mg/L) compared to 2-MTHF (LC50: 2980mg/L), 2-MF (LC50: 405mg/L) and water accommodated fractions of the reference fuels including gasoline (LC50: 244mg DOC/L). In addition, EL caused a statistically significant effect on head development resulting in elevated head lengths in zebrafish embryos. Results for EL reduce its likelihood of use as a biofuel since other substances with a lower toxic potential are available. The FET test applied at an early stage of development might be a useful tool to avoid further time and money requiring steps regarding research on unfavorable biofuels. Copyright © 2016 Elsevier B.V. All rights reserved.

Proton Beam Therapy Versus Conformal Photon Radiation Therapy for Childhood Craniopharyngioma: Multi-institutional Analysis of Outcomes, Cyst Dynamics, and Toxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bishop, Andrew J.; Greenfield, Brad; Mahajan, Anita

2014-10-01

Purpose: We compared proton beam therapy (PBT) with intensity modulated radiation therapy (IMRT) for pediatric craniopharyngioma in terms of disease control, cyst dynamics, and toxicity. Methods and Materials: We reviewed records from 52 children treated with PBT (n=21) or IMRT (n=31) at 2 institutions from 1996-2012. Endpoints were overall survival (OS), disease control, cyst dynamics, and toxicity. Results: At 59.6 months' median follow-up (PBT 33 mo vs IMRT 106 mo; P<.001), the 3-year outcomes were 96% for OS, 95% for nodular failure-free survival and 76% for cystic failure-free survival. Neither OS nor disease control differed between treatment groups (OS P=.742;more » nodular failure-free survival P=.546; cystic failure-free survival P=.994). During therapy, 40% of patients had cyst growth (20% requiring intervention); immediately after therapy, 17 patients (33%) had cyst growth (transient in 14), more commonly in the IMRT group (42% vs 19% PBT; P=.082); and 27% experienced late cyst growth (32% IMRT, 19% PBT; P=.353), with intervention required in 40%. Toxicity did not differ between groups. On multivariate analysis, cyst growth was related to visual and hypothalamic toxicity (P=.009 and .04, respectively). Patients given radiation as salvage therapy (for recurrence) rather than adjuvant therapy had higher rates of visual and endocrine (P=.017 and .024, respectively) dysfunction. Conclusions: Survival and disease-control outcomes were equivalent for PBT and IMRT. Cyst growth is common, unpredictable, and should be followed during and after therapy, because it contributes to late toxicity. Delaying radiation therapy until recurrence may result in worse visual and endocrine function.« less