Oxygen Toxicity and Special Operations Forces Diving: Hidden and Dangerous

PubMed Central

Wingelaar, Thijs T.; van Ooij, Pieter-Jan A. M.; van Hulst, Rob A.

2017-01-01

In Special Operations Forces (SOF) closed-circuit rebreathers with 100% oxygen are commonly utilized for covert diving operations. Exposure to high partial pressures of oxygen (PO2) could cause damage to the central nervous system (CNS) and pulmonary system. Longer exposure time and higher PO2 leads to faster development of more serious pathology. Exposure to a PO2 above 1.4 ATA can cause CNS toxicity, leading to a wide range of neurologic complaints including convulsions. Pulmonary oxygen toxicity develops over time when exposed to a PO2 above 0.5 ATA and can lead to inflammation and fibrosis of lung tissue. Oxygen can also be toxic for the ocular system and may have systemic effects on the inflammatory system. Moreover, some of the effects of oxygen toxicity are irreversible. This paper describes the pathophysiology, epidemiology, signs and symptoms, risk factors and prediction models of oxygen toxicity, and their limitations on SOF diving. PMID:28790955

DITOP: drug-induced toxicity related protein database.

PubMed

Zhang, Jing-Xian; Huang, Wei-Juan; Zeng, Jing-Hua; Huang, Wen-Hui; Wang, Yi; Zhao, Rui; Han, Bu-Cong; Liu, Qing-Feng; Chen, Yu-Zong; Ji, Zhi-Liang

2007-07-01

Drug-induced toxicity related proteins (DITRPs) are proteins that mediate adverse drug reactions (ADRs) or toxicities through their binding to drugs or reactive metabolites. Collection of these proteins facilitates better understanding of the molecular mechanisms of drug-induced toxicity and the rational drug discovery. Drug-induced toxicity related protein database (DITOP) is such a database that is intending to provide comprehensive information of DITRPs. Currently, DITOP contains 1501 records, covering 618 distinct literature-reported DITRPs, 529 drugs/ligands and 418 distinct toxicity terms. These proteins were confirmed experimentally to interact with drugs or their reactive metabolites, thus directly or indirectly cause adverse effects or toxicities. Five major types of drug-induced toxicities or ADRs are included in DITOP, which are the idiosyncratic adverse drug reactions, the dose-dependent toxicities, the drug-drug interactions, the immune-mediated adverse drug effects (IMADEs) and the toxicities caused by genetic susceptibility. Molecular mechanisms underlying the toxicity and cross-links to related resources are also provided while available. Moreover, a series of user-friendly interfaces were designed for flexible retrieval of DITRPs-related information. The DITOP can be accessed freely at http://bioinf.xmu.edu.cn/databases/ADR/index.html. Supplementary data are available at Bioinformatics online.

Structure-activity relationship analysis of mitochondrial toxicity caused by antiviral ribonucleoside analogs.

PubMed

Jin, Zhinan; Kinkade, April; Behera, Ishani; Chaudhuri, Shuvam; Tucker, Kathryn; Dyatkina, Natalia; Rajwanshi, Vivek K; Wang, Guangyi; Jekle, Andreas; Smith, David B; Beigelman, Leo; Symons, Julian A; Deval, Jerome

2017-07-01

Recent cases of severe toxicity during clinical trials have been associated with antiviral ribonucleoside analogs (e.g. INX-08189 and balapiravir). Some have hypothesized that the active metabolites of toxic ribonucleoside analogs, the triphosphate forms, inadvertently target human mitochondrial RNA polymerase (POLRMT), thus inhibiting mitochondrial RNA transcription and protein synthesis. Others have proposed that the prodrug moiety released from the ribonucleoside analogs might instead cause toxicity. Here, we report the mitochondrial effects of several clinically relevant and structurally diverse ribonucleoside analogs including NITD-008, T-705 (favipiravir), R1479 (parent nucleoside of balapiravir), PSI-7851 (sofosbuvir), and INX-08189 (BMS-986094). We found that efficient substrates and chain terminators of POLRMT, such as the nucleoside triphosphate forms of R1479, NITD-008, and INX-08189, are likely to cause mitochondrial toxicity in cells, while weaker chain terminators and inhibitors of POLRMT such as T-705 ribonucleoside triphosphate do not elicit strong in vitro mitochondrial effects. Within a fixed 3'-deoxy or 2'-C-methyl ribose scaffold, changing the base moiety of nucleotides did not strongly affect their inhibition constant (K i ) against POLRMT. By swapping the nucleoside and prodrug moieties of PSI-7851 and INX-08189, we demonstrated that the cell-based toxicity of INX-08189 is mainly caused by the nucleoside component of the molecule. Taken together, these results show that diverse 2' or 4' mono-substituted ribonucleoside scaffolds cause mitochondrial toxicity. Given the unpredictable structure-activity relationship of this ribonucleoside liability, we propose a rapid and systematic in vitro screen combining cell-based and biochemical assays to identify the early potential for mitochondrial toxicity. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Neurotoxicity of dental amalgam is mediated by zinc.

PubMed

Lobner, D; Asrari, M

2003-03-01

The use of dental amalgam is controversial largely because it contains mercury. We tested whether amalgam caused toxicity in neuronal cultures and whether that toxicity was caused by mercury. In this study, we used cortical cell cultures to show for the first time that amalgam causes nerve cell toxicity in culture. However, the toxicity was not blocked by the mercury chelator, 2,3-dimercaptopropane-1-sulphonate (DMPS), but was blocked by the metal chelator, calcium disodium ethylenediaminetetraacetate (CaEDTA). DMPS was an effective mercury chelator in this system, since it blocked mercury toxicity. Of the components that comprise amalgam (mercury, zinc, tin, copper, and silver), only zinc neurotoxicity was blocked by CaEDTA. These results indicate that amalgam is toxic to nerve cells in culture by releasing zinc. While zinc is known to be neurotoxic, ingestion of zinc is not a major concern because zinc levels in the body are tightly regulated.

Metallothionein provides zinc-mediated protective effects against methamphetamine toxicity in SK-N-SH cells.

PubMed

Ajjimaporn, Amornpan; Swinscoe, John; Shavali, Shaik; Govitrapong, Piyarat; Ebadi, Manuchair

2005-11-30

Methamphetamine (METH) is a drug of abuse and neurotoxin that induces Parkinson's-like pathology after chronic usage by targeting dopaminergic neurons. Elucidation of the intracellular mechanisms that underlie METH-induced dopaminergic neuron toxicity may help in understanding the mechanism by which neurons die in Parkinson's disease. In the present study, we examined the role of reactive oxygen species (ROS) in the METH-induced death of human dopaminergic SK-N-SH cells and further assessed the neuroprotective effects of zinc and metallothionein (MT) against METH-induced toxicity in culture. METH significantly increased the production of reactive oxygen species, decreased intracellular ATP levels and reduced the cell viability. Pre-treatment with zinc markedly prevented the loss of cell viability caused by METH treatment. Zinc pre-treatment mainly increased the expression of metallothionein and prevented the generation of reactive oxygen species and ATP depletion caused by METH. Chelation of zinc by CaEDTA caused a significant decrease in MT expression and loss of protective effects of MT against METH toxicity. These results suggest that zinc-induced MT expression protects dopaminergic neurons via preventing the accumulation of toxic reactive oxygen species and halting the decrease in ATP levels. Furthermore, MT may prevent the loss of mitochondrial functions caused by neurotoxins. In conclusion, our study suggests that MT, a potent scavenger of free radicals is neuroprotective against dopaminergic toxicity in conditions such as drug of abuse and in Parkinson's disease.

Reduction of Fumonisin Toxicity by Extrusion and Nixtamalization (Alkaline Cooking).

PubMed

Voss, Kenneth; Ryu, Dojin; Jackson, Lauren; Riley, Ronald; Gelineau-van Waes, Janee

2017-08-23

Fumonisins are mycotoxins found in corn. They are toxic to animals and cause cancer in rodents and neural tube defects in LM/Bc mice. Reducing their concentrations in corn-based foods is therefore desirable. Chemical analysis or in vitro bioassays of food extracts might not detect toxic fumonisin reaction products that are unknown or unextractable from food matrices, thus potentially underestimating in vivo toxicity. The effectiveness of two common cooking methods, extrusion and nixtamalization (alkaline cooking), to reduce the toxicity of fumonisin-contaminated corn grits (extrusion) and whole kernel corn (nixtamalization) was shown by means of rat feeding bioassays using fumonisin-specific kidney effects as indicators of potential toxicity. A third bioassay showed that in contrast to fumonisin B 1 (FB 1 ), hydrolyzed fumonisin B 1 (HFB 1 ; formed from FB 1 during nixtamalization) did not cause neural tube defects in LM/Bc mice. The findings indicate that extrusion and nixtamalization reduce the potential toxicity of FB 1 -contaminated corn.

Effect of Shodhana Treatment on Chronic Toxicity and Recovery of Aconite

PubMed Central

Sarkar, P.K.; Prajapati, P.K.; Shukla, V.J.; Ravishankar, B.

2012-01-01

Aconite is one of the poisonous plants used therapeutically in practice of Ayurveda after proper treatment called as ‘Shodhana’. To determine the effect of Shodhana treatment on chronic toxicity and to assess the effect of recovery period after chronic toxicity of aconite. Raw aconite (RV), urine treated aconite (SM), and milk treated aconite (SD) were administered in 6.25 mg/kg dose in Charles Foster strain albino rats for 90 days for chronic toxicity. Six rats from each were kept for another 30 days without test drugs treatment to observe recovery from chronic toxicity. RV was found to be highly toxic in chronic exposure, SM had no apparent toxicity, but SD had mild toxicity in kidney. The toxicities of RV and SD were reversible, but sudden withdrawal of SM caused adverse effects, suggestive of tapering withdrawal. Shodhana treatments remove toxic effects from raw aconite. Chronic toxicity of aconite is reversible. Confirmed the arrangement of abstract PMID:22736901

Residual toxicity after biodegradation: interactions among benzene, toluene, and chloroform.

PubMed

da Silva Nunes-Halldorson, Vânia; Steiner, Robert L; Smith, Geoffrey B

2004-02-01

A microbial enrichment originating from a pristine aquifer was found to aerobically biodegrade benzene and toluene, but not chloroform. This enrichment culture was used to study changes in pollutant toxicity as affected by biodegradative activity. Two assays for toxicity were used: (1) a 48-h acute toxicity test using the freshwater invertebrate Ceriodaphnia dubia and (2) microbial biodegradation activity as affected by the presence of mixed pollutants. At 20-ppm concentrations, toluene was significantly more toxic (99% mortality) to C. dubia than benzene (48% mortality) or chloroform (40% mortality). Also at 20-ppm concentrations, but before biodegradation, toluene was significantly more toxic (88% mortality) to C. dubia than benzene (33% mortality). After biodegradation of 98% of toluene and benzene, significant residual toxicity still remained in the bacterial supernatant: toluene-degraded supernatant caused 33% mortality in C. dubia and benzene-degraded supernatant caused 24% mortality. In the second toxicity assay, examining the effect of mixed pollutants on biodegradation activity, the presence of benzene slowed the biodegradation of toluene, but chloroform had no effect on either benzene or toluene biodegradation. Results indicate that significant toxicity remain after biodegradation and that halogenated aliphatic hydrocarbons may have little or no effect on aromatic hydrocarbon biodegradation at sites impacted by mixed pollutants.

[Toxic effects of medications on the cornea].

PubMed

Ravet, O

2007-01-01

We reviewed the most recent systemic drugs used in Belgium causing toxic corneal side effects. These adverse reactions are rarely specific and often ignored or unknown. This description can help the physician's evaluation for a better interdisciplinary approach.

Effects of sediment characteristics on the toxicity of chromium(III) and chromium(VI) to the amphipod, Hyalella azteca

USGS Publications Warehouse

Besser, J.M.; Brumbaugh, W.G.; Kemble, N.E.; May, T.W.; Ingersoll, C.G.

2004-01-01

We evaluated the influence of sediment characteristics, acid-volatile sulfide (AVS) and organic matter (OM), on the toxicity of chromium (Cr) in freshwater sediments. We conducted chronic (28-42-d) toxicity tests with the amphipod Hyalella azteca exposed to Cr(VI) and Cr(III) in water and in spiked sediments. Waterborne Cr(VI) caused reduced survival of amphipods with a median lethal concentration (LC50) of 40 ??g/L. Cr(VI) spiked into test sediments with differing levels of AVS resulted in graded decreases in AVS and sediment OM. Only Cr(VI)-spiked sediments with low AVS concentrations (<1 ??mol/g) caused significant amphipod mortality. Waterborne Cr(III) concentrations near solubility limits caused decreased survival of amphipods at pH 7 and pH 8 but not at pH 6. Sediments spiked with high levels of Cr(III) did not affect amphipod survival but had minor effects on growth and inconsistent effects on reproduction. Pore waters of some Cr(III)-spiked sediments contained measurable concentrations of Cr(VI), but observed toxic effects did not correspond closely to Cr concentrations in sediment or pore waters. Our results indicate that risks of Cr toxicity are low in freshwater sediments containing substantial concentrations of AVS.

Early Evolution of the Toxicity Identification Evaluation Process: Contributions from the USEPA Effluent Testing Program

EPA Science Inventory

As part of its whole effluent testing program, the USEPA developed an effects-directed analysis (EDA) approach to identifying the cause of toxicity in toxic effluents or ambient waters, an EDA process termed a “Toxicity Identification Evaluation” (TIE), which is the focus of this...

Relative toxicity of pyrolysis products of some materials used in home furnishings

NASA Technical Reports Server (NTRS)

Hilado, C. J.; Furst, A.

1976-01-01

Seventy samples of cushioning and upholstery materials used in home furnishings were evaluated for relative toxicity by means of the USF/NASA toxicity screening test. The materials were variably toxic under pyrolysis conditions, and this test appeared suitable for discriminating among them on the bases of time to incapacitation and time to death. The addition of fire retardants to these materials to comply with flammability regulations either had no significant effect on toxicity, or resulted in a reduction in relative toxicity. The modification of materials to comply with California upholstered furniture flammability regulations appears to have resulted in desirable limitations on toxicity. Fifty percent of the 70 materials tested caused incapacitation earlier than did the materials in compliance, and 30 percent caused death earlier.

Comparative effects of graphene and graphene oxide on copper toxicity to Daphnia magna: Role of surface oxygenic functional groups.

PubMed

Liu, Yingying; Fan, Wenhong; Xu, Zhizhen; Peng, Weihua; Luo, Shenglian

2018-05-01

Although the risk of graphene materials to aquatic organisms has drawn wide attention, the combined effects of graphene materials with other contaminants such as toxic metals, which may bring about more serious effects than graphene materials alone, have seldom been explored. Herein, the effects of graphene (GN) and graphene oxide (GO, an important oxidized derivative of graphene) on copper (Cu) toxicity to Daphnia magna were systematically investigated. The results indicated that GN remarkably increased the Cu accumulation in D. magna and enhanced the oxidative stress injury caused by Cu, whereas did not significantly alter D. magna acute mortality within the tested Cu concentrations (0-200 μg L -1 ). On the contrary, GO significantly decreased the Cu accumulation in D. magna and alleviated the oxidative stress injury caused by Cu. Meanwhile, the presence of GO significantly reduced the mortality of D. magna when Cu concentration exceeded 50 μg L -1 . The different effects of GN and GO on Cu toxicity were possibly dependent on the action of surface oxygenic functional group. Because of the introduction of surface oxygenic functional groups, the adsorption ability to metal ions, stability in water and interaction mode with organisms of GO are quite different from that of GN, causing different effects on Cu toxicity. This study provides important information on the bioavailability and toxicity of heavy metals as affected by graphene materials in natural water. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sediment Toxicity Identification Evaluations (TIEs): Manipulating Bioavailability to Whole Organisms to Identify Environmental Toxins

EPA Science Inventory

Toxicity tests are a common method for determining whether sediment contaminants represent an environmental risk. Toxicity tests indicate if contaminants in sediments are bioavailable and capable of causing adverse biological effects to whole aquatic organisms. Several environmen...

Status and future concerns of clinical and environmental aluminum toxicology.

PubMed

Flaten, T P; Alfrey, A C; Birchall, J D; Savory, J; Yokel, R A

1996-08-30

A wide range of toxic effects of aluminum (Al) have been demonstrated in plants and aquatic animals in nature, in experimental animals by several routes of exposure, and under different clinical conditions in humans. Aluminum toxicity is a major problem in agriculture, affecting perhaps as much as 40% of arable soils in the world. In fresh waters acidified by acid rain, Al toxicity has led to fish extinction. Aluminum is a very potent neurotoxicant. In humans with chronic renal failure on dialysis, Al causes encephalopathy, osteomalacia, and anemia. There are also reports of such effects in certain patient groups without renal failure. Subtle neurocognitive and psychomotor effects and electroencephalograph (EEG) abnormalities have been reported at plasma Al levels as low as 50 micrograms/L. Infants could be particularly susceptible to Al accumulation and toxicity, reduced renal function being one contributory cause. Recent reports clearly show that Al accumulation occurs in the tissues of workers with long-term occupational exposure to Al dusts or fumes, and also indicate that such exposure may cause subtle neurological effects. Increased efforts should be directed toward defining the full range of potentially harmful effects in humans. To this end, multidisciplinary collaborative research efforts are encouraged, involving scientists from many different specialties. Emphasis should be placed on increasing our understanding of the chemistry of Al in biological systems, and on determining the cellular and molecular mechanisms of Al toxicity.

Analyzing cytotoxic effects of selected isothiazol-3-one biocides using the toxic ratio concept and structure-activity relationship considerations.

PubMed

Arning, Jürgen; Matzke, Marianne; Stolte, Stefan; Nehen, Frauke; Bottin-Weber, Ulrike; Böschen, Andrea; Abdulkarim, Salha; Jastorff, Bernd; Ranke, Johannes

2009-12-01

To demonstrate how baseline toxicity can be separated from other more specific modes of toxic action and to address possible pitfals when dealing with hydrophobic substances, the four isothiazol-3-one biocides N-methylisothiazol-3-one (MIT), 5-chloro-N-methylisothiazol-3-one (CIT), N-octylisothiazol-3-one (OIT), and 4,5-dichloro-N-octylisothiazol-3-one (DCOIT) as an example for reactive electrophilic xenobiotics were tested for their cytotoxic effects on the human hepatoblastoma cell line Hep G2, on the marine bacterium Vibrio fischeri, and on the limnic green alga Scenedesmus vacuolatus. In each of the three test systems, toxic effects were observed in a consistent pattern. The two chlorinated compounds and OIT were found to be significantly more toxic than MIT. As compared to baseline toxicants, the small and polar MIT and CIT exhibited pronounced excess toxicity in each of the three test systems that is presumably triggered by their intrinsic reactivity toward cellular thiols. In contrast, OIT and DCOIT showed mainly toxicities that could be explained by their hydrophobicity. Analyzing and comparing these results using the toxic ratio concept and with data that indicate a dramatic depletion of cellular glutathione levels after incubation with DCOIT reveals that for highly hydrophobic substances, baseline level toxicity in an assay for acute toxicity can lead to an oversight of other more specific modes of toxic action that may cause significant effects that might be less reversible than those caused by unreactive baseline toxicants. This possibility should be taken into account in the hazard assessment of chemicals that are both hydrophobic and reactive.

Programmatic Life Cycle Environmental Assessment for Smoke/Obscurants. Volume 2. Red, White, and Plasticized White Phosphorus

DTIC Science & Technology

1983-07-01

data on toxic effects of unreacted P4 on soil systems are available. (3) Aquatic systems . Aquatic toxicity data on WP are presented in section IV.f...elevated phosphorus levels in aquatic systems will cause adverse effects . Phosphoric acids may lower water pH in systems with low water hardness. A pH...eutrophication of the system , will cause detrimental effects on the fish population. Fish kills can occur over the winter due to low oxygen levels. The

[Two cases of toxic hepatitis caused by arrowroot juice].

PubMed

Kim, Seung Young; Yim, Hyung Joon; Ahn, Jae Hong; Kim, Jeong Han; Kim, Jin Nam; Yoon, Ik; Kim, Dong Il; Lee, Hong Sik; Lee, Sang Woo; Choi, Jai Hyun

2009-12-01

Herbal remedies and health foods are widely used, and their side effects have been reported. We describe two cases of symptomatic toxic hepatitis that developed in middle-aged women after ingesting arrowroot juice. The clinical manifestations were nausea, vomiting, and jaundice. The diagnosis of toxic hepatitis was made using the Roussel Uclaf Causality Assessment Method score on the basis of the patient's history and laboratory data. After supportive care, the patients showed rapid improvements of clinical symptoms, laboratory findings, and liver stiffness. Clinicians should be aware that the consumption of arrowroot juice can cause toxic hepatitis.

Epigenetic perturbations in the pathogenesis of mustard toxicity; hypothesis and preliminary results

PubMed Central

Korkmaz, Ahmet; Yaren, Hakan; Kunak, Z. Ilker; Uysal, Bulent; Kurt, Bulent; Topal, Turgut; Kenar, Levent; Ucar, Ergun; Oter, Sukru

2008-01-01

Among the most readily available chemical warfare agents, sulfur mustard (SM), also known as mustard gas, has been the most widely used chemical weapon. SM causes debilitating effects that can leave an exposed individual incapacitated for days to months; therefore delayed SM toxicity is of much greater importance than its ability to cause lethality. Although not fully understood, acute toxicity of SM is related to reactive oxygen and nitrogen species, oxidative stress, DNA damage, poly(ADP-ribose) polymerase (PARP) activation and energy depletion within the affected cell. Therefore several antioxidants and PARP inhibitors show beneficial effects against acute SM toxicity. The delayed toxicity of SM however, currently has no clear mechanistic explanation. One third of the 100,000 Iranian casualties are still suffering from the detrimental effects of SM in spite of the extensive treatment. We, therefore, made an attempt whether epigenetic aberrations may contribute to pathogenesis of mustard poisoning. Preliminary evidence reveals that mechlorethamine (a nitrogen mustard derivative) exposure may not only cause oxidative stress, DNA damage, but epigenetic perturbations as well. Epigenetic refers to the study of changes that influence the phenotype without causing alteration of the genotype. It involves changes in the properties of a cell that are inherited but do not involve a change in DNA sequence. It is now known that in addition to mutations, epimutations contribute to a variety of human diseases. Under light of preliminary results, the current hypothesis will focus on epigenetic regulations to clarify mustard toxicity and the use of drugs to correct possible epigenetic defects. PMID:21218122

Developmental neurotoxicity of succeeding generations of insecticides

PubMed Central

Abreu-Villaça, Yael; Levin, Edward D.

2016-01-01

Insecticides are by design toxic. They must be toxic to effectively kill target species of insects. Unfortunately, they also have off-target toxic effects that can harm other species, including humans. Developmental neurotoxicity is one of the most prominent off-target toxic risks of insecticides. Over the past seven decades several classes of insecticides have been developed, each with their own mechanisms of effect and toxic side effects. This review covers the developmental neurotoxicity of the succeeding generations of insecticides including organochlorines, organophosphates, pyrethroids, carbamates and neonicotinoids. The goal of new insecticide development is to more effectively kill target species with fewer toxic side effects on non-target species. From the experience with the developmental neurotoxicity caused by the generations of insecticides developed in the past advice is offered how to proceed with future insecticide development to decrease neurotoxic risk. PMID:27908457

Surfactants present complex joint effects on the toxicities of metal oxide nanoparticles.

PubMed

Wang, Dali; Lin, Zhifen; Yao, Zhifeng; Yu, Hongxia

2014-08-01

The potential toxicities of nanoparticles (NPs) have been intensively discussed over the past decade. In addition to their single toxicities, NPs can interact with other environmental chemicals and thereby exert joint effects on biological systems and the environment. The present study investigated the combined toxicities of NPs and surfactants, which are among the chemicals that most likely coexist with NPs. Photobacterium phosphoreum was employed as the model organism. The results indicate that surfactants with different ion types can alter the properties of NPs (i.e., particle size and surface charge) in different ways and present complex joint effects on NP toxicities. Mixtures of different NPs and surfactants exhibited antagonistic, synergistic, and additive effects. In particular, the toxicity of ZnO was observed to result from its dissolved Zn(2+); thus, the joint effects of the ZnO NPs and surfactants can be explained by the interactions between the Zn ions and the surfactants. Our study suggests that the potential hazards caused by mixtures of NPs and surfactants are different from those caused by single NPs. Because surfactants are extensively used in the field of nanotechnology and are likely to coexist with NPs in natural waters, the ecological risk assessments of NPs should consider the impacts of surfactants. Copyright © 2014 Elsevier Ltd. All rights reserved.

SEDIMENT TOXICITY IDENTIFICATION EVALUATION (TIE) ...

EPA Pesticide Factsheets

Sediment contamination in the United States has been amply documented and, in order to comply with the 1972 Clean Water Act, the U.S. Environmental Protection Agency must address the issue of toxic sediments. Contaminated sediments from a number of freshwater and marine sites have demonstrated acute and/or chronic toxicity to a variety of test species, as well as adverse ecological effects such as population declines and changes in community structure. However, simply knowing that a sediment is toxic has limited use. This document provides guidance on the performance of sediment Toxicity Identification and Evaluation (TIE). TIE methods allow for the identification of toxic chemicals or chemical classes causing observed toxicity. The identification of pollutants responsible for toxicity of contaminated sediments has broad application in a number of EPA programs as the methods can be used within the total maximum daily load (TMDL) framework, to link sediment toxicity to specific dischargers, to design cost-effective remediation programs, and to identify environmentally protective options for dredged material disposal. In addition, the identification of specific problem contaminants in sediments could prove to be very useful to EPA programs involved in the development of water or sediment quality guidelines, and the registration of new products such as pesticides. Finally, knowledge of the causes of toxicity that influence ecological changes such as community struc

[Individualized clinical treatment from the prospective of hepatotoxicity of non-toxic traditional Chinese medicine].

PubMed

Yang, Nan; Chen, Juan; Hou, Xue-Feng; Song, Jie; Feng, Liang; Jia, Xiao-Bin

2017-04-01

Traditional Chinese medicine has a long history in clinical application, and been proved to be safe and effective. In recent years, the toxicity and side-effects caused by the western medicine have been attracted much attention. As a result, increasing people have shifted their attention to traditional Chinese medicine. Nonetheless, due to the natural origin of traditional Chinese medicine and the lack of basic knowledge about them, many people mistakenly consider the absolute safety of traditional Chinese medicine, except for well-known toxic ones, such as arsenic. However, according to the clinical practices and recent studies, great importance shall be attached to the toxicity of non-toxic traditional Chinese medicine, in particular the hepatotoxicity. Relevant studies indicated that the toxicity of non-toxic traditional Chinese medicine is closely correlated with individual gene polymorphism and constitution. By discussing the causes and mechanisms of the hepatotoxicity induced by non-toxic traditional Chinese medicine in clinical practices, we wrote this article with the aim to provide new ideas for individualized clinical therapy of traditional Chinese medicine and give guidance for rational and safe use of traditional Chinese medicine. Copyright© by the Chinese Pharmaceutical Association.

Effect of diisopropanolamine upon choline uptake and phospholipid synthesis in Chinese hamster ovary cells.

PubMed

Stott, W T; Kleinert, K M

2008-02-01

Aminoalcohols differ in mammalian toxicity at least in part based upon their ability to alter the metabolism of phospholipids and to cause depletion of the essential nutrient choline in animals. This study examined the incorporation of diisopropanolamine (DIPA) into phospholipids (PLs) and effects of DIPA upon choline uptake and phospholipid synthesis in Chinese hamster ovary (CHO) cells. Results were compared to those of a related secondary alcohol amine, diethanolamine (DEA), whose systemic toxicity is closely associated with its metabolic incorporation into PLs and depletion of choline pools. DIPA caused a dose-related inhibition of (3)H-choline uptake by CHO cells that was approximately 3-4 fold less potent, based upon an IC50, than that reported for DEA. DIPA, in contrast to DEA, did not cause changes in the synthesis rates of (33)P-phosphatidylethanolamine, (33)P-phosphatidylcholine or (33)P-sphingomyelin at either non-toxic or moderately toxic concentrations. Only approximately 0.004%, of administered (14)C-DIPA was metabolically incorporated into PLs, over 30-fold less than the incorporation of (14)C-DEA under similar conditions. Overall, these data and previous pharmacokinetic and toxicity data obtained in vivo suggests that DIPA is distinct from DEA and lacks significant choline and PL metabolism related toxicity in animals.

40 CFR 257.25 - Assessment monitoring program.

Code of Federal Regulations, 2012 CFR

2012-07-01

...) Minimum distance between upgradient edge of the unit and downgradient monitoring well screen (minimum... that is likely to be without appreciable risk of deleterious effects during a lifetime. For purposes of this subpart, systemic toxicants include toxic chemicals that cause effects other than cancer or...

40 CFR 257.25 - Assessment monitoring program.

Code of Federal Regulations, 2013 CFR

2013-07-01

...) Minimum distance between upgradient edge of the unit and downgradient monitoring well screen (minimum... that is likely to be without appreciable risk of deleterious effects during a lifetime. For purposes of this subpart, systemic toxicants include toxic chemicals that cause effects other than cancer or...

40 CFR 257.25 - Assessment monitoring program.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) Minimum distance between upgradient edge of the unit and downgradient monitoring well screen (minimum... that is likely to be without appreciable risk of deleterious effects during a lifetime. For purposes of this subpart, systemic toxicants include toxic chemicals that cause effects other than cancer or...

40 CFR 258.55 - Assessment monitoring program.

Code of Federal Regulations, 2013 CFR

2013-07-01

... upgradient edge of the MSWLF unit and downgradient monitoring well screen (minimum distance of travel); (5... effects during a lifetime. For purposes of this subpart, systemic toxicants include toxic chemicals that cause effects other than cancer or mutation. (ii) [Reserved] (j) In establishing ground-water protection...

40 CFR 258.55 - Assessment monitoring program.

Code of Federal Regulations, 2011 CFR

2011-07-01

... upgradient edge of the MSWLF unit and downgradient monitoring well screen (minimum distance of travel); (5... effects during a lifetime. For purposes of this subpart, systemic toxicants include toxic chemicals that cause effects other than cancer or mutation. (ii) [Reserved] (j) In establishing ground-water protection...

40 CFR 258.55 - Assessment monitoring program.

Code of Federal Regulations, 2012 CFR

2012-07-01

... upgradient edge of the MSWLF unit and downgradient monitoring well screen (minimum distance of travel); (5... effects during a lifetime. For purposes of this subpart, systemic toxicants include toxic chemicals that cause effects other than cancer or mutation. (ii) [Reserved] (j) In establishing ground-water protection...

Molecular signals regulating translocation and toxicity of graphene oxide in the nematode Caenorhabditis elegans

NASA Astrophysics Data System (ADS)

Wu, Qiuli; Zhao, Yunli; Li, Yiping; Wang, Dayong

2014-09-01

Both in vitro and in vivo studies have demonstrated the toxic effects of graphene oxide (GO). However, the molecular basis for the translocation and toxicity of GO is still largely unclear. In the present study, we employed an in vivo Caenorhabditis elegans assay system to identify molecular signals involved in the control of the translocation and toxicity of GO. We identified 7 genes whose mutations altered both the translocation and toxicity of GO. Mutations of the hsp-16.48, gas-1, sod-2, sod-3, and aak-2 genes caused greater GO translocation into the body and toxic effects on both primary and secondary targeted organs compared with wild type; however, mutations of the isp-1 and clk-1 genes resulted in significantly decreased GO translocation into the body and toxicity on both primary and secondary targeted organs compared with wild-type. Moreover, mutations of the hsp-16.48, gas-1, sod-2, sod-3, and aak-2 genes caused increased intestinal permeability and prolonged mean defecation cycle length in GO-exposed nematodes, whereas mutations of the isp-1 and clk-1 genes resulted in decreased intestinal permeability in GO-exposed nematodes. Therefore, for the underlying mechanism, we hypothesize that both intestinal permeability and defecation behavior may have crucial roles in controlling the functions of the identified molecular signals. The molecular signals may further contribute to the control of transgenerational toxic effects of GO. Our results provide an important insight into understanding the molecular basis for the in vivo translocation and toxicity of GO.Both in vitro and in vivo studies have demonstrated the toxic effects of graphene oxide (GO). However, the molecular basis for the translocation and toxicity of GO is still largely unclear. In the present study, we employed an in vivo Caenorhabditis elegans assay system to identify molecular signals involved in the control of the translocation and toxicity of GO. We identified 7 genes whose mutations altered both the translocation and toxicity of GO. Mutations of the hsp-16.48, gas-1, sod-2, sod-3, and aak-2 genes caused greater GO translocation into the body and toxic effects on both primary and secondary targeted organs compared with wild type; however, mutations of the isp-1 and clk-1 genes resulted in significantly decreased GO translocation into the body and toxicity on both primary and secondary targeted organs compared with wild-type. Moreover, mutations of the hsp-16.48, gas-1, sod-2, sod-3, and aak-2 genes caused increased intestinal permeability and prolonged mean defecation cycle length in GO-exposed nematodes, whereas mutations of the isp-1 and clk-1 genes resulted in decreased intestinal permeability in GO-exposed nematodes. Therefore, for the underlying mechanism, we hypothesize that both intestinal permeability and defecation behavior may have crucial roles in controlling the functions of the identified molecular signals. The molecular signals may further contribute to the control of transgenerational toxic effects of GO. Our results provide an important insight into understanding the molecular basis for the in vivo translocation and toxicity of GO. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr02688h

Final Rule for Industrial Process Cooling Towers: Fact Sheet

EPA Pesticide Factsheets

Fact sheet concerning a final rule to reduce air toxics emissions from industrial process cooling towers. Air toxics are those pollutants known or suspected of causing cancer or other serious health effects.

Toxicology of sulfur in ruminants: review

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

Kandylis, K.

1984-10-01

This review deals with the toxicology of sulfur in ruminants including toxicity, neurotoxic effects, and mechanism of toxic action of hydrogen sulfide, clinical signs, and treatment. It will report effects of excessive intake of sulfur by ruminants on feed intake, animal performance, ruminal digestion and motility, rumination, and other physiological functions. Poisoning of animals with sulfur from industrial emissions (sulfur dioxide) also is discussed. Excessive quantities of dietary sulfur (above .3 to .4%) as sulfate or elemental sulfur may cause toxic effects and in extreme cases can be fatal. The means is discussed whereby consumption of excessive amounts of sulfurmore » leads to toxic effects. 53 references, 1 table.« less

78 FR 21267 - Dinotefuran; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-10

... causes a low level of skin irritation. The main target of toxicity is the nervous system, but effects on the nervous system were only observed at high doses. Nervous system toxicity was manifested as... in motor activity which are consistent with effects on the nicotinic cholinergic nervous system seen...

DETERMINING THE CAUSES OF ADVERSE EFFECTS IN NEAR COASTAL ECOSYSTEMS: FROM TOXICITY IDENTIFICATION EVALUATIONS TO WATERSHED DIAGNOTICS

EPA Science Inventory

Several approaches are available for evaluating adverse effects in near coastal ecosystems. These range from performing toxicity tests with individual organisms on water column and sediment samples to conducting macrofaunal compositional analyses on pelagic and benthic communiti...

Health Risk Assessment Approach for 2,3,7,8-Tetrachlorodibenzo-P-Dioxin (Draft)

EPA Science Inventory

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is one of the most toxic and environmentally stable pollutants. In addition to various toxic effects, TCDD has been found to cause teratogenic, fetocidal, reproductive and carcinogenic effects in animals. In humans it adversely affects v...

Acute toxicity of leachates of tire wear material to Daphnia magna--variability and toxic components.

PubMed

Wik, Anna; Dave, Göran

2006-09-01

Large amounts of tire rubber are deposited along the roads due to tread wear. Several compounds may leach from the rubber and cause toxicity to aquatic organisms. To investigate the toxic effects of tire wear material from different tires, rubber was abraded from the treads of twenty-five tires. Leachates were prepared by allowing the rubber to equilibrate with dilution water at 44 degrees C for 72 h. Then the rubber was filtered from the leachates, and test organisms (Daphnia magna) were added. Forty-eight hour EC50s ranged from 0.5 to >10.0 g l(-1). The toxicity identification evaluation (TIE) indicated that non-polar organic compounds caused most of the toxicity. UV exposure of the filtered tire leachates caused no significant increase in toxicity. However, when tested as unfiltered leachates (the rubber was not filtered from the leachates before addition of D. magna) photo-enhanced toxicity was considerable for some tires, which means that test procedures are important when testing tire leachates for aquatic (photo) toxicity. The acute toxicity of tire wear for Daphnia magna was found to be <40 times a predicted environmental concentration based on reports on the concentration of a tire component found in environmental samples, which emphasizes the need for a more extensive risk assessment of tire wear for the environment.

Comparative acute toxicity of leachates from plastic products made of polypropylene, polyethylene, PVC, acrylonitrile-butadiene-styrene, and epoxy to Daphnia magna.

PubMed

Lithner, Delilah; Nordensvan, Ildikó; Dave, Göran

2012-06-01

The large global production of plastics and their presence everywhere in the society and the environment create a need for assessing chemical hazards and risks associated with plastic products. The aims of this study were to determine and compare the toxicity of leachates from plastic products made of five plastics types and to identify the class of compounds that is causing the toxicity. Selected plastic types were those with the largest global annual production, that is, polypropylene, polyethylene, and polyvinyl chloride (PVC), or those composed of hazardous monomers (e.g., PVC, acrylonitrile-butadiene-styrene [ABS], and epoxy). Altogether 26 plastic products were leached in deionized water (3 days at 50°C), and the water phases were tested for acute toxicity to Daphnia magna. Initial Toxicity Identification Evaluations (C18 filtration and EDTA addition) were performed on six leachates. For eleven leachates (42%) 48-h EC50s (i.e the concentration that causes effect in 50 percent of the test organisms) were below the highest test concentration, 250 g plastic/L. All leachates from plasticized PVC (5/5) and epoxy (5/5) products were toxic (48-h EC50s ranging from 2 to 235 g plastic/L). None of the leachates from polypropylene (5/5), ABS (5/5), and rigid PVC (1/1) products showed toxicity, but one of the five tested HDPE leachates was toxic (48-h EC50 17-24 g plastic/L). Toxicity Identification Evaluations indicated that mainly hydrophobic organics were causing the toxicity and that metals were the main cause for one leachate (metal release was also confirmed by chemical analysis). Toxic chemicals leached even during the short-term leaching in water, mainly from plasticized PVC and epoxy products.

Comparative toxicity of metal oxide nanoparticles (CuO, ZnO and TiO2) to developing zebrafish embryos

NASA Astrophysics Data System (ADS)

Vicario-Parés, Unai; Castañaga, Luis; Lacave, Jose Maria; Oron, Miriam; Reip, Paul; Berhanu, Deborah; Valsami-Jones, Eugenia; Cajaraville, Miren P.; Orbea, Amaia

2014-08-01

Increasing use of nanomaterials is resulting in their release into the environment, making necessary to determine the toxicity of these materials. With this aim, the effects of CuO, ZnO and TiO2 nanoparticles (NPs) on zebrafish development were assessed in comparison with the effects caused by the ionic forms (for copper and zinc), bulk counterparts and the stabilizer used for rutile TiO2 NPs. None of the NPs caused significant embryo mortality. CuO NPs were the most toxic affecting hatching and increasing malformation prevalence (≥1 mg Cu/L), followed by ZnO NPs that affected hatching at ≥5 mg Zn/L and stabilized TiO2 NPs that caused mortality and decreased hatching at 100 mg Ti/L. Exposure to the stabilizer alone provoked the same effect. Thus, toxicity of the TiO2 NP suspension can be linked to the surfactant. For all the endpoints, the greatest effects were exerted by the ionic forms, followed by the NPs and finally by the bulk compounds. By autometallography, metal-bearing deposits were observed in embryos exposed to CuO and ZnO NPs, being more abundant in the case of embryos exposed to CuO NPs. The largest and most abundant metal-bearing deposits were detected in embryos exposed to ionic copper. In conclusion, metal oxide NPs affected zebrafish development altering hatching and increasing the prevalence of malformations. Thus, the use and release of metal oxide NPs to the environment may pose a risk to aquatic organisms as a result of the toxicity caused by NPs themselves or by the additives used in their production.

Insecticide toxicity to the borer Neoleucinodes elegantalis (Guenée) (Lepidoptera: Crambidae): developmental and egg-laying effects.

PubMed

Silva, R S; Arcanjo, L P; Soares, J R S; Ferreira, D O; Serrão, J E; Martins, J C; Costa, Á H; Picanço, M C

2018-04-01

Neoleucinodes elegantalis (Guenée) (Lepidoptera: Crambidae) is one of the major pests of solanaceous plants in South America. It is considered a great threat by the European and Mediterranean Plant Protection Organization due to the serious economic damage that it causes on tomato farms; therefore, controlling this pest is a challenging task in South America. Controlling N. elegantalis at the egg stage is the best way to prevent it from damaging crops; however, thorough studies about the effectiveness of chemicals on the different life stages of this insect pest are lacking. In this study, the effects of different chemical classes were evaluated on N. elegantalis adults, female oviposition behavior, larvae, eggs, and embryonic development. None of the tested insecticides demonstrated toxicity to the adults; however, the results showed that cartap hydrochloride affects oviposition behavior. Moreover, methomyl and cartap hydrochloride exhibited high toxicity against the eggs and larvae, with higher than 80% of mortality. These insecticides interrupted larval hatching and caused alterations in the chorion layer. Flubendiamide and deltamethrin demonstrated toxicity on N. elegantalis larvae; however, lufenuron, indoxacarb, methoxyfenozide, and chlorantraniliprole demonstrated low toxicity on both eggs and larvae, with lower than 70% of mortality. Fruit treated with cartap hydrochloride had a deterrent effect. The ovicidal activity revealed by methomyl and cartap hydrochloride might provide new approaches regarding insecticide effects on eggs. Methomyl, cartap hydrochloride, flubendiamide, and deltamethrin demonstrated toxicity on larvae. The evaluation of the chorion of the eggshell in this study has clarified the toxic effect of methomyl and cartap hydrochloride on eggs.

Combined use of ursodeoxycholic acid and bosentan prevents liver toxicity caused by endothelin receptor antagonist bosentan monotherapy: two case reports.

PubMed

Ito, Tomoki; Ozaki, Yoshio; Son, Yonsu; Nishizawa, Tohru; Amuro, Hideki; Tanaka, Akihiro; Tamaki, Takeshi; Nomura, Shosaku

2014-07-11

Pulmonary arterial hypertension is a fatal disease characterized by progressive remodeling of the pulmonary arteries and an increase in pulmonary vascular resistance. Up to 50% of patients with systemic sclerosis have pulmonary arterial hypertension, which significantly affects the prognosis. The endothelin receptor antagonist bosentan is used for the treatment of pulmonary arterial hypertension and shows a great beneficial effect. However, the most frequent side effect of bosentan is liver toxicity, which often requires dose reduction and discontinuation. We report two cases (a 64-year-old Japanese woman and a 69-year old Japanese woman) of systemic sclerosis, both with severe Raynaud's phenomenon and pulmonary arterial hypertension. Both patients had initially received bosentan monotherapy, which caused liver toxicity as indicated by increased levels of alanine aminotransferase, alkaline phosphatase, and gamma-glutamyltransferase. After dose reduction or discontinuation of bosentan, these liver function abnormalities were normalized and the patients subsequently received retreatment with a combination of bosentan and ursodeoxycholic acid. The results of liver function tests did not show any abnormalities after this combination therapy. These reports suggest the usefulness of ursodeoxycholic acid for preventing liver toxicity caused by bosentan. Thus, the addition of ursodeoxycholic acid to the treatment protocol is expected to be useful when liver toxicity emerges as a side effect of bosentan.

Ultrafine particle libraries for exploring mechanisms of PM2.5-induced toxicity in human cells.

PubMed

Bai, Xue; Liu, Yin; Wang, Shenqing; Liu, Chang; Liu, Fang; Su, Gaoxing; Peng, Xiaowu; Yuan, Chungang; Jiang, Yiguo; Yan, Bing

2018-08-15

Air pollution worldwide, especially in China and India, has caused serious health issues. Because PM 2.5 particles consist of solid particles of diverse properties with payloads of inorganic, organic and biological pollutants, it is still not known what the major toxic components are and how these components induce toxicities. To explore this complex issue, we apply reductionism principle and an ultrafine particle library approach in this work. From investigation of 63 diversely functionalized ultrafine particles (FUPs) with adsorbed key pollutants, our findings indicate that 1) only certain pollutants in the payloads of PM 2.5 are responsible for causing cellular oxidative stress, cell apoptosis, and cytotoxicity while the particle carriers are much less toxic; 2) pollutant-induced cellular oxidative stress and oxidative stress-triggered apoptosis are identified as one of the dominant mechanisms for PM 2.5 -induced cytotoxicity; 3) each specific toxic component on PM 2.5 (such as As, Pb, Cr or BaP) mainly affects its specific target organ(s) and, adding together, these pollutants may cause synergistic or just additive effects. Our findings demonstrate that reductionism concept and model PM 2.5 particle library approach are very effective in our endeavor to search for a better understanding of PM 2.5 -induced health effects. Copyright © 2018 Elsevier Inc. All rights reserved.

Nephrotoxic effects of lead nitrate exposure in diabetic and nondiabetic rats: Involvement of oxidative stress and the protective role of sodium selenite.

PubMed

Baş, Hatice; Kalender, Yusuf

2016-10-01

Heavy metals are known to be toxic to organisms. The present study was undertaken to evaluate the protective effect of sodium selenite against lead nitrate (LN)-induced nephrotoxicity in diabetic and nondiabetic rats. Animals were divided into eight groups where the first was served as a control, whereas the remaining groups were treated with sodium selenite (1 mg/kg b.w.), LN (22.5 mg/kg b.w.) and a combination of LN and sodium selenite and diabetic forms of these groups. Changes in antioxidant enzyme activities, malondialdehide levels, serum urea, uric acid, creatinine levels, body, and kidney weights and histopathological changes were determined after 28 days. LN caused severe histopathological changes, increment in urea, uric acid, creatinine, and MDA levels, also decreasing in antioxidant enzyme activities, body, and kidney weights. In sodium selenite + LN group, we observed the protective effect of sodium selenite on examining parameters. Also diabetes caused alterations on these parameters compared with nondiabetic animals. We found that sodium selenite did not show protective effect on diabetes caused damages. As a result, LN caused nephrotoxicity and sodium selenite alleviated this toxicity but sodium selenite did not protect kidneys against diabetes mediated toxicity. Also, LN caused more harmfull effects in diabetic groups compared with nondiabetic groups. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1229-1240, 2016. © 2015 Wiley Periodicals, Inc.

The uncertainty of the toxic effect of stings from the Urtica nettle on hunting dogs.

PubMed

Edom, Gillian

2002-02-01

This paper questions the effect of the sting from the Urtica species of nettle on hunting dogs, particularly in the US. Research in this area is limited and is reflected in the wide use of a particularly unsound literature reference on the subject. A general account is given of which types of "nettle" plant have a toxic sting, how the mechanism of the sting works, and the toxic substances it contains. The effects experienced by hunting dogs appear to represent a condition other than contact urticaria, which is normall the result of being stung by nettles (Urticas in particular). The possibility is discussed that the signs were caused by another plant, also commonly labelled a nettle, or that possibly they were caused by other than the direct stinging of soft tissues. Further research should be done on the toxic elements in the sting of Urtica chamaedryoides, indicated in some literature as the "guilty" plant.

The effect of body condition on serum concentrations of two teratogenic alkaloids (anagyrine and ammodendrine) from Lupines (Lupinus spp.) that cause crooked calf disease.

USDA-ARS?s Scientific Manuscript database

Several species of lupine (Lupinus spp.) are toxic to livestock, causing death losses in sheep and cattle but more commonly “crooked calf disease” in pregnant range cows. The major toxic alkaloids in lupine are of the quinolizidine alkaloid group and include the teratogen anagyrine, which is primari...

Combined effect of salt and drought on boron toxicity in Puccinellia tenuiflora.

PubMed

Liu, Chunguang; Dai, Zheng; Xia, Jingye; Chang, Can; Sun, Hongwen

2018-08-15

Boron toxicity is a worldwide problem, usually accompanied by salt (NaCl) and drought. The combined stresses may induce complex toxicity to the plant. The aim of the present study was to investigate how the combined stresses of salt and drought affect B toxicity in plants. Puccinellia tenuiflora seedlings were planted in vermiculite. A three (B) × three (salt) × three (drought) factorial experiment (for a total of 27 treatments) was conducted. After a 30-day cultivation, plants were harvested to determine dry weight and the concentrations of B, Na + , K + , Ca 2+ , and Mg 2+ . Plant growth was inhibited by B toxicity, which was alleviated by salt and drought. B stress enhanced B uptake and transport of the plant, which was inhibited by salt and drought. B stress had a little effect on K + and Na + concentration and caused Ca 2+ and Mg 2+ accumulation in the plant. Salt addition increased Na + concentration and inhibited Ca 2+ and Mg 2+ accumulation. Drought addition inhibited Na + accumulation and enhanced Ca 2+ and Mg 2+ accumulation. The combined stresses of salt and drought had a greater alleviation on the inhibition of dry weight caused by B than individual salt and drought. Besides, the combined stresses of salt and drought also enhanced B uptake and inhibited B transport. The results indicate that salt, drought, and the combined stresses of salt and drought all can alleviate B toxicity in P. tenuiflora, the main mechanism of which is the restriction of B and Na + uptake caused by salt and drought. The combined stresses of salt and drought have a greater effect on B toxicity than individual salt and drought. Copyright © 2018 Elsevier Inc. All rights reserved.

Hyperthyroidism: diagnosis and treatment.

PubMed

Reid, Jeri R; Wheeler, Stephen F

2005-08-15

The proper treatment of hyperthyroidism depends on recognition of the signs and symptoms of the disease and determination of the etiology. The most common cause of hyperthyroidism is Graves' disease. Other common causes include thyroiditis, toxic multinodular goiter, toxic adenomas, and side effects of certain medications. The diagnostic workup begins with a thyroid-stimulating hormone level test. When test results are uncertain, measuring radionuclide uptake helps distinguish among possible causes. When thyroiditis is the cause, symptomatic treatment usually is sufficient because the associated hyperthyroidism is transient. Graves' disease, toxic multinodular goiter, and toxic adenoma can be treated with radioactive iodine, antithyroid drugs, or surgery, but in the United States, radioactive iodine is the treatment of choice in patients without contraindications. Thyroidectomy is an option when other treatments fail or are contraindicated, or when a goiter is causing compressive symptoms. Some new therapies are under investigation. Special treatment consideration must be given to patients who are pregnant or breastfeeding, as well as those with Graves' ophthalmopathy or amiodarone-induced hyperthyroidism. Patients' desires must be considered when deciding on appropriate therapy, and dose monitoring is essential.

Sucrose acetate isobutyrate (SAIB): historical aspects of its use in beverages and a review of toxicity studies prior to 1988.

PubMed

Reynolds, R C; Chappel, C I

1998-02-01

Sucrose acetate isobutyrate (SAIB), a mixture of esters of sucrose with a composition approximating the name sucrose diacetate hexaisobutyrate, has been used for over 30 yr in many countries as a 'weighting' or 'density-adjusting' agent in non-alcoholic carbonated and non-carbonated beverages. As part of the demonstration of safety of SAIB as a direct food additive in human diets, a program of toxicity testing was started in the late 1950s that culminated in extensive studies of SAIB in rodents, monkeys and humans over the last decade. This review summarizes the toxicity data, accrued up until 1988, that precede the safety studies published elsewhere in this issue. SAIB has been shown to have very low acute and chronic toxicities in rats, monkeys, and, except for effects on the liver, in dogs at feeding levels of up to 10% in the diet. Slight effects seen in rats and monkeys at levels of 10% in the diet are unlikely to be directly caused by exposure to SAIB. In dogs, however, SAIB causes decreases in bromosulfophthalein (BSP) and indocyanine green (ICG) elimination from the serum immediately following a single dose, indicative of interference with biliary excretion. On repeated feeding in dogs, SAIB caused increases in serum alkaline phosphatase levels, but enzymes indicative of toxic effects on the liver were unaffected. On prolonged feeding to dogs, SAIB caused changes in liver morphology revealed by electron microscopy. All of these effects were reversed when SAIB was withdrawn from the diet. The no-effect level for these effects in dogs was near 5 mg/kg body weight, but these effects were not seen in rats fed up to 4 g/kg body weight/day, monkeys fed up to 10 g/kg body weight/day, or humans fed up to 20 mg/kg body weight/day. The toxicity and pharmacological studies in dogs, rats and monkeys suggest that the effect of SAIB on biliary excretion and liver morphology in dogs is essentially pharmacological rather than toxicological in nature and that the difference between the effects in dogs at levels as low as 5 mg/kg body weight/day, and the lack of effects in rats or monkeys at levels up to 10 g/kg/day is not merely a quantitative difference between species, but an absolute qualitative difference.

Metabolomics reveals the mechanisms for the cardiotoxicity of Pinelliae Rhizoma and the toxicity-reducing effect of processing

NASA Astrophysics Data System (ADS)

Su, Tao; Tan, Yong; Tsui, Man-Shan; Yi, Hua; Fu, Xiu-Qiong; Li, Ting; Chan, Chi Leung; Guo, Hui; Li, Ya-Xi; Zhu, Pei-Li; Tse, Anfernee Kai Wing; Cao, Hui; Lu, Ai-Ping; Yu, Zhi-Ling

2016-10-01

Pinelliae Rhizoma (PR) is a commonly used Chinese medicinal herb, but it has been frequently reported about its toxicity. According to the traditional Chinese medicine theory, processing can reduce the toxicity of the herbs. Here, we aim to determine if processing reduces the toxicity of raw PR, and to explore the underlying mechanisms of raw PR-induced toxicities and the toxicity-reducing effect of processing. Biochemical and histopathological approaches were used to evaluate the toxicities of raw and processed PR. Rat serum metabolites were analyzed by LC-TOF-MS. Ingenuity pathway analysis of the metabolomics data highlighted the biological pathways and network functions involved in raw PR-induced toxicities and the toxicity-reducing effect of processing, which were verified by molecular approaches. Results showed that raw PR caused cardiotoxicity, and processing reduced the toxicity. Inhibition of mTOR signaling and activation of the TGF-β pathway contributed to raw PR-induced cardiotoxicity, and free radical scavenging might be responsible for the toxicity-reducing effect of processing. Our data shed new light on the mechanisms of raw PR-induced cardiotoxicity and the toxicity-reducing effect of processing. This study provides scientific justifications for the traditional processing theory of PR, and should help in optimizing the processing protocol and clinical combinational application of PR.

The Prestige oil spill: a laboratory study about the toxicity of the water-soluble fraction of the fuel oil.

PubMed

Navas, José M; Babín, Mar; Casado, Susana; Fernández, Carlos; Tarazona, José V

2006-07-01

The Prestige oil spill caused severe effects on the coastal fauna and flora due to direct contact of organisms with the fuel oil. However, the water soluble fraction (WSF) of the fuel oil can also provoke deleterious effects in the long term and even in regions not directly affected by the spill. Our objective was to determine the toxicity of the WSF using a battery of laboratory toxicity tests. To obtain a WSF in the laboratory, a sample of the spilled fuel was mixed with adequate medium, sonicated, agitated and filtered. No cytotoxic effects were detected in RTG-2 cells exposed to the WSF. In an algae growth inhibition test (OECD test guideline 201) the WSF did not affect the growth of Chlorella vulgaris. Furthermore, acute and reproductive toxicity tests (OECD test guideline 202) carried out using Daphnia magna did not indicate any deleterious effect of the WSF. In a bioassay designed in our laboratory, D. magna were fed with algae previously exposed to the fuel, but no toxic effects were detected. However, the WSF was able to induce a dose-dependent increase of ethoxyresorufin-O-deethylase activity in RTG-2 cells, indicating the presence of chemicals that could cause sub-lethal effects to organisms. After chemical analyses it was established that the final total quantity of polyaromatic hydrocarbons dissolved in medium was approximately 70 ng/ml. These low concentrations explain the observed lack of toxicity.

[Hydroxymethyluracil in the correction of adverse effects caused by chemotherapy of malignant neoplasms].

PubMed

Sakaeva, D D

2004-01-01

Hydroxymethyluracil (HMU) in a dose of 1.5-3 g/day produces a stimulant effect upon leukopoiesis and granulocytopoiesis in cases of toxic neutropenia caused by chemotherapy. In the same dose range, HMU produces immunostimulant action in patients with immune deficit caused by oncopathology and chemotherapy.

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.

Myristicin and phenytoin toxicity in an infant

PubMed Central

Sivathanu, Shobhana; Sampath, Sowmya; David, Henry Suresh; Rajavelu, Kulandai Kasthuri

2014-01-01

A developmentally normal infant presented with repeated episodes of afebrile status epilepticus following nutmeg ingestion. He had developed two episodes of afebrile status epilepticus and had received different treatments earlier, but the details of treatment were not available. On admission, he redeveloped convulsions and loading doses of phenytoin, phenobarbitone and midazolam were administered. However, seizures persisted and extrapyramidal movements, nystagmus and visual dysfunction were noted. Iatrogenic phenytoin toxicity was considered and confirmed by drug levels. His symptoms completely disappeared after discontinuation of phenytoin therapy. The initial seizures were attributed to myristicin, an active component of nutmeg, because of the temporal association. However, the subsequent seizures were due to phenytoin toxicity caused by administration of multiple loading doses. This case highlights that nutmeg, a spice, can cause serious toxic effects like status epilepticus. Furthermore, treatment of status epilepticus with phenytoin can cause iatrogenic seizures due to its narrow therapeutic range. PMID:24903724

Protective effects of a natural herbal compound quercetin against snake venom-induced hepatic and renal toxicities in rats.

PubMed

Al-Asmari, Abdulrahman K; Khan, Haseeb A; Manthiri, Rajamohamed A; Al-Khlaiwi, Ahmad A; Al-Asmari, Bayan A; Ibrahim, Khalid E

2018-05-08

Echis pyramidum is a highly poisonous viper snake. Previous studies have shown acute phase hepatic and renal toxicities of Echis pyramidum venom (EPV) in rats. This study reports the protective effects of a natural herbal compound quercetin (QRC) on EPV-induced hepatic and renal toxicities in rats. A singly injection of EPV (4.76 mg/kg) caused significant increase in serum biomarkers of liver and kidney function. Pre-treatment of QRC (10 mg/kg) significantly reduced the toxic effects of EPV on functional impairment in liver and kidneys of rats. Administration of QRC also reversed EPV-induced increase in lipid peroxidation and decrease in total thiols. The histopathology of liver showed fat accumulation, focal degeneration and cytoplasmic vacuolation of hepatocytes in EPV treated rats. EPV also caused renal tubular dilation and focal atrophy of glomerular tufts in rat kidneys. Administration of QRC prevented EPV-induced structural tissue damage in liver and kidneys of rats. In conclusion, QRC significantly inhibited the acute phase toxic effects of EPV on liver and kidneys of rats by preventing the oxidative stress in these organs. QRC is also known for its anti-inflammatory, anti-edema, anti-hemorrhagic and PLA2-inhibitory properties and therefore may be regarded as a multi-action antidote against snake venom toxicity. Copyright © 2018 Elsevier Ltd. All rights reserved.

Synergistic effect of piperonyl butoxide on acute toxicity of pyrethrins to Hyalella azteca.

PubMed

Giddings, Jeffrey; Gagne, James; Sharp, Janice

2016-08-01

A series of acute toxicity tests with the amphipod Hyalella azteca was performed to quantify the synergistic effect of piperonyl butoxide (PBO) on pyrethrin toxicity. Concentrations of PBO <4 µg/L caused no toxicity enhancement, whereas toxicity increased with PBO concentrations between 4 µg/L and 15 µg/L. Additive toxicity calculations showed that true synergism accounted for an increase in pyrethrin toxicity (decrease in median lethal concentration) of 1.4-fold to 1.6-fold and varied only slightly between 4 µg/L and 15 µg/L PBO, whereas direct toxicity of PBO accounted for an additional increase in mixture toxicity (up to 3.2-fold) that was proportional to PBO concentration. The results can be used to assess the risk of measured or predicted co-occurring concentrations of PBO and pyrethrins in surface waters. Environ Toxicol Chem 2016;35:2111-2116. © 2016 SETAC. © 2016 SETAC.

Acute cardiovascular toxicity of sterilizers, PHMG, and PGH: severe inflammation in human cells and heart failure in zebrafish.

PubMed

Kim, Jae-Yong; Kim, Hak Hyeon; Cho, Kyung-Hyun

2013-06-01

In 2011, dozens of children and pregnant women in Korea died by exposure to sterilizer for household humidifier, such as Oxy(®) and Cefu(®). Until now, however, it remains unknown how the sterilizer affect the human health to cause the acute deaths. To find its toxicity for organ, we investigated the putative toxicity of the sterilizer in the cardiovascular system. The sterilizers, polyhexamethylene guanidine phosphate (PHMG, Cefu(®)), and oligo-[2-(2-ethoxy)-ethoxyethyl)-guanidinium-chloride (PGH, Oxy(®)) were treated to human lipoproteins, macrophages, and dermal fibroblast cells. The PGH and PHMG at normal dosages caused severe atherogenic process in human macrophages, cytotoxic effect, and aging in human dermal cell. Zebrafish embryos, which were exposed to the sterilizer, showed early death with acute inflammation and attenuated developmental speed. All zebrafish exposed to the working concentration of PHMG (final 0.3 %) and PGH (final 10 mM) died within 70 min and displayed acute increases in serum triacylglycerol level and fatty liver induction. The dead zebrafish showed severe accumulation of fibrous collagen in the bulbous artery of the heart with elevation of reactive oxygen species. In conclusion, the sterilizers showed acute toxic effect in blood circulation system, causing by severe inflammation, atherogenesis, and aging, with embryo toxicity.

Acrolein Can Cause Cardiovascular Disease: A Review.

PubMed

Henning, Robert J; Johnson, Giffe T; Coyle, Jayme P; Harbison, Raymond D

2017-07-01

Acrolein is a highly reactive unsaturated aldehyde that is formed during the burning of gasoline and diesel fuels, cigarettes, woods and plastics. In addition, acrolein is generated during the cooking or frying of food with fats or oils. Acrolein is also used in the synthesis of many organic chemicals and as a biocide in agricultural and industrial water supply systems. The total emissions of acrolein in the United States from all sources are estimated to be 62,660 tons/year. Acrolein is classified by the Environmental Protection Agency as a high-priority air and water toxicant. Acrolein can exert toxic effects following inhalation, ingestion, and dermal exposures that are dose dependent. Cardiovascular tissues are particularly sensitive to the toxic effects of acrolein based primarily on in vitro and in vivo studies. Acrolein can generate free oxygen radical stress in the heart, decrease endothelial nitric oxide synthase phosphorylation and nitric oxide formation, form cytoplasmic and nuclear protein adducts with myocyte and vascular endothelial cell proteins and cause vasospasm. In this manner, chronic exposure to acrolein can cause myocyte dysfunction, myocyte necrosis and apoptosis and ultimately lead to cardiomyopathy and cardiac failure. Epidemiological studies of acrolein exposure and toxicity should be developed and treatment strategies devised that prevent or significantly limit acrolein cardiovascular toxicity.

PERSISTENT, BIOACCUMULATIVE, AND TOXIC POLLUTANTS (PBTS)

EPA Science Inventory

Article describes the class of compounds known as persistent, bioaccumulative, and toxic pollutants (known as PBTs), including the mechanisms responsible for ability to build up the food chain and for causing adverse health effects and ecosystem damage. Exposure to numerous PBTs ...

Differences between co-cultures and monocultures in testing the toxicity of particulate matter derived from log wood and pellet combustion.

PubMed

Kasurinen, Stefanie; Happo, Mikko S; Rönkkö, Teemu J; Orasche, Jürgen; Jokiniemi, Jorma; Kortelainen, Miika; Tissari, Jarkko; Zimmermann, Ralf; Hirvonen, Maija-Riitta; Jalava, Pasi I

2018-01-01

In vitro studies with monocultures of human alveolar cells shed deeper knowledge on the cellular mechanisms by which particulate matter (PM) causes toxicity, but cannot account for mitigating or aggravating effects of cell-cell interactions on PM toxicity. We assessed inflammation, oxidative stress as well as cytotoxic and genotoxic effects induced by PM from the combustion of different types of wood logs and softwood pellets in three cell culture setups: two monocultures of either human macrophage-like cells or human alveolar epithelial cells, and a co-culture of these two cell lines. The adverse effects of the PM samples were compared between these setups. We detected clear differences in the endpoints between the mono- and co-cultures. Inflammatory responses were more diverse in the macrophage monoculture and the co-culture compared to the epithelial cells where only an increase of IL-8 was detected. The production of reactive oxygen species was the highest in epithelial cells and macrophages seemed to have protective effects against oxidative stress from the PM samples. With no metabolically active cells at the highest doses, the cytotoxic effects of the PM samples from the wood log combustion were far more pronounced in the macrophages and the co-culture than in the epithelial cells. All samples caused DNA damage in macrophages, whereas only beech and spruce log combustion samples caused DNA damage in epithelial cells. The organic content of the samples was mainly associated with cytotoxicity and DNA damage, while the metal content of the samples correlated with the induction of inflammatory responses. All of the tested PM samples induce adverse effects and the chemical composition of the samples determines which pathway of toxicity is induced. In vitro testing of the toxicity of combustion-derived PM in monocultures of one cell line, however, is inadequate to account for all the possible pathways of toxicity.

Differences between co-cultures and monocultures in testing the toxicity of particulate matter derived from log wood and pellet combustion

PubMed Central

Happo, Mikko S.; Rönkkö, Teemu J.; Orasche, Jürgen; Jokiniemi, Jorma; Kortelainen, Miika; Tissari, Jarkko; Zimmermann, Ralf; Hirvonen, Maija-Riitta; Jalava, Pasi I.

2018-01-01

Background In vitro studies with monocultures of human alveolar cells shed deeper knowledge on the cellular mechanisms by which particulate matter (PM) causes toxicity, but cannot account for mitigating or aggravating effects of cell-cell interactions on PM toxicity. Methods We assessed inflammation, oxidative stress as well as cytotoxic and genotoxic effects induced by PM from the combustion of different types of wood logs and softwood pellets in three cell culture setups: two monocultures of either human macrophage-like cells or human alveolar epithelial cells, and a co-culture of these two cell lines. The adverse effects of the PM samples were compared between these setups. Results We detected clear differences in the endpoints between the mono- and co-cultures. Inflammatory responses were more diverse in the macrophage monoculture and the co-culture compared to the epithelial cells where only an increase of IL-8 was detected. The production of reactive oxygen species was the highest in epithelial cells and macrophages seemed to have protective effects against oxidative stress from the PM samples. With no metabolically active cells at the highest doses, the cytotoxic effects of the PM samples from the wood log combustion were far more pronounced in the macrophages and the co-culture than in the epithelial cells. All samples caused DNA damage in macrophages, whereas only beech and spruce log combustion samples caused DNA damage in epithelial cells. The organic content of the samples was mainly associated with cytotoxicity and DNA damage, while the metal content of the samples correlated with the induction of inflammatory responses. Conclusions All of the tested PM samples induce adverse effects and the chemical composition of the samples determines which pathway of toxicity is induced. In vitro testing of the toxicity of combustion-derived PM in monocultures of one cell line, however, is inadequate to account for all the possible pathways of toxicity. PMID:29466392

Toxic Proteins in Neurodegenerative Disease

NASA Astrophysics Data System (ADS)

Taylor, J. Paul; Hardy, John; Fischbeck, Kenneth H.

2002-06-01

A broad range of neurodegenerative disorders is characterized by neuronal damage that may be caused by toxic, aggregation-prone proteins. As genes are identified for these disorders and cell culture and animal models are developed, it has become clear that a major effect of mutations in these genes is the abnormal processing and accumulation of misfolded protein in neuronal inclusions and plaques. Increased understanding of the cellular mechanisms for disposal of abnormal proteins and of the effects of toxic protein accumulation on neuronal survival may allow the development of rational, effective treatment for these disorders.

A Marine Hazardous Substances Data System. Volume 2.

DTIC Science & Technology

1985-12-01

substances are considered by the Task III panel ill to exhibit the greatest potential for occupational health effects and warrant the greatest precautions for...Hazards Branch 1111 N NIOSH Registry of Toxic Effects of Chemical Substances 1121 P NIOSH/OSHA Pocket Guideto Chemical Hazards [61 U Undocumented Source...NAS Hazard Liquid or -- Rating Vapor Irritant Solid Irritant Poisons 0 No effect No effect No effect 1 Slight Effect Causes skin Slightly toxic

Pulmonary effects induced by ultrafine PTFE particles.

PubMed

Johnston, C J; Finkelstein, J N; Mercer, P; Corson, N; Gelein, R; Oberdörster, G

2000-11-01

PTFE (polytetrafluoroethylene) fumes consisting of large numbers of ultrafine (uf) particles and low concentrations of gas-phase compounds can cause severe acute lung injury. Our studies were designed to test three hypotheses: (i) uf PTFE fume particles are causally involved in the induction of acute lung injury, (ii) uf PTFE elicit greater pulmonary effects than larger sized PTFE accumulation mode particles, and (iii) preexposure to the uf PTFE fume particles will induce tolerance. We used uf Teflon (PTFE) fumes (count median particle size approximately 16 nm) generated by heating PTFE in a tube furnace to 486 degrees C to evaluate principles of ultrafine particle toxicity. Teflon fumes at ultrafine particle concentrations of 50 microg/m(3) were extremely toxic to rats when inhaled for only 15 min. We found that when generated in argon, the ultrafine Teflon particles alone are not toxic at these exposure conditions; neither were Teflon fume gas-phase constituents when generated in air. Only the combination of both phases when generated in air caused high toxicity, suggesting either the existence of radicals on the surface or a carrier mechanism of the ultrafine particles for adsorbed gas compounds. Aging of the fresh Teflon fumes for 3.5 min led to a predicted coagulation to >100 nm particles which no longer caused toxicity in exposed animals. This result is consistent with a greater toxicity of ultrafine particles compared to accumulation mode particles, although changes in particle surface chemistry during the aging process may have contributed to the diminished toxicity. Furthermore, the pulmonary toxicity of the ultrafine Teflon fumes could be prevented by adapting the animals with short 5-min exposures on 3 days prior to a 15-min exposure. Messages encoding antioxidants and chemokines were increased substantially in nonadapted animals, yet were unaltered in adapted animals. This study shows the importance of preexposure history for the susceptibility to acute ultrafine particle effects. Copyright 2000 Academic Press.

[The toxicity variation of organic extracts in drinking water treatment processes].

PubMed

Mei, M; Wei, S; Zijian, W; Wenhua, W; Baohua, Z; Suxia, Z

2001-01-01

Source water samples and outlet water samples from different treatment processes of the Beijing Ninth Water Works were concentrated in situ with XAD-2 filled columns. GC-MS analysis and toxic assessment including acute toxicity evaluation by luminescent bacterium bioassay(Q67 strains) and mutagenicity assessment by Ames test(TA98 and TA100 strains with and without S9 addition) were conducted on these samples. The results showed that prechlorination caused the direct and indirect frame shift mutagenicity as well as indirect base pair substitute mutagenicity. Addition of coagulant may increase the base pair substitute mutagenic effects greatly. Sand and coal filtration and granular activated carbon filtration could effectively remove most of the formed mutagens. The rechlorination do not obviously increase the mutagenic effects. No mutagenic effect was observed in tap water. Acute toxicity showed the same variation with that of mutagenicity during the treatment processes. Sample from flocculation treatment process was found to be the most toxic sample. Results of GC-MS analysis showed that water in this plant was not contaminated by PCB. Concentrations of toluene, naphthalene and phenol increased in flocculation treatment process and in tap water. However, the concentrations of these substances were at the level of microgram/L, therefore, were not high enough to cause mutagenicity.

Effects of glyphosate and its formulation, roundup, on reproduction in zebrafish (Danio rerio).

PubMed

Uren Webster, Tamsyn M; Laing, Lauren V; Florance, Hannah; Santos, Eduarda M

2014-01-21

Roundup and its active ingredient glyphosate are among the most widely used herbicides worldwide and may contaminate surface waters. Research suggests both Roundup and glyphosate induce oxidative stress in fish and may also cause reproductive toxicity in mammalian systems. We aimed to investigate the reproductive effects of Roundup and glyphosate in fish and the potential associated mechanisms of toxicity. To do this, we conducted a 21-day exposure of breeding zebrafish (Danio rerio) to 0.01, 0.5, and 10 mg/L (glyphosate acid equivalent) Roundup and 10 mg/L glyphosate. 10 mg/L glyphosate reduced egg production but not fertilization rate in breeding colonies. Both 10 mg/L Roundup and glyphosate increased early stage embryo mortalities and premature hatching. However, exposure during embryogenesis alone did not increase embryo mortality, suggesting that this effect was caused primarily by exposure during gametogenesis. Transcript profiling of the gonads revealed 10 mg/L Roundup and glyphosate induced changes in the expression of cyp19a1 and esr1 in the ovary and hsd3b2, cat, and sod1 in the testis. Our results demonstrate that these chemicals cause reproductive toxicity in zebrafish, although only at high concentrations unlikely to occur in the environment, and likely mechanisms of toxicity include disruption of the steroidogenic biosynthesis pathway and oxidative stress.

Screening of Toxic Effects of Bisphenol A and Products of Its Degradation: Zebrafish (Danio rerio) Embryo Test and Molecular Docking.

PubMed

Makarova, Katerina; Siudem, Pawel; Zawada, Katarzyna; Kurkowiak, Justyna

2016-10-01

Bisphenol A (BPA) acts as an endocrine-disrupting compound even at a low concentration. Degradation of BPA could lead to the formation of toxic products. In this study, we compare the toxicity of BPA and seven intermediate products of its degradation. The accuracy of three molecular docking programs (Surflex, Autodock, and Autodock Vina) in predicting the binding affinities of selected compounds to human (ERα, ERβ, and ERRγ) and zebrafish (ERα, ERRγA, and ERRγB) estrogen and estrogen-related receptors was evaluated. The docking experiments showed that 4-isopropylphenol could have similar toxicity to that of BPA due to its high affinity to ERRγ and ERRγB and high octanol-water partitioning coefficient. The least toxic compounds were hydroquinone and phenol. Those compounds as well as BPA were screened in the zebrafish (Danio rerio) embryo test. 4-isopropylphenol had the strongest toxic effect on zebrafish embryos and caused 100% lethality shortly after exposure. BPA caused the delay in development, multiple deformations, and low heartbeats (30 bps), whereas hydroquinone had no impact on the development of the zebrafish embryo. Thus, the results of zebrafish screening are in good agreement with our docking experiment. The molecular docking could be used to screen the toxicity of other xenoestrogens and their products of degradation.

The toxicity of zinc oxide nanoparticles to Lemna minor (L.) is predominantly caused by dissolved Zn.

PubMed

Chen, Xiaolin; O'Halloran, John; Jansen, Marcel A K

2016-05-01

Nano-ZnO particles have been reported to be toxic to many aquatic organisms, although it is debated whether this is caused by nanoparticles per sé, or rather dissolved Zn. This study investigated the role of dissolved Zn in nano-ZnO toxicity to Lemna minor. The technical approach was based on modulating nano-ZnO dissolution by either modifying the pH of the growth medium and/or surface coating of nano-ZnO, and measuring resulting impacts on L. minor growth and physiology. Results show rapid and total dissolution of nano-ZnO in the medium (pH 4.5). Quantitatively similar toxic effects were found when L. minor was exposed to nano-ZnO or the "dissolved Zn equivalent of dissolved nano-ZnO". The conclusion that nano-ZnO toxicity is primarily caused by dissolved Zn was further supported by the observation that phytotoxicity was absent on medium with higher pH-values (>7), where dissolution of nano-ZnO almost ceased. Similarly, the reduced toxicity of coated nano-ZnO, which displays a slower Zn dissolution, is also consistent with a major role for dissolved Zn in nano-ZnO toxicity. Copyright © 2016 Elsevier B.V. All rights reserved.

A review of the use of clozapine levels to guide treatment and determine cause of death.

PubMed

Stark, Anne; Scott, James

2012-09-01

To review the literature to examine the use of clozapine levels to (i) guide therapy and prevent toxicity in clinical care and (ii) determine cause of death in post-mortem examination of patients who were treated with clozapine. MEDLINE was searched in December 2010 using the following keywords: 'clozapine levels', 'clozapine and toxicity', 'clozapine and death', 'clozapine and mortality' and 'post-mortem redistribution'. Data was also collected from the 2010 MIMS Annual. The literature reported significant variation in clozapine levels attained with any given dose, and considerable variability in the clinical response achieved at any given clozapine level. The lowest effective clozapine levels ranged from 250 to 550 µg/L, while the recommended upper limit to prevent toxicity varied from 600 to 2000 µg/L. There was minimal correlation between clozapine levels and side effects, with the exception of sedation, hypotension and seizure activity. The risk of seizures increased with plasma clozapine levels greater than 600 µg/L or rapid upward titration. In addition to prescribed dose, there are many factors that influence plasma clozapine levels. After death, the process of post-mortem drug redistribution resulted in 3.00 to 4.89 times increases in clozapine levels in central blood vessels and 1.5 fold increases in peripheral vessels compared to ante-mortem levels. The exact range of clozapine levels that corresponds to toxicity remains unclear. However, levels between 350 µg/L and 1000 µg/L achieved with gradual upward titration are more likely to be effective and less likely to cause toxicity. Ongoing clozapine level monitoring is indicated, especially when (i) prescribing higher doses (> 600 mg/day) of clozapine, (ii) there has been a change in a patient's concomitant pharmacotherapy or cigarette use and (iii) there has been a suboptimal response to treatment. The use of post-mortem clozapine levels to determine clozapine toxicity as a cause of death is unreliable.

Effects of arsenic toxicity on morphological characters in blackgram (Vigna mungo L.) during early growth stage.

PubMed

Shamim, M Z; Pandey, A

2017-07-31

Blackgram is an important pulse crop of the tropic and sub-tropic area and has been identified as a potential crop in many countries. In the south-East Asia arsenic toxicity in soil and water is one of the most environmental problems. Crop productivity is highly affected by cultivation in arsenic polluted soil or irrigation through arsenic polluted water. The present study was conducted to evaluate the effect of arsenic (As) on fresh shoot length, fresh shoot weight, fresh root length, fresh shoot weight and total fresh biomass, The results indicate that root length is more affected than shoot length due to arsenic toxicity. The fresh shoot weight observed was more affected than fresh root weight. This study indicates that arsenic toxicity causes the deleterious effect on blackgram growth. The toxic effect of blackgram depends on the genotypic variability. Some blackgram genotypes show very less toxic effect of arsenic due to its genetic makeup. Experimental findings of study indicate that longer root length and more shoot weight in arsenic stress condition may be tolerant blackgram genotype to arsenic toxicity.

The Ability of PAS, Acetylsalicylic Acid and Calcium Disodium EDTA to Protect Against the Toxic Effects of Manganese on Mitochondrial Respiration in Gill of Crassostrea virginica.

PubMed

Crawford, Sherine; Davis, Kiyya; Saddler, Claudette; Joseph, Jevaun; Catapane, Edward J; Carroll, Margaret A

2011-01-01

Manganese (Mn) is an essential metal that at excessive levels in brain causes Manganism, a condition similar to Parkinson's disease. Previously we showed that Mn had a neurotoxic effect on the dopaminergic, but not serotonergic, innervation of the lateral ciliated cells in the gill of the Eastern Oyster, Crassostrea virginica. While the mechanism of action of Mn toxicity is not completely understood, studies suggest that Mn toxicity may involve mitochondrial damage and resulting neural dysfunction in the brain's dopaminergic system. In this study we utilized micro-batch chambers and oxygen probes to measure oyster gill mitochondrial respiration in the presence of Mn and potential Mn blockers. The addition of Mn to respiring mitochondria caused a dose dependent decrease in mitochondrial O(2) consumption. Pretreating mitochondria with calcium disodium EDTA (caEDTA), p aminosalicylic acid (PAS) or acetylsalicylic acid (ASA) before Mn additions, provided full protection against the toxic effects of Mn. While mitochondrial pretreatment with any of the 3 drugs effectively blocked Mn toxicity, none of the drugs tested was able to reverse the decrease in mitochondrial O(2) consumption seen in Mn treated mitochondria. The study found that high levels of Mn had a toxic effect on gill mitochondrial O(2) consumption and that this effect could be blocked by the drugs caEDTA, PAS and ASA. C. virginica continues to be a good model with which to investigate the mechanism that underlies manganese neurotoxcity and in the pharmacological study of drugs to treat or prevent Manganism.

The Ability of PAS, Acetylsalicylic Acid and Calcium Disodium EDTA to Protect Against the Toxic Effects of Manganese on Mitochondrial Respiration in Gill of Crassostrea virginica

PubMed Central

Crawford, Sherine; Davis, Kiyya; Saddler, Claudette; Joseph, Jevaun; Catapane, Edward J.; Carroll, Margaret A.

2011-01-01

Manganese (Mn) is an essential metal that at excessive levels in brain causes Manganism, a condition similar to Parkinson's disease. Previously we showed that Mn had a neurotoxic effect on the dopaminergic, but not serotonergic, innervation of the lateral ciliated cells in the gill of the Eastern Oyster, Crassostrea virginica. While the mechanism of action of Mn toxicity is not completely understood, studies suggest that Mn toxicity may involve mitochondrial damage and resulting neural dysfunction in the brain’s dopaminergic system. In this study we utilized micro-batch chambers and oxygen probes to measure oyster gill mitochondrial respiration in the presence of Mn and potential Mn blockers. The addition of Mn to respiring mitochondria caused a dose dependent decrease in mitochondrial O2 consumption. Pretreating mitochondria with calcium disodium EDTA (caEDTA), p aminosalicylic acid (PAS) or acetylsalicylic acid (ASA) before Mn additions, provided full protection against the toxic effects of Mn. While mitochondrial pretreatment with any of the 3 drugs effectively blocked Mn toxicity, none of the drugs tested was able to reverse the decrease in mitochondrial O2 consumption seen in Mn treated mitochondria. The study found that high levels of Mn had a toxic effect on gill mitochondrial O2 consumption and that this effect could be blocked by the drugs caEDTA, PAS and ASA. C. virginica continues to be a good model with which to investigate the mechanism that underlies manganese neurotoxcity and in the pharmacological study of drugs to treat or prevent Manganism. PMID:21977482

[Comparative toxicity of photosensitizers in varying destruction].

PubMed

Sinitsina, O O; Zholdakova, Z I; Poliakova, E E; Golovach, E N; Sycheva, L P; Beliaeva, N N; Kuznetsova, N A

2007-01-01

The toxicity of the photosensitizers proflavine acetate (PA) versus methylene blue (MB) was evaluated during their varying destruction. Under the influence of visible light, a partial (25%) transformation of the photosensitizers was shown to be attended by their enhanced toxicity and 100% destruction of the parent substances caused a reduction in their hazard. PA and its phototransformation products mainly affect the antiperoxide protection system and the structural and functional states of the liver, kidney, and duodenum. The maximum noneffective dose is 0.002 mg/kg. The possibility of using PA for water disinfection depends on the ratio of safe and effective concentrations. A partial (25%) MB destruction products cause mutagenic effects; the permissible dose of the mutagen is 0.00025 mg/kg. MB is not recommended for disinfection of all types of waters.

Dietary strategies for the treatment of cadmium and lead toxicity.

PubMed

Zhai, Qixiao; Narbad, Arjan; Chen, Wei

2015-01-14

Cadmium (Cd) and lead (Pb) are toxic heavy metals that cause adverse health effects in humans and animals. Chelation therapy, the conventional treatment for heavy metal toxicity, is reported to have a number of safety and efficacy issues. Recent studies have shown that dietary supplements play important roles in protecting against Cd and Pb toxicity. This paper reviews the evidence for protective effects of essential metals, vitamins, edible plants, phytochemicals, probiotics and other dietary supplements against Cd and Pb toxicity and describes the proposed possible mechanisms. Based on these findings, dietary strategies are recommended for people at risk of Cd and Pb exposure. The application of these strategies is advantageous for both the prevention and alleviation of Cd and Pb toxicity, as such supplements can be added easily and affordably to the daily diet and are expected to have very few side effects compared to the chelation therapy.

Dietary Strategies for the Treatment of Cadmium and Lead Toxicity

PubMed Central

Zhai, Qixiao; Narbad, Arjan; Chen, Wei

2014-01-01

Cadmium (Cd) and lead (Pb) are toxic heavy metals that cause adverse health effects in humans and animals. Chelation therapy, the conventional treatment for heavy metal toxicity, is reported to have a number of safety and efficacy issues. Recent studies have shown that dietary supplements play important roles in protecting against Cd and Pb toxicity. This paper reviews the evidence for protective effects of essential metals, vitamins, edible plants, phytochemicals, probiotics and other dietary supplements against Cd and Pb toxicity and describes the proposed possible mechanisms. Based on these findings, dietary strategies are recommended for people at risk of Cd and Pb exposure. The application of these strategies is advantageous for both the prevention and alleviation of Cd and Pb toxicity, as such supplements can be added easily and affordably to the daily diet and are expected to have very few side effects compared to the chelation therapy. PMID:25594439

Nitric oxide is a mediator of methamphetamine (METH)-induced neurotoxicity. In vitro evidence from primary cultures of mesencephalic cells.

PubMed

Sheng, P; Cerruti, C; Ali, S; Cadet, J L

1996-10-31

METH is a monoaminergic toxic that destroys dopamine terminals in vivo. Oxidative mechanisms associated with DA metabolism are thought to play an important role in its toxic effects. These ideas were supported by the demonstration that CuZn-superoxide dismutase (CuZnSOD) transgenic mice were protected against the toxic effects of the drug. In the present study, we sought to determine if nitric oxide (NO) production was also involved in METH-induced neurotoxicity using primary cultures obtained from fetal rat mesencephalon. METH caused dose- and time-dependent cell death in vitro. Blockade of nitric oxide (NO) formation with several nitric oxide (NO) synthase blockers attenuated METH-mediated toxicity. Moreover, inhibition of ADP-ribosylation with nicotinamide and benzamide also provided protection against the toxicity of the drug. These results, together with our previous results in transgenic mice, support a role for free radicals in METH-induced toxic effects.

Assessment of toxic effects of triclosan on the terrestrial snail (Achatina fulica).

PubMed

Wang, Xiaonan; Liu, Zhengtao; Wang, Wanhua; Yan, Zhenguang; Zhang, Cong; Wang, Weili; Chen, Lihong

2014-08-01

Triclosan (TCS) is a broad-spectrum antimicrobial agent used in personal care products, and as a result, is widespread in the environment. Toxicity tests of TCS on aquatic organisms have been reported, but limited toxicity data on terrestrial species are available. In this study, the 28-d chronic toxicity of TCS on the biomass, shell diameter growth, and total food intake of the terrestrial snail Achatina fulica were tested. Moreover, biochemical responses, including changes in the activity of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), and the content of malondialdehyde (MDA), were examined after 14-d and 28-d exposure. Results showed that TCS had toxic effects on the biomass, shell diameter growth, and total food intake of A. fulica with no observed effect concentration (NOEC) values of 24 mg kg(-1). As for the antioxidant enzymes, TCS caused significant oxidative stress even at the low concentration of 24 mg kg(-1). The CAT and POD activities at the high concentrations of 200 and 340 mg kg(-1), respectively, were significantly inhibited. The SOD and CAT activity in treatments below 118 mg kg(-1) and the MDA content in all treatments showed dose-effect relationships. This study demonstrated that TCS caused adverse effects on terrestrial invertebrates, and provided valuable information for the risk assessment imposed by TCS in the terrestrial environment. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cytotoxic responses of selected insecticides in chick ganglia cultures.

PubMed Central

Sharma, R P; Obersteiner, E J

1981-01-01

Various agricultural chemicals, e.g. pesticides, are known to cause different toxic effects in man and animals. Some of these produce responses involving the nervous tissue. Total of 52 such chemicals, representing organophosphates, carbamates and other miscellaneous insecticides were evaluated to determine their relative cytotoxic effects in avian dorsal root ganglia cultures. Many of these chemicals caused a slight stimulation of cellular growth at very low concentrations. At toxic concentrations, a dose-related but nonspecific inhibition of cell growth occurred. The cytotoxic changes included the decreased migration of cells from the culture implant, varicosities in and shortening of various cells and vacuolization and rounding of neuroglial cells. At high concentrations, pigmentary degeneration and complete abolition of cell growth were observed. The toxic effects were numerically scored in a random blind fashion and the concentrations of individual chemicals to produce a half maximal effect (IC50) in culture were determined from the dose-response curves. The IC50 values for various chemicals ranged from approximately 10(-6) M for compounds like methylparathion, diazinon, paraoxon and Vendex to greater than 10(-2) M for chlorpyriphos and methylchlorpyriphos. No significant correlations of nerve fiber or glial cell cytotoxicity were apparent with other toxic or physico-chemical properties such as lethal dose in animals, cholinesterase inhibition, lipophilicity or water solubility of chemicals. Clinically neurotoxic and nonneurotoxic compounds caused similar cytotoxic effects in ganglia cultures. Images Fig. 3. Fig. 4. Fig. 5. Fig. 6. PMID:7272842

Epidemics of mold poisoning past and present.

PubMed

Meggs, William J

2009-01-01

Molds are ubiquitous throughout the biosphere of planet earth and cause infectious, allergic, and toxic diseases. Toxic diseases arise from exposure to mycotoxins produced by molds. Throughout history, there have been a number of toxic epidemics associated with exposure to mycotoxins. Acute epidemics of ergotism are caused by consumption of grain infested by fungi of the genus Claviceps, which produce the bioactive amine ergotamine that mimics the neurotransmitters norepinephrine, serotonin, and dopamine. Acute aflatoxin outbreaks have occurred from ingestion of corn stored in damp conditions that potentiate growth of the molds of the species Aspergillus. Contemporary construction methods that use cellulose substrates such as fiber board and indoor moisture have caused an outbreak of contaminated buildings with Stachybotrys chartarum, with the extent of health effects still a subject of debate and ongoing research. This article reviews several of the more prominent epidemics and discusses the nature of the toxins. Two diseases that were leading causes of childhood mortality in England in the 1970s and vanished with changing dietary habits, putrid malignant fever, and slow nervous fever were most likely toxic mold epidemics.

Health and Ecological Hazards Caused by Hazardous Substances

EPA Pesticide Factsheets

In some cases, hazardous substances may irritate the skin or eyes, make it difficult to breathe, cause headaches and nausea, result in other types of illness, or far more severe health effects. Toxic effects on the environment can be just as devastating.

Cutaneous toxicity from epidermal growth factor receptor inhibitors: would a subcutaneous desensitization be helpful? Case report.

PubMed

D'Alessio, Andrea; Cecchini, Sara; Di Mauro, Daniela; Geroli, Luca; Villa, Simonetta; Quadri, Antonello; Resta, Davide; Fortugno, Carmelo

2016-11-11

Cetuximab and panitumumab are monoclonal antibody inhibitors that bind the epidermal growth factor receptor (EGFR) currently used in the treatment of metastatic colorectal cancer. The main adverse event related to EGFR inhibitors (EGFR-Is) is cutaneous toxicity, which can cause dosage reduction and interruption of treatment. State-of-the-art management of skin toxicity associated with EGFR-Is therapy involves the topical administration of corticosteroids and oral antibiotics, but is not completely effective in the management of toxicity. Subcutaneous desensitization with increasing concentrations of monoclonal antibodies can induce a tolerance to drug administration and reduce cutaneous adverse effects. To our knowledge, this is the first case in which a reduction or a disappearance of skin toxicity caused by EGFR-Is through subcutaneous desensitization has been achieved. We present cases of 2 Caucasian patients with adenocarcinoma of the colon treated with EGFR-Is who developed severe cutaneous toxicity. A 73-year-old man presented grade 4 skin toxicity of the face and grade 3 skin toxicity of the trunk during treatment with cetuximab. A 68-year-old woman developed G2 rash on the face after the first administration of cetuximab. These patients underwent subcutaneous desensitization with increasing concentrations of EGFR-Is. After this procedure, patients restarted therapy at the optimal dosage with reduction or disappearance of skin toxicity. These cases suggest that by giving rising doses of antibody it is possible to obtain desensitization able to prevent severe cutaneous adverse events in patients treated with EGFR-Is.

The role of the chemical burns caused by hydroxide ion in the toxicity of dermal exposure to tetramethylammonium ion in a rat model.

PubMed

Wu, Chen-Long; Su, Shih-Bin; Lien, Hsiao-Yin; Guo, How-Ran

2012-11-01

To evaluate the role of the chemical burns caused by hydroxide ion in the fatal effects of tetramethylammonium ion (TMA) in dermal exposure to tetramethylammonium hydroxide (TMAH), we conducted a rat study consisting of two-step treatments with dermal exposure to NaOH and tetramethylammonium chloride (TMACl). In the first step, NaOH or saline was administered in the gauze on the shaved skin for 5 min, and in the second step, TMAH, TMACl, or saline was administered in the same way. The mean blood pressure (MBP), heart rate (HR), and survival in rats were compared among seven groups. Dermal exposure to saline and then 2.75 M TMACl introduced limited and temporary non-fatal effects. Exposure to 2.75 M NaOH and then saline had almost no effects and caused no deaths. Treatments with more concentrated NaOH or TMACl resulted in suppressions of MBP and HR, and deaths were observed after the dosing of TMACl. The toxicity of dermal exposure to TMA alone is limited, but fatal effects can be introduced by pre-treatment with hydroxide ion. Therefore, the chemical burn caused by hydroxide ion plays an essential role in the toxicity, implicating that effective neutralizing may help decreasing the fatality rate. Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.

Identification of compounds bound to suspended solids causing sub-lethal toxic effects in Daphnia magna. A field study on re-suspended particles during river floods in Ebro River.

PubMed

Rivetti, Claudia; Gómez-Canela, Cristian; Lacorte, Silvia; Díez, Sergi; Lázaro, Wilkinson L; Barata, Carlos

2015-04-01

Identifying chemicals causing adverse effects in organisms present in water remains a challenge in environmental risk assessment. This study aimed to assess and identify toxic compounds bound to suspended solids re-suspended during a prolonged period of flushing flows in the lower part of Ebro River (NE, Spain). This area is contaminated with high amounts of organochlorine and mercury sediment wastes. Chemical characterization of suspended material was performed by solid phase extraction using a battery of non-polar and polar solvents and analyzed by GC-MS/MS and LC-MS/MS. Mercury content was also determined for all sites. Post-exposure feeding rates of Daphnia magna were used to assess toxic effects of whole and filtered water samples and of re-constituted laboratory water with re-suspended solid fractions. Organochlorine and mercury residues in the water samples increased from upstream to downstream locations. Conversely, toxic effects were greater at the upstream site than downstream of the superfund Flix reservoir. A further analysis of the suspended solid fraction identified a toxic component eluted within the 80:20 methanol:water fraction. Characterization of that toxic component fraction by LC-MS/MS identified the phytotoxin anatoxin-a, whose residue levels were correlated with observed feeding inhibition responses. Further feeding inhibition assays conducted in the lab using anatoxin-a produced from Planktothrix agardhii, a filamentous cyanobacteria, confirmed field results. This study provides evidence that in real field situation measured contaminant residues do not always agree with toxic effects. Copyright © 2015 Elsevier B.V. All rights reserved.

The acute toxic effects of 1-alkyl-3-methylimidazolium nitrate ionic liquids on Chlorella vulgaris and Daphnia magna.

PubMed

Zhang, Cheng; Zhang, Shuai; Zhu, Lusheng; Wang, Jinhua; Wang, Jun; Zhou, Tongtong

2017-10-01

Given their increasingly widespread application, the toxic effects of ionic liquids (ILs) have become the subject of significant attention in recent years. Therefore, the present study assessed the acute toxic effects of 1-alkyl-3-methylimidazolium nitrate ([C n mim]NO 3 (n = 2, 4, 6, 8, 10, 12)) on Chlorella vulgaris and Daphnia magna. The sensitivity of the tested organism Daphnia magna and the investigated IL concentrations in water using high-performance liquid chromatography (HPLC) were also evaluated to demonstrate the reliability of the present study. The results illustrated that Daphnia magna is indeed sensitive to the reference toxicant and the investigated ILs were stable in the aquatic environment. The 50% effect concentration (EC 50 ) was used to represent the acute toxic effects on Chlorella vulgaris and Daphnia magna. With the increasing alkyl-chain lengths, the toxicity of the investigated ILs increased in both the test organisms. Accordingly, the alkyl-chain lengths can cause significantly toxic effects on aquatic organisms, and Daphnia magna are much more sensitive than Chlorella vulgaris to the imidazolium-based ILs used in the present study. Furthermore, the present study provides more information on the acute toxic effects of 1-alkyl-3-methylimidazolium nitrate. Copyright © 2017 Elsevier Ltd. All rights reserved.

Gasoline ingestion: a rare cause of pancytopenia.

PubMed

Rahman, Ifad; Narasimhan, Kanakasabai; Aziz, Shahid; Owens, William

2009-11-01

The majority of reported cases of gasoline intoxication involves inhalation or percutaneous absorption. Data are scarce on complications and outcomes after gasoline poisoning by oral ingestion. The major cause of mortality and morbidity associated with the ingestion of gasoline is related to pulmonary aspiration. Despite the high frequency of the ingestions, there is little documentation of nonpulmonary toxic effects of gasoline. After ingestion, the principal toxicity is aspiration pneumonia, but any documented extra pulmonary manifestations of this condition may be important in the overall management of these patients. We are reporting a rare case of pancytopenia along with aspiration pneumonia and multisystem organ failure in a 58-year-old male after prolonged intentional ingestion of gasoline. To our knowledge, this is the only reported case of gasoline toxicity causing pancytopenia.

Assessment of microplastic toxicity to embryonic development of the sea urchin Lytechinus variegatus (Echinodermata: Echinoidea).

PubMed

Nobre, C R; Santana, M F M; Maluf, A; Cortez, F S; Cesar, A; Pereira, C D S; Turra, A

2015-03-15

Apart from the physiological impacts on marine organisms caused by ingesting microplastics, the toxicity caused by substances leaching from these particles into the environment requires investigation. To understand this potential risk, we evaluated the toxicity of virgin (raw) and beach-stranded plastic pellets to the development of embryos of Lytechinus variegatus, simulating transfers of chemical compounds to interstitial water and water column by assays of pellet-water interface and elutriate, respectively. Both assays showed that virgin pellets had toxic effects, increasing anomalous embryonic development by 58.1% and 66.5%, respectively. The toxicity of stranded pellets was lower than virgin pellets, and was observed only for pellet-water interface assay. These results show that (i) plastic pellets act as a vector of pollutants, especially for plastic additives found on virgin particles; and that (ii) the toxicity of leached chemicals from pellets depends on the exposure pathway and on the environmental compartment in which pellets accumulate. Copyright © 2015 Elsevier Ltd. All rights reserved.

Dioxin Toxicity In Vivo Results from an Increase in the Dioxin-Independent Transcriptional Activity of the Aryl Hydrocarbon Receptor

PubMed Central

Céspedes, Miguel Angel; Galindo, Maximo Ibo; Couso, Juan Pablo

2010-01-01

The Aryl hydrocarbon receptor (Ahr) is the nuclear receptor mediating the toxicity of dioxins -widespread and persistent pollutants whose toxic effects include tumor promotion, teratogenesis, wasting syndrome and chloracne. Elimination of Ahr in mice eliminates dioxin toxicity but also produces adverse effects, some seemingly unrelated to dioxin. Thus the relationship between the toxic and dioxin-independent functions of Ahr is not clear, which hampers understanding and treatment of dioxin toxicity. Here we develop a Drosophila model to show that dioxin actually increases the in vivo dioxin-independent activity of Ahr. This hyperactivation resembles the effects caused by an increase in the amount of its dimerisation partner Ahr nuclear translocator (Arnt) and entails an increased transcriptional potency of Ahr, in addition to the previously described effect on nuclear translocation. Thus the two apparently different functions of Ahr, dioxin-mediated and dioxin-independent, are in fact two different levels (hyperactivated and basal, respectively) of a single function. PMID:21079739

ADAPTING THE MEDAKA EMBRYO ASSAY TO A HIGH-THROUGHPUT APPROACH FOR DEVELOPMENTAL TOXICITY TESTING.

EPA Science Inventory

Chemical exposure during embryonic development may cause persistent effects, yet developmental toxicity data exist for very few chemicals. Current testing procedures are time consuming and costly, underlining the need for rapid and low cost screening strategies. While in vitro ...

Status and Assessment of Chesapeake Bay Wildlife Contamination

USGS Publications Warehouse

Heinz, G.H.; Wiemeyer, Stanley N.; Clark, D.R.; Albers, P.H.; Henry, P.; Batiuk, R.A.

1992-01-01

As an integral component of its priority setting process, the Chesapeake Bay Program`s Toxics Subcommittee has sought the expertise of Chesapeake Bay researchers and managers in developing a series of Chesapeake Bay toxics status and assessment papers. In the report, evidence for historical and current contaminant effects on key bird species, mammals, reptiles and amphibians which inhabit the Chesapeake Bay basin is examined. For each group of wildlife species, a general overview of effects caused by specific toxic substances is followed by detailed accounts of contaminant effects on selected species. Sponsored by Environmental Protection Agency, Annapolis, MD. Chesapeake Bay Program.

Sustained Effects of Ecstasy on the Human Brain: A Prospective Neuroimaging Study in Novel Users

ERIC Educational Resources Information Center

de Win, Maartje M. L.; Jager, Gerry; Booij, Jan; Reneman, Liesbeth; Schilt, Thelma; Lavini, Christina; Olabarriaga, Silvia D.; den Heeten, Gerard J.; van den Brink, Wim

2008-01-01

Previous studies have suggested toxic effects of recreational ecstasy use on the serotonin system of the brain. However, it cannot be excluded that observed differences between users and non-users are the cause rather than the consequence of ecstasy use. As part of the Netherlands XTC Toxicity (NeXT) study, we prospectively assessed sustained…

Lactobacillus plantarum CCFM8661 alleviates lead toxicity in mice.

PubMed

Tian, Fengwei; Zhai, Qixiao; Zhao, Jianxin; Liu, Xiaoming; Wang, Gang; Zhang, Hao; Zhang, Heping; Chen, Wei

2012-12-01

Lead causes a broad range of adverse effects in humans and animals. The objective was to evaluate the potency of lactobacilli to bind lead in vitro and the protective effects of a selected Lactobacillus plantarum CCFM8661 against lead-induced toxicity in mice. Nine strains of bacteria were used to investigate their binding abilities of lead in vitro, and L. plantarum CCFM8661 was selected for animal experiments because of its excellent lead binding capacity. Both living and dead L. plantarum CCFM8661 were used to treat 90 male Kunming mice during or after the exposure to 1 g/L lead acetate in drinking water. The results showed oral administration of both living and dead L. plantarum CCFM8661 offered a significant protective effect against lead toxicity by recovering blood δ-aminolevulinic acid dehydratase activity, decreasing the lead levels in blood and tissues, and preventing alterations in the levels of glutathione, glutathione peroxidase, malondialdehyde, superoxide dismutase, and reactive oxygen species caused by lead exposure. Moreover, L. plantarum CCFM8661 was more effective when administered consistently during the entire lead exposure, not after the exposure. Our results suggest that L. plantarum CCFM8661 has the potency to provide a dietary strategy against lead toxicity.

Acute toxicity and associated mechanisms of four strobilurins in algae.

PubMed

Liu, Xiaoxu; Wang, Yu; Chen, Hao; Zhang, Junli; Wang, Chengju; Li, Xuefeng; Pang, Sen

2018-06-01

Strobilurins have been reported highly toxic to non-target aquatic organisms but few illustrated how they cause toxic effects on algae. This study investigated the acute toxicity of Kresoxim-methy (KRE), Pyraclostrobin (PYR), Trifloxystrobin (TRI) and Picoxystrobin (PIC) on two algae and their toxicity mechanisms. Four strobilurins showed lower toxic effects on Chlorella pyrenoidsa but higher on Chlorella vulgaris. bc1 complex activities in C. vulgaris were significantly inhibited by all strobilurins, suggesting bc 1 complex might be the target of strobilurin toxicity in algae. Moreover, SOD, CAT and POD activities were significantly up-regulated by all doses of KRE, PYR and PIC. In contrast, low concentrations of TRI stimulated SOD and POD activities but highest concentration significantly inhibited those activities. Comet assays showed damaged DNA in C. vulgaris by four strobulirins, suggesting their potential genotoxic threats to algae. The results illustrated acute toxicity by strobulirins on algae and their possible toxicity mechanisms. Copyright © 2018 Elsevier B.V. All rights reserved.

Assessment of sulforaphane-induced protective mechanisms against cadmium toxicity in human mesenchymal stem cells.

PubMed

Alkharashi, Nouf Abdulkareem Omer; Periasamy, Vaiyapuri Subbarayan; Athinarayanan, Jegan; Alshatwi, Ali A

2018-04-01

Cd is a hazardous substance and carcinogen that is present in the environment; it is known to cause toxic effects in living organisms. Sulforaphane is a naturally available phytochemical with antioxidant, anti-inflammatory, and anticarcinogenic properties. However, the effects of sulforaphane on Cd toxicity in human mesenchymal stem cells (hMSCs) are unknown. In the present study, we investigated the molecular mechanisms of the effects of sulforaphane on Cd toxicity in hMSCs by using MTT assays, acridine orange/ethidium bromide staining, Hoechst staining, LysoRed staining, assessment of mitochondrial membrane potential, and gene expression analysis. Cd decreased hMSC viability in a dose-dependent manner with an IC 50 value of 56.5 μM. However, sulforaphane did not induce any significant reduction in cell viability. Nuclear morphological analysis revealed that Cd induced necrotic cell death. Additionally, Cd caused mitochondrial membrane potential loss in hMSCs. The treatment of Cd-exposed cells with sulforaphane (Cd-sulforaphane co-treatment) resulted in a significant recovery of the cell viability and nuclear morphological changes compared with that of cells treated with Cd only. The gene expression pattern of cells co-treated with Cd-sulforaphane was markedly different from that of Cd-treated cells, owing to the reduction in Cd toxicity. Our results clearly indicated that sulforaphane reduced Cd-induced toxic effects in hMSCs. Overall, the results of our study suggested that sulforaphane-rich vegetables and fruits can help to improve human health through amelioration of the molecular effects of Cd poisoning.

Effects of heavy metals on sea urchin embryo development. Part 2. Interactive toxic effects of heavy metals in synthetic mine effluents.

PubMed

Kobayashi, Naomasa; Okamura, Hideo

2005-12-01

Interactive toxic effects between heavy metals were investigated using a sea urchin (Anthocidaris crassispina) bioassay. An effluent from an abandoned mine showed significant inhibitory effects on embryo development as well as producing specific malformations. The effects on the embryos were reproduced by synthetic polluted seawater consisting of eight metals (manganese, lead, cadmium, nickel, zinc, chromium, iron, and copper) at the concentrations detected in the mine effluent. This indicated that the heavy metals were responsible for the effects observed. Five heavy metals were ranked in decreasing order of toxicity as follows: Cu>Zn>Pb>Fe>Mn. Among these, zinc and manganese could cause malformation of the embryos. From bioassay results using 27 combinations of heavy metals, 16 combinations including zinc could produce specific malformations, such as radialized, exo-gastrulal, and spaceship Apollo-like gastrulal embryos. Zinc was one of the elements responsible for causing malformations and its effects were intensified by the presence of the other metals, such as manganese, lead, iron, and copper.

Evaluation of processed borax as antidote for aconite poisoning.

PubMed

Sarkar, Prasanta Kumar; Prajapati, Pradeep K; Shukla, Vinay J; Ravishankar, Basavaiah

2017-06-09

Aconite root is very poisonous; causes cardiac arrhythmias, ventricular fibrillation and ventricular tachycardia. There is no specific antidote for aconite poisoning. In Ayurveda, dehydrated borax is mentioned for management of aconite poisoning. The investigation evaluated antidotal effect of processed borax against acute and sub-acute toxicity, cardiac toxicity and neuro-muscular toxicity caused by raw aconite. For acute protection Study, single dose of toxicant (35mg/kg) and test drug (22.5mg/kg and 112.5mg/kg) was administered orally, and then 24h survival of animals was observed. The schedule was continued for 30 days in sub-acute protection Study with daily doses of toxicant (6.25mg/kg), test drug (22.5mg/kg and 112.5mg/kg) and vehicle. Hematological and biochemical tests of blood and serum, histopathology of vital organs were carried out. The cardiac activity Study was continued for 30 days with daily doses of toxicant (6.25mg/kg), test drug (22.5mg/kg), processed borax solution (22.5mg/kg) and vehicle; ECG was taken after 1h of drug administration on 1 TB , 15th and on 30th day. For neuro-muscular activity Study, the leech dorsal muscle response to 2.5µg of acetylcholine followed by response of toxicant at 25µg and 50µg doses and then response of test drug at 25µg dose were recorded. Protection index indicates that treated borax gave protection to 50% rats exposed to the lethal dose of toxicant in acute protection Study. Most of the changes in hematological, biochemical parameters and histopathological Study induced by the toxicant in sub-acute protection Study were reversed significantly by the test drug treatment. The ventricular premature beat and ventricular tachyarrhythmia caused by the toxicant were reversed by the test drug indicate reversal of toxicant induced cardio-toxicity. The acetylcholine induced contractions in leech muscle were inhibited by toxicant and it was reversed by test drug treatment. The processed borax solution is found as an effective protective agent to acute and sub-acute aconite poisoning, and aconite induced cardiac and neuro-muscular toxicity. Processed borax at therapeutic dose (22.5mg/kg) has shown better antidotal activity profile than five times more than therapeutic dose (112.5mg/kg). Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Synthesis of axially disubstituted silicon phthalocyanines and investigation of photodynamic effects on HCT-116 colorectal cancer cell line.

PubMed

Sarı, Ceren; Eyüpoğlu, Figen Celep; Değirmencioğlu, İsmail; Bayrak, Rıza

2018-05-15

Photodynamic therapy is one of the hot topics in cancer studies recently. Basically, photosensitizing chemical substrates which are stimulated by light having a specific wavelength cause fatal effect on different kind of cells in photodynamic therapy. In this study, axially 4-{[(1E)-2-furylmethylene]amino}phenol, 4-{[(1E)-2-thienylmethylene]amino}phenol and 4-{[(1E)-(4-nitro-2-thienyl)methylene]amino}phenol disubstituted silicon phthalocyanines were synthesized as Photosensitizers for photodynamic therapy in cancer treatment for the first time. The structural characterizations of these novel compounds were performed by a combination of FT-IR, 1 H-NMR, UV-vis and mass. All these newly prepared compounds did not show aggregation at the concentration range of 2 × 10 -6 -12 × 10 -6 M in tetrahydrofurane and also did not show aggregation in different organic solvents at 2 × 10 -6 M concentration. Phthalocyanines which are synthesized in this study are tested on HCT-116 colorectal cancer cells and stimulated by light has wavelength of 680 nm. The toxic effects on cancer cells which are caused by different concentrations of photosensitizing molecules have been examined and compared with the toxic effects on cancer cells that were kept in the dark. It is confirmed that these molecules caused toxic effects on colorectal cancer cells when they were stimulated by light but there was no toxic effect in the dark. Copyright © 2018. Published by Elsevier B.V.

[Comparative Sensitivity of the Luminescent Photobacterium phosphoreum, Escherichia coli, and Bacillus subtilis Strains to Toxic Effects of Carbon-Based Nanomaterials and Metal Nanoparticles].

PubMed

Deryabina, D G; Efremova, L V; Karimov, I F; Manukhov, I V; Gnuchikh, E Yu; Miroshnikov, S A

2016-01-01

A comparative analysis of the four commercially available and laboratory luminescent sensor strains to the toxic effect of 10 carbon-based nanomatherials (CBNs) and 10 metal nanoparticles (MNPs) was carried out in this study. The bioluminescence inhibition assays with marine Photobacterium phosphoreum and recombinant Escherichia coli strains were varied in minimal toxic concentrations and EC50 values but led to well correlated biotoxicity evaluation for the most active compounds were ranked as Cu > (MgO, CuO) > (fullerenol, graphene oxide). The novel sensor strain Bacillus subtilis EG 168-1 exhibited the highest sensitivity to CBNs and MNPs that increased significantly number of toxic compounds causing the bacterial bioluminescence inhibition effect.

Consensus definitions of 14 severe acute toxic effects for childhood lymphoblastic leukaemia treatment: a Delphi consensus.

PubMed

Schmiegelow, Kjeld; Attarbaschi, Andishe; Barzilai, Shlomit; Escherich, Gabriele; Frandsen, Thomas Leth; Halsey, Christina; Hough, Rachael; Jeha, Sima; Kato, Motohiro; Liang, Der-Cherng; Mikkelsen, Torben Stamm; Möricke, Anja; Niinimäki, Riitta; Piette, Caroline; Putti, Maria Caterina; Raetz, Elizabeth; Silverman, Lewis B; Skinner, Roderick; Tuckuviene, Ruta; van der Sluis, Inge; Zapotocka, Ester

2016-06-01

Although there are high survival rates for children with acute lymphoblastic leukaemia, their outcome is often counterbalanced by the burden of toxic effects. This is because reported frequencies vary widely across studies, partly because of diverse definitions of toxic effects. Using the Delphi method, 15 international childhood acute lymphoblastic leukaemia study groups assessed acute lymphoblastic leukaemia protocols to address toxic effects that were to be considered by the Ponte di Legno working group. 14 acute toxic effects (hypersensitivity to asparaginase, hyperlipidaemia, osteonecrosis, asparaginase-associated pancreatitis, arterial hypertension, posterior reversible encephalopathy syndrome, seizures, depressed level of consciousness, methotrexate-related stroke-like syndrome, peripheral neuropathy, high-dose methotrexate-related nephrotoxicity, sinusoidal obstructive syndrome, thromboembolism, and Pneumocystis jirovecii pneumonia) that are serious but too rare to be addressed comprehensively within any single group, or are deemed to need consensus definitions for reliable incidence comparisons, were selected for assessment. Our results showed that none of the protocols addressed all 14 toxic effects, that no two protocols shared identical definitions of all toxic effects, and that no toxic effect definition was shared by all protocols. Using the Delphi method over three face-to-face plenary meetings, consensus definitions were obtained for all 14 toxic effects. In the overall assessment of outcome of acute lymphoblastic leukaemia treatment, these expert opinion-based definitions will allow reliable comparisons of frequencies and severities of acute toxic effects across treatment protocols, and facilitate international research on cause, guidelines for treatment adaptation, preventive strategies, and development of consensus algorithms for reporting on acute lymphoblastic leukaemia treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Assessing neurodevelopmental effects of arsenolipids in pre-differentiated human neurons.

PubMed

Witt, Barbara; Ebert, Franziska; Meyer, Sören; Francesconi, Kevin A; Schwerdtle, Tanja

2017-11-01

In the general population exposure to arsenic occurs mainly via diet. Highest arsenic concentrations are found in seafood, where arsenic is present predominantly in its organic forms including arsenolipids. Since recent studies have provided evidence that arsenolipids could reach the brain of an organism and exert toxicity in fully differentiated human neurons, this work aims to assess the neurodevelopmental toxicity of arsenolipids. Neurodevelopmental effects of three arsenic-containing hydrocarbons (AsHC), two arsenic-containing fatty acids (AsFA), arsenite and dimethylarsinic acid (DMA V ) were characterized in pre-differentiated human neurons. AsHCs and arsenite caused substantial cytotoxicity in a similar, low concentration range, whereas AsFAs and DMA V were less toxic. AsHCs were highly accessible for cells and exerted pronounced neurodevelopmental effects, with neurite outgrowth and the mitochondrial membrane potential being sensitive endpoints; arsenite did not substantially decrease those two endpoints. In fully differentiated neurons, arsenite and AsHCs caused neurite toxicity. These results indicate for a neurodevelopmental potential of AsHCs. Taken into account the possibility that AsHCs might easily reach the developing brain when exposed during early life, neurotoxicity and neurodevelopmental toxicity cannot be excluded. Further studies are needed in order to progress the urgently needed risk assessment. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Computer Simulation Lends New Insights Into Cyanide-Caused Cardiac Toxicity

DTIC Science & Technology

2004-12-01

COMPUTER SIMULATION LENDS NEW INSIGHTS INTO CYANIDE-CAUSED CARDIAC TOXICITY C.K. Zoltani* U.S. Army Research Laboratory Computational and...Into Cyanide-Caused Cardiac Toxicity 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK...disequilibrium in the membrane currents caused by the cyanide has grave implications for the cell’s electrophysiology. CN-caused cardiac toxicity shares

Perturbational Metabolic Profiling of Human Breast Cancer Cells

EPA Science Inventory

A major goal of toxicity testing is to obtain toxicity data for protecting public health and the environment from adverse effects that may be caused by exposure to environmental agents in the air, water, soil and food. The current toxicological studies that target human health ef...

Effects of lead nitrate and sodium selenite on DNA damage and oxidative stress in diabetic and non-diabetic rat erythrocytes and leucocytes.

PubMed

Baş, Hatice; Kalender, Yusuf; Pandir, Dilek; Kalender, Suna

2015-05-01

The adverse effects of lead nitrate (LN) and the preventive role of sodium selenite were investigated in diabetic and non-diabetic rat blood by measuring trolox equivalent antioxidant capacity (TEAC), ferric reducing antioxidant power (FRAP), malondialdehyde (MDA) levels and activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) also by evaluating DNA damage with comet assay. LN increased the levels of MDA, tail DNA%, mean tail length and tail moment, decreased the enzymes activities, FRAP and TEAC values. In sodium selenite+LN group, we observed the protective effect of sodium selenite on examining parameters. Diabetes caused alterations on these parameters, too. We found that sodium selenite did not protect against diabetes caused damages. As a result, LN caused toxic effects on blood cells and sodium selenite alleviated this toxicity but it did not show preventive effect against diabetes. Also, LN caused more harmfull effects in diabetic groups than non-diabetic groups. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of heating rate on toxicity of pyrolysis gases from some elastomers

NASA Technical Reports Server (NTRS)

Hilado, C. J.; Kosola, K. L.; Solis, A. N.

1977-01-01

The effect of heating rate on the toxicity of the pyrolysis gases from six elastomers was investigated, using a screening test method. The elastomers were polyisoprene (natural rubber), styrene-butadiene rubber (SBR), ethylene propylene diene terpolymer (EPDM), acrylonitrile rubber, chlorosulfonated polyethylene rubber, and polychloroprene. The rising temperature and fixed temperature programs produced exactly the same rank order of materials based on time to death. Acrylonitrile rubber exhibited the greatest toxicity under these test conditions, and carbon monoxide was not found in sufficient concentrations to be the primary cause of death.

Causes of toxicity to Hyalella azteca in a stormwater management facility receiving highway runoff and snowmelt. Part II: salts, nutrients, and water quality.

PubMed

Bartlett, A J; Rochfort, Q; Brown, L R; Marsalek, J

2012-01-01

The Terraview-Willowfield Stormwater Management Facility (TWSMF) features a tandem of stormwater management ponds, which receive inputs of multiple contaminants from highway and residential runoff. Previous research determined that benthic communities in the ponds were impacted by poor habitat quality, due to elevated sediment concentrations of metals and polycyclic aromatic hydrocarbons (PAHS), and salinity in the overlying water, but did not address seasonal changes, including those caused by the influx of contaminants with the snowmelt. In order to address this issue, water and sediment samples were collected from the TWSMF during the fall and spring, and four-week sediment toxicity tests were conducted with Hyalella azteca. The effects of metals and PAHs are discussed in a companion paper; the effects of road salt, nutrients, and water quality are discussed here. After exposure to fall samples, survival of Hyalella was reduced (64-74% of controls) at three out of four sites, but growth was not negatively affected. After exposure to spring samples, survival was 0-75% of controls at the two sites furthest downstream, and growth was significantly lower in four out of five sites when comparing Hyalella exposed to site water overlying site sediment versus control water overlying site sediment. Toxicity appeared to be related to chloride concentrations: little or no toxicity occurred in fall samples (200 mg Cl(-)/L), and significant effects on survival and growth occurred in spring samples above 1550 mg Cl(-)/L and 380 mg Cl(-)/L, respectively. Sodium chloride toxicity tests showed similar results: four-week LC50s and EC25s (growth) were 1200 and 420 mg Cl(-)/L, respectively. Although water quality and nutrients were associated with effects observed in the TWSMF, chloride from road salt was the primary cause of toxicity in this study. Chloride persists during much of the year at concentrations representing a significant threat to benthic communities in the TWSMF. Copyright © 2011. Published by Elsevier B.V.

Neem oil poisoning: Case report of an adult with toxic encephalopathy.

PubMed

Mishra, Ajay; Dave, Nikhil

2013-09-01

Neem oil has widespread use in Indian subcontinent due to its many bioactive properties. Azadirachtin, an active ingredient, is implicated in causing the effects seen in neem oil poisoning. Neem oil poisoning is rare in adults. This report highlights the toxicity associated with neem oil poisoning in an elderly male. The patient presented with vomiting, seizures, metabolic acidosis, and toxic encephalopathy. The patient recovered completely with symptomatic treatment.

Toxicity reduction of photo processing wastewaters

USGS Publications Warehouse

Wang, W.

1992-01-01

The photo processing industry can be characterized by treatment processes and subsequent silver recovery. The effluents generated all contain various amounts of silver. The objectives of this study were to determine toxicity of photo processing effluents and to explore their toxicity mitigation. Six samples, from small shops to a major photo processing center, were studied. Two samples (I and VI) were found to be extremely toxic, causing 100 and 99% inhibition of duckweed frond reproduction, respectively, and were used for subsequent toxicity reduction experiments. Lime and sodium sulfide were effective for the toxicity reduction of Sample VI; both reduced its toxicity to negligible. Sample I was far more toxic and was first diluted to 2.2% and then treated with 0.5 g lime/100 mL, reducing toxicity from 100% to 12% inhibition.

Toxicity assessment of individual ingredients of synthetic-based drilling muds (SBMs).

PubMed

Bakhtyar, Sajida; Gagnon, Marthe Monique

2012-09-01

Synthetic-based drilling muds (SBMs) offer excellent technical characteristics while providing improved environmental performance over other drilling muds. The low acute toxicity and high biodegradability of SBMs suggest their discharge at sea would cause minimal impacts on marine ecosystems, however, chronic toxicity testing has demonstrated adverse effects of SBMs on fish health. Sparse environmental monitoring data indicate effects of SBMs on bottom invertebrates. However, no environmental toxicity assessment has been performed on fish attracted to the cutting piles. SBM formulations are mostly composed of synthetic base oils, weighting agents, and drilling additives such as emulsifiers, fluid loss agents, wetting agents, and brine. The present study aimed to evaluate the impact of exposure to individual ingredients of SBMs on fish health. To do so, a suite of biomarkers [ethoxyresorufin-O-deethylase (EROD) activity, biliary metabolites, sorbitol dehydrogenase (SDH) activity, DNA damage, and heat shock protein] have been measured in pink snapper (Pagrus auratus) exposed for 21 days to individual ingredients of SBMs. The primary emulsifier (Emul S50) followed by the fluid loss agent (LSL 50) caused the strongest biochemical responses in fish. The synthetic base oil (Rheosyn) caused the least response in juvenile fish. The results suggest that the impact of Syndrill 80:20 on fish health might be reduced by replacement of the primary emulsifier Emul S50 with an alternative ingredient of less toxicity to aquatic biota. The research provides a basis for improving the environmental performance of SBMs by reducing the environmental risk of their discharge and providing environmental managers with information regarding the potential toxicity of individual ingredients.

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.

Oxidative Stress Response Induced by Butachlor in Zebrafish Embryo/Larvae: The Protective Effect of Vitamin C.

PubMed

Xiang, Qingqing; Xu, Bofan; Ding, Yilun; Liu, Xiaoyi; Zhou, Ying; Ahmad, Farooq

2018-02-01

The widespread contamination and persistence of the herbicide butachlor in the environment resulted in the exposure of non-target organisms. The present study investigated the toxicity effect of butachlor (1-15 µmol/L) and the protective effect of vitamin C (VC) against butachlor-induced toxicity in zebrafish. It was found that butachlor significantly increased the mortality and malformation rates in a dose-dependent manner, which caused elevation in reactive oxygen species (ROS) and malondialdehyde (MDA) after 72 h exposure. Compared with butachlor treatment group, the protective effect of VC against butachlor-induced toxicity were observed after adding 40, 80 mg/L VC respectively. VC significantly decreased the mortality, malformation rates, ROS, MDA, and normalized antioxidant enzymes activities of zebrafish after 72 h exposure. The result shows VC has mitigative effect on butachlor-induced toxicity and it can be used as an effective antioxidant in aquaculture.

Modeling Plant Uptake of Metal in Constructed Wetlands Supported by Experimentally Derived Uptake Rates.

DTIC Science & Technology

1996-12-01

nuttallii Waterweed Vallisneria spp. Wild Celery; Tape Grass Freshwater Marsh - Floating Eichhornia crassipes Water Hyacinth Lemna spp. Duckweed...for life, many others can cause toxic effects from seemingly minor exposure. All of these metals are 21 toxic to aquatic life at low concentrations

Screening for angiogenic inhibitors in zebrafish to evaluate a predictive model for developmental vascular toxicity

EPA Science Inventory

Chemically-induced vascular toxicity during embryonic development may cause a wide range of adverse effects. To identify putative vascular disrupting chemicals (pVDCs), a predictive signature was constructed from U.S. EPA ToxCast high-throughput screening (HTS) assays that map to...

Toxicities and risk assessment of heavy metals in sediments of Taihu Lake, China, based on sediment quality guidelines.

PubMed

Zhang, Yanfeng; Han, Yuwei; Yang, Jinxi; Zhu, Lingyan; Zhong, Wenjue

2017-12-01

The occurrence, toxicities, and ecological risks of five heavy metals (Pb, Cu, Cd, Zn and Ni) in the sediment of Taihu Lake were investigated in this study. To evaluate the toxicities caused by the heavy metals, the toxicities induced by organic contaminants and ammonia in the sediments were screened out with activated carbon and zeolite. The toxicities of heavy metals in sediments were tested with benthic invertebrates (tubificid and chironomid). The correlations between toxicity of sediment and the sediment quality guidelines (SQGs) derived previously were evaluated. There were significant correlations (p<0.0001) between the observed toxicities and the total risk quotients of the heavy metals based on SQGs, indicating that threshold effect level (TEL) and probable effect level (PEL) were reliable to predict the toxicities of heavy metals in the sediments of Taihu Lake. By contrast, the method based on acid volatile sulfides (AVS) and simultaneously extracted metals (SEM), such as ∑SEM/AVS and ∑SEM-AVS, did not show correlations with the toxicities. Moreover, the predictive ability of SQGs was confirmed by a total predicting accuracy of 77%. Ecological risk assessment based on TELs and PELs showed that the contaminations of Pb, Cu, Cd and Zn in the sediments of Taihu Lake were at relatively low or medium levels. The risks caused by heavy metals in the sediments of northern bay of the lake, which received more wastewater discharge from upper stream, were higher than other area of the lake. Copyright © 2017. Published by Elsevier B.V.

In vivo toxic and lethal cardiovascular effects of a synthetic polymeric 1,3-dodecylpyridinium salt in rodents

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

Grandic, Marjana; Sepcic, Kristina; Turk, Tom

2011-08-15

APS12-2 is one in a series of synthetic analogs of the polymeric alkylpyridinium salts isolated from the marine sponge Reniera sarai. As it is a potential candidate for treating non small cell lung cancer (NSCLC), we have studied its possible toxic and lethal effects in vivo. The median lethal dose (LD{sub 50}) of APS12-2 in mice was determined to be 11.5 mg/kg. Electrocardiograms, arterial blood pressure and respiratory activity were recorded under general anesthesia in untreated, pharmacologically vagotomized and artificially ventilated rats injected with APS12-2. In one group, the in vivo effects of APS12-2 were studied on nerve-evoked muscle contraction.more » Administration of APS12-2 at a dose of 8 mg/kg caused a progressive reduction of arterial blood pressure to a mid-circulatory value, accompanied by bradycardia, myocardial ischemia, ventricular extrasystoles, and second degree atrio-ventricular block. Similar electrocardiogram and arterial blood pressure changes caused by APS12-2 (8 mg/kg) were observed in animals pretreated with atropine and in artificially ventilated animals, indicating that hypoxia and cholinergic effects do not play a crucial role in the toxicity of APS12-2. Application of APS12-2 at sublethal doses (4 and 5.5 mg/kg) caused a decrease of arterial blood pressure, followed by an increase slightly above control values. We found that APS12-2 causes lysis of rat erythrocytes in vitro, therefore it is reasonable to expect the same effect in vivo. Indeed, hyperkalemia was observed in the blood of experimental animals. Hyperkalemia probably plays an important role in APS12-2 cardiotoxicity since no evident changes in histopathology of the heart were found. However, acute lesions were observed in the pulmonary vessels of rats after application of 8 mg/kg APS12-2. Predominant effects were dilation of interalveolar blood vessels and lysis of aggregated erythrocytes within their lumina. - Highlights: > LD{sub 50} estimated in mice (11.5 mg/kg) revealed that toxicity of APS12-2 is low. > APS12-2 causes dose dependent hemolysis of rat erythrocytes in vivo and in vitro. > Cardiac arrest by APS12-2 is caused by the high blood potassium concentration. > APS12-2 causes mild acute pulmonary edema.« less

Toxic effect of silver and platinum nanoparticles toward the freshwater microalga Pseudokirchneriella subcapitata.

PubMed

Książyk, Małgorzata; Asztemborska, Monika; Stęborowski, Romuald; Bystrzejewska-Piotrowska, Grażyna

2015-05-01

The growing use of nanoparticles in a wide range of products has resulted in their release into the aquatic environment; therefore, an understanding of the toxic effects of nanoparticles on aquatic organisms is of permanent importance. The aim of this study was to evaluate the toxicity of silver and platinum nanoparticles toward the freshwater microalga, Pseudokirchneriella subcapitata. Algal growth and photosynthetic pigments were determined to quantitate the effects of varying concentrations of Ag and Pt nanoparticles. The silver nanoparticles were much more toxic than the platinum ones. The concentrations causing total inhibition of algal growth were 5.0 and 22.2 mg L(-1), respectively. Similar results were obtained by analyzing the concentration of photosynthetic pigments in P. subcapitata exposed to nanoparticles. Thus, simple spectrophotometric determination of chlorophyll is a convenient tool for the analysis of nanoparticle toxicity to algae.

Metabolite toxicity determines the pace of molecular evolution within microbial populations.

PubMed

Lilja, Elin E; Johnson, David R

2017-02-14

The production of toxic metabolites has shaped the spatial and temporal arrangement of metabolic processes within microbial cells. While diverse solutions to mitigate metabolite toxicity have evolved, less is known about how evolution itself is affected by metabolite toxicity. We hypothesized that the pace of molecular evolution should increase as metabolite toxicity increases. At least two mechanisms could cause this. First, metabolite toxicity could increase the mutation rate. Second, metabolite toxicity could increase the number of available mutations with large beneficial effects that selection could act upon (e.g., mutations that provide tolerance to toxicity), which consequently would increase the rate at which those mutations increase in frequency. We tested this hypothesis by experimentally evolving the bacterium Pseudomonas stutzeri under denitrifying conditions. The metabolite nitrite accumulates during denitrification and has pH-dependent toxic effects, which allowed us to evolve P. stutzeri at different magnitudes of nitrite toxicity. We demonstrate that increased nitrite toxicity results in an increased pace of molecular evolution. We further demonstrate that this increase is generally due to an increased number of available mutations with large beneficial effects and not to an increased mutation rate. Our results demonstrate that the production of toxic metabolites can have important impacts on the evolutionary processes of microbial cells. Given the ubiquity of toxic metabolites, they could also have implications for understanding the evolutionary histories of biological organisms.

Local and systemic toxicity of JP-8 from cutaneous exposures.

PubMed

McDougal, James N; Rogers, James V

2004-04-01

Jet propellant-8 (JP-8) jet fuel is a version of commercial jet fuel, Jet A, and is a complex mixture of primarily aliphatic (but also aromatic) hydrocarbons that varies in composition from batch to batch. There is potential for dermal exposure to jet fuels with personnel involved in aircraft refueling and maintenance operations as well as ground personnel. Cutaneous exposures have the potential to cause skin irritation, sensitization or skin cancer. JP-8 has been shown to be irritating and causes molecular changes in the skin of laboratory animals. The mechanisms of some of these effects have been investigated in intact skin and cultured skin cells. Hydrocarbons have also been shown to cause skin cancer with repeated application to the skin. Additionally, there is concern about systemic toxicity from dermal exposures to jet fuels, such as JP-8. Assessing risks from systemic absorption of hydrocarbon components is complex because most of the components are present in the mixture in small quantities (less than 1%). The effect of the fuel as a vehicle, different rates of penetration through the skin and different target organ toxicities all complicate the assessment of the hazards of cutaneous exposures. The purpose of this manuscript is to review studies of local and systemic toxicity of JP-8.

A PEG-Based Hydrogel for Effective Wound Care Management

PubMed Central

Chen, Sen-Lu; Fu, Ru-Huei; Liao, Shih-Fei; Liu, Shih-Ping; Lin, Shinn-Zong; Wang, Yu-Chi

2018-01-01

It is extremely challenging to achieve strong adhesion in soft tissues while minimizing toxicity, tissue damage, and other side effects caused by wound sealing materials. In this study, flexible synthetic hydrogel sealants were prepared based on polyethylene glycol (PEG) materials. PEG is a synthetic material that is nontoxic and inert and, thus, suitable for use in medical products. We evaluated the in vitro biocompatibility tests of the dressings to assess cytotoxicity and irritation, sensitization, pyrogen toxicity, and systemic toxicity following the International Organization for Standardization 10993 standards and the in vivo effects of the hydrogel samples using Coloskin liquid bandages as control samples for potential in wound closure. PMID:29637814

Fatal encephalopathy after an isolated overdose of cocaine

PubMed Central

Kondziella, D; Danielsen, E R; Arlien-Soeborg, P

2009-01-01

Cocaine induced brain damage can be divided into primary neurotoxic effects causing toxic encephalopathy, secondary effects of compromised cerebral blood flow in ischaemic and haemorrhagic stroke, cerebral vasculitis and vasospasm, and tertiary effects due to hypoxia as a result of cardiopulmonary collapse. Toxic leucoencephalopathy mainly affects white matter (WM) tracts serving higher cerebral function, thereby leading to altered personality, attention deficits and memory impairment in mild cases and to dementia, coma and brain death in severe cases. Here we describe the case of a 21-year-old man who committed suicide by injecting cocaine. The cocaine induced a toxic leucoencephalopathy, which was proven at autopsy. PMID:21731586

Terpenoid constituents of cinnamon and clove essential oils cause toxic effects and behavior repellency response on granary weevil, Sitophilus granarius.

PubMed

Plata-Rueda, Angelica; Campos, Juliana Mendonça; da Silva Rolim, Gabriela; Martínez, Luis Carlos; Dos Santos, Marcelo Henrique; Fernandes, Flávio Lemes; Serrão, José Eduardo; Zanuncio, José Cola

2018-07-30

This study evaluated toxic effects, repellency and respiration rate caused by terpenoid constituents of cinnamon and clove essential oils and against Sitophilus granarius L. (Coleoptera: Curculionidae). The lethal concentrations (LC 50 and LC 90 ), repellent effect, and behavior repellency response on adults of S. granarius after exposure to six concentrations of each essential oil and terpenoids were evaluated. The chemical composition of the cinnamon oil was also determined and primary compounds were eugenol (10.5%), trans-3-caren-2-ol (10.2%), benzyl benzoate (9.99%), caryophyllene (9.34%), eugenyl acetate (7.71%), α-phellandrene (7.41%), and α-pinene (7.14%). In clove essential oil, the primary compounds were eugenol (27.1%), caryophyllene (24.5%), caryophyllene oxide (18.3%), 2-propenoic acid (12.2%), α-humulene (10.8%), γ-cadinene (5.01%), and humulene oxide (4.84%). Cinnamon and clove essential oil was toxic to S. granarius. In toxic terpenoids compounds, eugenol has stronger contact toxicity in S. granarius than caryophyllene oxide, followed by α-pinene, α-humulene, and α-phellandrene. Insects reduced their respiratory rates after being exposed to essential oil terpenoids and avoided or reduced their mobility on terpenoid-treated surfaces. Cinnamon and clove essential oil, and their terpenoid constituents were toxic and repellent to adult S. granarius and, therefore, have the potential to prevent or retard the development of insecticide resistance. Copyright © 2018 Elsevier Inc. All rights reserved.

Pesticide poisoning.

PubMed

Goel, Ashish; Aggarwal, Praveen

2007-01-01

Acute poisoning with pesticides is a global public health problem and accounts for as many as 300,000 deaths worldwide every year. The majority of deaths occur due to exposure to organophosphates, organochlorines and aluminium phosphide. Organophosphate compounds inhibit acetylcholinesterase resulting in acute toxicity. Intermediate syndrome can develop in a number of patients and may lead to respiratory paralysis and death. Management consists of proper oxygenation, atropine in escalating doses and pralidoxime in high doses. It is Important to decontaminate the skin while taking precautions to avoid secondary contamination of health personnel. Organochlorine pesticides are toxic to the central nervous system and sensitize the myocardium to catecholamines. Treatment involves supportive care and avoiding exogenous sympathomimetic agents. Ingestion of paraquat causes severe inflammation of the throat, corrosive injury to the gastrointestinal tract, renal tubular necrosis, hepatic necrosis and pulmonary fibrosis. Administration of oxygen should be avoided as it produces more fibrosis. Use of immunosuppressive agents have improved outcome in patients with paraquat poisoning. Rodenticides include thallium, superwarfarins, barium carbonate and phosphides (aluminium and zinc phosphide). Alopecia is an atypical feature of thallium toxicity. Most exposures to superwarfarins are harmless but prolonged bleeding may occur. Barium carbonate Ingestion can cause severe hypokalaemia and respiratory muscle paralysis. Aluminium phosphide is a highly toxic agent with mortality ranging from 37% to 100%. It inhibits mitochondrial cytochrome c oxidase and leads to pulmonary and cardiac toxicity. Treatment is supportive with some studies suggesting a beneficial effect of magnesium sulphate. Pyrethroids and insect repellants (e.g. diethyltoluamide) are relatively harmless but can cause toxic effects to pulmonary and central nervous systems. Ethylene dibromide-a highly toxic, fumigant pesticide-produces oral ulcerations, followed by liver and renal toxicity, and is almost uniformly fatal. Physicians working in remote and rural areas need to be educated about early diagnosis and proper management using supportive care and antidotes, wherever available.

[Superantigens and toxic shock syndrome. A report of three cases treated with intravenous gammaglobulin].

PubMed

Vázquez García, Rubén Eduardo; Hernández Bautista, Víctor; Espinosa Padilla, Sara

2006-01-01

The superantigens cause a massive polyclonal activation of T-cells, producing an immense liberation of proinflamatory cytokines, which induces the clinical data of toxic shock syndrome. In international studies the administration of polyclonal intravenous gammaglobulin has been observed to diminish the mortality 50 to 20%. But at the present it has not been reported in Mexico the clinical effectiveness of this therapeutic modality in toxic shock syndrome. We report three cases of toxic shock syndrome treated with gammaglobulin intravenous, and we describe their favorable clinical evolution.

Oral exposure to cylindrospermopsin in pregnant rats: reproduction and foetal toxicity studies.

PubMed

Sibaldo de Almeida, Cristhiano; Costa de Arruda, Andrea Caroline; Caldas de Queiroz, Erika; Matias de Lima Costa, Haline Tereza; Barbosa, Patrícia Fernandes; Araújo Moura Lemos, Telma Maria; Oliveira, Cláudia Nunes; Pinto, Ernani; Schwarz, Aline; Kujbida, Paula

2013-11-01

Cylindrospermopsin (CYN) induces toxicity in pregnant mice when administered intraperitoneally. This study investigated whether oral exposure to CYN (0.03, 0.3 and 3 μg/kg) during pregnancy causes toxic effects and impairs gestation in rats. The results of reproductive performance and teratology studies were similar between the control and experimental dams. Our findings suggest that CYN consumption within the guideline values for drinking water is not able to promote foetal toxicity or alterations in rat reproductive performance. Copyright © 2013 Elsevier Ltd. All rights reserved.

Neem oil poisoning: Case report of an adult with toxic encephalopathy

PubMed Central

Mishra, Ajay; Dave, Nikhil

2013-01-01

Neem oil has widespread use in Indian subcontinent due to its many bioactive properties. Azadirachtin, an active ingredient, is implicated in causing the effects seen in neem oil poisoning. Neem oil poisoning is rare in adults. This report highlights the toxicity associated with neem oil poisoning in an elderly male. The patient presented with vomiting, seizures, metabolic acidosis, and toxic encephalopathy. The patient recovered completely with symptomatic treatment. PMID:24339648

Effects of Shuang Wuzhen Tong Capsule on acute toxicity of mice caused by swelling and auricular dimethylbenzene

NASA Astrophysics Data System (ADS)

Hao, Shaojun; Sun, Youshu; Guo, Junyi; Chen, Weiliang; Wang, Hongyu; Sun, Jianhua; Guan, Zhijiang; Zhang, Zhengchen; Wang, Fang

2018-04-01

To observe the effect of Shuang Wuzhen Tong Capsule on acute toxicity of mice caused by swelling and auricular dimethylbenzene. 40 rats, weighing 18 ˜ 22G, half male and half female. Shuang Wuzhen Tong Capsule maximum concentration maximum volume to mice for 1 days by gavage for 1 times, for 7 consecutive days, to observe the situation of animal death, the maximum tolerance; the other 50 mice, were divided into 5 groups, were fed with Shuang Wuzhen Tong capsule suspension, Jingfukang granule suspension and the same volume 0.5%CMC. No death in 7 days. After death animal autopsy, heart, liver, spleen, lung, kidney, brain, stomach, intestine and no important organ obvious bleeding, hyperemia and edema, exudation, ulcer, perforation, pleural, peritoneal, pericardial cavity without effusion. Shuang Wuzhen Tong Capsule group and Jingfukang granule group could obviously reduce the xylene induced swelling of mouse ear, ear swelling degree decreased significantly (P<0.01). Shuang Wuzhen Tong Capsule has no obvious acute toxicity, anti-inflammatory effects.

Encapsulation of Aconitine in Self-Assembled Licorice Protein Nanoparticles Reduces the Toxicity In Vivo

NASA Astrophysics Data System (ADS)

Ke, Li-jing; Gao, Guan-zhen; Shen, Yong; Zhou, Jian-wu; Rao, Ping-fan

2015-11-01

Many herbal medicines and compositions are clinically effective but challenged by its safety risks, i.e., aconitine (AC) from aconite species. The combined use of Radix glycyrrhizae (licorice) with Radix aconite L. effectively eliminates toxicity of the later while increasing efficacy. In this study, a boiling-stable 31-kDa protein (namely GP) was purified from licorice and self-assembled into nanoparticles (206.2 ± 2.0 nm) at pH 5.0, 25 °C. The aconitine-encapsulated GP nanoparticles (238.2 ± 1.2 nm) were prepared following the same procedure and tested for its toxicity by intraperitoneal injection on ICR mouse ( n = 8). Injection of GP-AC nanoparticles and the mixed licorice-aconite decoction, respectively, caused mild recoverable toxic effects and no death, while the aconitine, particle-free GP-AC mixture and aconite decoction induced sever toxic effects and 100 % death. Encapsulation of poisonous alkaloids into self-assembled herbal protein nanoparticles contributes to toxicity attenuation of combined use of herbs, implying a prototype nanostructure and a universal principle for the safer clinical applications of herbal medicines.

Chromium(VI) Toxicity in Legume Plants: Modulation Effects of Rhizobial Symbiosis

PubMed Central

Lushchak, Volodymyr I.

2018-01-01

Most legume species have the ability to establish a symbiotic relationship with soil nitrogen-fixing rhizobacteria that promote plant growth and productivity. There is an increasing evidence of reactive oxygen species (ROS) important role in formation of legume-rhizobium symbiosis and nodule functioning. Environmental pollutants such as chromium compounds can cause damage to rhizobia, legumes, and their symbiosis. In plants, toxic effects of chromium(VI) compounds are associated with the increased production of ROS and oxidative stress development as well as with inhibition of pigment synthesis and modification of virtually all cellular components. These metabolic changes result in inhibition of seed germination and seedling development as well as reduction of plant biomass and crop yield. However, if plants establish symbiosis with rhizobia, heavy metals are accumulated preferentially in nodules decreasing the toxicity of metals to the host plant. This review summarizes data on toxic effects of chromium on legume plants and legume-rhizobium symbiosis. In addition, we discussed the role of oxidative stress in both chromium toxicity and formation of rhizobial symbiosis and use of nodule bacteria for minimizing toxic effects of chromium on plants. PMID:29662899

Isolation and characterization of pigmented algicidal bacteria from seawater

NASA Astrophysics Data System (ADS)

Shaima, A.; Gires, U.; Asmat, A.

2014-09-01

Some dinoflagellate species are toxic and widely distributed in Malaysian marines ecosystems. They can cause many problems to aquatic life due to the production of various potential and natural toxins that accumulate in filter feeding shellfish and cause food poisoning to human. In recent decades, bacteria have been widely used as a biological control against these harmful algae. In the present study, pigmented bacteria isolated from marine water of Port Dickson beach was studied for their anti-algal activity towards toxic dinoflagellate Alexandrium minutum. Four isolates were studied and only one was capable of inhibiting algal growth when treated with bacterial culture. The algilytic effect on dinoflagellate was evaluated based on direct cell count under the microscope. Results showed that only isolate Sdpd-310 with orange colour has an inhibitory effect on A. minutum growth. This study demonstrated the rapid algicidal activity of a marine pigmented bacteria against the toxic dinoflagellate A. minutum.

Ocular hydrofluoric acid burns: animal model, mechanism of injury and therapy.

PubMed Central

McCulley, J P

1990-01-01

A series of ocular HF burns was produced in rabbits in order to clarify the nature of the injury and to provide a description of the animal model. Burned eyes were evaluated clinically and allowed to progress for up to 65 days before histologic examination. The mechanism of HF toxicity was investigated through the study of burns produced by chemicals chosen to mimic its pH effects, osmotic effects, and effects of the free fluoride ion alone. The severe progressive caustic effect of HF on the eyes was found to depend on the combination of pH and the toxic effects of the free fluoride ion, together causing extensive dose-related damage to superficial and deep structures of the eye. Mild burns caused reversible ocular injury; whereas more severe burns lead to corneal stromal scarring, vascularization, edema, formation of calcific band keratopathy plus iris and ciliary body fibrosis. An investigation was made of potential treatments for experimental ocular HF burns in rabbits. Topical ointments containing MgO or MgSO4 and irrigations with or subconjunctival injections of H2O or solutions containing NaCl, MgCl2, CaCl2, LaCl3, hyamine, zephiran, calcium gluconate or a mixture of divalent metal ions were tested for toxicity and for therapeutic value in ocular HF burns. Immediate single irrigation with H2O, NaCl or MgCl2 solution was most effective. Other therapeutic agents commonly used in HF skin burn therapy were either too toxic in normal eyes or caused additive damage to burned eyes. Images FIGURE 1 FIGURE 6 FIGURE 7 FIGURE 8 PMID:2095035

Quercetin protects against radiocontrast medium toxicity in human renal proximal tubular cells.

PubMed

Andreucci, Michele; Faga, Teresa; Pisani, Antonio; Serra, Raffaele; Russo, Domenico; De Sarro, Giovambattista; Michael, Ashour

2018-05-01

Radiocontrast media (RCM)-induced acute kidney injury (CI-AKI) is a major clinical problem whose pathophysiology is not well understood. Direct toxic effects on renal cells, possibly mediated by reactive oxygen species, have been postulated as contributing to CI-AKI. We investigated the effect of quercetin on human renal proximal tubular (HK-2) cells treated with the radiocontrast medium (RCM) sodium diatrizoate. Quercetin is the most widely studied flavonoid, and the most abundant flavonol present in foods. It has been suggested to have many health benefits, including angioprotective properties and anti-cancer effects. These beneficial effects have been attributed to its antioxidant properties and its ability to modulate cell signaling pathways. Incubation of HK-2 cells with 100 μM quercetin caused a decrease in cell viability and pre-treatment of HK-2 cells with 100 μM quercetin followed by incubation with 75 mgI/ml sodium diatrizoate for 2 hr caused a decrease in cell viability which was worse than in cells treated with diatrizoate alone. However, further incubation of the cells (for 22 hr) after removal of the diatrizoate and quercetin caused a recovery in cell viability in those cells previously treated with quercetin + diatrizoate and quercetin alone. Analysis of signaling molecules by Western blotting showed that in RCM-treated cells receiving initial pre-treatment with quercetin, followed by its removal, an increase in phosphorylation of Akt (Ser473), pSTAT3 (Tyr705), and FoxO3a (Thr32) as well as an induction of Pim-1 and decrease in PARP1 cleavage were observed. Quercetin may alleviate the longer-term toxic effects of RCM toxicity and its possible beneficial effects should be further investigated. © 2017 Wiley Periodicals, Inc.

Injurious effects of wool and grain dusts on alveolar epithelial cells and macrophages in vitro.

PubMed Central

Brown, D M; Donaldson, K

1991-01-01

Epidemiological studies of workers in wool textile mills have shown a direct relation between the concentration of wool dust in the air and respiratory symptoms. Injurious effects of wool dust on the bronchial epithelium could be important in causing inflammation and irritation. A pulmonary epithelial cell line in vitro was therefore used to study the toxic effects of wool dust. Cells of the A549 epithelial cell line were labelled with 51Cr and treated with whole wool dusts and extracts of wool, after which injury was assessed. Also, the effects of grain dust, which also causes a form of airway obstruction, were studied. The epithelial injury was assessed by measuring 51Cr release from cells as an indication of lysis, and by monitoring cells which had detached from the substratum. No significant injury to A549 cells was caused by culture with any of the dusts collected from the air but surface "ledge" dust caused significant lysis at some doses. Quartz, used as a toxic control dust, caused significant lysis at the highest concentration of 100 micrograms/well. To determine whether any injurious material was soluble the dusts were incubated in saline and extracts collected. No extracts caused significant injury to epithelial cells. A similar lack of toxicity was found when 51Cr labelled control alveolar macrophages were targets for injury. Significant release of radiolabel was evident when macrophages were exposed to quartz at concentrations of 10 and 20 micrograms/well, there being no significant injury with either wool or grain dusts. These data suggest that neither wool nor grain dust produce direct injury to epithelial cells, and further studies are necessary to explain inflammation leading to respiratory symptoms in wool and grain workers. PMID:2015211

Targeted delivery of celastrol to mesangial cells is effective against mesangioproliferative glomerulonephritis.

PubMed

Guo, Ling; Luo, Shi; Du, Zhengwu; Zhou, Meiling; Li, Peiwen; Fu, Yao; Sun, Xun; Huang, Yuan; Zhang, Zhirong

2017-10-12

Mesangial cells-mediated glomerulonephritis is a frequent cause of end-stage renal disease. Here, we show that celastrol is effective in treating both reversible and irreversible mesangioproliferative glomerulonephritis in rat models, but find that its off-target distributions cause severe systemic toxicity. We thus target celastrol to mesangial cells using albumin nanoparticles. Celastrol-albumin nanoparticles crosses fenestrated endothelium and accumulates in mesangial cells, alleviating proteinuria, inflammation, glomerular hypercellularity, and excessive extracellular matrix deposition in rat anti-Thy1.1 nephritis models. Celastrol-albumin nanoparticles presents lower drug accumulation than free celastrol in off-target organs and tissues, thereby minimizing celastrol-related systemic toxicity. Celastrol-albumin nanoparticles thus represents a promising treatment option for mesangioproliferative glomerulonephritis and similar glomerular diseases.Mesangial cell-mediated glomerulonephritis is a frequent cause of kidney disease. Here the authors show that celastrol loaded in albumin nanoparticles efficiently targets mesangial cells, and is effective in rat models.

Evolving Role of Passive Samplers in Whole Sediment Toxicity Identification Evaluations

EPA Science Inventory

In Phase I of whole sediment TIEs, causes of toxicity to freshwater and marine organisms are characterized into broad toxicant classes including ammonia, metals and organic chemicals. In Phase II of the TIE, the specific toxicants causing observed toxicity are identified. For a...

The molecular mechanisms of liver and islets of Langerhans toxicity by benzene and its metabolite hydroquinone in vivo and in vitro.

PubMed

Bahadar, Haji; Maqbool, Faheem; Mostafalou, Sara; Baeeri, Maryam; Gholami, Mahdi; Ghafour-Boroujerdi, Elmira; Abdollahi, Mohammad

2015-01-01

Benzene (C6H6) is one of the most commonly used industrial chemicals causing environmental pollution. This study aimed to examine the effect of benzene and its metabolite hydroquinone on glucose regulating organs, liver and pancreas, and to reveal the involved toxic mechanisms, in rats. In the in vivo part, benzene was dissolved in corn oil and administered through intragastric route at doses of 200, 400 and 800 mg/kg/day, for 4 weeks. And, in the in vitro part, toxic mechanisms responsible for weakening the antioxidant system in islets of Langerhans by hydroquinone at different concentrations (0.25, 0.5 and 1 mM), were revealed. Benzene exposure raised the activity of phosphoenolpyruvate carboxykinase (PEPCK), glucose 6-phosphatase (G6Pase) enzymes and increased fasting blood sugar (FBS) in comparison to control animals. Also, the activity of hepatic glucokinase (GK) was decreased significantly. Along with, a significant increase was observed in hepatic tumor necrosis factor (TNF-α) and plasma insulin in benzene treated rats. Moreover, benzene caused a significant rise in hepatic lipid peroxidation, DNA damage and oxidation of proteins. In islets of Langerhans, hydroquinone was found to decrease the capability of antioxidant system to fight free radicals. Also, the level of death proteases (caspase 3 and caspase 9) was found higher in hydroquinone exposed islets. The current study demonstrated that benzene and hydroquinone causes toxic effects on liver and pancreatic islets by causing oxidative impairment.

Accelerated Blood Clearance (ABC) Phenomenon Favors the Accumulation of Tartar Emetic in Pegylated Liposomes in BALB/c Mice Liver.

PubMed

Lopes, Tamara C M; Silva, Débora F; Costa, Walyson C; Frézard, Frédéric; Barichello, José M; Silva-Barcellos, Neila M; de Lima, Wanderson G; Rezende, Simone A

2018-01-01

Tartar emetic (TE) was the first drug used to treat leishmaniasis. However, its use was discontinued due to high toxicity. Association of TE with liposomes is a strategy to reduce its side effects. Pegylated liposomes (Lpeg) present lower rates of uptake by macrophages and prolonged circulation compared to their nonpegylated counterparts. However, repeated administration of Lpeg can cause an Accelerated Blood Clearance (ABC) phenomenon, whereby recognition of liposomes by antibodies results in faster phagocytosis. This work evaluated the effect of TE administration on histopathological aspects and the effect of the ABC phenomenon on targeting and toxicity in mice. Our results show that treatment with free or liposomal TE had no effect on the erythrocyte count, on liver and spleen weight, and on hepatic, splenic, and cardiac histology in mice. Severe lesions were observed on the kidneys of animals treated with a single dose of free TE. Treatment with TE in Lpeg after induction of ABC phenomenon caused a significant increase in Sb level in the liver without toxicity. Furthermore, mice treated with TE in liposomes showed normal renal histopathology. These results suggest site-specific targeting of Sb to the liver after induction of ABC phenomenon with no toxicity to other organs.

Accelerated Blood Clearance (ABC) Phenomenon Favors the Accumulation of Tartar Emetic in Pegylated Liposomes in BALB/c Mice Liver

PubMed Central

Lopes, Tamara C. M.; Silva, Débora F.; Costa, Walyson C.; Barichello, José M.; Silva-Barcellos, Neila M.; de Lima, Wanderson G.

2018-01-01

Tartar emetic (TE) was the first drug used to treat leishmaniasis. However, its use was discontinued due to high toxicity. Association of TE with liposomes is a strategy to reduce its side effects. Pegylated liposomes (Lpeg) present lower rates of uptake by macrophages and prolonged circulation compared to their nonpegylated counterparts. However, repeated administration of Lpeg can cause an Accelerated Blood Clearance (ABC) phenomenon, whereby recognition of liposomes by antibodies results in faster phagocytosis. This work evaluated the effect of TE administration on histopathological aspects and the effect of the ABC phenomenon on targeting and toxicity in mice. Our results show that treatment with free or liposomal TE had no effect on the erythrocyte count, on liver and spleen weight, and on hepatic, splenic, and cardiac histology in mice. Severe lesions were observed on the kidneys of animals treated with a single dose of free TE. Treatment with TE in Lpeg after induction of ABC phenomenon caused a significant increase in Sb level in the liver without toxicity. Furthermore, mice treated with TE in liposomes showed normal renal histopathology. These results suggest site-specific targeting of Sb to the liver after induction of ABC phenomenon with no toxicity to other organs. PMID:29593857

Toxicity of benthic dinoflagellates on grazing, behavior and survival of the brine shrimp Artemia salina

PubMed Central

Neves, Raquel A. F.; Fernandes, Tainá; dos Santos, Luciano Neves; Nascimento, Silvia M.

2017-01-01

Harmful algae may differently affect their primary grazers, causing sub-lethal effects and/or leading to their death. The present study aim to compare the effects of three toxic benthic dinoflagellates on clearance and grazing rates, behavioral changes, and survival of Artemia salina. Feeding assays consisted in 1-h incubations of brine shrimps with the toxic Prorocentrum lima, Gambierdiscus excentricus and Ostreopsis cf. ovata and the non-toxic Tetraselmis sp. Brine shrimps fed unselectively on all toxic and non-toxic algal preys, without significant differences in clearance and ingestion rates. Acute toxicity assays were performed with dinoflagellate cells in two growth phases during 7-h to assess differences in cell toxicity to A. salina. Additionally, exposure to cell-free medium was performed to evaluate its effects on A. salina survival. The behavior of brine shrimps significantly changed during exposure to the toxic dinoflagellates, becoming immobile at the bottom by the end of the trials. Dinoflagellates significantly affected A. salina survival with 100% mortality after 7-h exposure to cells in exponential phase (all treatments) and to P. lima in stationary phase. Mortality rates of brine shrimps exposed to O. cf. ovata and G. excentricus in stationary phase were 91% and 75%, respectively. However, incubations of the brine shrimps with cell-free medium did not affect A. salina survivorship. Significant differences in toxic effects between cell growth phases were only found in the survival rates of A. salina exposed to G. excentricus. Acute exposure to benthic toxic dinoflagellates induced harmful effects on behavior and survival of A. salina. Negative effects related to the toxicity of benthic dinoflagellates are thus expected on their primary grazers making them more vulnerable to predation and vectors of toxins through the marine food webs. PMID:28388672

Toxicity of benthic dinoflagellates on grazing, behavior and survival of the brine shrimp Artemia salina.

PubMed

Neves, Raquel A F; Fernandes, Tainá; Santos, Luciano Neves Dos; Nascimento, Silvia M

2017-01-01

Harmful algae may differently affect their primary grazers, causing sub-lethal effects and/or leading to their death. The present study aim to compare the effects of three toxic benthic dinoflagellates on clearance and grazing rates, behavioral changes, and survival of Artemia salina. Feeding assays consisted in 1-h incubations of brine shrimps with the toxic Prorocentrum lima, Gambierdiscus excentricus and Ostreopsis cf. ovata and the non-toxic Tetraselmis sp. Brine shrimps fed unselectively on all toxic and non-toxic algal preys, without significant differences in clearance and ingestion rates. Acute toxicity assays were performed with dinoflagellate cells in two growth phases during 7-h to assess differences in cell toxicity to A. salina. Additionally, exposure to cell-free medium was performed to evaluate its effects on A. salina survival. The behavior of brine shrimps significantly changed during exposure to the toxic dinoflagellates, becoming immobile at the bottom by the end of the trials. Dinoflagellates significantly affected A. salina survival with 100% mortality after 7-h exposure to cells in exponential phase (all treatments) and to P. lima in stationary phase. Mortality rates of brine shrimps exposed to O. cf. ovata and G. excentricus in stationary phase were 91% and 75%, respectively. However, incubations of the brine shrimps with cell-free medium did not affect A. salina survivorship. Significant differences in toxic effects between cell growth phases were only found in the survival rates of A. salina exposed to G. excentricus. Acute exposure to benthic toxic dinoflagellates induced harmful effects on behavior and survival of A. salina. Negative effects related to the toxicity of benthic dinoflagellates are thus expected on their primary grazers making them more vulnerable to predation and vectors of toxins through the marine food webs.

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

Phenazine derivatives cause proteotoxicity and stress in C. elegans

PubMed Central

Ray, Arpita; Rentas, Courtney; Caldwell, Guy A.; Caldwell, Kim A.

2014-01-01

It is widely recognized that bacterial metabolites have toxic effects in animal systems. Phenazines are a common bacterial metabolite within the redox-active exotoxin class. These compounds have been shown to be toxic to the soil invertebrate Caenorhabditis elegans with the capability of causing oxidative stress and lethality. Here we report that chronic, low-level exposure to three separate phenazine molecules (phenazine-1-carboxylic acid, pyocyanin and 1-hydroxyphenazine) upregulated ER stress response and enhanced expression of a superoxide dismutase reporter in vivo. Exposure to these molecules also increased of polyglutamine and α-synuclein in the bodywall muscle cells of C. elegans. Exposure of worms to these phenazines caused additional sensitivity in dopamine neurons expressing wild-type α-synuclein, indicating a possible defect in protein homeostasis. The addition of an anti-oxidant failed to rescue the neurotoxic and protein aggregation phenotypes caused by these compounds. Thus, increased production of superoxide radicals that occurs in whole animals in response to these phenazines appears independent from the toxicity phenotype observed. Collectively, these data provide cause for further consideration of the neurodegenerative impact of phenazines. PMID:25304539

Changes in metabolic activities of Fusarium oxysporum f. fabae and Rhizoctonia solani in response to Dithan A-40 fungicide.

PubMed

Zaki, M M; Mahmoud, S A; Hamed, A S; Sahab, A F

1979-01-01

The effect of different concentrations of Dithan A-40 fungicide on the metabolic activities of the wilt fungus Fusarium oxysporum f. fabae and the root rot agent Rhizoctonia solani was studied. All toxicant concentrations reduced energy generation, total phosphorus and nitrogen content of both fungi. In addition, the toxicant caused a shift in free amino acids pool. As a result of these changes, the mycelium dry weight of both fungi was greatly reduced. R. solani was more sensitive to the toxic effect of Dithan A-40 than F. oxysporum.

Effects of gestational exposure to PFOA on PPAR protein and mRNA expression in vital organs of fetal and postnatal mice

EPA Science Inventory

Perfluorooctanoic acid (PFOA) is developmentally toxic, causing in utero and neonatal mortality, and altering development and growth in mice. PFOA activates peroxisome proliferator-activated receptor (PPAR)a and PPARa signaling is required for toxicity. This study examines the ex...

Metabolomics of microliter hemolymph samples enables an improved understanding of the combined metabolic and transcriptional responses of Daphnia magna to cadmium

EPA Science Inventory

Cadmium is a toxic metal causing sublethal and chronic effects in crustaceans. Omic technologies offer unprecedented opportunities to better understand modes of toxicity by providing a holistic view of the molecular changes underlying physiological disruption. We sought to use ge...

The Impact of Pollution Prevention on Toxic Environmental Releases from U.S. Manufacturing Facilities.

PubMed

Ranson, Matthew; Cox, Brendan; Keenan, Cheryl; Teitelbaum, Daniel

2015-11-03

Between 1991 and 2012, the facilities that reported to the U.S. Environmental Protection Agency's Toxic Release Inventory (TRI) Program conducted 370,000 source reduction projects. We use this data set to conduct the first quasi-experimental retrospective evaluation of how implementing a source reduction (pollution prevention) project affects the quantity of toxic chemicals released to the environment by an average industrial facility. We use a differences-in-differences methodology, which measures how implementing a source reduction project affects a facility's releases of targeted chemicals, relative to releases of (a) other untargeted chemicals from the same facility, or (b) the same chemical from other facilities in the same industry. We find that the average source reduction project causes a 9-16% decrease in releases of targeted chemicals in the year of implementation. Source reduction techniques vary in effectiveness: for example, raw material modification causes a large decrease in releases, while inventory control has no detectable effect. Our analysis suggests that in aggregate, the source reduction projects carried out in the U.S. since 1991 have prevented between 5 and 14 billion pounds of toxic releases.

The Mauve Stinger Pelagia noctiluca (Forsskål, 1775). Distribution, Ecology, Toxicity and Epidemiology of Stings. A Review

PubMed Central

Mariottini, Gian Luigi; Giacco, Elisabetta; Pane, Luigi

2008-01-01

The toxicity of Cnidaria is a subject of concern due to its influence on humans. In particular, jellyfish blooms can highly affect human economical activities, such as bathing, fishery, tourism, etc., as well as the public health. Stinging structures of Cnidaria (nematocysts) produce remarkable effects on human skin, such as erythema, swelling, burning and vesicles, and at times further severe dermonecrotic, cardio- and neurotoxic effects, which are particularly dangerous in sensitive subjects. In several zones the toxicity of jellyfish is a very important health problem, thus it has stimulated the research on these organisms; to date toxicological research on Cnidarian venoms in the Mediterranean region is not well developed due to the weak poisonousness of venoms of jellyfish and anemones living in this area. In spite of this, during last decades several problems were also caused in the Mediterranean by stinging consequent to Cnidarian blooms mainly caused by Pelagia noctiluca (Forsskål, 1775) which is known to be the most venomous Mediterranean jellyfish. This paper reviews the knowledge on this jellyfish species, particularly considering its occurrence and toxicity. PMID:19005582

Global occurrence of pyrethroid insecticides in sediment and the associated toxicological effects on benthic invertebrates: An overview.

PubMed

Li, Huizhen; Cheng, Fei; Wei, Yanli; Lydy, Michael J; You, Jing

2017-02-15

Pyrethroids are the third most applied group of insecticides worldwide and are extensively used in agricultural and non-agricultural applications. Pyrethroids exhibit low toxicity to mammals, but have extremely high toxicity to fish and non-target invertebrates. Their high hydrophobicity, along with pseudo-persistence due to continuous input, indicates that pyrethroids will accumulate in sediment, pose long-term exposure concerns to benthic invertebrates and ultimately cause significant risk to benthic communities and aquatic ecosystems. The current review synthesizes the reported sediment concentrations of pyrethroids and associated toxicity to benthic invertebrates on a global scale. Geographically, the most studied area was North America, followed by Asia, Europe, Australia and Africa. Pyrethroids were frequently detected in both agricultural and urban sediments, and bifenthrin and cypermethrin were identified as the main contributors to toxicity in benthic invertebrates. Simulated hazard quotients (HQ) for sediment-associated pyrethroids to benthic organisms ranged from 10.5±31.1 (bifenthrin) to 41.7±204 (cypermethrin), suggesting significant risk. The current study has provided evidence that pyrethroids are not only commonly detected in the aquatic environment, but also can cause toxic effects to benthic invertebrates, and calls for better development of accurate sediment quality criteria and effective ecological risk assessment methods for this emerging class of insecticides. Copyright © 2016 Elsevier B.V. All rights reserved.

Residential exposure to air toxics is linked to lower grade point averages among school children in El Paso, Texas, USA

PubMed Central

Clark-Reyna, Stephanie E.; Grineski, Sara E.; Collins, Timothy W.

2015-01-01

Children in low-income neighborhoods tend to be disproportionately exposed to environmental toxicants. This is cause for concern because exposure to environmental toxicants negatively affect health, which can impair academic success. To date, it is unknown if associations between air toxics and academic performance found in previous school-level studies persist when studying individual children. In pairing the National Air Toxics Assessment (NATA) risk estimates for respiratory and diesel particulate matter risk disaggregated by source, with individual-level data collected through a mail survey, this paper examines the effects of exposure to residential environmental toxics on academic performance for individual children for the first time and adjusts for school-level effects using generalized estimating equations. We find that higher levels of residential air toxics, especially those from non-road mobile sources, are statistically significantly associated with lower grade point averages among fourth and fifth grade school children in El Paso (Texas, USA). PMID:27034529

Reproductive and developmental toxicity of hydrofluorocarbons used as refrigerants.

PubMed

Ema, Makoto; Naya, Masato; Yoshida, Kikuo; Nagaosa, Ryuichi

2010-04-01

The present paper summarizes data on the reproductive and developmental toxicity of hydrofluorocarbons (HFCs), including pentafluoroethane (HFC-125), 1,1,1,2-tetrafluoroethane (HFC-134a), 1,1,1-trifluoroethane (HFC-143a), 1,1-difluoroethane (HFC-152a), difluoromethane (HFC-32) and 1,1,1,3,3-pentafluoropropane (HFC-245fa), used as refrigerants, published in openly available scientific literature. No developmental toxicity of HFC-125 was found even at 50,000 ppm in rats or rabbits. Although HFC-134a exhibited no dominant lethal effect or reproductive toxicity in rats, it caused low body weight in pre- and postnatal offspring and slightly retarded skeletal ossification in fetuses at 50,000 ppm in rats. No maternal or developmental toxicity was noted after exposure to HFC-143a even at 40,000 ppm in rats or rabbits or HFC-152a even at 50,000 ppm in rats. HFC-32 is slightly maternally and developmentally toxic at 50,000 ppm in rats, but not in rabbits. HFC-245fa caused decreases in maternal body weight and food consumption at 10,000 and 50,000 ppm and fetal weight at 50 000ppm. No evidence of teratogenicity for these HFCs was noted in rats or rabbits. There is limited information about the reproductive toxicity of these HFCs. Animal studies remain necessary for risk assessments of chemicals because it is difficult to find alternative methods to determine the toxic effects of chemicals. It is required to reduce emissions of organic vapors containing HFCs to reduce the risk of exposure. Copyright 2009 Elsevier Inc. All rights reserved.

Semi-quantitative assessments of dextran toxicity on corneal endothelium: conceptual design of a predictive algorithm.

PubMed

Filev, Filip; Oezcan, Ceprail; Feuerstacke, Jana; Linke, Stephan J; Wulff, Birgit; Hellwinkel, Olaf J C

2017-03-01

Dextran is added to corneal culture medium for at least 8 h prior to transplantation to ensure that the cornea is osmotically dehydrated. It is presumed that dextran has a certain toxic effect on corneal endothelium but the degree and the kinetics of this effect have not been quantified so far. We consider that such data regarding the toxicity of dextran on the corneal endothelium could have an impact on scheduling and logistics of corneal preparation in eye banking. In retrospective statistic analyses, we compared the progress of corneal endothelium (endothelium cell loss per day) of 1334 organ-cultured corneal explants in media with and without dextran. Also, the influence of donor-age, sex and cause of death on the observed dextran-mediated effect on endothelial cell counts was studied. Corneas cultured in dextran-free medium showed a mean endothelium cell count decrease of 0.7% per day. Dextran supplementation led to a mean endothelium cell loss of 2.01% per day; this reflects an increase by the factor of 2.9. The toxic impact of dextran was found to be time dependent; while the prevailing part of the effect was observed within the first 24 h after dextran-addition. Donor age, sex and cause of death did not seem to have an influence on the dextran-mediated toxicity. Based on these findings, we could design an algorithm which approximately describes the kinetics of dextran-toxicity. We reproduced the previously reported toxic effect of dextran on the corneal endothelium in vitro. Additionally, this is the first work that provides an algorithmic instrument for the semi-quantitative calculation of the putative endothelium cell count decrease in dextran containing medium for a given incubation time and could thus influence the time management and planning of corneal transplantations.

EDTA ameliorates phytoextraction of lead and plant growth by reducing morphological and biochemical injuries in Brassica napus L. under lead stress.

PubMed

Kanwal, Urooj; Ali, Shafaqat; Shakoor, Muhammad Bilal; Farid, Mujahid; Hussain, Sabir; Yasmeen, Tahira; Adrees, Muhammad; Bharwana, Saima Aslam; Abbas, Farhat

2014-01-01

Brassica species are very effective in remediation of heavy metal contaminated sites. Lead (Pb) as a toxic pollutant causes number of morphological and biochemical variations in the plants. Synthetic chelator such as ethylenediaminetetraacetic acid (EDTA) improves the capability of plants to uptake heavy metals from polluted soil. In this regard, the role of EDTA in phytoextraction of lead, the seedlings of Brassica napus L. were grown hydroponically. Lead levels (50 and 100 μM) were supplied alone or together with 2.5 mM EDTA in the nutrient culture. After 7 weeks of stress, plants indicated that toxicity of Pb caused negative effects on plants and significantly reduced growth, biomass, chlorophyll content, gas exchange characteristics, and antioxidant enzymes activities such as superoxide dismutase (SOD), guaiacol peroxidase (POD), ascorbate peroxidase (APX), and catalase (CAT). Exposure to Pb induced the malondialdehyde (MDA), and hydrogen peroxide (H2O2) generation in both shoots and roots. The addition of EDTA alone or in combination with Pb significantly improved the plant growth, biomass, gas exchange characteristics, chlorophyll content, and antioxidant enzymes activities. EDTA also caused substantial improvement in Pb accumulation in Brassica plants. It can be deduced that application of EDTA significantly lessened the adverse effects of lead toxicity. Additionally, B. napus L. exhibited greater degree of tolerance against Pb toxicity and it also accumulated significant concentration of Pb from media.

Environmental toxicants and male reproductive function

PubMed Central

Wong, Elissa W.P; Lie, Pearl P.Y; Li, Michelle W.M; Su, Linlin; Siu, Erica R; Yan, Helen H.N; Mannu, Jayakanthan; Mathur, Premendu P; Bonanomi, Michele; Silvestrini, Bruno; Mruk, Dolores D

2011-01-01

Environmental toxicants, such as cadmium and bisphenol A (BPA) are endocrine disruptors. In utero, perinatal or neonatal exposure of BPA to rats affect the male reproductive function, such as the blood-testis barrier (BTB) integrity. This effect of BPA on BTB integrity in immature rats is likely mediated via a loss of gap junction function at the BTB, failing to coordinate tight junction and anchoring junction function at the site to maintain the immunological barrier integrity. This in turn activates the extracellular signal-regulated kinases 1/2 (Erk1/2) downstream and an increase in protein endocytosis, destabilizing the BTB. The cadmium-induced disruption of testicular dysfunction is mediated initially via its effects on the occludin/ZO-1/focal adhesion kinase (FAK) complex at the BTB, causing redistribution of proteins at the Sertoli-Sertoli cell interface, leading to the BTB disruption. The damaging effects of these toxicants to testicular function are mediated by mitogen-activated protein kinases (MAPK) downstream, which in turn perturbs the actin bundling and accelerates the actin-branching activity, causing disruption of the Sertoli cell tight junction (TJ)-barrier function at the BTB and perturbing spermatid adhesion at the apical ectoplasmic specialization (apical ES, a testis-specific anchoring junction type) that leads to premature release of germ cells from the testis. However, the use of specific inhibitors against MAPK was shown to block or delay the cadmium-induced testicular injury, such as BTB disruption and germ cell loss. These findings suggest that there may be a common downstream p38 and/or Erk1/2 MAPK-based signaling pathway involving polarity proteins and actin regulators that is shared between different toxicants that induce male reproductive dysfunction. As such, the use of inhibitors and/or antagonists against specific MAPKs can possibly be used to “manage” the illnesses caused by these toxicants and/or “protect” industrial workers being exposed to high levels of these toxicants in their work environment. PMID:21866273

Acute toxicity of ingested fluoride.

PubMed

Whitford, Gary Milton

2011-01-01

This chapter discusses the characteristics and treatment of acute fluoride toxicity as well as the most common sources of overexposure, the doses that cause acute toxicity, and factors that can influence the clinical outcome. Cases of serious systemic toxicity and fatalities due to acute exposures are now rare, but overexposures causing toxic signs and symptoms are not. The clinical course of systemic toxicity from ingested fluoride begins with gastric signs and symptoms, and can develop with alarming rapidity. Treatment involves minimizing absorption by administering a solution containing calcium, monitoring and managing plasma calcium and potassium concentrations, acid-base status, and supporting vital functions. Approximately 30,000 calls to US poison control centers concerning acute exposures in children are made each year, most of which involve temporary gastrointestinal effects, but others require medical treatment. The most common sources of acute overexposures today are dental products - particularly dentifrices because of their relatively high fluoride concentrations, pleasant flavors, and their presence in non-secure locations in most homes. For example, ingestion of only 1.8 ounces of a standard fluoridated dentifrice (900-1,100 mg/kg) by a 10-kg child delivers enough fluoride to reach the 'probably toxic dose' (5 mg/kg body weight). Factors that may influence the clinical course of an overexposure include the chemical compound (e.g. NaF, MFP, etc.), the age and acid-base status of the individual, and the elapsed time between exposure and the initiation of treatment. While fluoride has well-established beneficial dental effects and cases of serious toxicity are now rare, the potential for toxicity requires that fluoride-containing materials be handled and stored with the respect they deserve. Copyright © 2011 S. Karger AG, Basel.

The effect of olanzapine pretreatment on acute cocaine toxicity in mice.

PubMed

Heard, Kennon J; Cleveland, Nathan R; Krier, Shay

2009-07-01

Acute cocaine poisoning causes neuroexcitation and can be fatal. The toxic effects of cocaine can be attenuated by antagonists of serotonin, muscarinic cholinergic, and dopamine receptors. Olanzapine, an atypical antipsychotic medication, is an antagonist of these receptors. The objective of this study is to evaluate the efficacy of olanzapine pretreatment for attenuation of acute cocaine toxicity using a mouse model. Eighty male CF-1 mice were randomly assigned to olanzapine (1 mg/kg) or placebo pretreatment. Fifteen minutes later, all animals received 103 mg/kg intraperitoneal cocaine. Overall mortality was 11% for olanzapine-treated animals and 45% for placebo. Olanzapine also appeared to alter the characteristics of seizures due to cocaine. In this model of acute cocaine toxicity, olanzapine pretreatment attenuated acute cocaine toxicity. Olanzapine should be evaluated further as a potential treatment for acute cocaine poisoning.

A case of pediatric age anticholinergic intoxication due to accidental Datura stramonium ingestion admitting with visual hallucination.

PubMed

Şanlıdağ, Burçin; Derinöz, Okşan; Yıldız, Nagehan

2014-01-01

Datura stramonium (DS) is a hallucinogenic plant that can produce anticholinergic toxicity because of its significant concentrations of toxic alkaloids, such as atropine, hyoscyamine, and scopolamine. DS grows in both rural and urban areas in Turkey. Clinical findings of toxicity are similar to those of atropine toxicity. DS abuse is common among adolescents because of its hallucinatory effects. However, accidental DS poisoning from contaminated food is very rare. Accidental poisonings are commonly seen among children. Children are more prone to the toxic effects of atropine; ingestion of even a small amount can cause serious central nervous system symptoms. Treatment is supportive; antidote treatment is given rarely. An eight-year-old male with accidental DS poisoning who presented to the Pediatric Emergency Department with aggression, agitation, delirium, and visual hallucinations is reported.

An Embryonic Field of Study: The Aquatic Fate and Toxicity of Diluted Bitumen.

PubMed

Alsaadi, Ftoon; Hodson, Peter V; Langlois, Valerie S

2018-01-01

Canada has experienced a significant increase in the transport of diluted bitumen (dilbit), a predominant oil sands product that combines bitumen with diluents derived from oil-gas condensates and other proprietary compounds. The proportion of diluent and the chemical composition of dilbit vary to meet seasonal transport requirements. While the toxic effects of a variety of crude and refined oils are well-studied, the toxicity of dilbit to aquatic species is less well known. This focused review summarizes dilbit production, chemistry, and the few data on toxicity to aquatic species. These data suggest that un-weathered dilbit would cause effects on fish equivalent to those of conventional oils, but its toxicity may be lower, depending on interactions among test conditions, the behavior of dilbit added to water and the species tested.

TiO2 nanoparticles in the marine environment: impact on the toxicity of tributyltin to abalone (Haliotis diversicolor supertexta) embryos.

PubMed

Zhu, Xiaoshan; Zhou, Jin; Cai, Zhonghua

2011-04-15

Little information is available on the potential ecotoxicity of manufactured nanomaterials (MNMs) in the marine environment. To carefully address this issue, the toxicity of nanosized titanium dioxide (nTiO(2)) aggregates in the marine environment was evaluated using abalone (Haliotis diversicolor supertexta) embryonic development as a model. The effect of nTiO(2) aggregates on the toxicity of the highly toxic marine antifouling compound tributyltin (TBT) to abalone embryos was also investigated. No developmental effects of nTiO(2) were observed at 2 mg/L but concentrations ≥10 mg/L caused hatching inhibition and malformations. The presence of 2 mg/L nTiO(2) increased the toxicity of TBT up to 20-fold compared with TBT alone. This enhancement of TBT may be due to the combined effects of TBT adsorption onto nTiO(2) aggregates and the internalization of nTiO(2) aggregates by abalone embryos. These observations indicate that MNMs may have important indirect impacts on aquatic organisms by varying the toxicity of coexisting pollutants. Thus, risk assessments for MNMs should consider both their direct effects and possible indirect effects of interactions with other environmental contaminants.

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

Ammann, H.M.; Bradow, F.; Fennell, D.

Hydrogen sulfide is a highly toxic gas which is immediately lethal in concentrations greater than 2000 ppm. The toxic end-point is due to anoxia to brain and heart tissues which results from its interaction with the celluar enzyme cytochrome oxidase. Inhibition of the enzyme halts oxidative metabolism which is the primary energy source for cells. A second toxic end-point is the irritative effect of hydrogen sulfide on mucous membranes, particularly edema at sublethal doses (250 to 500 ppm) in which sufficient exposure occurs before conciousness is lost. Recovered victims of exposure report neurologic symptoms such as headache, fatigue, irritability, vertigo,more » and loss of libido. Long-term effects are similar to those caused by anoxia due to other toxic agents like CO, and probably are not due to specific H/sub 2/S effects. H/sub 2/S is not a cumulative poison. No mutagenic, carcinogenic, reproductive, or teratogenic effects have been reported in the literature.« less

Potential protective effect of L-cysteine against the toxicity of acrylamide and furan in exposed Xenopus laevis embryos: an interaction study.

PubMed

Williams, John Russell; Rayburn, James R; Cline, George R; Sauterer, Roger; Friedman, Mendel

2014-08-06

The embryo toxicities of two food-processing-induced toxic compounds, acrylamide and furan, with and without added L-cysteine were examined individually and in mixtures using the frog embryo teratogenesis assay-Xenopus (FETAX). The following measures of developmental toxicity were used: (a) 96 h LC50, the median concentration causing 50% embryo lethality; (b) 96 h EC50, the median concentration causing 50% malformations of the surviving embryos; and (c) teratogenic index (96 h LC50/96 h EC50), an estimate of teratogenic risk. Calculations of toxic units (TU) were used to assess possible antagonism, synergism, or response addition of several mixtures. The evaluated compounds demonstrated counterintuitive effects. Furan had lower than expected toxicity in Xenopus embryos and, unlike acrylamide, does not seem to be teratogenic. However, the short duration of the tests may not show the full effects of furan if it is truly primarily genotoxic and carcinogenic. L-Cysteine showed unexpected properties in the delay of hatching of the embryos. The results from the interaction studies between combination of two or three components (acrylamide plus L-cysteine; furan plus L-cysteine; acrylamide plus furan; acrylamide plus furan and L-cysteine) show that furan and acrylamide seem to have less than response addition at 1:1 toxic unit ratio in lethality. Acrylamide and L-cysteine show severe antagonism even at low 19 acrylamide/1 L-cysteine TU ratios. Data from the mixture of acrylamide, furan, and L-cysteine show a slight antagonism, less than would have been expected from binary mixture exposures. Bioalkylation mechanisms and their prevention are discussed. There is a need to study the toxicological properties of mixtures of acrylamide and furan concurrently formed in heat-processed food.

Influence of salinity and organic carbon on the chronic toxicity of silver to mysids (Americamysis bahia) and silversides (Menidia beryllina).

PubMed

Ward, Timothy J; Boeri, Robert L; Hogstrand, Christer; Kramer, James R; Lussier, Suzanne M; Stubblefield, William A; Wyskiel, Derek C; Gorsuch, Joseph W

2006-07-01

Tests were conducted with mysids (Americamysis bahia) and silversides (Menidia beryllina) to evaluate the influence of salinity and organic carbon on the chronic toxicity of silver. During 7- and 28-d tests conducted at 10, 20, and 30% per hundred salinity, higher concentrations of dissolved silver generally were required to cause a chronic effect as the salinity of the seawater was increased. The 28-d mysid and silverside 20%-effective concentration values (expressed as dissolved silver) ranged from 3.9 to 60 and from 38 to 170 microg/L, respectively, over the salinity range. This pattern was not observed when the same test results were evaluated against the concentrations of free ionic silver (measured directly during toxicity tests), as predicted by the free-ion activity model. Increasing the concentration of dissolved organic carbon from 1 mg/L to the apparent maximum achievable concentration of 6 mg/L in seawater caused a slight decrease in chronic toxicity to silversides but had no effect on the chronic toxicity to mysids. The possible additive toxicity of silver in both food and water also was investigated. Even at the maximum achievable foodborne concentration, the chronic toxicity of silver added to the water was not affected when silver was also added to the food, based on the most sensitive endpoint (growth). However, although fecundity was unaffected at all five tested concentrations during the test with silver in water only, it was significantly reduced at the two highest waterborne silver concentrations (12 and 24 microg/L) during the test with silver dosed into food and water.

Molecular evidence of offspring liver dysfunction after maternal exposure to zinc oxide nanoparticles.

PubMed

Hao, Yanan; Liu, Jing; Feng, Yanni; Yu, Shuai; Zhang, Weidong; Li, Lan; Min, Lingjiang; Zhang, Hongfu; Shen, Wei; Zhao, Yong

2017-08-15

Recently, reproductive, embryonic and developmental toxicity have been considered as one important sector of nanoparticle (NP) toxicology, with some studies already suggesting varying levels of toxicity and possible transgenerational toxic effects. Even though many studies have investigated the toxic effects of zinc oxide nanoparticles (ZnO NPs), little is known of their impact on overall reproductive outcome and transgenerational effects. Previously we found ZnO NPs caused liver dysfunction in lipid synthesis. This investigation, for the first time, explored the liver dysfunction at the molecular level of gene and protein expression in offspring after maternal exposure to ZnO NPs. Three pathways were investigated: lipid synthesis, growth related factors and cell toxic biomarkers/apoptosis at 5 different time points from embryonic day-18 to postnatal day-20. It was found that the expression of 15, 16, and 16 genes in lipid synthesis, growth related factors and cell toxic biomarkers/apoptosis signalling pathway respectively in F1 animal liver were altered by ZnO NPs compared to ZnSO 4 . The proteins in these signalling pathways (five in each pathways analyzed) in F1 animal liver were also changed by ZnO NPs compared to ZnSO 4 . The results suggest that ZnO NPs caused maternal liver defects can also be detected in offspring that might result in problems on offspring liver development, mainly on lipid synthesis, growth, and lesions or apoptosis. Along with others, this study suggests that ZnO NPs may pose reproductive, embryonic and developmental toxicity; therefore, precautions should be taken with regard to human exposure during daily life. Copyright © 2017 Elsevier Inc. All rights reserved.

FIELD VALIDATION OF SEDIMENT TIE METHODS

EPA Science Inventory

Sediment toxicity is a widely recognized problem in many regions of the world. Frequently, however, the cause of toxicity is not known. The ability to identify the cause(s) of toxicity in sediments allows managers to determine sources of continuing contamination to support sele...

The evaluation of long-term effects of cinnamon bark and olive leaf on toxicity induced by streptozotocin administration to rats.

PubMed

Onderoglu, S; Sozer, S; Erbil, K M; Ortac, R; Lermioglu, F

1999-11-01

The effects of cinnamon bark and olive leaf have been investigated on streptozotocin-induced tissue injury, and some biochemical and haematological changes in rats. The effects on glycaemia were also evaluated. Long-term administration of olive leaf caused significant improvement in tissue injury induced by streptozotocin treatment; the effect of cinnamon bark was less extent. No effects on blood glucose levels were detected. However, significant decreases in some increased biochemical and haematological parameters of streptozotocin-treated rats were observed. Aspartate aminotransferase, urea and cholesterol levels were significantly decreased by treatment with both plant materials, and alanine aminotransferase by treatment with olive leaf. Cinnamon bark also caused a significant decrease in platelet counts. In addition, any visible toxicity, except decrease in body weight gain, attributable to the long-term use of plant materials was not established in normal rats. The data indicate that long-term use of olive leaf and cinnamon bark may provide benefit against diabetic conditions. Determination of underlying mechanism(s) of beneficial effects, toxicity to other systems and clinical assessments of related plant materials are major topics requiring further studies.

Genetic tests for predicting the toxicity and efficacy of anticancer chemotherapy.

PubMed

Mladosievicova, B; Carter, A; Kristova, V

2007-01-01

The standard anticancer therapy based "on one size fits all" modality has been determined to be ineffective or to be the cause of adverse drug reactions in many oncologic patients. Most pharmacogenetic and pharmacogenomic studies so far have been focused on toxicity of anticancer drugs such as 6-mercaptopurine, thioguanine, irinotecan, methotrexate, 5-fluorouracil (5-FU). Variation in genes are known to influence not only toxicity, but also efficacy of chemotherapeutics such as platinum analogues, 5-FU and irinotecan. The majority of current pharmacogenetic studies focus on single enzyme deficiencies as predictors of drug effects; however effects of most anticancer drugs are determined by the interplay of several gene products. These effects are polygenic in nature. This review briefly describes genetic variations that may impact efficacy and toxicity of drugs used in cancer chemotherapy.

Effect of dissolved aromatic hydrocarbons on the growth of marine bacteria in batch culture.

PubMed Central

Calder, J A; Lader, J H

1976-01-01

Dissolved aromatic hydrocarbons were found to decrease growth rate and maximum cell density of marine bacteria in batch cultures. The magnitude of the decrement was observed to be a function of concentration of the hydrocarbon and inherent toxicity. The inherent toxicity was observed to increase inversely with solubility such that naphthalene at 100 muM concentration demonstrated a toxic effect similar to benzopyrene at 0.02 muM. A partial oxidation product of naphthalene was found to be more effective in decreasing growth parameters than naphthalene at equivalent concentrations and to cause complete cessation of growth at the higher concentrations permitted by its polar structure. PMID:970939

Pesticide body burden of the crustacean Gammarus pulex as a measure of toxic pressure in agricultural streams.

PubMed

Shahid, Naeem; Becker, Jeremias Martin; Krauss, Martin; Brack, Werner; Liess, Matthias

2018-06-22

Risk assessments of toxicants in aquatic environments are typically based on the evaluation of concentrations in water or sediment. However, concentrations in water are highly variable, while the body burden may provide a better time-integrated measure of pesticide exposure and potential effects in aquatic organisms. Here, we quantified pesticide body burdens in a dominant invertebrate species from agricultural streams, Gammarus pulex, compared them pesticide concentrations in water samples, and linked the pesticide contamination with observed ecological effects on macroinvertebrate communities. In total, 19 of 61 targeted analytes were found in the organisms, ranging from 0.037 to 93.94 ng g-1 (wet weight). Neonicotinoids caused the highest toxic pressure among the pesticides detected in G. pulex. Using linear solvation energy relationships (LSERs), we derived equivalent pesticide concentrations in stream water based on the body burden. These equivalent concentrations correlated with the concentrations in water samples collected after run-off (65% of variance explained). Pesticide pressure significantly affected the aquatic macroinvertebrate community structure, expressed as SPEARpesticides, and caused, on average, threefold increased insecticide tolerance in G. pulex as a result of adaptation. The toxic pressure derived from body burden and from water samples similarly explained the change in community structure (68% and 64%). However, the increased tolerance of G. pulex to pesticides was better explained by the toxicity derived from body burden (70%) than by the toxicity from water samples (53%). We conclude that the internal body burden of macroinvertebrates is suitable to assess the overall pesticide exposure and effects in agricultural streams.

Probing the toxicity of nanoparticles: a unified in silico machine learning model based on perturbation theory.

PubMed

Concu, Riccardo; Kleandrova, Valeria V; Speck-Planche, Alejandro; Cordeiro, M Natália D S

2017-09-01

Nanoparticles (NPs) are part of our daily life, having a wide range of applications in engineering, physics, chemistry, and biomedicine. However, there are serious concerns regarding the harmful effects that NPs can cause to the different biological systems and their ecosystems. Toxicity testing is an essential step for assessing the potential risks of the NPs, but the experimental assays are often very expensive and usually too slow to flag the number of NPs that may cause adverse effects. In silico models centered on quantitative structure-activity/toxicity relationships (QSAR/QSTR) are alternative tools that have become valuable supports to risk assessment, rationalizing the search for safer NPs. In this work, we develop a unified QSTR-perturbation model based on artificial neural networks, aimed at simultaneously predicting general toxicity profiles of NPs under diverse experimental conditions. The model is derived from 54,371 NP-NP pair cases generated by applying the perturbation theory to a set of 260 unique NPs, and showed an accuracy higher than 97% in both training and validation sets. Physicochemical interpretation of the different descriptors in the model are additionally provided. The QSTR-perturbation model is then employed to predict the toxic effects of several NPs not included in the original dataset. The theoretical results obtained for this independent set are strongly consistent with the experimental evidence found in the literature, suggesting that the present QSTR-perturbation model can be viewed as a promising and reliable computational tool for probing the toxicity of NPs.

Sex differences in the toxicity of polyethylene glycol-coated gold nanoparticles in mice

PubMed Central

Chen, Jie; Wang, Hao; Long, Wei; Shen, Xiu; Wu, Di; Song, Sha-Sha; Sun, Yuan-Ming; Liu, Pei-Xun; Fan, Saijun; Fan, Feiyue; Zhang, Xiao-Dong

2013-01-01

Gold nanoparticles have received wide interest in disease diagnosis and therapy, but one of the important issues is their toxicological effects in vivo. Sex differences in the toxicity of gold nanoparticles are not clear. In this work, body weight, organ weight, hematology, and biochemistry were used to evaluate sex differences in immune response and liver and kidney damage. Pathology was used to observe the general toxicity of reproductive organs. The immune response was influenced significantly in female mice, with obvious changes in spleen and thymus index. Hematology results showed that male mice treated with 22.5 nm gold nanoparticles received more significant infection and inflammation than female mice. Meanwhile, the biochemistry results showed that 4.4 and 22.5 nm gold nanoparticles caused more significant liver damage in male mice than female mice, while 22.5, 29.3, and 36.1 nm gold nanoparticles caused more significant kidney damage in female mice than male mice. No significant toxicological response was found in the reproductive system for female or male mice. It was found that gold nanoparticles caused more serious liver toxicity and infection in male mice than female mice. These findings indicated that sex differences may be one of the important elements for in vivo toxicity of gold nanoparticles. PMID:23861586

Exposure to nano-size titanium dioxide causes oxidative damages in human mesothelial cells: The crystal form rather than size of particle contributes to cytotoxicity.

PubMed

Hattori, Kenji; Nakadate, Kazuhiko; Morii, Akane; Noguchi, Takumi; Ogasawara, Yuki; Ishii, Kazuyuki

2017-10-14

Exposure to nanoparticles such as carbon nanotubes has been shown to cause pleural mesothelioma similar to that caused by asbestos, and has become an environmental health issue. Not only is the percutaneous absorption of nano-size titanium dioxide particles frequently considered problematic, but the possibility of absorption into the body through the pulmonary route is also a concern. Nevertheless, there are few reports of nano-size titanium dioxide particles on respiratory organ exposure and dynamics or on the mechanism of toxicity. In this study, we focused on the morphology as well as the size of titanium dioxide particles. In comparing the effects between nano-size anatase and rutile titanium dioxide on human-derived pleural mesothelial cells, the anatase form was shown to be actively absorbed into cells, producing reactive oxygen species and causing oxidative damage to DNA. In contrast, we showed for the first time that the rutile form is not easily absorbed by cells and, therefore, does not cause oxidative DNA damage and is significantly less damaging to cells. These results suggest that with respect to the toxicity of titanium dioxide particles on human-derived mesothelial cells, the crystal form rather than the particle size has a greater effect on cellular absorption. Also, it was indicated that the difference in absorption is the primary cause of the difference in the toxicity against mesothelial cells. Copyright © 2017 Elsevier Inc. All rights reserved.

New insights into the mechanism of methoxyflurane nephrotoxicity and implications for anesthetic development (part 2): Identification of nephrotoxic metabolites.

PubMed

Kharasch, Evan D; Schroeder, Jesara L; Liggitt, H Denny; Ensign, Dustin; Whittington, Dale

2006-10-01

Methoxyflurane nephrotoxicity results from its metabolism, which occurs by both dechlorination (to methoxydifluoroacetic acid [MDFA]) and O-demethylation (to fluoride and dichloroacetic acid [DCAA]). Inorganic fluoride can be toxic, but it remains unknown why other anesthetics, commensurately increasing systemic fluoride concentrations, are not toxic. Fluoride is one of many methoxyflurane metabolites and may itself cause toxicity and/or reflect formation of other toxic metabolite(s). This investigation evaluated the disposition and renal effects of known methoxyflurane metabolites. Rats were given by intraperitoneal injection the methoxyflurane metabolites MDFA, DCAA, or sodium fluoride (0.22, 0.45, 0.9, or 1.8 mmol/kg followed by 0.11, 0.22, 0.45, or 0.9 mmol/kg on the next 3 days) at doses relevant to metabolite exposure after methoxyflurane anesthesia, or DCAA and fluoride in combination. Renal histology and function (blood urea nitrogen, urine volume, urine osmolality) and metabolite excretion in urine were assessed. Methoxyflurane metabolite excretion in urine after injection approximated that after methoxyflurane anesthesia, confirming the appropriateness of metabolite doses. Neither MDFA nor DCAA alone had any effects on renal function parameters or necrosis. Fluoride at low doses (0.22, then 0.11 mmol/kg) decreased osmolality, whereas higher doses (0.45, then 0.22 mmol/kg) also caused diuresis but not significant necrosis. Fluoride and DCAA together caused significantly greater tubular cell necrosis than fluoride alone. Methoxyflurane nephrotoxicity seems to result from O-demethylation, which forms both fluoride and DCAA. Because their co-formation is unique to methoxyflurane compared with other volatile anesthetics and they are more toxic than fluoride alone, this suggests a new hypothesis of methoxyflurane nephrotoxicity. This may explain why increased fluoride formation from methoxyflurane, but not other anesthetics, is associated with toxicity. These results may have implications for the interpretation of clinical anesthetic defluorination, use of volatile anesthetics, and the laboratory methods used to evaluate potential anesthetic toxicity.

Aqueous humor tyrosinase activity is indicative of iris melanocyte toxicity.

PubMed

Mahanty, Sarmistha; Kawali, Ankush A; Dakappa, Shruthi Shirur; Mahendradas, Padmamalini; Kurian, Mathew; Kharbanda, Varun; Shetty, Rohit; Setty, Subba Rao Gangi

2017-09-01

Antibiotics such as fluoroquinolones (FQLs) are commonly used to treat ocular infections but are also known to cause dermal melanocyte toxicity. The release of dispersed pigments from the iris into the aqueous humor has been considered a possible ocular side effect of the systemic administration of FQLs such as Moxifloxacin, and this condition is known as bilateral acute iris transillumination (BAIT). Bilateral acute depigmentation of iris (BADI) is a similar condition, with iris pigment released into the aqueous, but it has not been reported as a side effect of FQL. Iris pigments are synthesized by the melanogenic enzyme tyrosinase (TYR) and can be detected but not quantified by using slit-lamp biomicroscopy. The correlation between dispersed pigments in the aqueous and the extent of melanocyte toxicity due to topical antibiotics in vivo is not well studied. Here, we aimed to study the effect of topical FQLs on iris tissue, the pigment release in the aqueous humor and the development of clinically evident iris atrophic changes. We evaluated this process by measuring the activity of TYR in the aqueous humor of 82 healthy eyes undergoing cataract surgery following topical application of FQLs such as Moxifloxacin (27 eyes, preservative-free) or Ciprofloxacin (29 eyes, with preservative) or the application of non-FQL Tobramycin (26 eyes, with preservative) as a control. In addition, the patients were questioned and examined for ocular side effects in pre- and post-operative periods. Our data showed a significantly higher mean TYR activity in the aqueous humor of Ciprofloxacin-treated eyes compared to Moxifloxacin- (preservative free, p < 0.0001) or Tobramycin-treated eyes (p < 0.0001), which indicated that few quinolones under certain conditions are toxic to the iris melanocytes. However, the reduced TYR activity in the aqueous of Moxifloxacin-treated eyes was possibly due to the presence of a higher drug concentration, which inhibits TYR activity. Consistently, immunoblotting analysis of the aqueous humor from both Ciprofloxacin- and Moxifloxacin-treated eyes showed the presence of soluble TYR enzyme, thus reflecting its toxicity to iris melanocytes and corresponding to its activity in the aqueous humor. Intriguingly, none of these patients developed any clinically appreciable ocular side effects characteristic of BAIT or BADI. Overall, our results suggest that topical antibiotics cause different levels of iris melanocyte toxicity, releasing dispersed pigments into the aqueous humor, which can be measured through TYR enzyme activity. Hence, we conclude that topical FQLs may cause subclinical toxicity to the iris melanocytes but may not be the sole cause of the development of BAIT or BADI. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

ECVAM and new technologies for toxicity testing.

PubMed

Bouvier d'Yvoire, Michel; Bremer, Susanne; Casati, Silvia; Ceridono, Mara; Coecke, Sandra; Corvi, Raffaella; Eskes, Chantra; Gribaldo, Laura; Griesinger, Claudius; Knaut, Holger; Linge, Jens P; Roi, Annett; Zuang, Valérie

2012-01-01

The development of alternative empirical (testing) and non-empirical (non-testing) methods to traditional toxicological tests for complex human health effects is a tremendous task. Toxicants may potentially interfere with a vast number of physiological mechanisms thereby causing disturbances on various levels of complexity of human physiology. Only a limited number of mechanisms relevant for toxicity ('pathways' of toxicity) have been identified with certainty so far and, presumably, many more mechanisms by which toxicants cause adverse effects remain to be identified. Recapitulating in empirical model systems (i.e., in vitro test systems) all those relevant physiological mechanisms prone to be disturbed by toxicants and relevant for causing the toxicity effect in question poses an enormous challenge. First, the mechanism(s) of action of toxicants in relation to the most relevant adverse effects of a specific human health endpoint need to be identified. Subsequently, these mechanisms need to be modeled in reductionist test systems that allow assessing whether an unknown substance may operate via a specific (array of) mechanism(s). Ideally, such test systems should be relevant for the species of interest, i.e., based on human cells or modeling mechanisms present in humans. Since much of our understanding about toxicity mechanisms is based on studies using animal model systems (i.e., experimental animals or animal-derived cells), designing test systems that model mechanisms relevant for the human situation may be limited by the lack of relevant information from basic research. New technologies from molecular biology and cell biology, as well as progress in tissue engineering, imaging techniques and automated testing platforms hold the promise to alleviate some of the traditional difficulties associated with improving toxicity testing for complex endpoints. Such new technologies are expected (1) to accelerate the identification of toxicity pathways with human relevance that need to be modeled in test methods for toxicity testing (2) to enable the reconstruction of reductionist test systems modeling at a reduced level of complexity the target system/organ of interest (e.g., through tissue engineering, use of human-derived cell lines and stem cells etc.), (3) to allow the measurement of specific mechanisms relevant for a given health endpoint in such test methods (e.g., through gene and protein expression, changes in metabolites, receptor activation, changes in neural activity etc.), (4) to allow to measure toxicity mechanisms at higher throughput rates through the use of automated testing. In this chapter, we discuss the potential impact of new technologies on the development, optimization and use of empirical testing methods, grouped according to important toxicological endpoints. We highlight, from an ECVAM perspective, the areas of topical toxicity, skin absorption, reproductive and developmental toxicity, carcinogenicity/genotoxicity, sensitization, hematopoeisis and toxicokinetics and discuss strategic developments including ECVAM's database service on alternative methods. Neither the areas of toxicity discussed nor the highlighted new technologies represent comprehensive listings which would be an impossible endeavor in the context of a book chapter. However, we feel that these areas are of utmost importance and we predict that new technologies are likely to contribute significantly to test development in these fields. We summarize which new technologies are expected to contribute to the development of new alternative testing methods over the next few years and point out current and planned ECVAM projects for each of these areas.

Curcumin reduces the toxic effects of iron loading in rat liver epithelial cells

PubMed Central

Messner, Donald J.; Sivam, Gowsala; Kowdley, Kris V.

2008-01-01

Background/aims Iron overload can cause liver toxicity and increase the risk of liver failure or hepatocellular carcinoma in humans. Curcumin (diferuloylmethane), a component of the food spice turmeric, has antioxidant, iron binding, and hepatoprotective properties. The aim of this study was to quantify its effects on iron overload and resulting downstream toxic effects in cultured T51B rat liver epithelial cells. Methods T51B cells were loaded with ferric ammonium citrate (FAC) with or without the iron delivery agent 8-hydroxyquinoline. Cytotoxicity was measured by MTT assay. Iron uptake and iron bioavailability were documented by chemical assay, quench of calcein fluorescence, and ferritin induction. Reactive oxygen species (ROS) were measured by fluorescence assay using 2′,7′-dichlorodihydrofluorescein diacetate. Oxidative stress signaling to jnk, c-jun, and p38 was measured by western blot with phospho-specific antibodies. Results Curcumin bound iron, but did not block iron uptake or bioavailability in T51B cells given FAC. However, it reduced cytotoxicity, blocked generation of ROS, and eliminated signaling to cellular stress pathways caused by iron. Inhibition was observed over a wide range of FAC concentrations (50 – 500 μM), with an apparent IC50 in all cases between 5 and 10 μM curcumin. In contrast, desferoxamine blocked both iron uptake and toxic effects of iron at concentrations that depended on the FAC concentration. Effects of curcumin also differed from those of α-tocopherol, which did not bind iron and was less effective at blocking iron-stimulated ROS generation. Conclusions Curcumin reduced iron-dependent oxidative stress and iron toxicity in T51B cells without blocking iron uptake. PMID:18492020

Microcystin uptake and biochemical responses in the freshwater clam Corbicula leana P. exposed to toxic and non-toxic Microcystis aeruginosa: Evidence of tolerance to cyanotoxins.

PubMed

Pham, Thanh-Luu; Shimizu, Kazuya; Dao, Thanh-Son; Hong-Do, Lan-Chi; Utsumi, Motoo

2015-01-01

We investigated the accumulation and adverse effects of toxic and non-toxic Microcystis in the edible clam Corbicula leana . Treated clams were exposed to toxic Microcystis at 100 μg of MC (microcystin)-LR eq  L -1 for 10 days. The experimental organism was then placed in toxin-free water and fed on non-toxic Microcystis for the following 10 days for depuration. Filtering rates (FRs) by C. leana of toxic and non-toxic Microcystis and of the green alga Chlorella vulgaris as a control were estimated. Adverse effects were evaluated though the activity of catalase (CAT), superoxide dismutase (SOD) and glutathione S-transferase (GST). Clam accumulated MCs (up to 12.7 ± 2.5 μg g -1 dry weight (DW) of free MC and 4.2 ± 0.6 μg g -1 DW of covalently bound MC). Our results suggest that although both toxic and non-toxic cyanobacteria caused adverse effects by inducing the detoxification and antioxidant defense system, the clam was quite resistant to cyanotoxins. The estimated MC concentration in C. leana was far beyond the World Health Organization's (WHO) provisional tolerable daily intake (0.04 μg kg -1  day -1 ), suggesting that consuming clams harvested during cyanobacterial blooms carries a high health risk.

Toxic effects of combined effects of anthracene and UV radiation on Brachionus plicatilis

NASA Astrophysics Data System (ADS)

Gao, Ceng; Zhang, Xinxin; Xu, Ningning; Tang, Xuexi

2017-05-01

Anthracene is a typical polycyclic aromatic hydrocarbon, with photo activity, can absorb ultraviolet light a series of chemical reactions, aquatic organisms in the ecosystem has a potential light induced toxicity. In this paper, the effects of anthracene and UV radiation on the light-induced toxicity of Brachionus plicatilis were studied. The main methods and experimental results were as follows: (1) The semi-lethal concentration of anthracene in UV light was much lower than that in normal light, The rotifers have significant light-induced acute toxicity. (2) Under UV irradiation, anthracene could induce the increase of ROS and MDA content in B. plicatilis, and the activity of antioxidant enzymes in B. plicatilis significantly changed, Where SOD, GPx activity was induced within 24 hours of the beginning of the experiment. And the content of GPX and CAT was inhibited after 48 hours. Therefore, the anthracite stress induced by UV radiation could more strongly interfere with the ant oxidative metabolism of B. plicatilis, and more seriously cause oxidative damage, significant light-induced toxicity.

THE USE OF INSITU TREATMENT TO REDUCE TOXICITY

EPA Science Inventory

Mining or smelting of lead and zinc ores generates mine tailing and smelter slags rich in lead, zinc, and cadmium. Old smelting operations have commonly caused severly contaminated sites and adverse effects in the terrestrial environment. Research has clarified the causes of s...

MICROBIAL SEQUESTRATION OF LEAD AND OTHER HEAVY METALS

EPA Science Inventory

Human activity resulting in heavy metal contamination is a worldwide concern. Lead is a potent neurotoxin that can cause heart problems, kidney damage, and mental retardation. Mercury causes toxicity based on its form and route of exposure. Effects range from allergic reactions t...

Neurotoxic effects of subchronic intratracheal Mn nanoparticle exposure alone and in combination with other welding fume metals in rats.

PubMed

Máté, Zsuzsanna; Horváth, Edina; Papp, András; Kovács, Krisztina; Tombácz, Etelka; Nesztor, Dániel; Szabó, Tamás; Szabó, Andrea; Paulik, Edit

2017-04-01

Manganese (Mn) is a toxic heavy metal exposing workers in various occupational settings and causing, among others, nervous system damage. Metal fumes of welding, a typical source of Mn exposure, contain a complex mixture of metal oxides partly in nanoparticle form. As toxic effects of complex substances cannot be sufficiently understood by examining its components separately, general toxicity and functional neurotoxicity of a main pathogenic welding fume metal, Mn, was examined alone and combined with iron (Fe) and chromium (Cr), also frequently found in fumes. Oxide nanoparticles of Mn, Mn + Fe, Mn + Cr and the triple combination were applied, in aqueous suspension, to the trachea of young adult Wistar rats for 4 weeks. The decrease of body weight gain during treatment, caused by Mn, was counteracted by Fe, but not Cr. At the end of treatment, spontaneous and evoked cortical electrical activity was recorded. Mn caused a shift to higher frequencies, and lengthened evoked potential latency, which were also strongly diminished by co-application of Fe only. The interaction of the metals seen in body weight gain and cortical activity were not related to the measured blood and brain metal levels. Fe might have initiated protective, e.g. antioxidant, mechanisms with a more general effect.

Lead toxicity induces autophagy to protect against cell death through mTORC1 pathway in cardiofibroblasts

PubMed Central

Sui, Li; Zhang, Rui-Hong; Zhang, Ping; Yun, Ke-Li; Zhang, Hong-Cai; Liu, Li; Hu, Ming-Xu

2015-01-01

Heavy metals, such as lead (Pb2+), are usually accumulated in human bodies and impair human's health. Lead is a metal with many recognized adverse health side effects and yet the molecular processes underlying lead toxicity are still poorly understood. In the present study, we proposed to investigate the effects of lead toxicity in cultured cardiofibroblasts. After lead treatment, cultured cardiofibroblasts showed severe endoplasmic reticulum (ER) stress. However, the lead-treated cardiofibroblasts were not dramatically apoptotic. Further, we found that these cells determined to undergo autophagy through inhibiting mammalian target of rapamycin complex 1 (mTORC1) pathway. Moreover, inhibition of autophagy by 3-methyladenine (3-MA) may dramatically enhance lead toxicity in cardiofibroblasts and cause cell death. Our data establish that lead toxicity induces cell stress in cardiofibroblasts and protective autophagy is activated by inhibition of mTORC1 pathway. These findings describe a mechanism by which lead toxicity may promote the autophagy of cardiofibroblasts cells, which protects cells from cell stress. Our findings provide evidence that autophagy may help cells to survive under ER stress conditions in cardiofibroblasts and may set up an effective therapeutic strategy for heavy metal toxicity. PMID:25686247

Lead toxicity induces autophagy to protect against cell death through mTORC1 pathway in cardiofibroblasts.

PubMed

Sui, Li; Zhang, Rui-Hong; Zhang, Ping; Yun, Ke-Li; Zhang, Hong-Cai; Liu, Li; Hu, Ming-Xu

2015-03-31

Heavy metals, such as lead (Pb(2+)), are usually accumulated in human bodies and impair human's health. Lead is a metal with many recognized adverse health side effects and yet the molecular processes underlying lead toxicity are still poorly understood. In the present study, we proposed to investigate the effects of lead toxicity in cultured cardiofibroblasts. After lead treatment, cultured cardiofibroblasts showed severe endoplasmic reticulum (ER) stress. However, the lead-treated cardiofibroblasts were not dramatically apoptotic. Further, we found that these cells determined to undergo autophagy through inhibiting mammalian target of rapamycin complex 1 (mTORC1) pathway. Moreover, inhibition of autophagy by 3-methyladenine (3-MA) may dramatically enhance lead toxicity in cardiofibroblasts and cause cell death. Our data establish that lead toxicity induces cell stress in cardiofibroblasts and protective autophagy is activated by inhibition of mTORC1 pathway. These findings describe a mechanism by which lead toxicity may promote the autophagy of cardiofibroblasts cells, which protects cells from cell stress. Our findings provide evidence that autophagy may help cells to survive under ER stress conditions in cardiofibroblasts and may set up an effective therapeutic strategy for heavy metal toxicity.

Toxicological aspects of photocatalytic degradation of selected xenobiotics with nano-sized Mn-doped TiO2.

PubMed

Ozmen, Murat; Güngördü, Abbas; Erdemoglu, Sema; Ozmen, Nesrin; Asilturk, Meltem

2015-08-01

The toxic effects of two selected xenobiotics, bisphenol A (BPA) and atrazine (ATZ), were evaluated after photocatalytic degradation using nano-sized, Mn-doped TiO2. Undoped and Mn-doped TiO2 nanoparticles were synthesized. The samples were characterized by X-ray diffractometry (XRD), scanning electron microscopy (SEM), UV-vis-diffuse reflectance spectra (DRS), X-ray fluorescence spectroscopy (XRF), and BET surface area. The photocatalytic efficiency of the undoped and Mn-doped TiO2 was evaluated for BPA and ATZ. The toxicity of the synthesized photocatalysts and photocatalytic by-products of BPA and ATZ was determined using frog embryos and tadpoles, zebrafish embryos, and bioluminescent bacteria. Possible toxic effects were also evaluated using selected enzyme biomarkers. The results showed that Mn-doped TiO2 nanoparticles did not cause significant lethality in Xenopus laevis embryos and tadpoles, but nonfiltered samples caused lethality in zebrafish. Furthermore, Mn-doping of TiO2 increased the photocatalytic degradation capability of nanoparticles, and it successfully degraded BPA and AZT, but degradation of AZT caused an increase of the lethal effects on both tadpoles and fish embryos. Degradation of BPA caused a significant reduction of lethal effects, especially after 2-4h of degradation. However, biochemical assays showed that both Mn-doped TiO2 and the degradation by-products caused a significant change of selected biomarkers on X. laevis tadpoles; thus, the ecological risks of Mn-doped TiO2 should be considered due to nanomaterial applications and for spilled nanoparticles in an aquatic ecosystem. Also, the risk of nanoparticles should be considered using indicator reference biochemical markers to verify the environmental health impacts. Copyright © 2015 Elsevier B.V. All rights reserved.

Effects of cadmium and zinc toxicity on orientation behaviour of Echinoparyphium recurvatum (Digenea: Echinostomatidae) cercariae.

PubMed

Morley, N J; Crane, M; Lewis, J W

2003-08-15

The effects of cadmium and zinc toxicity on orientation behaviour (photo- and geo-taxis) of Echinoparyphium recurvatum cercariae was investigated at concentrations ranging from 10 to 1000 microg l(-1). Exposure to the toxicants at all metal concentrations caused a change in orientation to negative phototaxis and positive geotaxis during the submaximal dispersal phase (0.5 h cercarial age). Autometallography staining of cercariae exposed to 1000 microg l(-1) cadmium or zinc showed selective binding of heavy metals to tegumental surface sites associated with sensory receptors. The significance to parasite transmission of changes in cercarial orientation behaviour in metal polluted environments is discussed.

Benzo[a]pyrene exposure increases toxic biomarkers and morphological disorders in mouse cervix.

PubMed

Gao, Meili; Li, Yongfei; Sun, Ying; Shah, Walayat; Yang, Shuiyun; Wang, Yili; Long, Jiangang

2011-11-01

Benzo[a]pyrene (BaP) is a representative compound of polycyclic aromatic hydrocarbons exerting cytotoxicity and genotoxicity in the human liver, lung, stomach and skin. However, the toxic effect of BaP on cervical tissue remains unclear. This study was carried out to investigate the toxic effects of BaP on the cervix of ICR mice. Female mice were treated with BaP by intraperitoneal injection and oral gavage at a dose of 2.5, 5 and 10 mg/kg body-weight, twice a week for 14 weeks. BaP treatment caused a significant increase in the levels of MDA and IL-6 with significantly increased activity of CYP1A1, creatine kinase and aspartate aminotransferase (AST) and decreased activity of glutathione-S-transferase in the cervix and liver. The relative cervix weight was markedly reduced in the intraperitoneal BaP injection groups, whereas only a slight reduction was observed in the oral gavage groups. The increase in weight decreased with increasing BaP dose. Moreover, BaP treatment induced significant pathomorphological changes in the cervical tissue and increased the mortality of the mice. Taken together, these results suggest that BaP causes a certain toxic effect on cervical tissue. © 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.

Toxic Effects of Nickel Oxide Bulk and Nanoparticles on the Aquatic Plant Lemna gibba L.

PubMed Central

Oukarroum, Abdallah; Barhoumi, Lotfi; Samadani, Mahshid

2015-01-01

The aquatic plant Lemna gibba L. was used to investigate and compare the toxicity induced by 30 nm nickel oxide nanoparticles (NiO-NPs) and nickel(II) oxide as bulk (NiO-Bulk). Plants were exposed during 24 h to 0–1000 mg/L of NiO-NPs or NiO-Bulk. Analysis of physicochemical characteristics of nanoparticles in solution indicated agglomerations of NiO-NPs in culture medium and a wide size distribution was observed. Both NiO-NPs and NiO-Bulk caused a strong increase in reactive oxygen species (ROS) formation, especially at high concentration (1000 mg/L). These results showed a strong evidence of a cellular oxidative stress induction caused by the exposure to NiO. Under this condition, NiO-NPs and NiO-Bulk induced a strong inhibitory effect on the PSII quantum yield, indicating an alteration of the photosynthetic electron transport performance. Under the experimental conditions used, it is clear that the observed toxicity impact was mainly due to NiO particles effect. Therefore, results of this study permitted determining the use of ROS production as an early biomarker of NiO exposure on the aquatic plant model L. gibba used in toxicity testing. PMID:26075242

Determinants of Toxicity of Environmental Asbestos Fibers ...

EPA Pesticide Factsheets

Recent EPA-led studies have addressed the comparative toxicity and pathological mechanisms of environmental asbestos samples from Libby, Montana and other communities in the United States. Longer amosite fibers induce a 4-10 fold greater induction of pro-inflammatory mediators COX-2 and HO-1 than Libby fibers in human airway epithelial cells, as well as a number of other genes involved in cellular stress and toxicity. Similarly, equal mass doses of longer amosite fibers administered intratracheally to F344 rats cause greater pathological effects than Libby fibers, from 1 day to 2 years post-exposure. However, both intratracheal and inhalation studies show comparable effects of Libby fibers and shorter UICC amosite fibers. Dosimetry modeling and potency analysis studies are using these data to predict effects in humans. Libby fibers induce an acute phase response and systemic increases in selected markers of inflammation, and induce components of the NALP-3 inflammasome in the lung, while surface complexed iron inhibits these responses. Libby fibers alter genes involved in inflammation, immune regulation, and cell-cycle control, and also induce autoimmune responses in a rat model. Comparative toxicity studies showed that chrysotile fibers from Sumas Mountain, Washington caused greater lung interstitial fibrosis than Libby fibers, which were significantly more potent than tremolite fibers from El Dorado, California and actinolite “cleavage fragments” from

Inhalation of substance P and thiorphan: acute toxicity and effects on respiration in conscious guinea pigs.

PubMed

Koch, B L; Edvinsson, A A; Koskinen, L O

1999-01-01

Substance P is a tachykinin and a biologically active neuropeptide. The peptide produces salivation, neuronal excitation, vasodilatation, increased vascular permeability and contraction of smooth muscles in the respiratory tract. The study was designed to evaluate the acute effects in guinea pigs of inhaled aerosolized Substance P (SP). Apart from the acute toxic effect of the peptide, the distribution in different organs was also investigated. The acute inhalation toxicity of SP (LC50, 15 min) when co-administrated with the neutral endopeptidase inhibitor thiorphan was 368 microg m(-3). The peptide caused an increase in respiratory rate proceeding a decrease in tidal volume. As the exposure proceeded, a decrease in both respiratory rate and further decreases in tidal volume were observed until either the animal died or the exposure was terminated. The decreases in respiratory rate and tidal volume were probably due to bronchoconstriction caused by SP. Eighteen per cent of the inhaled amount of radioactive SP was retained in the body, and the highest concentrations of radioactivity were found in the kidney, lung and liver. Substance P in combination with thiorphan administered as an aerosol is extremely toxic and highly potent. Exposure to the substance at extremely low air concentrations may result in incapacitation in humans.

Evaluation of the Polyethylene Reverse Sampler as a Dosing System in Marine Phase II Whole Sediment Toxicity Identification Evaluations (TIEs)

EPA Science Inventory

Contaminated marine sediments can cause acute and chronic impairments to benthic organisms. Nonionic organic contaminants (NOCs) are often a primary cause of impairment. Toxicity Identification Evaluations (TIEs) are used to identify chemicals causing toxicity in sediments. Ph...

Differential impacts of six insecticides on a mealybug and its coccinellid predator.

PubMed

Barbosa, Paulo R R; Oliveira, Martin D; Barros, Eduardo M; Michaud, J P; Torres, Jorge B

2018-01-01

Broad-spectrum insecticides may disrupt biological control and cause pest resurgence due to their negative impacts on natural enemies. The preservation of sustainable pest control in agroecosystems requires parallel assessments of insecticide toxicity to target pests and their key natural enemies. In the present study, the leaf dipping method was used to evaluate the relative toxicity of six insecticides to the striped mealybug, Ferrisia dasylirii (Cockerell) (Hemiptera: Pseudococcidae) and its predator, Tenuisvalvae notata (Mulsant) (Coleoptera: Coccinellidae). Three neurotoxic insecticides, lambda-cyhalothrin, methidathion and thiamethoxam, caused complete mortality of both pest and predator when applied at their highest field rates. In contrast, lufenuron, pymetrozine and pyriproxyfen caused moderate mortality of third-instar mealybug nymphs, and exhibited low or no toxicity to either larvae or adults of the lady beetle. At field rates, lufenuron and pymetrozine had negligible effects on prey consumption, development or reproduction of T. notata, but adults failed to emerge from pupae when fourth instar larvae were exposed to pyriproxyfen. In addition, pyriproxyfen caused temporary sterility; T. notata females laid non-viable eggs for three days after exposure, but recovered egg fertility thereafter. Our results indicate that the three neurotoxic insecticides can potentially control F. dasylirii, but are hazardous to its natural predator. In contrast, lufenuron and pymetrozine appear compatible with T. notata, although they appear less effective against the mealybug. Although the acute toxicity of pyriproxyfen to T. notata was low, some pupal mortality and reduced egg fertility suggest that this material could impede the predator's numerical response to mealybug populations. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of soil properties on the toxicity of Pb: assessment of the appropriateness of guideline values.

PubMed

Romero-Freire, A; Martin Peinado, F J; van Gestel, C A M

2015-05-30

Soil contamination with lead is a worldwide problem. Pb can cause adverse effects, but its mobility and availability in the terrestrial environment are strongly controlled by soil properties. The present study investigated the influence of different soil properties on the solubility of lead in laboratory spiked soils, and its toxicity in three bioassays, including Lactuca sativa root elongation and Vibrio fischeri illumination tests applied to aqueous extracts and basal soil respiration assays. Final aim was to compare soil-dependent toxicity with guideline values. The L. sativa bioassay proved to be more sensitive to Pb toxicity than the V. fischeri and soil respiration tests. Toxicity was significantly correlated with soil properties, with soil pH, carbonate and organic carbon content being the most important factors. Therefore, these variables should be considered when defining guideline values. Copyright © 2015 Elsevier B.V. All rights reserved.

Acute toxicity of live and decomposing green alga Ulva ( Enteromorpha) prolifera to abalone Haliotis discus hannai

NASA Astrophysics Data System (ADS)

Wang, Chao; Yu, Rencheng; Zhou, Mingjiang

2011-05-01

From 2007 to 2009, large-scale blooms of green algae (the so-called "green tides") occurred every summer in the Yellow Sea, China. In June 2008, huge amounts of floating green algae accumulated along the coast of Qingdao and led to mass mortality of cultured abalone and sea cucumber. However, the mechanism for the mass mortality of cultured animals remains undetermined. This study examined the toxic effects of Ulva ( Enteromorpha) prolifera, the causative species of green tides in the Yellow Sea during the last three years. The acute toxicity of fresh culture medium and decomposing algal effluent of U. prolifera to the cultured abalone Haliotis discus hannai were tested. It was found that both fresh culture medium and decomposing algal effluent had toxic effects to abalone, and decomposing algal effluent was more toxic than fresh culture medium. The acute toxicity of decomposing algal effluent could be attributed to the ammonia and sulfide presented in the effluent, as well as the hypoxia caused by the decomposition process.

Does active psychosis cause neurobiological pathology? A critical review of the neurotoxicity hypothesis.

PubMed

Rund, B R

2014-06-01

Since the neurotoxicity hypothesis was launched in 1991, it has generated a great deal of interest and given rise to several studies investigating the validity of the hypothesis that being psychotic has a toxic effect on the brain. The toxicity argument is used to justify early treatment. This review attempts to assess the studies that have addressed the question: Does an active psychosis, indexed by the duration of untreated psychosis (DUP), cause neurobiological pathology? The validity of the hypothesis has been studied primarily by correlation analyses that assess whether there are significant correlations between DUP and changes in neurocognitive functioning or brain structure. In this review, relevant reports were identified by a literature survey. Of the 35 studies (33 papers) evaluated, six neurocognitive studies supported the hypothesis and 16 did not. Eight morphology studies supported the hypothesis and five did not. In general, the studies that did not support the neurotoxicity hypothesis were larger in size and had more adequate designs (longitudinal) than those that supported the hypothesis. Overall, there is limited empirical evidence for the neurotoxicity hypothesis in the studies reviewed. However, it is possible that there is a threshold value for a toxic effect of psychosis, rather than a linear relationship between DUP and a neurotoxic effect, and that several of the studies evaluated did not have a long enough DUP to detect a toxic effect of active psychosis.

Relative toxicity and residual activity of insecticides used in blueberry pest management: mortality of natural enemies.

PubMed

Roubos, Craig R; Rodriguez-Saona, Cesar; Holdcraft, Robert; Mason, Keith S; Isaacs, Rufus

2014-02-01

A series of bioassays were conducted to determine the relative toxicities and residual activities of insecticides labeled for use in blueberry (Vaccinium corymbosum L.) on natural enemies, to identify products with low toxicity or short duration effects on biological control agents. In total, 14 insecticides were evaluated using treated petri dishes and four commercially available natural enemies (Aphidius colemani Viereck, Orius insidiosus [Say], Chrysoperla rufilabris [Burmeister], and Hippodamia convergens [Guérin-Menéville]). Dishes were aged under greenhouse conditions for 0, 3, 7, or 14 d before introducing insects to test residual activity. Acute effects (combined mortality and knockdown) varied by insecticide, residue age, and natural enemy species. Broad-spectrum insecticides caused high mortality to all biocontrol agents, whereas products approved for use in organic agriculture had little effect. The reduced-risk insecticide acetamiprid consistently caused significant acute effects, even after aging for 14 d. Methoxyfenozide, novaluron, and chlorantraniliprole, which also are classified as reduced-risk insecticides, had low toxicity, and along with the organic products could be compatible with biological control. This study provides information to guide blueberry growers in their selection of insecticides. Further research will be needed to determine whether adoption of a pest management program based on the use of more selective insecticides will result in higher levels of biological control in blueberry.

Inflammatory effects of the toxic cyanobacterium Geitlerinema amphibium.

PubMed

Dogo, Camila Ranzatto; Bruni, Fernanda Miriane; Elias, Fabiana; Rangel, Marisa; Pantoja, Patricia Araujo; Sant'anna, Célia Leite; Lima, Carla; Lopes-Ferreira, Monica; de Carvalho, Luciana Retz

2011-11-01

Toxic cyanobacteria in public water reservoirs may cause severe health issues for livestock and human beings. Geitlerinema amphibium, which is frequently found in São Paulo City's drinking water supplies, showed toxicity in the standard mouse bioassay, while displaying signs of intoxication and post-mortem findings different from those showed by animals intoxicated by known cyanotoxins. We report here the alterations caused by G. amphibium methanolic extract on mouse microcirculatory network, as seen by in vivo intravital microscopy, besides observations on leukocyte migration, cytokine quantitation, and results of toxicological essays. Our data showed that G. amphibium methanolic extract displayed time- and dose-dependent pro-inflammatory activity, and that at lower doses [125 and 250 mg/kg body weight (b.w.)] increased the leukocyte rolling, caused partial venular stasis, as well as induced an increase in leukocyte counts in the peripheral blood and peritoneal washings. At higher doses (500 and 1000 mg/kg b.w.), the extract caused ischemic injury leading to animal death. As confirmed by mass spectrometric studies and polymyxin B test, the G. amphibium methanolic extract did not contain lipopolysaccharides. Copyright © 2011 Elsevier Ltd. All rights reserved.

Toxic Shock Syndrome

MedlinePlus

... toxic shock syndrome results from toxins produced by Staphylococcus aureus (staph) bacteria, but the condition may also be ... a skin or wound infection. Causes Most commonly, Staphylococcus aureus (staph) bacteria cause toxic shock syndrome. The syndrome ...

Aryl hydrocarbon receptor 2 mediates the toxicity of Paclobutrazol on the digestive system of zebrafish embryos.

PubMed

Wang, Wen-Der; Chen, Guan-Ting; Hsu, Hwei-Jan; Wu, Chang-Yi

2015-02-01

Paclobutrazol (PBZ), a trazole-containing fungicide and plant growth retardant, has been widely used for over 30 years to regulate plant growth and promote early fruit setting. Long-term usage of PBZ in agriculture and natural environments has resulted in residual PBZ in the soil and water. Chronic exposure to waterborne PBZ can cause various physiological effects in fish, including hepatic steatosis, antioxidant activity, and disruption of spermatogenesis. We have previously shown that PBZ also affects the rates of zebrafish embryonic survival and hatching, and causes developmental failure of the head skeleton and eyes; here, we further show that PBZ has embryonic toxic effects on digestive organs of zebrafish, and describe the underlying mechanisms. PBZ treatment of embryos resulted in dose-dependent morphological and functional abnormalities of the digestive organs. Real-time RT-PCR and in situ hybridization were used to show that PBZ strongly induces cyp1a1 expression in the digestive system, and slightly induces ahr2 expression in zebrafish embryos. Knockdown of ahr2 with morpholino oligonucleotides prevents PBZ toxicity. Thus, the toxic effect of PBZ on digestive organs is mediated by AhR2, as was previously reported for retene and TCDD. These findings have implications for understanding the potential toxicity of PBZ during embryogenesis, and thus the potential impact of fungicides on public health and the environment. Copyright © 2014 Elsevier B.V. All rights reserved.

Chloride: from Nutrient to Toxicant.

PubMed

Geilfus, Christoph-Martin

2018-05-01

In salinized soils in which chloride (Cl-) is the dominant salt anion, growth of plants that tolerate only low concentrations of salt (glycophytes) is disturbed by Cl- toxicity. Chlorotic discolorations precede necrotic lesions, causing yield reductions. Little is known about the effects of Cl- toxicity on these dysfunctions. A lack of understanding exists regarding (i) the molecular and physiological mechanisms that lead to Cl--induced damage and (ii) the adaptive aspects of induced tolerance to Cl- salinity. Here, mechanistic explanations for the Cl--induced stress responses are proposed and novel ideas and strategies by which glycophytic plants avoid the excessive accumulation of Cl- are reviewed. New experiments are suggested to test the proposed hypotheses. Cl- salinity constrains global food security and thus we urgently need more research into the causes and consequences of Cl- salinity.

Toxicological approach to setting spacecraft maximum allowable concentrations for carbon monoxide

NASA Technical Reports Server (NTRS)

Wong, K. L.; Limero, T. F.; James, J. T.

1992-01-01

The Spacecraft Maximum Allowable Concentrations (SMACs) are exposure limits for airborne chemicals used by NASA in spacecraft. The aim of these SMACs is to protect the spacecrew against adverse health effects and performance decrements that would interfere with mission objectives. Because of the 1 and 24 hr SMACs are set for contingencies, minor reversible toxic effects that do not affect mission objectives are acceptable. The 7, 30, or 180 day SMACs are aimed at nominal operations, so they are established at levels that would not cause noncarcinogenic toxic effects and more than one case of tumor per 1000 exposed individuals over the background. The process used to set the SMACs for carbon monoxide (CO) is described to illustrate the approach used by NASA. After the toxicological literature on CO was reviewed, the data were summarized and separated into acute, subchronic, and chronic toxicity data. CO's toxicity depends on the formation of carboxyhemoglobin (COHb) in the blood, reducing the blood's oxygen carrying capacity. The initial task was to estimate the COHb levels that would not produce toxic effects in the brain and heart.

Oocyte exposure to ZnO nanoparticles inhibits early embryonic development through the γ-H2AX and NF-κB signaling pathways.

PubMed

Liu, Jing; Zhao, Yong; Ge, Wei; Zhang, Pengfei; Liu, Xinqi; Zhang, Weidong; Hao, Yanan; Yu, Shuai; Li, Lan; Chu, Meiqiang; Min, Lingjiang; Zhang, Hongfu; Shen, Wei

2017-06-27

The impacts of zinc oxide nanoparticles on embryonic development following oocyte stage exposure are unknown and the underlying mechanisms are sparsely understood. In the current investigation, intact nanoparticles were detected in ovarian tissue in vivo and cultured cells in vitro under zinc oxide nanoparticles treatment. Zinc oxide nanoparticles exposure during the oocyte stage inhibited embryonic development. Notably, in vitro culture data closely matched in vivo embryonic data, in that the impairments caused by Zinc oxide nanoparticles treatment passed through cell generations; and both gamma-H2AX and NF-kappaB pathways were involved in zinc oxide nanoparticles caused embryo-toxicity. Copper oxide and silicon dioxide nanoparticles have been used to confirm that particles are important for the toxicity of zinc oxide nanoparticles. The toxic effects of zinc oxide nanoparticles emanate from both intact nanoparticles and Zn2+. Our investigation along with others suggests that zinc oxide nanoparticles are toxic to the female reproductive system [ovaries (oocytes)] and subsequently embryo-toxic and that precaution should be taken regarding human exposure to their everyday use.

Oocyte exposure to ZnO nanoparticles inhibits early embryonic development through the γ-H2AX and NF-κB signaling pathways

PubMed Central

Liu, Jing; Zhao, Yong; Ge, Wei; Zhang, Pengfei; Liu, Xinqi; Zhang, Weidong; Hao, Yanan; Yu, Shuai; Li, Lan; Chu, Meiqiang; Min, Lingjiang; Zhang, Hongfu; Shen, Wei

2017-01-01

The impacts of zinc oxide nanoparticles on embryonic development following oocyte stage exposure are unknown and the underlying mechanisms are sparsely understood. In the current investigation, intact nanoparticles were detected in ovarian tissue in vivo and cultured cells in vitro under zinc oxide nanoparticles treatment. Zinc oxide nanoparticles exposure during the oocyte stage inhibited embryonic development. Notably, in vitro culture data closely matched in vivo embryonic data, in that the impairments caused by Zinc oxide nanoparticles treatment passed through cell generations; and both gamma-H2AX and NF-kappaB pathways were involved in zinc oxide nanoparticles caused embryo-toxicity. Copper oxide and silicon dioxide nanoparticles have been used to confirm that particles are important for the toxicity of zinc oxide nanoparticles. The toxic effects of zinc oxide nanoparticles emanate from both intact nanoparticles and Zn2+. Our investigation along with others suggests that zinc oxide nanoparticles are toxic to the female reproductive system [ovaries (oocytes)] and subsequently embryo-toxic and that precaution should be taken regarding human exposure to their everyday use. PMID:28487501

WHAT’S CAUSING TOXICITY IN SEDIMENTS? RESULTS OF 20 YEARS OF TOXICITY IDENTIFICATION AND EVALUATIONS

EPA Science Inventory

Sediment toxicity identification and evaluation (TIE) methods have been used for 20 yr to identify the causes of toxicity in sediments around the world. In the present study, the authors summarize and categorize results of 36 peer-reviewed TIE studies (67 sediments) into nonioni...

What’s Causing Toxicity in Sediments? Results of Twenty Years of Toxicity Identification and Evaluations (TIEs)

EPA Science Inventory

Sediment Toxicity Identification and Evaluation (TIEs) methods have been used for twenty years to identify the causes of toxicity in sediments around the world. We summarized and categorized results of more than 80 peer-reviewed TIE studies into non-ionic organic, cationic, ammo...

Toxic effects of acid rain on aquatic and terrestrial ecosystems.

PubMed

Rutherford, G K

1984-08-01

The historical perspective as well as the nature and causes of acid precipitation are presented. The toxicological effects of acid precipitation on lakes, other water bodies, fish, and invertebrate fauna are reviewed. In addition, the effects of this phenomenon on soil productivity and forest growth are examined. It appears that grave toxic effects have been and are being experienced by aquatic systems, but there is little reliable evidence of economic damage to crops, natural vegetation, and soil and biological processes. There may be insidious long-term effects on terrestrial ecosystems, particularly in the more susceptible areas.

Sulfate transport kinetics and toxicity are modulated by sodium in aquatic insects.

PubMed

Scheibener, Shane; Conley, Justin M; Buchwalter, David

2017-09-01

The salinization of freshwater ecosystems is emerging as a major ecological issue. Several anthropogenic causes of salinization (e.g. surface coal mining, hydro-fracking, road de-icing, irrigation of arid lands, etc.) are associated with biodiversity losses in freshwater ecosystems. Because insects tend to dominate freshwater ecology, it is important that we develop a better understanding of how and why different species respond to salinity matrices dominated by different major ions. This study builds upon previous work demonstrating that major ion toxicity to the mayfly Neocloeon triangulifer was apparently due to the ionic composition of water rather than specific conductance. Synthetic waters with low Ca:Mg ratios and high SO 4 :Na ratios produced toxicity, whereas waters with higher Ca:Mg ratios and lower SO 4 :Na ratios were not toxic to mayflies at comparable conductivities. Here we used a radiotracer approach to show that Mg did not competitively exclude Ca uptake at environmentally realistic ratios in 4 aquatic insect species. We characterized SO 4 uptake kinetics in 5 mayflies and assessed the influence of different ions on SO 4 uptake. Dual label experiments show an inverse relationship between SO 4 and Na transport rates as SO 4 was held constant and Na was increased, suggesting that Na (and not Cl or HCO 3 ) is antagonistic to SO 4 transport. Based on this observation, we tested the hypothesis that increasing Na would protect against SO 4 induced toxicity in a Na-dependent manner. Increasing Na from 0.7 to 10.9mM improved 96-h survivorship associated with 20.8mM SO 4 from 44% to 73% in a concentration dependent manner. However, when Na reached 21.8mM, survivorship decreased to 16%, suggesting that other interactive effects of major ions caused toxicity under those conditions. Thus, the combination of elevated sulfate and low sodium commonly observed in streams affected by mountaintop coal mining has the potential to cause toxicity in sensitive aquatic insects. Overall, it is important that we develop a better understanding of major ion toxicity to effectively mitigate and protect freshwater biodiversity from salinization. Copyright © 2017 Elsevier B.V. All rights reserved.

A systematic review on the role of environmental toxicants in stem cells aging.

PubMed

Hodjat, Mahshid; Rezvanfar, Mohammad Amin; Abdollahi, Mohammad

2015-12-01

Stem cells are an important target for environmental toxicants. As they are the main source for replenishing of organs in the body, any changes in their normal function could affect the regenerative potential of organs, leading to the appearance of age-related disease and acceleration of the aging process. Environmental toxicants could exert their adverse effect on stem cell function via multiple cellular and molecular mechanisms, resulting in changes in the stem cell differentiation fate and cell transformation, and reduced self-renewal capacity, as well as induction of stress-induced cellular senescence. The present review focuses on the effect of environmental toxicants on stem cell function associated with the aging process. We categorized environmental toxicants according to their preferred molecular mechanism of action on stem cells, including changes in genomic, epigenomic, and proteomic levels and enhancing oxidative stress. Pesticides, tobacco smoke, radiation and heavy metals are well-studied toxicants that cause stem cell dysfunction via induction of oxidative stress. Transgenerational epigenetic changes are the most important effects of a variety of toxicants on germ cells and embryos that are heritable and could affect health in the next several generations. A better understanding of the underlying mechanisms of toxicant-induced stem cell aging will help us to develop therapeutic intervention strategies against environmental aging. Meanwhile, more efforts are required to find the direct in vivo relationship between adverse effect of environmental toxicants and stem cell aging, leading to organismal aging. Copyright © 2015 Elsevier Ltd. All rights reserved.

"Excess gooD can be Dangerous". A case series of iatrogenic symptomatic hypercalcemia due to hypervitaminosis D.

PubMed

Pandita, Kamal Kishore; Razdan, Sushil; Kudyar, Rattan Parkash; Beigh, Aadil; Kuchay, Shafi; Banday, Tanveer

2012-05-01

Vitamin D is increasingly recognized to have several beneficial effects. Its toxicity, causing hypercalcemia, is considered as extremely rare. We report case series of 15 patients (most of them being elderly subjects) with iatrogenic symptomatic hypercalcemia in whom toxicity occurred due to empirical excessive administration of vitamin D by oral and parenteral route.

Study of toxic properties of prototypes of photo inactivated vaccines against tularemia and brucellosis by speckle microscopy

NASA Astrophysics Data System (ADS)

Ulianova, Onega V.; Ulyanov, Sergey

2010-10-01

Testing of prototypes of vaccines against extremely dangerous diseases, such as tularemia and brucellosis has been performed using speckle-microscopy. Changes of microcirculation caused by effect of toxins at applications of suspension of photoinactivated bacteria have been studied. Toxic properties of prototypes of vaccines against tularemia and brucellosis have been analyzed.

Study of toxic properties of prototypes of photo inactivated vaccines against tularemia and brucellosis by speckle microscopy

NASA Astrophysics Data System (ADS)

Ulianova, Onega V.; Ulyanov, Sergey

2011-03-01

Testing of prototypes of vaccines against extremely dangerous diseases, such as tularemia and brucellosis has been performed using speckle-microscopy. Changes of microcirculation caused by effect of toxins at applications of suspension of photoinactivated bacteria have been studied. Toxic properties of prototypes of vaccines against tularemia and brucellosis have been analyzed.

Differential genomic effects of six different TiO2 nanomaterials on human liver HepG2 cells

EPA Science Inventory

Engineered nanoparticles are reported to cause liver toxicity in vivo. To better assess the mechanism of the in vivo liver toxicity, we used the human hepatocarcinoma cells (HepG2) as a model system. Human HepG2 cells were exposed to 6 TiO2 nanomaterials (with dry primary partic...

An unusual case of prolonged post-endoscopic retrograde cholangiopancreatography jaundice.

PubMed

Tziatzios, Georgios; Gkolfakis, Paraskevas; Papanikolaou, Ioannis S; Dimitriadis, George; Triantafyllou, Konstantinos

2016-04-01

Despite the effectiveness of endoscopic retrograde cholangiopancreatography (ERCP) for the treatment of choledocholithiasis, various complications have been described. We herein report the first case of prolonged post-ERCP jaundice due to toxicity of the contrast agent Iobitridol (®XENETIX, Guerbet, Roissy CdG Cedex, France) in a patient who underwent ERCP with sphincterectomy and common bile duct stone removal. While clinical improvement and normalization of aminotransferases and cholestatic enzymes after the procedure, an unexplained increase of direct bilirubin was noticed. A second ERCP was performed one week later, excluding possible remaining choledocholithiasis. Nevertheless, serum direct bilirubin increased further up to 15 mg/dL. Other potential causes of direct hyperbilirubinemia were ruled out and patient's liver biopsy was compatible with drug-induced liver toxicity. Additionally, the cause-result time connection between the use of Iobitridol and bilirubin increase indicated the possibility of a toxic effect related to the repeated use of the particular contrast agent. Iobitridol, a contrast agent, can induce prolonged direct hyperbilirubinemia.

Toxic effects of chlorate on three plant species inoculated with arbuscular mycorrhizal fungi.

PubMed

Li, Huashou; Zhang, Xiuyu; Lin, Chuxia; Wu, Qitang

2008-11-01

Pot experiments were conducted to examine the toxic effects of chlorate on bermudagrass, bahiagrass, and longan seedling with a focus on arbuscular mycorrhizal fungi-plant associations. The results show that application of chlorate could cause slight soil acidification, but the resulting pH was still around 5.5, which is unlikely to adversely affect plant growth. Increase in the application rate of chlorate resulted in a decrease in colonization rate of arbuscular mycorrhizal fungi in plant roots, P uptake by the plants and plant biomass. This appears to suggest that the reduction in plant growth may be related to impeded uptake of P by the plants due to the failure of the plants to form sufficient mycorrhizal associations when chlorate is in sufficient amounts to cause toxicity to arbuscular mycorrhizal fungi. Under the experimental conditions set for this study, bermudagrass suffered from stronger chlorate stress than bahiagrass and longan seedling did in terms of plant-arbuscular mycorrhizal fungi (AMF) symbiosis development.

Dioxin-induced up-regulation of the active form of vitamin D is the main cause for its inhibitory action on osteoblast activities, leading to developmental bone toxicity

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

Nishimura, Noriko; Nishimura, Hisao; Ito, Tomohiro

2009-05-01

Dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) is known to cause bone toxicity, particularly during animal development, although its action mechanism to cause this toxicity has yet to be elucidated. Mouse pups were exposed to TCDD via dam's milk that were administered orally with 15 {mu}g TCDD/kg b.w. on postnatal day 1. Here we report that TCDD causes up-regulation of vitamin D 1{alpha}-hydroxylase in kidney, resulting in a 2-fold increase in the active form of vitamin D, 1,25-dihydroxyvitamin D{sub 3}, in serum. This action of TCDD is not caused by changes in parathyroid hormone, a decrease in vitamin D degrading enzyme, vitamin D 24-hydroxylase,more » or alterations in serum Ca{sup 2+} concentration. Vitamin D is known to affect bone mineralization. Our data clearly show that TCDD-exposed mice exhibit a marked decrease in osteocalcin and collagen type 1 as well as alkaline phosphatase gene expression in tibia by postnatal day 21, which is accompanied with a mineralization defect in the tibia, lowered activity of osteoblastic bone formation, and an increase in fibroblastic growth factor-23, a sign of increased vitamin D effect. Despite these significant effects of TCDD on osteoblast activities, none of the markers of osteoclast activities was found to be affected. Histomorphometry confirmed that osteoblastic activity, but not bone resorption activity, was altered by TCDD. A prominent lesion commonly observed in these TCDD-treated mice was impaired bone mineralization that is characterized by an increased volume and thickness of osteoids lining both the endosteum of the cortical bone and trabeculae. Together, these data suggest that the impaired mineralization resulting from reduction of the osteoblastic activity, which is caused by TCDD-induced up-regulation of vitamin D, is responsible for its bone developmental toxicity.« less

Nanostructured TiO2 and ZnO prepared by using pressurized hot water and their eco-toxicological evaluation

NASA Astrophysics Data System (ADS)

Troppová, Ivana; Matějová, Lenka; Sezimová, Hana; Matěj, Zdeněk; Peikertová, Pavlína; Lang, Jaroslav

2017-06-01

The eco-toxicological effects of unconventionally prepared nanostructured TiO2 and ZnO were evaluated in this study, since both oxides are keenly investigated semiconductor photocatalysts in the last three decades. Unconventional processing by pressurized hot water was applied in order to crystallize oxide materials as an alternative to standard calcination. Acute biological toxicity of the synthesized oxides was evaluated using germination of Sinapis alba seed (ISO 11269-1) and growth of Lemna minor fronds (ISO 20079) and was compared to commercially available TiO2 Degussa P25. Toxicity results revealed that synthesized ZnO as well as TiO2 is toxic contrary to commercial TiO2 Degussa P25 which showled stimulation effect to L. minor and no toxicity to S. alba. ZnO was significantly more toxic than TiO2. The effect of crystallite size was considered, and it was revealed that small crystallite size and large surface area are not the toxicity-determining factors. Factors such as the rate of nanosized crystallites aggregation and concentration, shape and surface properties of TiO2 nanoparticles affect TiO2 toxicity to both plant species. Seriously, the dissolution of Ti4+ ions from TiO2 was also observed which may contribute to its toxicity. In case of ZnO, the dissolution of Zn2+ ions stays the main cause of its toxicity.

The influence of salinity on the toxicity of selected sulfonamides and trimethoprim towards the green algae Chlorella vulgaris.

PubMed

Borecka, Marta; Białk-Bielińska, Anna; Haliński, Łukasz P; Pazdro, Ksenia; Stepnowski, Piotr; Stolte, Stefan

2016-05-05

This paper presents the investigation of the influence of salinity variations on the toxicity of sulfapyridine, sulfamethoxazole, sulfadimethoxine and trimethoprim towards the green algae Chlorella vulgaris after exposure times of 48 and 72 h. In freshwater the EC50 values ranged from 0.98 to 123.22 mg L(-1) depending on the compound. The obtained results revealed that sulfamethoxazole and sulfapyridine were the most toxic, while trimethoprim was the least toxic pharmaceutical to the selected organism. Deviations between the nominal and real test concentrations were determined via instrumental analysis to support the interpretation of ecotoxicological data. The toxicity effects were also tested in saline water (3, 6 and 9 PSU). The tendency that the toxicity of selected pharmaceuticals decreases with increasing salinity was observed. Higher salinity implies an elevated concentration of inorganic monovalent cations that are capable of binding with countercharges available on algal surfaces (hydroxyl functional groups). Hence it can reduce the permeability of pharmaceuticals through the algal cell walls, which could be the probable reason for the observed effect. Moreover, for the classification of the mode of toxic action, the toxic ratio concept was applied, which indicated that the effects of the investigated drugs towards algae are caused by the specific mode of toxic action. Copyright © 2016 Elsevier B.V. All rights reserved.

Human biology-based drug safety evaluation: scientific rationale, current status and future challenges.

PubMed

Kenna, J Gerry

2017-05-01

Animal toxicity studies used to assess the safety of new candidate pharmaceuticals prior to their progression into human clinical trials are unable to assess the risk of non-pharmacologically mediated idiosyncratic adverse drug reactions (ADRs), the most frequent of which are drug-induced liver injury and cardiotoxicity. Idiosyncratic ADRs occur only infrequently and in certain susceptible humans, but are caused by many hundreds of different drugs and may lead to serious illness. Areas covered: Idiosyncratic ADRs are initiated by drug-related chemical insults, which cause toxicity due to susceptibility factors that manifest only in certain patients. The chemical insults can be detected using in vitro assays. These enable useful discrimination between drugs that cause high versus low levels of idiosyncratic ADR concern. Especially promising assays, which have been described recently in peer-reviewed scientific literature, are highlighted. Expert opinion: Effective interpretation of in vitro toxicity data requires integration of endpoints from multiple assays, which each address different mechanisms, and must also take account of human systemic and tissue drug exposure in vivo. Widespread acceptance and use of such assays has been hampered by the lack of correlation between idiosyncratic human ADR risk and toxicities observed in vivo in animals.

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.

The in vitro protective effect of salicylic acid against paclitaxel and cisplatin-induced neurotoxicity.

PubMed

Cetin, Damla; Hacımuftuoglu, Ahmet; Tatar, Abdulgani; Turkez, Hasan; Togar, Basak

2016-08-01

Paclitaxel (PAC) and cisplatin (CIS) are two established chemotherapeutic drugs used in combination for the treatment of various solid tumors. However, the usage of PAC and CIS are limited because of the incidence of their moderate or severe neurotoxic side effects. In this study, we aimed to assess the protective role of salicylic acid (SA) against neurotoxicity caused by PAC and CIS. For this purpose, newborn Sprague Dawley rats were decapitated in sterile atmosphere and primary cortex neuron cultures were established. On the 10th day SA was added into culture plates. PAC and CIS were added on the 12th day. The cytotoxicity was determined by using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. Oxidative alterations were assessed using total antioxidant capacity and total oxidative stress assays in rat primary neuron cell cultures. It was shown that both concentrations of PAC and CIS treatments caused neurotoxicity. Although SA decreased the neurotoxicity by CIS and PAC, it was more effective against the toxicity caused by CIS rather than the toxicity caused by PAC. In conclusion it was clearly revealed that SA decreased the neurotoxic effect of CIS and PAC in vitro.

Reversal of radiocontrast medium toxicity in human renal proximal tubular cells by white grape juice extract.

PubMed

Andreucci, Michele; Faga, Teresa; Pisani, Antonio; Sabbatini, Massimo; Russo, Domenico; Mattivi, Fulvio; De Sarro, Giovambattista; Navarra, Michele; Michael, Ashour

2015-03-05

Radiocontrast media (RCM)-induced nephrotoxicity (CIN) is a major clinical problem accounting for 12% of all hospital-acquired cases of acute kidney injury. The pathophysiology of CIN is not well understood, but direct toxic effects on renal cells have been postulated as contributing to CIN. We have investigated the effect of a white grape (Vitis vinifera) juice extract (WGJe) on human renal proximal tubular (HK-2) cells treated with the radiocontrast medium (RCM) sodium diatrizoate. WGJe caused an increase in phosphorylation of the prosurvival kinases Akt and ERK1/2 in HK-2 cells. Treatment of HK-2 cells with 75 mgI/ml sodium diatrizoate for 2.5h and then further incubation (for 27.5h) after removal of the RCM caused a drastic decrease in cell viability. However, pre-treatment with WGJe, prior to incubation with diatrizoate, dramatically improved cell viability. Analysis of key signaling molecules by Western blotting showed that diatrizoate caused a drastic decrease in phosphorylation of Akt (Ser473), FOXO1 (Thr24) and FOXO3a (Thr32) during the initial 2.5h incubation period, and WGJe pre-treatment caused a reversal of these effects. Further analysis by Western blotting of samples from HK-2 cells cultured for longer periods of time (for up to 27.5h after an initial 2.5h exposure to diatrizoate with or without WGJe pre-treatment) showed that WGJe pre-treatment caused a negative effect on phosphorylation of p38, NF-κB (Ser276) and pERK1/2 whilst having a positive effect on the phosphorylation of Akt, FOXO1/FOXO3a and maintained levels of Pim-1 kinase. WGJe may alleviate RCM toxicity through modulation of signaling molecules that are known to be involved in cell death and cell survival and its possible beneficial effects should be further investigated. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Cytotoxic Effects of Environmental Toxins on Human Glial Cells.

PubMed

D'Mello, Fiona; Braidy, Nady; Marçal, Helder; Guillemin, Gilles; Rossi, Fanny; Chinian, Mirielle; Laurent, Dominique; Teo, Charles; Neilan, Brett A

2017-02-01

Toxins produced by cyanobacteria and dinoflagellates have increasingly become a public health concern due to their degenerative effects on mammalian tissue and cells. In particular, emerging evidence has called attention to the neurodegenerative effects of the cyanobacterial toxin β-N-methylamino-L-alanine (BMAA). Other toxins such as the neurotoxins saxitoxin and ciguatoxin, as well as the hepatotoxic microcystin, have been previously shown to have a range of effects upon the nervous system. However, the capacity of these toxins to cause neurodegeneration in human cells has not, to our knowledge, been previously investigated. This study aimed to examine the cytotoxic effects of BMAA, microcystin-LR (MC-LR), saxitoxin (STX) and ciguatoxin (CTX-1B) on primary adult human astrocytes. We also demonstrated that α-lipoate attenuated MC-LR toxicity in primary astrocytes and characterised changes in gene expression which could potentially be caused by these toxins in primary astrocytes. Herein, we are the first to show that all of these toxins are capable of causing physiological changes consistent with neurodegeneration in glial cells, via oxidative stress and excitotoxicity, leading to a reduction in cell proliferation culminating in cell death. In addition, MC-LR toxicity was reduced significantly in astrocytes-treated α-lipoic acid. While there were no significant changes in gene expression, many of the probes that were altered were associated with neurodegenerative disease pathogenesis. Overall, this is important in advancing our current understanding of the mechanism of toxicity of MC-LR on human brain function in vitro, particularly in the context of neurodegeneration.

Mitochondrial Toxicity of Cadmium Telluride Quantum Dot Nanoparticles in Mammalian Hepatocytes

PubMed Central

Nguyen, Kathy C.; Rippstein, Peter; Tayabali, Azam F.; Willmore, William G.

2015-01-01

There are an increasing number of studies indicating that mitochondria are relevant targets in nanomaterial-induced toxicity. However, the underlying mechanisms by which nanoparticles (NPs) interact with these organelles and affect their functions are unknown. The aim of this study was to investigate the effects of cadmium telluride quantum dot (CdTe-QD) NPs on mitochondria in human hepatocellular carcinoma HepG2 cells. CdTe-QD treatment resulted in the enlargement of mitochondria as examined with transmission electron microscopy and confocal microscopy. CdTe-QDs appeared to associate with the isolated mitochondria as detected by their inherent fluorescence. Further analyses revealed that CdTe-QD caused disruption of mitochondrial membrane potential, increased intracellular calcium levels, impaired cellular respiration, and decreased adenosine triphosphate synthesis. The effects of CdTe-QDs on mitochondrial oxidative phosphorylation were evidenced by changes in levels and activities of the enzymes of the electron transport chain. Elevation of peroxisome proliferator-activated receptor-γ coactivator levels after CdTe-QD treatment suggested the effects of CdTe-QDs on mitochondrial biogenesis. Our results also showed that the effects of CdTe-QDs were similar or greater to those of cadmium chloride at equivalent concentrations of cadmium, suggesting that the toxic effects of CdTe-QDs were not solely due to cadmium released from the NPs. Overall, the study demonstrated that CdTe-QDs induced multifarious toxicity by causing changes in mitochondrial morphology and structure, as well as impairing their function and stimulating their biogenesis. PMID:25809595

Chemical toxicity and radioactivity of depleted uranium: The evidence from in vivo and in vitro studies.

PubMed

Asic, Adna; Kurtovic-Kozaric, Amina; Besic, Larisa; Mehinovic, Lejla; Hasic, Azra; Kozaric, Mirza; Hukic, Mirsada; Marjanovic, Damir

2017-07-01

The main aim of this review is to summarize and discuss the current state of knowledge on chemical toxicity and radioactivity of depleted uranium (DU) and their effect on living systems and cell lines. This was done by presenting a summary of previous investigations conducted on different mammalian body systems and cell cultures in terms of potential changes caused by either chemical toxicity or radioactivity of DU. In addition, the authors aimed to point out the limitations of those studies and possible future directions. The majority of both in vitro and in vivo studies performed using animal models regarding possible effects caused by acute or chronic DU exposure has been reviewed. Furthermore, exposure time and dose, DU particle solubility, and uranium isotopes as factors affecting the extent of DU effects have been discussed. Special attention has been dedicated to chromosomal aberrations, DNA damage and DNA breaks, as well as micronuclei formation and epigenetic changes, as DU has recently been considered a possible causative factor of all these processes. Therefore, this approach might represent a novel area of study of DU-related irradiation effects on health. Since different studies offer contradictory results, the main aim of this review is to summarize and briefly discuss previously obtained results in order to identify the current opinion on DU toxicity and radioactivity effects in relation to exposure type and duration, as well as DU properties. Copyright © 2017 Elsevier Inc. All rights reserved.

Lead toxicity and metabolism in animals

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

Neathery, M.W.; Miller, W.J.

1976-02-16

The main biological interest in lead is its toxicity. Among farm animals, ruminants are most often affected, followed by horses, poultry and swine. Although information is sparse, inhalation of airborne lead is of much less practical importance than ingestion. Most commonly, acute lead poisoning in cattle arises from eating flaking paint, motor oil, linoleum and certain types of grease and putty. Ingestion of lead is one of the most frequently reported causes of acute poisoning, especially in cattle. General clinical symptoms of lead toxicity in farm animals include anemia, depressed appearance, anorexia and muscular incoordination. A special effect in horsesmore » is a laryngeal paralysis which produces an obstruction in the air passage causing them to roar. Lead absorption from the intestine is relatively low (less than 2%), and accumulation occurs mostly in the bone, liver and kidney. Very little is secreted into the milk or concentrated into the muscles. However, lead easily passes the placental barrier, causing serious damage and sometimes death to the fetus. 48 references, 2 tables.« less

Identifying the causes of sediment-associated toxicity in urban waterways in South China: incorporating bioavailabillity-based measurements into whole-sediment toxicity identification evaluation.

PubMed

Yi, Xiaoyi; Li, Huizhen; Ma, Ping; You, Jing

2015-08-01

Sediments in urban waterways of Guangzhou, China, were contaminated by a variety of chemicals and showed prevalent toxicity to benthic organisms. A combination of whole-sediment toxicity identification evaluation (TIE) and bioavailability-based extraction was used to identify the causes of sediment toxicity. Of the 6 sediment samples collected, 4 caused 100% mortality to Chironomus dilutus in 10-d bioassays, and the potential toxicants were assessed using TIE in these sediments after dilution. The results of phase I characterization showed that organic contaminants were the principal contributors to the mortality of the midges in 2 sediments and that metals and organics jointly caused the mortality in the other 2 sediments. Ammonia played no role in the mortality for any samples. Conventional toxic unit analysis in phase II testing identified Cr, Cu, Ni, Pb, and Zn as the toxic metals, with cypermethrin, lambda-cyhalothrin, deltamethrin, and fipronils being the toxic organics. To improve the accuracy of identifying the toxicants, 4-step sequential extraction and Tenax extraction were conducted to analyze the bioavailability of the metals and organics, respectively. Bioavailable toxic unit analysis narrowed the list of toxic contributors, and the putative toxicants included 3 metals (Zn, Ni, and Pb) and 3 pesticides (cypermethrin, lambda-cyhalothrin, and fipronils). Metals contributed to the mortality in all sediments, but sediment dilution reduced the toxicity and confounded the characterization of toxicity contribution from metals in 2 sediments in phase I. Incorporating bioavailability-based measurements into whole-sediment TIE improved the accuracy of identifying the causative toxicants in urban waterways where multiple stressors occurred and contributed to sediment toxicity jointly. © 2015 SETAC.

CONSEQUENCES OF ACUTE AND CHRONIC EXPOSURE TO ARSENIC

EPA Science Inventory

Arsenic is a toxic chemical and may cause adverse health effects in children and adults. It is known to affect the nervous, gastrointestinal, and hematological systems and cause skin and internal cancers in people exposed to levels greater than 300 ppb in their drinking water. Fo...

Ternary copper(II) complex: NCI60 screening, toxicity studies, and evaluation of efficacy in xenograft models of nasopharyngeal carcinoma.

PubMed

Ahmad, Munirah; Suhaimi, Shazlan-Noor; Chu, Tai-Lin; Abdul Aziz, Norazlin; Mohd Kornain, Noor-Kaslina; Samiulla, D S; Lo, Kwok-Wai; Ng, Chew-Hee; Khoo, Alan Soo-Beng

2018-01-01

Copper(II) ternary complex, [Cu(phen)(C-dmg)(H2O)]NO3 was evaluated against a panel of cell lines, tested for in vivo efficacy in nasopharyngeal carcinoma xenograft models as well as for toxicity in NOD scid gamma mice. The Cu(II) complex displayed broad spectrum cytotoxicity against multiple cancer types, including lung, colon, central nervous system, melanoma, ovarian, and prostate cancer cell lines in the NCI-60 panel. The Cu(II) complex did not cause significant induction of cytochrome P450 (CYP) 3A and 1A enzymes but moderately inhibited CYP isoforms 1A2, 2C9, 2C19, 2D6, 2B6, 2C8 and 3A4. The complex significantly inhibited tumor growth in nasopharyngeal carcinoma xenograft bearing mice models at doses which were well tolerated without causing significant or permanent toxic side effects. However, higher doses which resulted in better inhibition of tumor growth also resulted in toxicity.

Protective Effect of Morocco Carob Honey Against Lead-Induced Anemia and Hepato-Renal Toxicity.

PubMed

Fihri, Aicha Fassi; Al-Waili, Noori S; El-Haskoury, Redouan; Bakour, Meryem; Amarti, Afaf; Ansari, Mohammad J; Lyoussi, Badiaa

2016-01-01

Natural honey has many biological activities including protective effect against toxic materials. The aim of this study was to evaluate the protective effect of carob honey against lead-induced hepato-renal toxicity and lead-induced anemia in rabbits. Twenty four male rabbits were allocated into four groups six rabbits each; group 1: control group, received distilled water (0.1 ml / kg.b.wt /daily); group 2: received oral lead acetate (2 g/kg.b.wt/daily); group 3: treated with oral honey (1g /kg.b.wt/daily) and oral lead (2 g/kg.b.wt/daily), and group 4: received oral honey (1 g/kg.b.wt/daily). Honey and lead were given daily during 24 days of experimentation. Laboratory tests and histopathological evaluations of kidneys were done. Oral administration of lead induced hepatic and kidney injury and caused anemia during three weeks of the exposure. Treatment with honey prevented hepato-renal lead toxicity and ameliorated lead-induced anemia when honey was given to animals during lead exposure. It might be concluded that honey has a protective effect against lead-induced blood, hepatic and renal toxic effects. © 2016 The Author(s) Published by S. Karger AG, Basel.

Developmental Toxicity of Endocrine Disrupters Bisphenol A and Vinclozolin in a Terrestrial Isopod

PubMed Central

van Gestel, C. A. M.; Soares, A. M. V. M.

2010-01-01

Studies of the effects of endocrine-disrupting compounds (EDCs) on invertebrates are still largely underrepresented. This work aims to fill this gap by assessing the effects of bisphenol A (BPA) and vinclozolin (Vz) on the terrestrial isopod Porcellio scaber (common rough woodlouse). Male adult and sexually undifferentiated juvenile woodlice were exposed to the toxicants. Effects on molting regime and growth were investigated independently for males and female woodlice after sexual differentiation. Both chemicals elicited developmental toxicity to P. scaber by causing overall decreased growth. Nevertheless, BPA induced molting, whereas Vz delayed it. Although the LC50 values for juvenile and adult survival were fairly similar, juvenile woodlice showed an increased chronic sensitivity to both chemicals, and female woodlice were most the sensitive to BPA. We recommend the use of adults, juveniles, female, and male woodlice, as well as a large range of toxicant concentrations, to provide valuable information regarding differential dose responses, effects, and threshold values for EDCs. PMID:20148245

Developmental toxicity of endocrine disrupters bisphenol A and vinclozolin in a terrestrial isopod.

PubMed

Lemos, M F L; van Gestel, C A M; Soares, A M V M

2010-08-01

Studies of the effects of endocrine-disrupting compounds (EDCs) on invertebrates are still largely underrepresented. This work aims to fill this gap by assessing the effects of bisphenol A (BPA) and vinclozolin (Vz) on the terrestrial isopod Porcellio scaber (common rough woodlouse). Male adult and sexually undifferentiated juvenile woodlice were exposed to the toxicants. Effects on molting regime and growth were investigated independently for males and female woodlice after sexual differentiation. Both chemicals elicited developmental toxicity to P. scaber by causing overall decreased growth. Nevertheless, BPA induced molting, whereas Vz delayed it. Although the LC50 values for juvenile and adult survival were fairly similar, juvenile woodlice showed an increased chronic sensitivity to both chemicals, and female woodlice were most the sensitive to BPA. We recommend the use of adults, juveniles, female, and male woodlice, as well as a large range of toxicant concentrations, to provide valuable information regarding differential dose responses, effects, and threshold values for EDCs.

C9ORF72 hexanucleotide repeat exerts toxicity in a stable, inducible motor neuronal cell model, which is rescued by partial depletion of Pten

PubMed Central

Stopford, Matthew J.; Higginbottom, Adrian; Hautbergue, Guillaume M.; Cooper-Knock, Johnathan; Mulcahy, Padraig J.; De Vos, Kurt J.; Renton, Alan E.; Pliner, Hannah; Calvo, Andrea; Chio, Adriano; Traynor, Bryan J.; Azzouz, Mimoun; Heath, Paul R.; Kirby, Janine

2017-01-01

Abstract Amyotrophic lateral sclerosis (ALS) is a devastating and incurable neurodegenerative disease, characterised by progressive failure of the neuromuscular system. A (G4C2)n repeat expansion in C9ORF72 is the most common genetic cause of ALS and frontotemporal dementia (FTD). To date, the balance of evidence indicates that the (G4C2)n repeat causes toxicity and neurodegeneration via a gain-of-toxic function mechanism; either through direct RNA toxicity or through the production of toxic aggregating dipeptide repeat proteins. Here, we have generated a stable and isogenic motor neuronal NSC34 cell model with inducible expression of a (G4C2)102 repeat, to investigate the gain-of-toxic function mechanisms. The expression of the (G4C2)102 repeat produces RNA foci and also undergoes RAN translation. In addition, the expression of the (G4C2)102 repeat shows cellular toxicity. Through comparison of transcriptomic data from the cellular model with laser-captured spinal motor neurons from C9ORF72-ALS cases, we also demonstrate that the PI3K/Akt cell survival signalling pathway is dysregulated in both systems. Furthermore, partial knockdown of Pten rescues the toxicity observed in the NSC34 (G4C2)102 cellular gain-of-toxic function model of C9ORF72-ALS. Our data indicate that PTEN may provide a potential therapeutic target to ameliorate toxic effects of the (G4C2)n repeat. PMID:28158451

Reactive oxygen species mediate Terbufos-induced apoptosis in mouse testicular cell lines via the modulation of cell cycle and pro-apoptotic proteins.

PubMed

Hung, Jui-Hsiang; Chen, Chia-Yun; Omar, Hany A; Huang, Kuo-Yuan; Tsao, Che-Chia; Chiu, Chien-Chih; Chen, Yi-Ling; Chen, Po-Han; Teng, Yen-Ni

2016-12-01

Terbufos (S-t-butylthiomethyl-O,O-diethyl phosphorodithioate) is a highly toxic organophosphate which is extensively used as an insecticide and nematicide. Chronic exposure to terbufos causes neuronal injury and predisposes to neurodegenerative diseases. Accumulating evidence has shown that the exposure to terbufos, as an occupational risk factor, may also cause reproductive disorders. However, the exact mechanisms of reproductive toxicity remain unclear. The present study aimed to investigate the toxic effect of terbufos on testicular cells and to explore the mechanism of toxicity on a cellular level. The cytotoxic effects of terbufos on mouse immortalized spermatogonia (GC-1), spermatocytes (GC-2), Leydig (TM3), and Sertoli (TM4) cell lines were assessed by MTT assays, caspase activation, flow cytometry, TUNEL assay, Western blot, and cell cycle analysis. The exposure to different concentrations of terbufos ranging from 50 to 800 μM for 6 h caused significant death in all the used testicular cell lines. Terbufos increased reactive oxygen species (ROS) production, reduced mitochondrial membrane potential, and initiated apoptosis, which was confirmed by a dose-dependent increase in the number of TUNEL-positive apoptotic cells. Blocking ROS production by N-acetyl cysteine (NAC) protected GC-1 cells from terbufos-induced cell death. The results demonstrated that terbufos induces ROS, apoptosis, and DNA damage in testicular cell lines and it should be considered potentially hazardous to testis. Together, this study provided potential molecular mechanisms of terbufos-induced toxicity in testicular cells and suggests a possible protective measure. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1888-1898, 2016. © 2015 Wiley Periodicals, Inc.

Paracrine signalling of inflammatory cytokines from an in vitro blood brain barrier model upon exposure to polymeric nanoparticles.

PubMed

Raghnaill, Michelle Nic; Bramini, Mattia; Ye, Dong; Couraud, Pierre-Olivier; Romero, Ignacio A; Weksler, Babette; Åberg, Christoffer; Salvati, Anna; Lynch, Iseult; Dawson, Kenneth A

2014-03-07

Nanoparticle properties, such as small size relative to large highly modifiable surface area, offer great promise for neuro-therapeutics and nanodiagnostics. A fundamental understanding and control of how nanoparticles interact with the blood-brain barrier (BBB) could enable major developments in nanomedical treatment of previously intractable neurological disorders, and help ensure that nanoparticles not intended to reach the brain do not cause adverse effects. Nanosafety is of utmost importance to this field. However, a distinct lack of knowledge exists regarding nanoparticle accumulation within the BBB and the biological effects this may induce on neighbouring cells of the Central Nervous System (CNS), particularly in the long-term. This study focussed on the exposure of an in vitro BBB model to model carboxylated polystyrene nanoparticles (PS COOH NPs), as these nanoparticles are well characterised for in vitro experimentation and have been reported as non-toxic in many biological settings. TEM imaging showed accumulation but not degradation of 100 nm PS COOH NPs within the lysosomes of the in vitro BBB over time. Cytokine secretion analysis from the in vitro BBB post 24 h 100 nm PS COOH NP exposure showed a low level of pro-inflammatory RANTES protein secretion compared to control. In contrast, 24 h exposure of the in vitro BBB endothelium to 100 nm PS COOH NPs in the presence of underlying astrocytes caused a significant increase in pro-survival signalling. In conclusion, the tantalising possibilities of nanomedicine must be balanced by cautious studies into the possible long-term toxicity caused by accumulation of known 'toxic' and 'non-toxic' nanoparticles, as general toxicity assays may be disguising significant signalling regulation during long-term accumulation.

Research Advances on Pathways of Nickel-Induced Apoptosis

PubMed Central

Guo, Hongrui; Chen, Lian; Cui, Hengmin; Peng, Xi; Fang, Jing; Zuo, Zhicai; Deng, Junliang; Wang, Xun; Wu, Bangyuan

2015-01-01

High concentrations of nickel (Ni) are harmful to humans and animals. Ni targets a number of organs and produces multiple toxic effects. Apoptosis is important in Ni-induced toxicity of the kidneys, liver, nerves, and immune system. Apoptotic pathways mediated by reactive oxygen species (ROS), mitochondria, endoplasmic reticulum (ER), Fas, and c-Myc participate in Ni-induced cell apoptosis. However, the exact mechanism of apoptosis caused by Ni is still unclear. Understanding the mechanism of Ni-induced apoptosis may help in designing measures to prevent Ni toxicity. PMID:26703593

Inhalational mold toxicity: fact or fiction? A clinical review of 50 cases.

PubMed

Khalili, Barzin; Montanaro, Marc T; Bardana, Emil J

2005-09-01

Three well-accepted mechanisms of mold-induced disease exist: allergy, infection, and oral toxicosis. Epidemiologic studies suggest a fourth category described as a transient aeroirritation effect. Toxic mold syndrome or inhalational toxicity continues to cause public concern despite a lack of scientific evidence that supports its existence. To conduct a retrospective review of 50 cases of purported mold-induced toxic effects and identify unrecognized conditions that could explain presenting symptoms; to characterize a subgroup with a symptom complex suggestive of an aeroirritation-mediated mechanism and compare this group to other diagnostic categories, such as sick building syndrome and idiopathic chemical intolerance; and to discuss the evolution of toxic mold syndrome from a clinical perspective. Eighty-two consecutive medical evaluations were analyzed of which 50 met inclusion criteria. These cases were critically reviewed and underwent data extraction of 23 variables, including demographic data, patient symptoms, laboratory, imaging, and pulmonary function test results, and an evaluation of medical diagnoses supported by medical record review, examination, and/or test results. Upper respiratory tract, lower respiratory tract, systemic, and neurocognitive symptoms were reported in 80%, 94%, 74%, and 84% of patients, respectively. Thirty patients had evidence of non-mold-related conditions that explained their presenting complaints. Two patients had evidence of allergy to mold allergens, whereas 1 patient exhibited mold-induced psychosis best described as toxic agoraphobia. Seventeen patients displayed a symptom complex that could be postulated to be caused by a transient mold-induced aeroirritation. The clinical presentation of patients with perceived mold-induced toxic effects is characterized by a disparate constellation of symptoms. Close scrutiny revealed a number of preexisting diagnoses that could plausibly explain presenting symptoms. The pathogenesis of aeroirritation implies completely transient symptoms linked to exposures at the incriminated site. Toxic mold syndrome represents the furtive evolution of aeroirritation from a transient to permanent symptom complex in patients with a psychogenic predisposition. In this respect, the core symptoms of toxic mold syndrome and their gradual transition to chronic symptoms related to nonspecific environmental fragrances and irritants appear to mimic what has been observed with other pseudodiagnostic categories, such as sick building syndrome and idiopathic chemical intolerance.

Toxicities of topical ophthalmic anesthetics.

PubMed

McGee, Hall T; Fraunfelder, F W

2007-11-01

Topical ocular anesthesia has been part of ophthalmology for more than a century. The most commonly used drugs today are proparacaine, tetracaine, benoxinate (oxybuprocaine) cocaine and lidocaine. Although generally well tolerated, all these can be toxic, particularly when abused. The most common toxicities are to the ocular surface, but abuse can cause deep corneal infiltrates, ulceration and even perforation. Fortunately, systemic side effects are rare. Cocaine is unique for its higher incidence of systemic side effects and high abuse potential, both of which impede its clinical use. When used appropriately, all these drugs are remarkably safe. They are generally not prescribed for home use, as prolonged abuse of these drugs can be expected to result in serious complications.

Toxic and inhibitory effects of trichloroethylene aerobic co-metabolism on phenol-grown aerobic granules.

PubMed

Zhang, Yi; Tay, JooHwa

2015-04-09

Aerobic granule, a form of microbial aggregate, exhibits good potential in degrading toxic and recalcitrant substances. In this study, the inhibitory and toxic effects of trichloroethylene (TCE), a model compound for aerobic co-metabolism, on phenol-grown aerobic granules were systematically studied, using respiratory activities after exposure to TCE as indicators. High TCE concentration did not exert positive or negative effects on the subsequent endogenous respiration rate or phenol dependent specific oxygen utilization rate (SOUR), indicating the absence of solvent stress and induction effect on phenol-hydroxylase. Phenol-grown aerobic granules exhibited a unique response to TCE transformation product toxicity, that small amount of TCE transformation enhanced the subsequent phenol SOUR. Granules that had transformed between 1.3 and 3.7 mg TCE gSS(-1) showed at most 53% increase in the subsequent phenol SOUR, and only when the transformation exceeded 6.6 mg TCE gSS(-1) did the SOUR dropped below that of the control. This enhancing effect was found to sustain throughout several phenol dosages, and TCE transformation below the toxicity threshold also lessened the granules' sensitivity to higher phenol concentration. The unique toxic effect was possibly caused by the granule's compact structure as a protection barrier against the diffusive transformation product(s) of TCE co-metabolism. Copyright © 2015 Elsevier B.V. All rights reserved.

Effects of heavy metals on sea urchin embryo development. 1. Tracing the cause by the effects.

PubMed

Kobayashi, Naomasa; Okamura, Hideo

2004-06-01

The toxicity of the polluted waters originating from a disused lead mine was evaluated using both sea urchin bioassays and heavy metal analysis. Samples from three polluted waters (a seawater and two freshwaters) were collected from the mine area and one seawater sample was taken from a non-contaminated reference site. The test waters contained higher concentrations of heavy metals such as manganese, lead, cadmium, zinc, chromium, nickel, iron, and copper than did ambient seawater. The three test waters had inhibitory effects, in a dose-dependent manner, on the first cleavage of sea urchin embryos and on pluteus formation during the development. Some malformations, such as a radialized pluteus, exo-gastrula, and spaceship Apollo-like embryos were induced by the test waters without dilution. Zinc alone also induced the same anomaly. Zinc in the test seawater was ascertained as one of the metals that caused the anomalies, but not all of the toxicity was caused by zinc. It was speculated that interactive effects, involving zinc and possibly manganese and nickel, were occurring.

Evaluation of water treatment sludges toxicity using the Daphnia bioassay.

PubMed

Sotero-Santos, Rosana B; Rocha, Odete; Povinelli, Jurandyr

2005-10-01

Alum and ferric chloride sludges from two water treatment plants (WTPs) were analyzed regarding their physicochemical characteristics and toxicity to Daphnia similis. Experiments were carried out in the dry and rainy seasons. Acute and chronic toxicity was measured using survival and reproduction as measurement endpoints. No acute toxicity of the sludge was observed in 48 h exposure. Ferric chloride sludge caused chronic toxicity, demonstrated by low fecundity and some mortality, while alum sludge caused chronic toxicity characterized by low fecundity. Some sludge characteristics varied between samplings, including turbidity, solids contents, N, P and metal (Al and Fe) concentrations. These variables and the increase of chemical oxygen demand (COD) were identified as the main cause of degradation of the receiving waters. However, no relationship was observed between these variables and degree of toxicity. It is apparent from these results that water treatment sludges may be toxic and therefore may impair receiving waters. Alum sludge was less toxic than ferric chloride sludge.

USE OF MARINE TOXICITY IDENTIFICATION AND EVALUATION (TIE) METHODS IN DETERMINING CAUSES OF TOXICITY TO FISH IN A MARINE AQUARIUM FACILITY

EPA Science Inventory

We obtained a water sample containing broken pieces of a tropical coral reef decor that was suspected of causing fish toxicity in a major aquarium. A toxicity identification and evaluation (TIE) was performed using three species: a mysid shrimp, Americamysis bahia; inland silvers...

Maternal ingestion of Ipomoea carnea: Effects on goat-kid bonding and behavior

USDA-ARS?s Scientific Manuscript database

Ipomoea carnea is a toxic plant found in Brazil and other tropical and subtropical countries and often causes poisoning of livestock. The plant contains the alkaloids swainsonine and calystegines, which inhibit key cellular enzymes and cause systematic cell death. This study evaluated the behavioral...

“Excess gooD can be Dangerous”. A case series of iatrogenic symptomatic hypercalcemia due to hypervitaminosis D

PubMed Central

Pandita, Kamal Kishore; Razdan, Sushil; Kudyar, Rattan Parkash; Beigh, Aadil; Kuchay, Shafi; Banday, Tanveer

2012-01-01

Summary Vitamin D is increasingly recognized to have several beneficial effects. Its toxicity, causing hypercalcemia, is considered as extremely rare. We report case series of 15 patients (most of them being elderly subjects) with iatrogenic symptomatic hypercalcemia in whom toxicity occurred due to empirical excessive administration of vitamin D by oral and parenteral route. PMID:23087723

Yohimbine use for physical enhancement and its potential toxicity.

PubMed

Cimolai, Nevio; Cimolai, Tomas

2011-12-01

Yohimbine is a naturally sourced pharmacological agent, which produces hyperadrenergic physiological effects. In excess doses, it may typically cause agitation, anxiety, hypertension, and tachycardia. There is no conclusive evidence for this drug to be of benefit in bodybuilding, exercise tolerance, physical performance, or desirable alterations of body mass. Although tolerated generally well in low doses, the potential for dose-dependent toxicity should be recognized.

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

Molecular toxicity of triclosan and carbamazepine to green algae Chlorococcum sp.: A single cell view using synchrotron-based Fourier transform infrared spectromicroscopy.

PubMed

Xin, Xiaying; Huang, Guohe; Liu, Xia; An, Chunjiang; Yao, Yao; Weger, Harold; Zhang, Peng; Chen, Xiujuan

2017-07-01

Although pharmaceuticals and personal care products have been used and introduced into the environment in large quantities, little information on potential ecological risks is currently available considering their effects on living organisms. We verified the feasibility of using synchrotron-based Fourier Transform Infrared (SR-FTIR) spectromicroscopy to explore in vivo toxic effects on single living Chlorococcum sp. cells. The study provided important information to achieve a better understanding of the toxic mechanism of triclosan and carbamazepine on living algae Chlorococcum sp.. Triclosan and carbamazepine had distinctive toxic effects on unicellular living algae. Most strikingly, triclosan had more dramatic toxic effects on biochemical components than carbamazepine. Triclosan can affect algae primarily by inhibiting fatty acid synthesis and causing protein aggregation. The toxicity response was irreversible at higher concentration (100.000 μM), but attenuated at lower concentration (0.391 μM) as time extended. Carbamazepine can produce hydrophobic interactions to affect the phospholipid bilayer and work on specific proteins to disfunction the cell membrane. Carbamazepine-exposed cells developed a resistance while extending exposure time. This is the first demonstration from an ecological standpoint that SR-FTIR can provide an innovative approach to reveal the toxicity of emerging pollutants in aquatic environments. Copyright © 2017 Elsevier Ltd. All rights reserved.

Resolving disputes about toxicological risks during military conflict : the US Gulf War experience.

PubMed

Hyams, Kenneth C; Brown, Mark; White, David S

2005-01-01

In the last 15 years, the US and UK have fought two major wars in the Persian Gulf region. Controversy has arisen over the nature and causes of health problems among military veterans of these two wars. Toxic exposures have been hypothesised to cause the majority of the long-term health problems experienced by veterans of the 1991 Gulf War. The assessment of these toxic exposures and the resolution of controversy about their health effects provide a unique case study for understanding how toxicological disputes are settled in the US. Neither clinical examination of ill war veterans nor scientific research studies have been sufficient to answer contentious questions about toxic exposures. Numerous expert review panels have also been unable to resolve these controversies except for the US National Academy of Sciences Institute of Medicine (IOM). The IOM has conducted exhaustive and independent investigations based on peer-reviewed scientific literature related to potential health risks during the two Gulf Wars. In four recent studies, IOM committees identified a wide range of previously documented illnesses associated with common occupational and environmental exposures after considering thousands of relevant publications; however, they did not identify a new medical syndrome or a specific toxic exposure that caused widespread health problems among Gulf War veterans. These IOM studies have, therefore, added little to our basic knowledge of environmental hazards because most of the health effects were well known. Nevertheless, this expert review process, which is on-going, has been generally acceptable to a wide range of competing interests because the findings of the IOM have been perceived as scientifically credible and independent, and because none of the postulated toxicological risks have been completely ruled-out as possible causes of ill health among veterans.

Ketoconazole modulates the infectivity of Ichthyophonus sp. (Mesomycetozoa) in vivo in experimentally injected European sea bass.

PubMed

Hontoria, Francisco; González, Ma Angeles; Sitjà-Bobadilla, Ariadna; Palenzuela, Oswaldo; Alvarez-Pellitero, Pilar

2013-09-03

In vitro studies have confirmed the inhibitory effect of the azol-derivative ketoconazole (KZ) on the growth of Ichthyophonus, an important pathogen causing epizootics in wild and cultured fish. We evaluated the effect of KZ in vivo in European sea bass Dicentrarchus labrax experimentally infected with the same Ichthyophonus isolate. Liposomes were used to vehiculate different doses of KZ to increase the effect on Ichthyophonus and lower the toxicity of the drug, and KZ toxicity was assessed in cultured sea bass juveniles. We also studied the effect of liposome-vehiculated KZ included in medicated food on ichthyophoniasis. KZ causes clear toxic effects in D. labrax juveniles at doses >80 mg kg-1, apparent in the reduced survival of fish and histological alterations to livers, kidneys and spleens. Fish injected with Ichthyophonus and treated with KZ dosages of ≤80 mg kg-1 d-1 presented lower ichthyophoniasis prevalence, fewer organs infected per fish, and fewer spores in the affected organs than the untreated fish. KZ seems to delay the onset of infection, but cannot stop further progression once established. However, this behaviour is not clearly reflected in the biometric and haematological data collected from these fish. We hypothesise that KZ's delaying effect would increase, if lower infective doses (more similar to natural situations) were used. The drug administration vehicle (liposomes vs. emulsions) did not affect the results. Our data confirm the potential utility of KZ in treating ichthyophoniasis and reveal its low toxicity for sea bass. Nevertheless, the optimal dose and appropriate application protocol remain to be determined.

BDE 49 and developmental toxicity in zebrafish

PubMed Central

McClain, Valerie; Stapleton, Heather M.; Gallagher, Evan

2011-01-01

The polybrominated diphenyl ethers (PBDEs) are a group of brominated flame retardants. Human health concerns of these agents have largely centered upon their potential to elicit reproductive and developmental effects. Of the various congeners, BDE 49 (2,2’,4,5’-tetrabromodiphenyl ether) has been poorly studied, despite the fact that it is often detected in the tissues of fish and wildlife species. Furthermore, we have previously shown that BDE 49 is a metabolic debromination product of BDE 99 hepatic metabolism in salmon, carp and trout, underscoring the need for a better understanding of biological effects. In the current study, we investigated the developmental toxicity of BDE 49 using the zebrafish (Danio rerio) embryo larval model. Embryo and larval zebrafish were exposed to BDE 49 at either 5 hours post fertilization (hpf) or 24 hpf and monitored for developmental and neurotoxicity. Exposure to BDE 49 at concentrations of 4 µM- 32 µM caused a dose-dependent loss in survivorship at 6 days post fertilization (dpf). Morphological impairments were observed prior to the onset of mortality, the most striking of which included severe dorsal curvatures of the tail. The incidence of dorsal tail curvatures was dose and time dependent. Exposure to BDE 49 caused cardiac toxicity as evidenced by a significant reduction in zebrafish heart rates at 6 dpf but not earlier, suggesting that cardiac toxicity was non-specific and associated with physiological stress. Neurobehavioral injury from BDE 49 was evidenced by an impairment of touch-escape responses observed at 5 dpf. Our results indicate that BDE 49 is a developmental toxicant in larval zebrafish that can cause morphological abnormalities and adversely affect neurobehavior. The observed toxicities from BDE 49 were similar in scope to those previously reported for the more common tetrabrominated congener, BDE 47, and also for other lower brominated PBDEs, suggest that these compounds may share similarities in risk to aquatic species. PMID:21951712

Toxicity of cypermethrin and deltamethrin insecticides on embryos and larvae of Physalaemus gracilis (Anura: Leptodactylidae).

PubMed

Macagnan, Natani; Rutkoski, Camila F; Kolcenti, Cassiane; Vanzetto, Guilherme V; Macagnan, Luan P; Sturza, Paola F; Hartmann, Paulo A; Hartmann, Marilia T

2017-09-01

It is important to establish the toxicity pesticides against non-target species, especially those pesticides used in commercial formulations. Pyrethroid insecticides are widely used in agriculture despite their toxicity to aquatic animals. In this study, we determine the toxicity of commercial formulation of two pyrethroid insecticides, cypermethrin and deltamethrin, in two life stages of Physalaemus gracilis, a frog that breeds in agricultural ecosystems and has potential contact with pyrethroid pesticides. The acute toxicity test (96 h) was carried out with embryos of stage 17:18 and larvae of stages 24:25. Embryos were more resistant to both pesticides than larvae. In embryo mobility assays, we found that both pesticides caused spasmodic contractions, suggestive of neurological effects. In acute toxicity assays, we found that P. gracilis is more resistant to these insecticides than other studied species.

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.

Risk and Prognostic Factors of Inpatient Mortality Associated with Unintentional Insecticide and Herbicide Poisonings: A Retrospective Cohort Study

PubMed Central

Chien, Wu-Chien; Chung, Chi-Hsiang; Jaakkola, Jouni J. K.; Chu, Chi-Ming; Kao, Senyeong; Su, Sui-Lung; Lai, Ching-Huang

2012-01-01

Introduction Pesticide poisoning is an important public health problem worldwide. The study aimed to determine the risk of all-cause and cause-specific inpatient mortality and to identify prognostic factors for inpatient mortality associated with unintentional insecticide and herbicide pesticide poisonings. Methods We performed a retrospective cohort study of 3,986 inpatients recruited at hospitalization between 1999 and 2008 in Taiwan. We used the International Classification of Disease, 9th ed., Clinical Modification external causes of injury codes to classify poisoning agents into accidental poisoning by insecticides and herbicides. Comparisons in mortality rates were made between insecticide poisoning patients and herbicide poisoning patients by using the Cox proportional hazards models to estimate multivariable-adjusted hazard ratios (HRs) and their 95% confidence intervals (CIs). Results There were 168 deaths during 21,583 person-days of follow-up evaluation (7.8 per 1,000 person-days). The major causes of mortality for insecticide poisonings were the toxic effect of organophosphate and coma, and the major causes of mortality for herbicide poisonings were the toxic effect of other pesticides and the toxic effect of organophosphate. The mortality for herbicide exposure was fourfold higher than that for insecticide exposure. The factors associated with inpatient mortality were herbicide poisonings (HR = 4.58, 95% CI 3.29 to 6.37) and receiving mechanical ventilation treatment (HR = 3.85, 95% CI 2.73 to 5.42). Conclusions We demonstrated that herbicides stand out as the dominant agent for poisoning-related fatalities. The control of and limiting access to herbicide agents and developing appropriate therapeutic regimens, including emergency care, should be priorities. PMID:23029146

A toxicity reduction evaluation for an oily waste treatment plant exhibiting episodic effluent toxicity.

PubMed

Erten-Unal, M; Gelderloos, A B; Hughes, J S

1998-07-30

A Toxicity Reduction Evaluation (TRE) was conducted on the oily wastewater treatment plant (Plant) at a Naval Fuel Depot. The Plant treats ship and ballast wastes, berm water from fuel storage areas and wastes generated in the fuel reclamation plant utilizing physical/chemical treatment processes. In the first period of the project (Period I), the TRE included chemical characterization of the plant wastewaters, monitoring the final effluent for acute toxicity and a thorough evaluation of each treatment process and Plant operating procedures. Toxicity Identification Evaluation (TIE) procedures were performed as part of the overall TRE to characterize and identify possible sources of toxicity. Several difficulties were encountered because the effluent was saline, test organisms were marine species and toxicity was sporadic and unpredictable. The treatability approach utilizing enhancements, improved housekeeping, and operational changes produced substantial reductions in the acute toxicity of the final effluent. In the second period (Period II), additional acute toxicity testing and chemical characterization were performed through the Plant to assess the long-term effects of major unit process improvements for the removal of toxicity. The TIE procedures were also modified for saline wastewaters to focus on suspected class of toxicants such as surfactants. The TRE was successful in reducing acute toxicity of the final effluent through process improvements and operational modifications. The results indicated that the cause of toxicity was most likely due to combination of pollutants (matrix effect) rather than a single pollutant.

Early life exposure to PCB126 results in delayed mortality and growth impairment in the zebrafish larvae.

PubMed

Di Paolo, Carolina; Groh, Ksenia J; Zennegg, Markus; Vermeirssen, Etiënne L M; Murk, Albertinka J; Eggen, Rik I L; Hollert, Henner; Werner, Inge; Schirmer, Kristin

2015-12-01

The occurrence of chronic or delayed toxicity resulting from the exposure to sublethal chemical concentrations is an increasing concern in environmental risk assessment. The Fish Embryo Toxicity (FET) test with zebrafish provides a reliable prediction of acute toxicity in adult fish, but it cannot yet be applied to predict the occurrence of chronic or delayed toxicity. Identification of sublethal FET endpoints that can assist in predicting the occurrence of chronic or delayed toxicity would be advantageous. The present study characterized the occurrence of delayed toxicity in zebrafish larvae following early exposure to PCB126, previously described to cause delayed effects in the common sole. The first aim was to investigate the occurrence and temporal profiles of delayed toxicity during zebrafish larval development and compare them to those previously described for sole to evaluate the suitability of zebrafish as a model fish species for delayed toxicity assessment. The second aim was to examine the correlation between the sublethal endpoints assessed during embryonal and early larval development and the delayed effects observed during later larval development. After exposure to PCB126 (3-3000ng/L) until 5 days post fertilization (dpf), larvae were reared in clean water until 14 or 28 dpf. Mortality and sublethal morphological and behavioural endpoints were recorded daily, and growth was assessed at 28 dpf. Early life exposure to PCB126 caused delayed mortality (300 ng/L and 3000 ng/L) as well as growth impairment and delayed development (100 ng/L) during the clean water period. Effects on swim bladder inflation and cartilaginous tissues within 5 dpf were the most promising for predicting delayed mortality and sublethal effects, such as decreased standard length, delayed metamorphosis, reduced inflation of swim bladder and column malformations. The EC50 value for swim bladder inflation at 5 dpf (169 ng/L) was similar to the LC50 value at 8 dpf (188 and 202 ng/L in two experiments). Interestingly, the patterns of delayed mortality and delayed effects on growth and development were similar between sole and zebrafish. This indicates the comparability of critical developmental stages across divergent fish species such as a cold water marine flatfish and a tropical freshwater cyprinid. Additionally, sublethal effects in early embryo-larval stages were found promising for predicting delayed lethal and sublethal effects of PCB126. Therefore, the proposed method with zebrafish is expected to provide valuable information on delayed mortality and delayed sublethal effects of chemicals and environmental samples that may be extrapolated to other species. Copyright © 2015 Elsevier B.V. All rights reserved.

Integrated metabonomics analysis of the size-response relationship of silica nanoparticles-induced toxicity in mice

NASA Astrophysics Data System (ADS)

Lu, Xiaoyan; Tian, Yu; Zhao, Qinqin; Jin, Tingting; Xiao, Shun; Fan, Xiaohui

2011-02-01

Understanding the underlying properties-dependent interactions of nanostructures with biological systems is essential to nanotoxicological research. This study investigates the relationship between particle size and toxicity, and further reveals the mechanism of injury, using silica particles (SP) with diameters of 30, 70, and 300 nm (SP30, SP70, and SP300) as model materials. The biochemical compositions of liver tissues and serum of mice treated with SP30, SP70, and SP300 were analyzed by integrated metabonomics analysis based on gas chromatography-mass spectrometry (GC-MS) and in combination with pattern recognition approaches. Histopathological examinations and serum biochemical analysis were simultaneously performed. The toxicity induced by three different sizes of SP mainly involved hepatocytic necrosis, increased serum aminotransferase, and inflammatory cytokines. Moreover, the toxic effects of SP were dose-dependent for each particle size. The doses of SP30, SP70, and SP300 that were toxic to the liver were 10, 40, and 200 mg kg - 1, respectively. In this study, surface area has a greater effect than particle number on the toxicity of SP30, SP70, and SP300 in the liver. The disturbances in energy metabolism, amino acid metabolism, lipid metabolism, and nucleotide metabolism may be attributable to the hepatotoxicity induced by SP. In addition, no major differences were found in the response of biological systems caused by the different SP sizes among the metabolite profiles. The results suggest that not only nano-sized but also submicro-sized SP can cause similar extents of liver injury, which is dependent on the exposure dose, and the mechanism of toxicity may be almost the same.

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

Strayer, R.F.; Edwards, N.T.; Walton, B.T.

Contaminated soil samples collected from the site of a coal liquefaction product spill were used to study potential fates and effects of this synthetic fuel. Simulated weathering in the laboratory caused significant changes in residual oil composition. Soil column leachates contained high phenol levels that decreased exponentially over time. Toxicity tests demonstrated that the oil-contaminated soil was phytotoxic and caused embryotoxic and teratogenic effects on eggs of the cricket Acheta domesticus.

Local and Systemic Effects of Unpolymerised Monomers

PubMed Central

Gosavi, Sulekha Siddharth; Gosavi, Siddharth Yuvraj; Alla, Rama Krishna

2010-01-01

Methyl methacrylate (MMA), a widely used monomer in dentistry and medicine has been reported to cause abnormalities or lesions in several organs. Experimental and clinical studies have documented that monomers may cause a wide range of adverse health effects such as irritation to skin, eyes, and mucous membranes, allergic dermatitis, stomatitis, asthma, neuropathy, disturbances of the central nervous system, liver toxicity, and fertility disturbances. PMID:22013462

THE EFFECTS OF IONIZING RADIATIONS ON THE BIOCHEMISTRY OF MAMMALIAN TISSUES. III. STUDIES ON THE TOXICITY AND MECHANISM OF ACTION OF 2-MERCAPTOETHYLAMINE

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

Hietbrink, B.E.; Yam, K.M.

1964-10-31

A study was conducted to determine the effect of dibenzyline, dihydroergotamine, and adrenal demedullation on the mercaptoethylamine-induced increase in the blood glucose level of adult female rats. The results of these studies showed that the administration of dibenzyline or dihydroergotamine 10 min before 200 mg/kg of MEA inhibited the marked increase in blood glucose levels usually observed following this dose of MEA and substantially reduced the duration of action of this sulfur-containing compound. Adrenal demedullation almost completely prevented the increase in blood glucose levels caused by 200 mg/ kg of MEA. MEA caused a marked hypoglycemia in the demedullated animalsmore » during the latter part of the 5-hr observation period. Results of experiments on the influence of chronic administration of MEA on the blood glucose level of the rat indicated that repeated doses of MEA do not appear to cause drug tolerance. Studies on the influence of MEA on the acetylcholinesterase activity of the brain and serum of rats indicated that the gross toxic symptoms observed following the administration of MEA were not due to cholinesterase inhibition. The results of preliminary studies on the influence of sodium pentobarbital on the acute toxicity of MEA indicated that 25 mg/kg of pentobarbital prevented the lethal effect of doses of MEA as great as 325 mg/kg. (auth)« less

Effects of mipafox, paraoxon, chlorpyrifos and its metabolite chlorpyrifos-oxon on the expression of biomarker genes of differentiation in D3 mouse embryonic stem cells.

PubMed

Sogorb, Miguel A; Fuster, Encarnación; Del Río, Eva; Estévez, Jorge; Vilanova, Eugenio

2016-11-25

Chlorpyrifos (CPS) is an organophosphorus compound (OP) capable of causing well-known cholinergic and delayed syndromes through the inhibition of acetylcholinesterase and Neuropathy Target Esterase (NTE), respectively. CPS is also able to induce neurodevelopmental toxicity in animals. NTE is codified by the Pnpla6 gene and plays a central role in differentiation and neurodifferentiation. We tested, in D3 mouse embryonic stem cells under differentiation, the effects of the NTE inhibition by the OPs mipafox, CPS and its main active metabolite chlorpyrifos-oxon (CPO) on the expression of genes Vegfa, Bcl2, Amot, Nes and Jun, previously reported to be under- or overexpressed after Pnpla6 silencing in this same cellular model. Mipafox did not significantly alter the expression of such genes at concentrations that significantly inhibited NTE. However, CPS and CPO at concentrations that caused NTE inhibition at similar levels to mipafox statistically and significantly altered the expression of most of these genes. Paraoxon (another OP with capability to inhibit esterases but not NTE) caused similar effects to CPS and CPO. These findings suggest that the molecular mechanism for the neurodevelopmental toxicity induced by CPS is not based on NTE inhibition, and that other unknown esterases might be potential targets of neurodevelopmental toxicity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The new generation of intravenous iron: chemistry, pharmacology, and toxicology of ferric carboxymaltose.

PubMed

Funk, Felix; Ryle, Peter; Canclini, Camillo; Neiser, Susann; Geisser, Peter

2010-01-01

An ideal preparation for intravenous iron replacement therapy should balance effectiveness and safety. Compounds that release iron rapidly tend to cause toxicity, while large molecules can induce antibody formation and cause anaphylactic reactions. There is therefore a need for an intravenous iron preparation that delivers appropriate amounts of iron in a readily available form but with minimal side effects and thus with an excellent safety profile. In this paper, a review is given on the chemistry, pharmacology, and toxicology of ferric carboxymaltose (FCM, Ferinject), a stable and robust complex formulated as a colloidal solution with a physiological pH. The complex is gradually taken up mainly from the hepatic reticulo-endothelial system (RES), followed by effective delivery of iron to the endogeneous transport system for the haem synthesis in new erythrocytes, as shown in studies on the pharmacodynamics and pharmacokinetics with radio-labelled FCM. Studies with radio-labelled FCM also demonstrated a barrier function of the placenta and a low transfer of iron into the milk of lactating rats. Safety pharmacology studies indicated a favourable profile with regard to cardiovascular, central nervous, respiratory, and renal toxicity. A high maximum non-lethal dose was demonstrated in the single-dose toxicity studies. Furthermore, based on the No-Observed-Adverse-Effect-Levels (NOAELs) found in repeated-dose toxicity studies and on the cumulative doses administered, FCM has good safety margins. Reproductive and developmental toxicity studies did not reveal any direct or indirect harmful effects. No genotoxic potential was found in in vitro or in vivo studies. Moreover, antigenicity studies showed no cross-reactivity of FMC with anti-dextran antibodies and also suggested that FCM does not possess sensitizing potential. Lastly, no evidence of irritation was found in local tolerance studies with FCM. This excellent toxicity profile and the high effectiveness of FCM allow the administration of high doses as a single infusion or bolus injection, which will enhance the cost-effectiveness and convenience of iron replacement therapy. In conclusion, FCM has many of the characteristics of an ideal intravenous iron preparation.

The use of high-throughput screening techniques to evaluate mitochondrial toxicity.

PubMed

Wills, Lauren P

2017-11-01

Toxicologists and chemical regulators depend on accurate and effective methods to evaluate and predict the toxicity of thousands of current and future compounds. Robust high-throughput screening (HTS) experiments have the potential to efficiently test large numbers of chemical compounds for effects on biological pathways. HTS assays can be utilized to examine chemical toxicity across multiple mechanisms of action, experimental models, concentrations, and lengths of exposure. Many agricultural, industrial, and pharmaceutical chemicals classified as harmful to human and environmental health exert their effects through the mechanism of mitochondrial toxicity. Mitochondrial toxicants are compounds that cause a decrease in the number of mitochondria within a cell, and/or decrease the ability of mitochondria to perform normal functions including producing adenosine triphosphate (ATP) and maintaining cellular homeostasis. Mitochondrial dysfunction can lead to apoptosis, necrosis, altered metabolism, muscle weakness, neurodegeneration, decreased organ function, and eventually disease or death of the whole organism. The development of HTS techniques to identify mitochondrial toxicants will provide extensive databases with essential connections between mechanistic mitochondrial toxicity and chemical structure. Computational and bioinformatics approaches can be used to evaluate compound databases for specific chemical structures associated with toxicity, with the goal of developing quantitative structure-activity relationship (QSAR) models and mitochondrial toxicophores. Ultimately these predictive models will facilitate the identification of mitochondrial liabilities in consumer products, industrial compounds, pharmaceuticals and environmental hazards. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluation of the toxic effect of endocrine disruptor Bisphenol A (BPA) in the acute and chronic toxicity tests with Pomacea lineata gastropod.

PubMed

de Andrade, André Lucas Correa; Soares, Priscila Rafaela Leão; da Silva, Stephannie Caroline Barros Lucas; da Silva, Marília Cordeiro Galvão; Santos, Thamiris Pinheiro; Cadena, Marilia Ribeiro Sales; Soares, Pierre Castro; Cadena, Pabyton Gonçalves

2017-07-01

Bisphenol A (BPA) is a plasticizer and a risk when it interacts with organisms, and can cause changes in the development and reproduction of them. This study aimed to evaluate the effects of BPA, by acute and chronic toxicity tests with neonates and adults of Pomacea lineata. Adults and neonates were divided into groups exposed to BPA (1-20mg/L), or 17β-estradiol (1mg/L) and control in the acute and chronic toxicity tests. Behavior, heart rate, reproduction and hemolymph biochemical analysis were measured. In the acute toxicity test, the 96-h LC 50 with adults was 11.09 and with neonates was 3.14mg/L. In this test, it was observed lethargic behavior and an increase of 77.6% of aspartate aminotransferase in the adults' hemolymph (p<0.05); and neonates' heart rate decreased 72.7% (p<0.05). In the chronic toxicity test, it was observed behaviors associated with reproduction, as Copulate, in the groups exposed to BPA. The results that were found in this study proved that BPA is a potentially toxic agent to Pomacea lineata according to biological parameters evaluated. These data contribute to the understanding of BPA toxic effects' in the aquatic invertebrates. Copyright © 2017 Elsevier Inc. All rights reserved.

USE OF MERCENARIA MERCENARIA IN MULTIPLE SPECIES TESTING

EPA Science Inventory

The Toxicity Identification Evaluation (TIE) approach was first developed for determining the causes of toxicity in effluents discharged into the aquatic environment. Soon, TIEs were being used for assessing the causes of toxicity in sediment interstitial waters. Now, both fres...

Comparative toxicity of several metal oxide nanoparticle aqueous suspensions to Zebrafish (Danio rerio) early developmental stage.

PubMed

Zhu, Xiaoshan; Zhu, Lin; Duan, Zhenghua; Qi, Ruiqi; Li, Yan; Lang, Yupeng

2008-02-15

With the emergence of manufactured nanomaterials, it is urgent to carry out researches on their potential environmental impacts and biological effects. To better understand the potential ecotoxicological impacts of metal oxide nanoparticles released to aquatic environments, the zebrafish 96-h embryo-larval bioassay was used to assess and compare the developmental toxicities of nanoscale zinc oxide (nZnO), titanium dioxide (nTiO(2)) and alumina (nAl(2)O(3)) aqueous suspensions. Toxicological endpoints such as zebrafish embryos or larvae survival, hatching rate and malformation were noted and described within 96 h of exposure. Meanwhile, a comparative experiment with their bulk counterparts (i.e., ZnO/bulk, TiO(2)/bulk and Al(2)O(3)/bulk) was conducted to understand the effect of particle size on their toxicities. The results showed that: (i) both nZnO and ZnO/bulk aqueous suspensions delayed zebrafish embryo and larva development, decreased their survival and hatching rates, and caused tissue damage. The 96-h LC(50) of nZnO and ZnO/bulk aqueous suspensions on the zebrafish survival are 1.793 mg/L and 1.550 mg/L respectively; and the 84-h EC(50) on the zebrafish embryo hatching rate are 2.065 mg/L and 2.066 mg/L respectively. Serious tissue ulceration was found on zebrafish larvae exposed to nZnO and ZnO/bulk aqueous suspensions. (ii) In contrast, neither nTiO(2) and TiO(2)/bulk nor nAl(2)O(3) and Al(2)O(3)/bulk showed any toxicity to zebrafish embryos and larvae under the same experimental condition. It revealed that the metal oxide nanoparticles with different chemical composition have different zebrafish developmental toxicities. (iii) Exposures of nTiO(2), nZnO and nAl(2)O(3) produced toxic effects on zebrafish embryos and larvae, which was not different from the effects caused by exposing to their bulk counterparts. This is the first study about the developmental toxicity of metal oxide nanoparticles, and the results demonstrate that nZnO is very toxic to zebrafish embryos and larvae, which highlights the need to evaluate the potential eco-toxicity of these manufactured nanomaterials (MNMs).

Environmental enrichment and abstinence attenuate ketamine-induced cardiac and renal toxicity

PubMed Central

Li, Xingxing; Li, Shuangyan; Zheng, Wenhui; Pan, Jian; Huang, Kunyu; Chen, Rong; Pan, Tonghe; Liao, Guorong; Chen, Zhongming; Zhou, Dongsheng; Shen, Wenwen; Zhou, Wenhua; Liu, Yu

2015-01-01

The current study was designed to investigate the effect of abstinence in combination with environmental enrichment (EE) on cardiac and renal toxicity induced by 2 weeks of ketamine self-administration (SA) in rodents. In Experiment 1, one group of rats underwent ketamine SA for 14 days. In Experiment 2, the animals completed 2 weeks of ketamine SA followed by 2 and 4 weeks of abstinence. In Experiment 3, animals underwent 14 days of ketamine SA and 4 weeks of abstinence in which isolated environment (IE) and EE was introduced. The corresponding control groups were included for each experiment. Two weeks of ketamine SA caused significant increases in organ weight, Apoptosis Stimulating Fragment/Kidney Injury Molecule-1, and apoptotic level of heart and kidney. The extended length of withdrawal from ketamine SA partially reduced toxicity on the heart and kidney. Finally, introduction of EE during the period of abstinence greatly promoted the effect of abstinence on ketamine-induced cardiac and renal toxicity. The interactive effect of EE and abstinence was promising to promote the recovery of cardiac and renal toxicity of ketamine. PMID:26112338

The effects of multiple metal contamination on ectomycorrhizal Scots pine (Pinus sylvestris) seedlings.

PubMed

Hartley, J; Cairney, J W; Freestone, P; Woods, C; Meharg, A A

1999-09-01

Experiments were conducted to investigate the effects of single and multiple metal contamination (Cd, Pb, Zn, Sb, Cu) on Scots pine seedlings colonised by ectomycorrhizal (ECM) fungi from natural soil inoculum. Seedlings were grown in either contaminated field soil from the site of a chemical accident, soils amended with five metals contaminating the site, or in soil from an uncontaminated control site. Although contaminated and metal-amended soil significantly inhibited root and shoot growth of the Scots pine seedlings, total root tip density was not affected. Of the five metals tested in amended soils, Cd was the most toxic to ECM Scots pine. Field-contaminated soil had a toxic effect on ECM fungi associated with Scots pine seedlings and caused shifts in ECM species composition on ECM seedlings. When compared to soils amended with only one metal, soils amended with a combination of all five metals tested had lower relative toxicity and less accumulation of Pb, Zn and Sb into seedlings. This would indicate that the toxicity of multiple metal contamination cannot be predicted from the individual toxicity of the metals investigated.

Monitoring of toxicity of As(V) solutions by AMPHITOX test without and with treatment with zerovalent iron nanoparticles.

PubMed

Pérez Coll, Cristina S; Pabón-Reyes, Carolina; Meichtry, Jorge M; Litter, Marta I

2018-06-01

Changes in toxicity of As(V) solutions from acute to chronic exposure have been evaluated by the AMPHITOX test. This test employs Rhinella arenarum, a widely distributed toad in Argentine areas. LOEC values were 6.37 and 1.88 mg L -1 for embryos and larvae, respectively, and serious sublethal effects have been observed. Toxicity of As(V) solutions has been also evaluated after treatment with zerovalent iron nanoparticles (nZVI). After 60 min of treatment with nZVI, As(V) removal was 77%, and neither lethal nor sublethal effects were observed. However, nZVI had to be eliminated before the bioassay because they caused adverse effects in both embryos and larvae. This work highlights the high sensitivity of R. arenarum to As(V), the relevance to assess toxicity on different periods of the lifecycle, and the need to expand exposure to As(V) to chronic times. The utility of the test for monitoring toxicity changes in As(V) solutions after nZVI treatment has been also shown. Copyright © 2018 Elsevier B.V. All rights reserved.

Oxaliplatin-induced Oxidative Stress Provokes Toxicity in Isolated Rat Liver Mitochondria.

PubMed

Tabassum, Heena; Waseem, Mohammad; Parvez, Suhel; Qureshi, M Irfan

2015-11-01

Oxaliplatin is a widely employed platinum-derived chemotherapeutic agent commonly used for the treatment of colorectal cancer. Unfortunately, the benefit of this important drug is compromised by severe side effects such as neuropathy, ototoxicity, gastrointestinal toxicity, and hematological toxicity. Recently, few studies have also suggested the occurrence of hepatotoxicity in oxaliplatin-treated patients. Mitochondria have emerged as targets for anticancer drugs in various kinds of toxicity including hepatotoxicity that can lead to neoplastic disease. Oxidative stress is a well-established biomarker of mitochondrial toxicity. The purpose of this study was to investigate the dose-dependent damage caused by oxaliplatin on isolated liver mitochondria under in vitro conditions. The study was conducted in mitochondria isolated from liver of Wistar rats. Oxaliplatin was incubated with mitochondria in a dose-dependent manner under in vitro conditions. Oxidative stress indexes, non-enzymatic and enzymatic antioxidants were evaluated, looking at the overall armamentarium against the toxicity induced by oxaliplatin. Oxaliplatin caused a significant rise in the mitochondrial oxidative stress indexes lipid peroxidation and protein carbonyl. Alterations in the levels of non-enzymatic antioxidants and activities of enzymatic antioxidants were also observed. Oxidative stress plays an important role in the mitochondrial toxicity of oxaliplatin. The integrity of the hepatic tissue is compromised by the reactive oxygen species-mediated lipid peroxidation and protein carbonyl formation. Copyright © 2015 IMSS. Published by Elsevier Inc. All rights reserved.

ABC transporters affect the elimination and toxicity of CdTe quantum dots in liver and kidney cells

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

Chen, Mingli; Yin, Huancai; Bai, Pengli

This paper aimed to investigate the role of adenosine triphosphate-binding cassette (ABC) transporters on the efflux and the toxicity of nanoparticles in liver and kidney cells. In this study, we synthesized CdTe quantum dots (QDs) that were monodispersed and emitted green fluorescence (maximum peak at 530 nm). Such QDs tended to accumulate in human hepatocellular carcinoma cells (HepG2), human kidney cells 2 (HK-2), and Madin-Darby canine kidney (MDCK) cells, and cause significant toxicity in all the three cell lines. Using specific inhibitors and inducers of P-glycoprotein (Pgp) and multidrug resistance associated proteins (Mrps), the cellular accumulation and subsequent toxicity ofmore » QDs in HepG2 and HK-2 cells were significantly affected, while only slight changes appeared in MDCK cells, corresponding well with the functional expressions of ABC transporters in cells. Moreover, treatment of QDs caused concentration- and time- dependent induction of ABC transporters in HepG2 and HK-2 cells, but such phenomenon was barely found in MDCK cells. Furthermore, the effects of CdTe QDs on ABC transporters were found to be greater than those of CdCl{sub 2} at equivalent concentrations of cadmium, indicating that the effects of QDs should be a combination of free Cd{sup 2+} and specific properties of QDs. Overall, these results indicated a strong dependence between the functional expressions of ABC transporters and the efflux of QDs, which could be an important reason for the modulation of QDs toxicity by ABC transporters. - Highlights: • ABC transporters contributed actively to the cellular efflux of CdTe quantum dots. • ABC transporters affected the cellular toxicity of CdTe quantum dots. • Treatment of CdTe quantum dots induced the gene expression of ABC transporters. • Free Cd{sup 2+} should be partially involved in the effects of QDs on ABC transporters. • Cellular efflux of quantum dots could be an important modulator for its toxicity.« less

Cardiovascular Mitochondrial Dysfunction Induced by Cocaine: Biomarkers and Possible Beneficial Effects of Modulators of Oxidative Stress.

PubMed

Graziani, Manuela; Sarti, Paolo; Arese, Marzia; Magnifico, Maria Chiara; Badiani, Aldo; Saso, Luciano

2017-01-01

Cocaine abuse has long been known to cause morbidity and mortality due to its cardiovascular toxic effects. The pathogenesis of the cardiovascular toxicity of cocaine use has been largely reviewed, and the most recent data indicate a fundamental role of oxidative stress in cocaine-induced cardiovascular toxicity, indicating that mitochondrial dysfunction is involved in the mechanisms of oxidative stress. The comprehension of the mechanisms involving mitochondrial dysfunction could help in selecting the most appropriate mitochondria injury biological marker, such as superoxide dismutase-2 activity and glutathionylated hemoglobin. The potential use of modulators of oxidative stress (mitoubiquinone, the short-chain quinone idebenone, and allopurinol) in the treatment of cocaine cardiotoxic effects is also suggested to promote further investigations on these potential mitochondria-targeted antioxidant strategies.

Acute toxicity in five dogs after ingestion of a commercial snail and slug bait containing iron EDTA.

PubMed

Haldane, S L; Davis, R M

2009-07-01

This case series of five dogs describes the effects of ingesting large amounts of an iron EDTA snail-bait product. In all cases signs of toxicity occurred between 6 and 24 h after ingestion and included abdominal pain and haemorrhagic gastroenteritis. Two of the dogs had pretreatment serum iron levels measured and in both cases the levels were above normal limits. All of the dogs were treated with iron chelation therapy and supportive care including intravenous fluids, analgesics, gastric protectants and antibiotics. Chelation therapy with desferrioxamine mesylate did not cause adverse effects in any of the dogs and all survived to discharge. The effects of iron EDTA snail bait in dogs requires further study and minimum toxic doses need to be established.

Toxic shock syndrome

MedlinePlus

Staphylococcal toxic shock syndrome; Toxic shock-like syndrome; TSLS ... Toxic shock syndrome is caused by a toxin produced by some types of staphylococcus bacteria. A similar problem, called toxic shock- ...

The protective roles of TiO2 nanoparticles against UV-B toxicity in Daphnia magna.

PubMed

Liu, Jie; Wang, Wen-Xiong

2017-09-01

Aquatic environments are increasingly under environmental stress due to ultraviolet (UV) radiation and potential inputs of nanoparticles with intense application of nanotechnology. In this study, we investigated the interaction between UV-B radiation and titanium nanoparticles (TiO 2 -NPs) in a model freshwater cladoceran Daphnia magna. UV-B toxicity to Daphnia magna was examined when the daphnids were exposed to a range of TiO 2 -NPs concentrations with an initial 5 or 10min of 200μW/cm 2 UV-B radiation. In addition, UV-B toxicity was also examined in the presence of TiO 2 -NPs in the body of daphnids. Our results demonstrated that the daphnid mortality under UV-B radiation decreased significantly in the presence of TiO 2 -NPs both in the water and in the body, indicating that TiO 2 -NPs had some protective effects on D. magna against UV-B. Such protective effect was mainly caused by the blockage of UV-B by TiO 2 -NPs adsorption. UV-B produced reactive oxygen species (ROS) in the water and in the daphnids, which was not sufficient to cause mortality of daphnids over short periods of radiation. Previous studies focused on the effects of TiO 2 -NPs on the toxicity of total UV radiation, and did not attempt to differentiate the potential diverse roles of UV-A and UV-B. Our study indicated that TiO 2 -NPs may conversely protect the UV-B toxicity to daphnids. Copyright © 2017 Elsevier B.V. All rights reserved.

Toxicity evaluation of methoxy poly(ethylene oxide)-block-poly(ε-caprolactone) polymeric micelles following multiple oral and intraperitoneal administration to rats.

PubMed

Binkhathlan, Ziyad; Qamar, Wajhul; Ali, Raisuddin; Kfoury, Hala; Alghonaim, Mohammed

2017-09-01

Methoxy poly(ethylene oxide)- block -poly(ɛ-caprolactone) (PEO- b -PCL) copolymers are amphiphilic and biodegradable copolymers designed to deliver a variety of drugs and diagnostic agents. The aim of this study was to synthesize PEO- b -PCL block copolymers and assess the toxic effects of drug-free PEO- b -PCL micelles after multiple-dose administrations via oral or intraperitoneal (ip) administration in rats. Assembly of block copolymers was achieved by co-solvent evaporation method. To investigate the toxicity profile of PEO- b -PCL micelles, sixty animals were divided into two major groups: The first group received PEO- b -PCL micelles (100 mg/kg) by oral gavage daily for seven days, while the other group received the same dose of micelles by ip injections daily for seven days. Twenty-four hours following the last dose, half of the animals from each group were sacrificed and blood and organs (lung, liver, kidneys, heart and spleen) were collected. Remaining animals were observed for further 14 days and was sacrificed at the end of the third week, and blood and organs were collected. None of the polymeric micelles administered caused any significant effects on relative organ weight, animal body weight, leucocytes count, % lymphocytes, liver and kidney toxicity markers and organs histology. Although the dose of copolymers used in this study is much higher than those used for drug delivery, it did not cause any significant toxic effects in rats. Histological examination of all the organs confirmed the nontoxic nature of the micelles.

Evaluation of Toxic Effects of Aeration and Trichloroethylene Oxidation on Methanotrophic Bacteria Grown with Different Nitrogen Sources

PubMed Central

Chu, Kung-Hui; Alvarez-Cohen, Lisa

1999-01-01

In this study we evaluated specific and nonspecific toxic effects of aeration and trichloroethylene (TCE) oxidation on methanotrophic bacteria grown with different nitrogen sources (nitrate, ammonia, and molecular nitrogen). The specific toxic effects, exerted directly on soluble methane monooxygenase (sMMO), were evaluated by comparing changes in methane uptake rates and naphthalene oxidation rates following aeration and/or TCE oxidation. Nonspecific toxic effects, defined as general cellular damage, were examined by using a combination of epifluorescent cellular stains to measure viable cell numbers based on respiratory activity and measuring formate oxidation activities following aeration and TCE transformation. Our results suggest that aeration damages predominantly sMMO rather than other general cellular components, whereas TCE oxidation exerts a broad range of toxic effects that damage both specific and nonspecific cellular functions. TCE oxidation caused sMMO-catalyzed activity and respiratory activity to decrease linearly with the amount of substrate degraded. Severe TCE oxidation toxicity resulted in total cessation of the methane, naphthalene, and formate oxidation activities and a 95% decrease in the respiratory activity of methanotrophs. The failure of cells to recover even after 7 days of incubation with methane suggests that cellular recovery following severe TCE product toxicity is not always possible. Our evidence suggests that generation of greater amounts of sMMO per cell due to nitrogen fixation may be responsible for enhanced TCE oxidation activities of nitrogen-fixing methanotrophs rather than enzymatic protection mechanisms associated with the nitrogenase enzymes. PMID:9925614

Effect of dissolved organic matter (DOM) of contrasting origins on Cu and Pb speciation and toxicity to Paracentrotus lividus larvae.

PubMed

Sánchez-Marín, Paula; Santos-Echeandía, Juan; Nieto-Cid, Mar; Alvarez-Salgado, Xosé Antón; Beiras, Ricardo

2010-01-31

Water samples of contrasting origin, including natural seawater, two sediment elutriates and sewage-influenced seawater, were collected and obtained to examine the effect of the dissolved organic matter (DOM) present on metal bioavailability. The carbon content (DOC) and the optical properties (absorbance and fluorescence) of the coloured DOM fraction (CDOM) of these materials were determined. Cu and Pb complexation properties were measured by anodic stripping voltammetry (ASV) and the effect of DOM on Cu and Pb bioavailability was studied by means of the Paracentrotus lividus embryo-larval bioassay. Sediment elutriates and sewage-influenced water (1) were enriched 1.4-1.7 times in DOC; (2) absorbed and reemitted more light; and (3) presented higher Cu complexation capacities (L(Cu)) than the natural seawater used for their preparation. L(Cu) varied from 0.08 microM in natural seawater to 0.3 and 0.5 microM in sediment elutriates and sewage-influenced water, respectively. Differences in DOC, CDOM and Cu complexation capacities were reflected in Cu toxicity. DOM enriched samples presented a Cu EC(50) of 0.64 microM, significantly higher than the Cu EC(50) of natural and artificial seawater, which was 0.38 microM. The protecting effect of DOM on Cu toxicity greatly disappeared when the samples were irradiated with high intensity UV-light. Cu toxicity could be successfully predicted considering ASV-labile Cu concentrations in the samples. Pb complexation by DOM was only detected in the DOM-enriched samples and caused little effect on Pb EC(50). This effect was contrary for both elutriates: one elutriate reduced Pb toxicity in comparison with the control artificial seawater, while the other increased it. UV irradiation of the samples caused a marked increase in Pb toxicity, which correlated with the remaining DOC concentration. DOM parameters were related to Cu speciation and toxicity: good correlations were found between DOC and Cu EC(50), while L(Cu) correlated better with the fluorescence of marine humic substances. The present results stress the importance of characterizing not only the amount but also the quality of seawater DOM to better predict ecological effects from total metal concentration data. Copyright (c) 2009 Elsevier B.V. All rights reserved.

Investigation of toxic effects of imidazolium ionic liquids, [bmim][BF4] and [omim][BF4], on marine mussel Mytilus galloprovincialis with or without the presence of conventional solvents, such as acetone.

PubMed

Tsarpali, Vasiliki; Belavgeni, Alexia; Dailianis, Stefanos

2015-07-01

This study investigated the cytotoxic, oxidative and genotoxic effects of two commonly used imidazolium ionic liquids (ILs), [bmim][BF4] (1-butyl-3-methylimidazolium) and [omim][BF4] (1-methyl-3-octylimidazolium tetrafluoroborate), on the marine mussel Mytilus galloprovincialis, as well as whether acetone could mediate their toxic profile. In this context, mussels were firstly exposed to different concentrations of [bmim][BF4] or [omim][BF4], with or without the presence of acetone (at a final concentration of 0.06% v/v), for a period of 96h, in order to determine the concentration that causes 50% mussel mortality (LC50 values) in each case. Thereafter, mussels were exposed to sub- and non-lethal concentrations of ILs for investigating their ability to cause lysosomal membrane impairment (with the use of neutral red retention assay/NRRT), superoxide anion and lipid peroxidation byproduct (malondialdehyde/MDA) formation, as well as DNA damage and formation of nuclear abnormalities in hemocytes. The results showed that [omim][BF4] was more toxic than [bmim][BF4] in all cases, while the presence of acetone resulted in a slight attenuation of its toxicity. The different toxic behavior of ILs was further revealed by the significantly lower levels of NRRT values observed in [omim][BF4]-treated mussels, compared to those occurring in [bmim][BF4] in all cases. Similarly, [bmim][BF4]-mediated oxidative and genotoxic effects were observed only in the highest concentration tested (10mgL(-1)), while [omim][BF4]-mediated effects were enhanced at lower concentrations (0.01-0.05mgL(-1)). Overall, the present study showed that [bmim][BF4] and [omim][BF4] could induce not only lethal but also nonlethal effects on mussel M. galloprovincialis. The extent of [bmim][BF4] and/or [omim][BF4]-mediated effects could be ascribed to the length of each IL alkyl chain, as well as to their lipophilicity. Moreover, the role of acetone on the obtained toxic effects of the specific ILs was reported for the first time, giving evidence for its interaction with the ILs and the modulation of their toxicity. Copyright © 2015 Elsevier B.V. All rights reserved.

Lethal effects of short-wavelength visible light on insects.

PubMed

Hori, Masatoshi; Shibuya, Kazuki; Sato, Mitsunari; Saito, Yoshino

2014-12-09

We investigated the lethal effects of visible light on insects by using light-emitting diodes (LEDs). The toxic effects of ultraviolet (UV) light, particularly shortwave (i.e., UVB and UVC) light, on organisms are well known. However, the effects of irradiation with visible light remain unclear, although shorter wavelengths are known to be more lethal. Irradiation with visible light is not thought to cause mortality in complex animals including insects. Here, however, we found that irradiation with short-wavelength visible (blue) light killed eggs, larvae, pupae, and adults of Drosophila melanogaster. Blue light was also lethal to mosquitoes and flour beetles, but the effective wavelength at which mortality occurred differed among the insect species. Our findings suggest that highly toxic wavelengths of visible light are species-specific in insects, and that shorter wavelengths are not always more toxic. For some animals, such as insects, blue light is more harmful than UV light.

Lethal effects of short-wavelength visible light on insects

NASA Astrophysics Data System (ADS)

Hori, Masatoshi; Shibuya, Kazuki; Sato, Mitsunari; Saito, Yoshino

2014-12-01

We investigated the lethal effects of visible light on insects by using light-emitting diodes (LEDs). The toxic effects of ultraviolet (UV) light, particularly shortwave (i.e., UVB and UVC) light, on organisms are well known. However, the effects of irradiation with visible light remain unclear, although shorter wavelengths are known to be more lethal. Irradiation with visible light is not thought to cause mortality in complex animals including insects. Here, however, we found that irradiation with short-wavelength visible (blue) light killed eggs, larvae, pupae, and adults of Drosophila melanogaster. Blue light was also lethal to mosquitoes and flour beetles, but the effective wavelength at which mortality occurred differed among the insect species. Our findings suggest that highly toxic wavelengths of visible light are species-specific in insects, and that shorter wavelengths are not always more toxic. For some animals, such as insects, blue light is more harmful than UV light.

N-Acetyl Cysteine does not prevent liver toxicity from chronic low dose plus sub-acute high dose paracetamol exposure in young or old mice

PubMed Central

Kane, Alice-Elizabeth; Huizer-Pajkos, Aniko; Mach, John; McKenzie, Catriona; Mitchell, Sarah-Jayne; de Cabo, Rafael; Jones, Brett; Cogger, Victoria; Le Couteur, David G; Hilmer, Sarah-Nicole

2016-01-01

Paracetamol is an analgesic commonly used by people of all ages, which is well documented to cause severe hepatotoxicity with acute over-exposures. The risk of hepatotoxicity from non-acute paracetamol exposures is less extensively studied, and this is the exposure most common in older adults. Evidence on the effectiveness of N-acetyl cysteine (NAC) for non-acute paracetamol exposures, in any age group, is lacking. This study aimed to examine the effect of long-term exposure to therapeutic doses of paracetamol and sub-acute paracetamol over-exposure, in young and old mice, and to investigate whether NAC was effective at preventing paracetamol hepatotoxicity induced by these exposures. Young and old male C57BL/6 mice were fed a paracetamol-containing (1.33g/kg food) or control diet for 6 weeks. Mice were then dosed orally 8 times over 3 days with additional paracetamol (250mg/kg) or saline, followed by either one or two doses of oral NAC (1200mg/kg) or saline. Chronic low-dose paracetamol exposure did not cause hepatotoxicity in young or old mice, measured by serum alanine aminotransferase (ALT) elevation, and confirmed by histology and a DNA fragmentation assay. Sub-acute paracetamol exposure caused significant hepatotoxicity in young and old mice, measured by biochemistry (ALT) and histology. Neither a single nor double dose of NAC protected against this toxicity from sub-acute paracetamol in young or old mice. This finding has important clinical implications for treating toxicity due to different paracetamol exposure types in patients of all ages, and implies a need to develop new treatments for sub-acute paracetamol toxicity. PMID:26821200

Validating potential toxicity assays to assess petroleum hydrocarbon toxicity in polar soil.

PubMed

Harvey, Alexis Nadine; Snape, Ian; Siciliano, Steven Douglas

2012-02-01

Potential microbial activities are commonly used to assess soil toxicity of petroleum hydrocarbons (PHC) and are assumed to be a surrogate for microbial activity within the soil ecosystem. However, this assumption needs to be evaluated for frozen soil, in which microbial activity is limited by liquid water (θ(liquid)). Influence of θ(liquid) on in situ toxicity was evaluated and compared to the toxicity endpoints of potential microbial activities using soil from an aged diesel fuel spill at Casey Station, East Antarctica. To determine in situ toxicity, gross mineralization and nitrification rates were determined by the stable isotope dilution technique. Petroleum hydrocarbon-contaminated soil (0-8,000 mg kg(-1)), packed at bulk densities of 1.4, 1.7, and 2.0 g cm(-3) to manipulate liquid water content, was incubated at -5°C for one, two, and three months. Although θ(liquid) did not have a significant effect on gross mineralization or nitrification, gross nitrification was sensitive to PHC contamination, with toxicity decreasing over time. In contrast, gross mineralization was not sensitive to PHC contamination. Toxic response of gross nitrification was comparable to potential nitrification activity (PNA) with similar EC25 (effective concentration causing a 25% effect in the test population) values determined by both measurement endpoints (400 mg kg(-1) for gross nitrification compared to 200 mg kg(-1) for PNA), indicating that potential microbial activity assays are good surrogates for in situ toxicity of PHC contamination in polar regions. Copyright © 2011 SETAC.

[Household gas poisonings].

PubMed

Maloca, Ivana; Macan, Jelena; Varnai, Veda Marija; Turk, Rajka

2006-12-01

Exposure to toxic gases which can induce serious health effects, can occur in the working as well as in general environment, including home. The severity of gas poisoning is determined by its physical and chemical characteristics, intensity and duration of exposure, and concomitant diseases and injuries in the poisoned person. Manifestations of gas toxic action involve simple asphyxia, local irritation of respiratory mucosa, systemic toxicity, and a combination of these mechanisms. This article describes the characteristics, modes of exposure and health effects of most common gases causing poisoning at home. These include gas fuels, carbon monoxide, ammonia, chlorine, and fire gases such as nitrogen and sulphur oxides, hydrogen cyanide and phosgene. First aid as well as preventive measures to avoid exposure to toxic gases and prevent fire at home are also given. The Croatian Poison Control Centre gathered data on toxic gas exposures in households between November 2005 and July 2006. During this period 30 persons (3 % of the total number of cases) were exposed to toxic gases at home, including carbon monoxide, irritating vapours from cleaning agents and disinfectants, gas fuels, septic tank gases, tear-gas, and chlorofluorocarbons from refrigerators.

Environmental Determinants of Chronic Disease and Medical Approaches: Recognition, Avoidance, Supportive Therapy, and Detoxification

PubMed Central

Sears, Margaret E.; Genuis, Stephen J.

2012-01-01

The World Health Organization warns that chronic, noncommunicable diseases are rapidly becoming epidemic worldwide. Escalating rates of neurocognitive, metabolic, autoimmune and cardiovascular diseases cannot be ascribed only to genetics, lifestyle, and nutrition; early life and ongoing exposures, and bioaccumulated toxicants may also cause chronic disease. Contributors to ill health are summarized from multiple perspectives—biological effects of classes of toxicants, mechanisms of toxicity, and a synthesis of toxic contributors to major diseases. Healthcare practitioners have wide-ranging roles in addressing environmental factors in policy and public health and clinical practice. Public health initiatives include risk recognition and chemical assessment then exposure reduction, remediation, monitoring, and avoidance. The complex web of disease and environmental contributors is amenable to some straightforward clinical approaches addressing multiple toxicants. Widely applicable strategies include nutrition and supplements to counter toxic effects and to support metabolism; as well as exercise and sweating, and possibly medication to enhance excretion. Addressing environmental health and contributors to chronic disease has broad implications for society, with large potential benefits from improved health and productivity. PMID:22315626

Trastuzumab induces gastrointestinal side effects in HER2-overexpressing breast cancer patients.

PubMed

Al-Dasooqi, Noor; Bowen, Joanne M; Gibson, Rachel J; Sullivan, Thomas; Lees, Jude; Keefe, Dorothy M

2009-04-01

To characterise the gastrointestinal toxicities associated with Trastuzumab administration in HER2-overexpressing breast cancer patients. All patients (n = 46) who received Trastuzumab as a single agent or in conjunction with conventional anti-cancer treatment within the Royal Adelaide Hospital Cancer Centre from 2002-2007 were included in this study. A retrospective analysis of case-notes was conducted to investigate the toxicities associated with Trastuzumab. Trastuzumab as a single agent induced toxicities following 22% of administrations. Gastrointestinal toxicities were observed following 12% of administrations and included nausea and vomiting, diarrhoea, abdominal pain and bloating. However, other prominent toxicities that were not related to the gastrointestinal tract were also observed including fatigue and lung symptoms (10.4%). Elderly patients (> or =60 years) and those with metastatic disease experienced the highest frequency of toxicity. Trastuzumab induces a range of gastrointestinal toxicities in HER2-overexpressing breast cancer patients. These toxicities are separate to those caused by concurrent chemotherapy and/or radiotherapy.

In vivo toxic effects of 4-methoxy-5-hydroxy-canthin-6-one in zebrafish embryos via copper dyshomeostasis and oxidative stress.

PubMed

Gong, Guiyi; Jiang, Lingling; Lin, Qinghua; Liu, Wenyuan; He, Ming-Fang; Zhang, Jie; Feng, Feng; Qu, Wei; Xie, Ning

2018-01-01

Dysfunction of copper homeostasis can lead to a host of disorders, which might be toxic sometimes. 4-Methoxy-5-hydroxy-canthin-6-one (CAN) is one of the major constituents from Picrasma quassioides and responsible for its therapeutic effects. In this work, we evaluated the toxic effect of CAN (7.5μM) on zebrafish embryos. CAN treatment decreased survival, delayed hatching time and induced malformations (loss of pigmentation, pericardial edema, as well as hematologic and neurologic abnormalities). Besides, exogenous copper supplementation rescued the pigmentation and cardiovascular defects in CAN-treated embryos. Further spectroscopic studies revealed a copper-chelating activity of CAN. Then its regulation on the expressions of copper homeostasis related genes also be analyzed. In addition, CAN lowered the total activity of SOD, elevated the ROS production and altered the oxidative related genes transcriptions, which led to oxidative stress. In conclusion, we demonstrated that CAN (7.5μM) might exert its toxic effects in zebrafish embryos by causing copper dyshomeostasis and oxidative stress. It will give insight into the risk assessment and prevention of CAN-mediated toxicity. Copyright © 2017 Elsevier Inc. All rights reserved.

Leaching and toxicity behavior of coal-biomass waste cocombustion ashes.

PubMed

Skodras, G; Prokopidou, M; Sakellaropoulos, G P

2006-08-01

Land disposal of ash residues, obtained from the cocombustion of Greek lignite with biomass wastes, is known to create problems due to the harmful constituents present. In this regard, the leachability of trace elements from lignite, biomass, and blends cocombustion ashes was investigated by using the Toxicity Characteristic Leaching Procedure (TCLP) of the US Environmental Protection Agency (US EPA). In this work, the toxicity of the aqueous leachates and the concentrations of the metals obtained from the leaching procedure were measured using the Microtox test (Vibrio fischeri) and inductive coupled plasma-atomic emission spectrometer (ICP-AES), respectively. The toxic effects of most leachates on Vibrio fischeri were found to be significantly low in both 45% and 82% screening test protocols. However, the liquid sample originating from olive kernels fly ash (FA4) caused the highest toxic effect in both protocols, which can be attributed to its relatively high concentrations of As, Cd, Co, Cu, Mn, Ni, and Zn. Copyright 2006 Wiley Periodicals, Inc.

Effect of some herbicides on the toxicity of certain molluscacides against Biomphalaria alexandrina snails.

PubMed

el-Fiki, S A; Mohamed, A M

1978-01-01

Studies dealing with the effect of some herbicides on the molluscicidal action of certain molluscicides against B. alexandrina have been carried out. In the first part of the study the toxicity of 3 molluscicides (Copper sulphate, Niclosamide and Frescon) and 3 herbicides (Gramaxone, Preforan and Treflan) was tested individually. Results indicated that the molluscicides were more potent than the herbicides. In the second part, snails were exposed for 24 hr to one of the tested herbicides using LC0 or (Sub. lethal conc) then the toxicity of molluscicides was determined among the same snails. Data indicated that pre-exposure to herbicides caused a synergistic action with copper sulphate, while with Niclosamide and Frescon marked antagonistic effect was observed. In the third part molluscicides and herbicides were mixed in different ratios (1:2, 1:1 and 2:1) and the toxicity of the mixtures was tested. A synergistic effect was observed in the case of copper sulphate plus various herbicides especially with Treflan at 1:2 ratio. With Niclosamide and Frescon slight antagonistic effect was detected.

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.

Protective effect of vitamins e and C on endosulfan-induced reproductive toxicity in male rats.

PubMed

Takhshid, Mohammad Ali; Tavasuli, Ali Reza; Heidary, Yazdan; Keshavarz, Mojtaba; Kargar, Hussain

2012-09-01

The role of oxidative stress in endosulfan-induced reproductive toxicity has been implicated. This study was performed to evaluate the possible protective effect of vitamins E and C, against endosulfan-induced reproductive toxicity in rats. Fifty adult male Sprague-Dawley rats were randomly divided into five groups (n=10 each). The groups included a control receiving vehicle, a group treated with endosulfan (10 mg/kg/day) alone, and three endosulfan-treated group receiving vitamin C (20 mg/kg/day), vitamin E (200 mg/kg/day), or vitamine C+vitamin E at the same doses. After 10 days of treatment, sperm parameters, plasma lactate dehydrogenase (LDH), plasma testosterone and malondialdehyde (MDA) levels in the testis were determined. Oral administration of endosulfan caused a reduction in the sperm motility, viability, daily sperm production (DSP) and increased the number of sperm with abnormal chromatin condensation. Endosulfan administration increased testis MDA and plasma LDH. Supplementation of vitamin C and vitamin E to endosulfan-treated rats reduced the toxic effect of endosulfan on sperm parameters and lipid peroxidation in the testis. Vitamin E was more protective than vitamin C in reducing the adverse effects of the endosulfan. The findings data suggest that administration of vitamins C and E ameliorated the endosulfan-induced oxidative stress and sperm toxicity in rat. The effect of vitamin E in preventing endosulfan-induced sperm toxicity was superior to that of vitamin C.

Identification of Chemical Toxicity Using Ontology Information of Chemicals.

PubMed

Jiang, Zhanpeng; Xu, Rui; Dong, Changchun

2015-01-01

With the advance of the combinatorial chemistry, a large number of synthetic compounds have surged. However, we have limited knowledge about them. On the other hand, the speed of designing new drugs is very slow. One of the key causes is the unacceptable toxicities of chemicals. If one can correctly identify the toxicity of chemicals, the unsuitable chemicals can be discarded in early stage, thereby accelerating the study of new drugs and reducing the R&D costs. In this study, a new prediction method was built for identification of chemical toxicities, which was based on ontology information of chemicals. By comparing to a previous method, our method is quite effective. We hope that the proposed method may give new insights to study chemical toxicity and other attributes of chemicals.

Effects-Directed Analysis of Dissolved Organic Compounds in Oil Sands Process-Affected Water.

PubMed

Morandi, Garrett D; Wiseman, Steve B; Pereira, Alberto; Mankidy, Rishikesh; Gault, Ian G M; Martin, Jonathan W; Giesy, John P

2015-10-20

Acute toxicity of oil sands process-affected water (OSPW) is caused by its complex mixture of bitumen-derived organics, but the specific chemical classes that are most toxic have not been demonstrated. Here, effects-directed analysis was used to determine the most acutely toxic chemical classes in OSPW collected from the world's first oil sands end-pit lake. Three sequential rounds of fractionation, chemical analysis (ultrahigh resolution mass spectrometry), and acute toxicity testing (96 h fathead minnow embryo lethality and 15 min Microtox bioassay) were conducted. Following primary fractionation, toxicity was primarily attributable to the neutral extractable fraction (F1-NE), containing 27% of original organics mass. In secondary fractionation, F1-NE was subfractionated by alkaline water washing, and toxicity was primarily isolated to the ionizable fraction (F2-NE2), containing 18.5% of the original organic mass. In the final round, chromatographic subfractionation of F2-NE2 resulted in two toxic fractions, with the most potent (F3-NE2a, 11% of original organic mass) containing predominantly naphthenic acids (O2(-)). The less-toxic fraction (F3-NE2b, 8% of original organic mass) contained predominantly nonacid species (O(+), O2(+), SO(+), NO(+)). Evidence supports naphthenic acids as among the most acutely toxic chemical classes in OSPW, but nonacidic species also contribute to acute toxicity of OSPW.

The galactose-induced decrease in phosphate levels leads to toxicity in yeast models of galactosemia.

PubMed

Machado, Caio M; De-Souza, Evandro A; De-Queiroz, Ana Luiza F V; Pimentel, Felipe S A; Silva, Guilherme F S; Gomes, Fabio M; Montero-Lomelí, Mónica; Masuda, Claudio A

2017-06-01

Classic galactosemia is an inborn error of metabolism caused by deleterious mutations in the GALT gene. A number of evidences indicate that the galactose-1-phosphate accumulation observed in patient cells is a cause of toxicity in this disease. Nevertheless, the consequent molecular events caused by the galactose-1-phosphate accumulation remain elusive. Here we show that intracellular inorganic phosphate levels decreased when yeast models of classic galactosemia were exposed to galactose. The decrease in phosphate levels is probably due to the trapping of phosphate in the accumulated galactose-1-phosphate since the deletion of the galactokinase encoding gene GAL1 suppressed this phenotype. Galactose-induced phosphate depletion caused an increase in glycogen content, an expected result since glycogen breakdown by the enzyme glycogen phosphorylase is dependent on inorganic phosphate. Accordingly, an increase in intracellular phosphate levels suppressed the galactose effect on glycogen content and conferred galactose tolerance to yeast models of galactosemia. These results support the hypothesis that the galactose-induced decrease in phosphate levels leads to toxicity in galactosemia and opens new possibilities for the development of better treatments for this disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Boron Toxicity Causes Multiple Effects on Malus domestica Pollen Tube Growth.

PubMed

Fang, Kefeng; Zhang, Weiwei; Xing, Yu; Zhang, Qing; Yang, Liu; Cao, Qingqin; Qin, Ling

2016-01-01

Boron is an important micronutrient for plants. However, boron is also toxic to cells at high concentrations, although the mechanism of this toxicity is not known. This study aimed to evaluate the effect of boron toxicity on Malus domestica pollen tube growth and its possible regulatory pathway. Our results showed that a high concentration of boron inhibited pollen germination and tube growth and led to the morphological abnormality of pollen tubes. Fluorescent labeling coupled with a scanning ion-selective electrode technique detected that boron toxicity could decrease [Ca(2+)]c and induce the disappearance of the [Ca(2+)]c gradient, which are critical for pollen tube polar growth. Actin filaments were therefore altered by boron toxicity. Immuno-localization and fluorescence labeling, together with fourier-transform infrared analysis, suggested that boron toxicity influenced the accumulation and distribution of callose, de-esterified pectins, esterified pectins, and arabinogalactan proteins in pollen tubes. All of the above results provide new insights into the regulatory role of boron in pollen tube development. In summary, boron likely plays a structural and regulatory role in relation to [Ca(2+)]c, actin cytoskeleton and cell wall components and thus regulates Malus domestica pollen germination and tube polar growth.

Boron Toxicity Causes Multiple Effects on Malus domestica Pollen Tube Growth

PubMed Central

Fang, Kefeng; Zhang, Weiwei; Xing, Yu; Zhang, Qing; Yang, Liu; Cao, Qingqin; Qin, Ling

2016-01-01

Boron is an important micronutrient for plants. However, boron is also toxic to cells at high concentrations, although the mechanism of this toxicity is not known. This study aimed to evaluate the effect of boron toxicity on Malus domestica pollen tube growth and its possible regulatory pathway. Our results showed that a high concentration of boron inhibited pollen germination and tube growth and led to the morphological abnormality of pollen tubes. Fluorescent labeling coupled with a scanning ion-selective electrode technique detected that boron toxicity could decrease [Ca2+]c and induce the disappearance of the [Ca2+]c gradient, which are critical for pollen tube polar growth. Actin filaments were therefore altered by boron toxicity. Immuno-localization and fluorescence labeling, together with fourier-transform infrared analysis, suggested that boron toxicity influenced the accumulation and distribution of callose, de-esterified pectins, esterified pectins, and arabinogalactan proteins in pollen tubes. All of the above results provide new insights into the regulatory role of boron in pollen tube development. In summary, boron likely plays a structural and regulatory role in relation to [Ca2+]c, actin cytoskeleton and cell wall components and thus regulates Malus domestica pollen germination and tube polar growth. PMID:26955377

Determination of toxic metals in drinking water sources in the Chief Albert Luthuli Local Municipality in Mpumalanga, South Africa

NASA Astrophysics Data System (ADS)

Nthunya, Lebea N.; Masheane, Monaheng L.; Malinga, Soraya P.; Nxumalo, Edward N.; Mamba, Bhekie B.; Mhlanga, Sabelo D.

2017-08-01

This study was conducted to determine the presence and levels of toxic metals on selected water sources in a rural community in Lochiel, South Africa. Collection of water samples from identified drinking water sources (open wells, community tanks, water treatment works and boreholes) was done in all seasons of the year (winter, spring, summer and autumn) between 2014 and 2015. The concentrations of identified toxic metals (cobalt, chromium, copper, lead, zinc, manganese and iron) were measured using ICP-OES. Some water sources were found to contain concentrations of toxic metals at levels slightly higher than USEPA, WHO and SANS241 set limits (e.g. manganese and cobalt), while others were found to be within the acceptable limits. This suggested that the residents residing in locations that have water sources containing toxic metals at the concentrations above the set limits are at risk and susceptible to suffer diseases caused by these toxic metals. The side effects of the metals may not be acute; however prolonged exposure to the toxic metals may result in detrimental effects since they are known to bioaccumulate in the body.

Toxicity assessment of industrial chemicals and airborne contaminants: transition from in vivo to in vitro test methods: a review.

PubMed

Bakand, S; Winder, C; Khalil, C; Hayes, A

2005-12-01

Exposure to occupational and environmental contaminants is a major contributor to human health problems. Inhalation of gases, vapors, aerosols, and mixtures of these can cause a wide range of adverse health effects, ranging from simple irritation to systemic diseases. Despite significant achievements in the risk assessment of chemicals, the toxicological database, particularly for industrial chemicals, remains limited. Considering there are approximately 80,000 chemicals in commerce, and an extremely large number of chemical mixtures, in vivo testing of this large number is unachievable from both economical and practical perspectives. While in vitro methods are capable of rapidly providing toxicity information, regulatory agencies in general are still cautious about the replacement of whole-animal methods with new in vitro techniques. Although studying the toxic effects of inhaled chemicals is a complex subject, recent studies demonstrate that in vitro methods may have significant potential for assessing the toxicity of airborne contaminants. In this review, current toxicity test methods for risk evaluation of industrial chemicals and airborne contaminants are presented. To evaluate the potential applications of in vitro methods for studying respiratory toxicity, more recent models developed for toxicity testing of airborne contaminants are discussed.

Sublethal effects of imidacloprid on targeting muscle and ribosomal protein related genes in the honey bee Apis mellifera L.

PubMed

Wu, Yan-Yan; Luo, Qi-Hua; Hou, Chun-Sheng; Wang, Qiang; Dai, Ping-Li; Gao, Jing; Liu, Yong-Jun; Diao, Qing-Yun

2017-11-21

A sublethal concentration of imidacloprid can cause chronic toxicity in bees and can impact the behavior of honey bees. The nectar- and water-collecting, and climbing abilities of bees are crucial to the survival of the bees and the execution of responsibilities in bee colonies. Besides behavioral impact, data on the molecular mechanisms underlying the toxicity of imidacloprid, especially by the way of RNA-seq at the transcriptomic level, are limited. We treated Apis mellifera L. with sublethal concentrations of imidacloprid (0.1, 1 and 10 ppb) and determined the effect on behaviors and the transcriptomic changes. The sublethal concentrations of imidacloprid had a limited impact on the survival and syrup consumption of bees, but caused a significant increase in water consumption. Moreover, the climbing ability was significantly impaired by 10 ppb imidacloprid at 8 d. In the RNA-seq analysis, gene ontology (GO) term enrichment indicated a significant down-regulation of muscle-related genes, which might contribute to the impairment in climbing ability of bees. The enriched GO terms were attributed to the up-regulated ribosomal protein genes. Considering the ribosomal and extra-ribosomal functions of the ribosomal proteins, we hypothesized that imidacloprid also causes cell dysfunction. Our findings further enhance the understanding of imidacloprid sublethal toxicity.

The Simplest Flowchart Stating the Mechanisms for Organic Xenobiotics-induced Toxicity: Can it Possibly be Accepted as a "Central Dogma" for Toxic Mechanisms?

PubMed

Park, Yeong-Chul; Lee, Sundong; Cho, Myung-Haing

2014-09-01

Xenobiotics causing a variety of toxicity in biological systems could be classified as two types, inorganic and organic chemicals. It is estimated that the organic xenobiotics are responsible for approximately 80~90% of chemical-induced toxicity in human population. In the class for toxicology, we have encountered some difficulties in explaining the mechanisms of toxicity caused especially by organic chemicals. Here, a simple flowchart was introduced for explaining the mechanism of toxicity caused by organic xenobiotics, as the central dogma of molecular biology. This flowchart, referred to as a central dogma, was described based on a view of various aspects as follows: direct-acting chemicals vs. indirect-acting chemicals, cytochrome P450-dependent vs. cytochrome P450-independent biotransformation, reactive intermediates, reactivation, toxicokinetics vs. toxicodynamics, and reversibility vs. irreversibility. Thus, the primary objective of this flowchart is to help better understanding of the organic xenobiotics-induced toxic mechanisms, providing a major pathway for toxicity occurring in biological systems.

Dissolved Solids as HD Bioeffluent Toxicants.

DTIC Science & Technology

1998-12-01

12 The question still remains about whether the toxicity of the SBR effluent was caused by either the animals’ inability to osmoregulate in a high...the dissolved solids. The inability of freshwater organisms to osmoregulate in such high saline environments caused toxicity. Freshwater organisms are

Inorganic arsenic causes fatty liver and interacts with ethanol to cause alcoholic liver disease in zebrafish.

PubMed

Bambino, Kathryn; Zhang, Chi; Austin, Christine; Amarasiriwardena, Chitra; Arora, Manish; Chu, Jaime; Sadler, Kirsten C

2018-02-26

The rapid increase in fatty liver disease (FLD) incidence is attributed largely to genetic and lifestyle factors; however, environmental toxicants are a frequently overlooked factor that can modify the effects of more common causes of FLD. Chronic exposure to inorganic arsenic (iAs) is associated with liver disease in humans and animal models, but neither the mechanism of action nor the combinatorial interaction with other disease-causing factors has been fully investigated. Here, we examined the contribution of iAs to FLD using zebrafish and tested the interaction with ethanol to cause alcoholic liver disease (ALD). We report that zebrafish exposed to iAs throughout development developed specific phenotypes beginning at 4 days post-fertilization (dpf), including the development of FLD in over 50% of larvae by 5 dpf. Comparative transcriptomic analysis of livers from larvae exposed to either iAs or ethanol revealed the oxidative stress response and the unfolded protein response (UPR) caused by endoplasmic reticulum (ER) stress as common pathways in both these models of FLD, suggesting that they target similar cellular processes. This was confirmed by our finding that arsenic is synthetically lethal with both ethanol and a well-characterized ER-stress-inducing agent (tunicamycin), suggesting that these exposures work together through UPR activation to cause iAs toxicity. Most significantly, combined exposure to sub-toxic concentrations of iAs and ethanol potentiated the expression of UPR-associated genes, cooperated to induce FLD, reduced the expression of as3mt , which encodes an arsenic-metabolizing enzyme, and significantly increased the concentration of iAs in the liver. This demonstrates that iAs exposure is sufficient to cause FLD and that low doses of iAs can potentiate the effects of ethanol to cause liver disease.This article has an associated First Person interview with the first author of the paper. © 2018. Published by The Company of Biologists Ltd.

Inorganic arsenic causes fatty liver and interacts with ethanol to cause alcoholic liver disease in zebrafish

PubMed Central

Zhang, Chi; Austin, Christine; Amarasiriwardena, Chitra; Arora, Manish

2018-01-01

ABSTRACT The rapid increase in fatty liver disease (FLD) incidence is attributed largely to genetic and lifestyle factors; however, environmental toxicants are a frequently overlooked factor that can modify the effects of more common causes of FLD. Chronic exposure to inorganic arsenic (iAs) is associated with liver disease in humans and animal models, but neither the mechanism of action nor the combinatorial interaction with other disease-causing factors has been fully investigated. Here, we examined the contribution of iAs to FLD using zebrafish and tested the interaction with ethanol to cause alcoholic liver disease (ALD). We report that zebrafish exposed to iAs throughout development developed specific phenotypes beginning at 4 days post-fertilization (dpf), including the development of FLD in over 50% of larvae by 5 dpf. Comparative transcriptomic analysis of livers from larvae exposed to either iAs or ethanol revealed the oxidative stress response and the unfolded protein response (UPR) caused by endoplasmic reticulum (ER) stress as common pathways in both these models of FLD, suggesting that they target similar cellular processes. This was confirmed by our finding that arsenic is synthetically lethal with both ethanol and a well-characterized ER-stress-inducing agent (tunicamycin), suggesting that these exposures work together through UPR activation to cause iAs toxicity. Most significantly, combined exposure to sub-toxic concentrations of iAs and ethanol potentiated the expression of UPR-associated genes, cooperated to induce FLD, reduced the expression of as3mt, which encodes an arsenic-metabolizing enzyme, and significantly increased the concentration of iAs in the liver. This demonstrates that iAs exposure is sufficient to cause FLD and that low doses of iAs can potentiate the effects of ethanol to cause liver disease. This article has an associated First Person interview with the first author of the paper. PMID:29361514

Evidence for Tissue Toxicity in BALB/c Exposed to a Long-Term Treatment with Oxiranes Compared to Meglumine Antimoniate

PubMed Central

Oliveira, Luiz Filipe Gonçalves; Souza-Silva, Franklin; Cysne-Finkelstein, Léa; Rabelo, Kíssila; Amorim, Juliana Fernandes; Azevedo, Adriana de Souza; Bourguignon, Saulo Cabral; Ferreira, Vitor Francisco; Paes, Marciano Viana

2017-01-01

Leishmaniasis remains a serious public health problem in developing countries without effective control, whether by vaccination or chemotherapy. Part of the failure of leishmaniasis control is due to the lack of new less toxic and more effective drugs able to eliminate both the lesions and the parasite. Oxiranes derived from naphthoquinones now being assayed are promising drugs for the treatment of this group of diseases. The predicted pharmacokinetic properties and toxicological profiles of epoxy-α-lapachone and epoxymethoxy-lawsone have now been compared to those of meglumine antimoniate, and histological changes induced by these drugs in noninfected BALB/c mice tissues are described. Effects of these compounds on liver, kidney, lung, heart, and cerebral tissues of healthy mice were examined. The data presented show that both these oxiranes and meglumine antimoniate induce changes in all BALB/c mice tissues, with the lung, heart, and brain being the most affected. Epoxymethoxy-lawsone was the most toxic to lung tissue, while most severe damage was caused in the heart by epoxy-α-lapachone. Meglumine antimoniate caused mild-to-moderate changes in heart and lung tissues. PMID:28798938

Behavioral effects of ketamine and toxic interactions with psychostimulants

PubMed Central

Hayase, Tamaki; Yamamoto, Yoshiko; Yamamoto, Keiichi

2006-01-01

Background The anesthetic drug ketamine (KT) has been reported to be an abused drug and fatal cases have been observed in polydrug users. In the present study, considering the possibility of KT-enhanced toxic effects of other drugs, and KT-induced promotion of an overdose without making the subject aware of the danger due to the attenuation of several painful subjective symptoms, the intraperitoneal (i.p.) KT-induced alterations in behaviors and toxic interactions with popular co-abused drugs, the psychostimulants cocaine (COC) and methamphetamine (MA), were examined in ICR mice. Results A single dose of KT caused hyperlocomotion in a low (30 mg/kg, i.p.) dose group, and hypolocomotion followed by hyperlocomotion in a high (100 mg/kg, i.p.) dose group. However, no behavioral alterations derived from enhanced stress-related depression or anxiety were observed in the forced swimming or the elevated plus-maze test. A single non-fatal dose of COC (30 mg/kg, i.p.) or MA (4 mg/kg, i.p.) caused hyperlocomotion, stress-related depression in swimming behaviors in the forced swimming test, and anxiety-related behavioral changes (preference for closed arms) in the elevated plus-maze test. For the COC (30 mg/kg) or MA (4 mg/kg) groups of mice simultaneously co-treated with KT, the psychostimulant-induced hyperlocomotion was suppressed by the high dose KT, and the psychostimulant-induced behavioral alterations in the above tests were reversed by both low and high doses of KT. For the toxic dose COC (70 mg/kg, i.p.)- or MA (15 mg/kg, i.p.)-only group, mortality and severe seizures were observed in some animals. In the toxic dose psychostimulant-KT groups, KT attenuated the severity of seizures dose-dependently. Nevertheless, the mortality rate was significantly increased by co-treatment with the high dose KT. Conclusion Our results demonstrated that, in spite of the absence of stress-related depressive and anxiety-related behavioral alterations following a single dose of KT treatment, and in spite of the KT-induced anticonvulsant effects and attenuation of stress- and anxiety-related behaviors caused by COC or MA, the lethal effects of these psychostimulants were increased by KT. PMID:16542420

Treatment of local-anesthetic toxicity with lipid emulsion therapy.

PubMed

Burch, Melissa S; McAllister, Russell K; Meyer, Tricia A

2011-01-15

The use of lipid emulsion to treat local-anesthetic toxicity is discussed. Systemic toxicity from local anesthetics is a rare but potentially fatal complication of regional anesthesia. There is increasing evidence that lipid emulsion may be an effective treatment to reverse the cardiac and neurologic effects of local-anesthetic toxicity. A literature search identified seven case reports of local-anesthetic toxicity in which lipid emulsion was used. Lipid emulsion was found to be successful in the treatment of local-anesthetic toxicity associated with various regional anesthetic techniques and multiple local anesthetics. The majority of patients in the case reports reviewed were unresponsive to initial management of local-anesthetic toxicity with standard resuscitative measures, but all recovered completely after receiving lipid emulsion therapy. The initial dose of lipid emulsion administered varied among the case reports, as well as whether a lipid emulsion infusion was started and at what point during resuscitation. Based on the case reports reviewed, an initial bolus dose of 1.5 mL/kg followed by an infusion of 10 mL/min as soon as local-anesthetic toxicity is suspected seems most beneficial. The pharmacokinetics of lipid emulsion therapy in the treatment of local-anesthetic toxicity has not been fully elucidated but likely involves increasing metabolism, distribution, or partitioning of the local anesthetic away from receptors into lipid within tissues. Lipid emulsion has been reported useful in the treatment of systemic toxicity caused by local anesthetics. The mechanism of effect is unclear, and evidence for the benefit of lipid therapy in humans is from case reports only.

Glycyl-alanyl-histidine protects PC12 cells against hydrogen peroxide toxicity.

PubMed

Shimura, Hideki; Tanaka, Ryota; Shimada, Yoshiaki; Yamashiro, Kazuo; Hattori, Nobutaka; Urabe, Takao

2017-11-22

Peptides with cytoprotective functions, including antioxidants and anti-infectives, could be useful therapeutics. Carnosine, β-alanine-histidine, is a dipeptide with anti-oxidant properties. Tripeptides of Ala-His-Lys, Pro-His-His, or Tyr-His-Tyr are also of interest in this respect. We synthesized several histidine-containing peptides including glycine or alanine, and tested their cytoprotective effects on hydrogen peroxide toxicity for PC12 cells. Of all these peptides (Gly-His-His, Ala-His-His, Ala-His-Ala, Ala-Ala-His, Ala-Gly-His, Gly-Ala-His (GAH), Ala-His-Gly, His-Ala-Gly, His-His-His, Gly-His-Ala, and Gly-Gly-His), GAH was found to have the strongest cytoprotective activity. GAH decreased lactate dehydrogenase (LDH) leakage, apoptosis, morphological changes, and nuclear membrane permeability changes against hydrogen peroxide toxicity in PC12 cells. The cytoprotective activity of GAH was superior to that of carnosine against hydrogen peroxide toxicity in PC12 cells. GAH also protected PC12 cells against damage caused by actinomycin D and staurosporine. Additionally, it was found that GAH also protected SH-SY5Y and Jurkat cells from damage caused by hydrogen peroxide, as assessed by LDH leakage. Thus, a novel tripeptide, GAH, has been identified as having broad cytoprotective effects against hydrogen peroxide-induced cell damage.

Boron Toxicity Reduces Water Transport from Root to Shoot in Arabidopsis Plants. Evidence for a Reduced Transpiration Rate and Expression of Major PIP Aquaporin Genes.

PubMed

Macho-Rivero, Miguel A; Herrera-Rodríguez, M Begoña; Brejcha, Ramona; Schäffner, Anton R; Tanaka, Nobuhiro; Fujiwara, Toru; González-Fontes, Agustín; Camacho-Cristóbal, Juan J

2018-04-01

Toxic boron (B) concentrations cause impairments in several plant metabolic and physiological processes. Recently we reported that B toxicity led to a decrease in the transpiration rate of Arabidopsis plants in an ABA-dependent process within 24 h, which could indicate the occurrence of an adjustment of whole-plant water relations in response to this stress. Since plasma membrane intrinsic protein (PIP) aquaporins are key components influencing the water balance of plants because of their involvement in root water uptake and tissue hydraulic conductance, the aim of the present work was to study the effects of B toxicity on these important parameters affecting plant water status over a longer period of time. For this purpose, transpiration rate, water transport to the shoot and transcript levels of genes encoding four major PIP aquaporins were measured in Arabidopsis plants treated or not with a toxic B concentration. Our results indicate that, during the first 24 h of B toxicity, increased shoot ABA content would play a key role in reducing stomatal conductance, transpiration rate and, consequently, the water transport to the shoot. These physiological responses to B toxicity were maintained for up to 48 h of B toxicity despite shoot ABA content returning to control levels. In addition, B toxicity also caused the down-regulation of several genes encoding root and shoot aquaporins, which could reduce the cell to cell movement of water in plant tissues and, consequently, the water flux to shoot. All these changes in the water balance of plants under B toxicity could be a mechanism to prevent excess B accumulation in plant tissues.

Sub-lethal and lethal toxicities of elevated CO2 on embryonic, juvenile, and adult stages of marine medaka Oryzias melastigma.

PubMed

Lee, Changkeun; Kwon, Bong-Oh; Hong, Seongjin; Noh, Junsung; Lee, Junghyun; Ryu, Jongseong; Kang, Seong-Gil; Khim, Jong Seong

2018-06-06

The potential leakage from marine CO 2 storage sites is of increasing concern, but few studies have evaluated the probable adverse effects on marine organisms. Fish, one of the top predators in marine environments, should be an essential representative species used for water column toxicity testing in response to waterborne CO 2 exposure. In the present study, we conducted fish life cycle toxicity tests to fully elucidate CO 2 toxicity mechanism effects. We tested sub-lethal and lethal toxicities of elevated CO 2 concentrations on marine medaka (Oryzias melastigma) at different developmental stages. At each developmental stage, the test species was exposed to varying concentrations of gaseous CO 2 (control air, 5%, 10%, 20%, and 30%), with 96 h of exposure at 0-4 d (early stage), 4-8 d (middle stage), and 8-12 d (late stage). Sub-lethal and lethal effects, including early developmental delays, cardiac edema, tail abnormalities, abnormal pigmentation, and mortality were monitored daily during the 14 d exposure period. At the embryonic stage, significant sub-lethal and lethal effects were observed at pH < 6.30. Hypercapnia can cause long-term and/or delayed developmental embryonic problems, even after transfer back to clean seawater. At fish juvenile and adult stages, significant mortality was observed at pH < 5.70, indicating elevated CO 2 exposure might cause various adverse effects, even during short-term exposure periods. It should be noted the early embryonic stage was found more sensitive to CO 2 exposure than other developmental stages of the fish life cycle. Overall, the present study provided baseline information for potential adverse effects of high CO 2 concentration exposure on fish developmental processes at different life cycle stages in marine ecosystems. Copyright © 2018 Elsevier Ltd. All rights reserved.

Toxicity of Piper aduncum (Piperaceae) Essential Oil Against Euschistus heros (F.) (Hemiptera: Pentatomidae) and Non-Effect on Egg Parasitoids.

PubMed

Turchen, L M; Piton, L P; Dall'Oglio, E L; Butnariu, A R; Pereira, M J B

2016-10-01

Plant essential oils have been recognized as significant natural resources for insecticides. Herein, we have assessed the toxicity of the essential oil of Piper aduncum (Piperaceae) against Euschistus heros (F.) (Hemiptera: Pentatomidae), a key soybean pest in Neotropical America. In addition, we have assessed its effect on the performance of egg parasitoids. The essential oil was obtained from the leaves of P. aduncum via hydrodistillation. Subsequently, bioassays of the concentration response to eggs (contact and immersion methods), nymphs, and adults (topical application) were conducted, to assess the lethal effects on the stink bug. We also evaluated the performance of parasitism and adult emergence of egg parasitoids, when the host eggs were treated with essential oil. In the egg bioassay, both exposure methods were efficient for unviable eggs (immersion LC 50  = 15.64 mg mL -1 ; contact LC 50  = 21.29 mg mL -1 ), with the highlight on the immersion method. The bioassay with nymphs indicated a higher toxicity of essential oil, with lower concentrations (LC 50  = 11.37 mg mL -1 ) being required to cause the death of insects. For adults, a reduction in survival of insects was observed, and consequently, there was a reduction in the number of individuals in the next generation. Although the essential oil was toxic to E. heros, it exhibited lower toxicity for egg parasitoids, as there was no effect on parasitism and the emergence of wasps. We discuss likely explanations for such selectivity. In summary, we found that the essential oil was promising for the control of E. heros, because it caused deleterious effects at all development stages of the stink bug and had no effect on parasitism and emergence of the egg parasitoids, which suggested compatibility with biological control.

Effects of titanium dioxide nanoparticles derived from consumer products on the marine diatom Thalassiosira pseudonana.

PubMed

Galletti, Andrea; Seo, Seokju; Joo, Sung Hee; Su, Chunming; Blackwelder, Pat

2016-10-01

Increased manufacture of TiO 2 nanoproducts has caused concern about the potential toxicity of these products to the environment and in public health. Identification and confirmation of the presence of TiO 2 nanoparticles derived from consumer products as opposed to industrial TiO 2 NPs warrant examination in exploring the significance of their release and resultant impacts on the environment. To this end, we examined the significance of the release of these particles and their toxic effect on the marine diatom algae Thalassiosira pseudonana. Our results indicate that nano-TiO 2 sunscreen and toothpaste exhibit more toxicity in comparison to industrial TiO 2 and inhibited the growth of the marine diatom T. pseudonana. This inhibition was proportional to the exposure time and concentrations of nano-TiO 2 . Our findings indicate a significant effect, and therefore, further research is warranted in evaluation and assessment of the toxicity of modified nano-TiO 2 derived from consumer products and their physicochemical properties.

Effects of titanium dioxide nanoparticles derived from ...

EPA Pesticide Factsheets

Increased manufacture of TiO2 nano-products has caused concern about the potential toxicity of these products to the environment and in public health. Identification and confirmation of the presence of TiO2 nanoparticles derived from consumer products as opposed to industrial TiO2 NPs warrants examination in exploring the significance of their release and resultant impacts on the environment. To this end we examined the significance of the release of these particles and their toxic effect on the marine diatom algae Thalassiosira pseudonana. Our results indicate that nano-TiO2 sunscreen and toothpaste exhibit more toxicity in comparison to industrial TiO2, and inhibited the growth of the marine diatom Thalassiosira pseudonana. This inhibition was proportional to the exposure time and concentrations of nano-TiO2. Our findings indicate a significant effect, and therefore further research is warranted in evaluation and assessment of the toxicity of modified nano-TiO2 derived from consumer products and their physicochemical properties. Submit to journal Environmental Science and Pollution Research.

Inhibitory effect of selenium against Penicillium expansum and its possible mechanisms of action

USDA-ARS?s Scientific Manuscript database

Penicillium expansum is a widely spread fungal pathogen that causes blue mold rot in a variety of fruits. This pathogen not only induces blue mold rot but also produces patulin in affected apple fruit, a secondary metabolite that is toxic to humans and animals. Currently, diseases caused by P. expan...

Temperature preference as an indicator of the chronic toxicity of cupric ions to Mozambique Tilapia

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

Welch, T.J.; Stauffer, J.R. Jr.; Morgan, R.P. II

1989-11-01

Evaluation of the effects of environmental contaminants on aquatic communities has focused primarily on acute bioassays. These bioassays provide rapid and reproducible concentration response curves based on death as an endpoint. In recent years, however, emphasis has shifted towards monitoring sublethal effects of toxicants. Temperature is an easily quantifiable parameter influencing both the behavior and survival of fishes. As poikilotherms, fish use behavioral responses to help regulate body temperature. Fish thermoregulatory behavior may be altered by various toxic substances. Some researchers found that a 24 hr exposure of sublethal concentrations of copper caused a significant decrease in preferred temperature ofmore » fathead minnows (Pimephales promelas), although the results were confounded due to variations in copper concentrations. In this study, the authors examined the feasibility of using acute temperature preference tests to assess the chronic toxicity of low concentrations of free cupric ions to Mozambique tilapia, Oreochromis mossambicus (Peters).« less

Does lipophilicity of toxic compounds determine effects on drought tolerance of the soil collembolan Folsomia candida?

PubMed

Skovlund, Gitte; Damgaard, Christian; Bayley, Mark; Holmstrup, Martin

2006-12-01

The ability of Collembola to survive drought stress is crucial for their distribution in the terrestrial environment. Previous studies have suggested that several toxic compounds affect the drought tolerance of Folsomia candida in a synergistic manner and that these compounds have the feature in common that they elicit their toxicity by causing membrane damage. We hypothesised that the detrimental effect of toxic chemicals on drought tolerance in F. candida depends on the lipophilicity (log K(ow)) of the compound because a higher log K(ow) would mean a closer interaction with membranes. In this study the three chemicals 4-nonylphenol, pyrene and p,p'-DDE were tested. Surprisingly, 4-nonylphenol, with the lowest log K(ow), was the most potent with respect to reducing drought tolerance followed by pyrene, suggesting that interactions between drought tolerance and chemical stress do not depend on lipophilicity alone.

Thiocyanate, calcium and sulfate as causes of toxicity to Ceriodaphnia dubia in a hard rock mining effluent.

PubMed

Brix, Kevin V; Gerdes, Robert; Grosell, Martin

2010-10-01

A series of Toxicity Identification Evaluations (TIEs) to identify the cause(s) of observed toxicity to Ceriodaphnia dubia have been conducted on a hard rock mining effluent. Characteristic of hard rock mining discharges, the effluent has elevated (∼3000 mg l(-1)) total dissolved solids (TDS) composed primarily of Ca(2+) and SO(4)(2-). The effluent typically exhibits 6-12 toxic units (TUs) when tested with C. dubia. Phase I and II toxicity identification evaluations (TIEs) indicated Ca(2+) and SO(4)(2-) contributed only ∼4 TUs of toxicity, but this was likely an underestimate due to problems with simulating the supersaturated CaSO(4) concentrations in the effluent. Treatment of the effluent with BaCO(3) to precipitate Ca(2+) and SO(4)(2-) revealed that these ions contribute ∼6 TUs of the observed toxicity, but the remaining source(s) of toxicity (up to 6 TUs) remained unidentified. Subsequent investigations identified thiocyanate (SCN(-)) in the effluent at 100-150 μM. Toxicity tests reveal that C. dubia are sensitive to SCN(-) with an estimated IC25 of 8.3 μΜ for reproduction in moderately hard water suggesting between 12 and 18 TUs of toxicity in the effluent. Additional experiments demonstrated that SCN(-) toxicity is reduced in the high TDS matrix of the mining effluent. Testing of a mock effluent simulating the major ion and SCN(-) concentrations resulted in 10.4 TUs, suggesting that Ca(2+), SO(4)(2-) and SCN(-) are the three toxicants present in this effluent. This research suggests SCN(-) may be a more common cause of toxicity in mining effluents than is generally recognized. Copyright © 2010 Elsevier Inc. All rights reserved.

Mechanistic studies of the toxicity of zinc gluconate in the olfactory neuronal cell line Odora

PubMed Central

Hsieh, Heidi; Vignesh, Kavitha Subramanian; Deepe, George S.; Choubey, Divaker; Shertzer, Howard G.; Genter, Mary Beth

2016-01-01

Zinc is both an essential and potentially toxic metal. It is widely believed that oral zinc supplementation can reduce the effects of the common cold; however, there is strong clinical evidence that intranasal (IN) zinc gluconate (ZG) gel treatment for this purpose causes anosmia, or the loss of the sense of smell, in humans. Using the rat olfactory neuron cell line, Odora, we investigated the molecular mechanism by which zinc exposure exerts its toxic effects on olfactory neurons. Following treatment of Odora cells with 100 and 200 μM ZG for 0-24 h, RNA-seq and in silico analyses revealed up-regulation of pathways associated with zinc metal response, oxidative stress, and ATP production. We observed that Odora cells recovered from zinc-induced oxidative stress, but ATP depletion persisted with longer exposure to ZG. ZG exposure increased levels of NLRP3 and IL-1β protein levels in a time-dependent manner, suggesting that zinc exposure may cause an inflammasome-mediated cell death, pyroptosis, in olfactory neurons. PMID:27179668

Mechanistic studies of the toxicity of zinc gluconate in the olfactory neuronal cell line Odora.

PubMed

Hsieh, Heidi; Vignesh, Kavitha Subramanian; Deepe, George S; Choubey, Divaker; Shertzer, Howard G; Genter, Mary Beth

2016-09-01

Zinc is both an essential and potentially toxic metal. It is widely believed that oral zinc supplementation can reduce the effects of the common cold; however, there is strong clinical evidence that intranasal (IN) zinc gluconate (ZG) gel treatment for this purpose causes anosmia, or the loss of the sense of smell, in humans. Using the rat olfactory neuron cell line, Odora, we investigated the molecular mechanism by which zinc exposure exerts its toxic effects on olfactory neurons. Following treatment of Odora cells with 100 and 200μM ZG for 0-24h, RNA-seq and in silico analyses revealed up-regulation of pathways associated with zinc metal response, oxidative stress, and ATP production. We observed that Odora cells recovered from zinc-induced oxidative stress, but ATP depletion persisted with longer exposure to ZG. ZG exposure increased levels of NLRP3 and IL-1β protein levels in a time-dependent manner, suggesting that zinc exposure may cause an inflammasome-mediated cell death, pyroptosis, in olfactory neurons. Copyright © 2016 Elsevier Ltd. All rights reserved.

Selenium alleviates cadmium toxicity by preventing oxidative stress in sunflower (Helianthus annuus) seedlings.

PubMed

Saidi, Issam; Chtourou, Yacine; Djebali, Wahbi

2014-03-01

The present study investigated the possible mediatory role of selenium (Se) in protecting plants from cadmium (Cd) toxicity. The exposure of sunflower seedlings to 20μM Cd inhibited biomass production, decreased chlorophyll and carotenoid concentrations and strongly increased accumulation of Cd in both roots and shoots. Similarly, Cd enhanced hydrogen peroxides content and lipid peroxidation as indicated by malondialdehyde accumulation. Pre-soaking seeds with Se (5, 10 and 20μM) alleviated the negative effect of Cd on growth and led to a decrease in oxidative injuries caused by Cd. Furthermore, Se enhanced the activities of catalase, ascorbate peroxidase and glutathione reductase, but lowered that of superoxide dismutase and guaiacol peroxidase. As important antioxidants, ascorbate and glutathione contents in sunflower leaves exposed to Cd were significantly decreased by Se treatment. The data suggest that the beneficial effect of Se during an earlier growth period could be related to avoidance of cumulative damage upon exposure to Cd, thus reducing the negative consequences of oxidative stress caused by heavy metal toxicity. Copyright © 2013 Elsevier GmbH. All rights reserved.

Behavioural sensitivity of a key Southern Ocean species (Antarctic krill, Euphausia superba) to p,p'-DDE exposure.

PubMed

Poulsen, Anita H; Kawaguchi, So; King, Catherine K; King, Robert A; Bengtson Nash, Susan M

2012-01-01

Persistent organic pollutants (POPs) have been frequently measured throughout the Southern Ocean food web for which little information is available to assess the potential risks of POP exposure. The current study evaluated the toxicological sensitivity of a key Southern Ocean species, Antarctic krill, to aqueous exposure of p,p'-dichlorodiphenyl dichloroethylene (p,p'-DDE). Behavioural endpoints were used as indicators of sublethal toxicity. Immediate behavioural responses (partial immobility and tail flicking) most likely reflect neurotoxicity, while the p,p'-DDE body residue causing a median level of sublethal toxicity in Antarctic krill following 96h exposure (IEC50(sublethal toxicity)=3.9±0.21mmol/kg lipid weight) is comparable to those known to cause sublethal narcosis in temperate aquatic species. Critical body residues (CBRs) were more reproducible across tests than effective seawater concentrations. These findings support the concept of the CBR approach, that effective tissue residues are comparable across species and geographical ranges despite differences in environmental factors. Copyright © 2011 Elsevier Inc. All rights reserved.

Analysis of Toxic Amyloid Fibril Interactions at Natively Derived Membranes by Ellipsometry

PubMed Central

Smith, Rachel A. S.; Nabok, Aleksey; Blakeman, Ben J. F.; Xue, Wei-Feng; Abell, Benjamin; Smith, David P.

2015-01-01

There is an ongoing debate regarding the culprits of cytotoxicity associated with amyloid disorders. Although small pre-fibrillar amyloid oligomers have been implicated as the primary toxic species, the fibrillar amyloid material itself can also induce cytotoxicity. To investigate membrane disruption and cytotoxic effects associated with intact and fragmented fibrils, the novel in situ spectroscopic technique of Total Internal Reflection Ellipsometry (TIRE) was used. Fibril lipid interactions were monitored using natively derived whole cell membranes as a model of the in vivo environment. We show that fragmented fibrils have an increased ability to disrupt these natively derived membranes by causing a loss of material from the deposited surface when compared with unfragmented fibrils. This effect was corroborated by observations of membrane disruption in live cells, and by dye release assay using synthetic liposomes. Through these studies we demonstrate the use of TIRE for the analysis of protein-lipid interactions on natively derived lipid surfaces, and provide an explanation on how amyloid fibrils can cause a toxic gain of function, while entangled amyloid plaques exert minimal biological activity. PMID:26172440

Toxic effects of ethylene oxide residues on bovine embryos in vitro.

PubMed

Holyoak, G R; Wang, S; Liu, Y; Bunch, T D

1996-04-15

The potential of ethylene oxide (EtO) residues in exposed plastic tissue culture dishes to adversely affect bovine oocyte maturation, fertilization and subsequent embryonic development was monitored. In experiment 1, the effects of aeration time and aeration combined with washing of EtO-gassed culture dishes on the extent of residual toxicity were investigated. There was no cleavage in any treatment in which oocytes were matured and fertilized in dishes exposed to EtO. EtO residues caused functional degeneration of oocytes even when culture dishes were aerated for more than 12 days post EtO-exposure and repeatedly washed. In experiment 2, the residual toxicity of EtO gas on in vitro maturation (IVM), in vitro fertilization (IVF) and in vitro culture (IVC) were evaluated. Cleavage rate significantly decreased and post-cleavage development was retarded in ova maintained in dishes treated with EtO either during IVM or IVF. EtO residues may be more detrimental to spermatozoa than to oocytes which may have been the primary cause of fertilization failure during IVF.

Identifying the causes of oil sands coke leachate toxicity to aquatic invertebrates.

PubMed

Puttaswamy, Naveen; Liber, Karsten

2011-11-01

A previous study found that coke leachates (CL) collected from oil sands field sites were acutely toxic to Ceriodaphnia dubia; however, the cause of toxicity was not known. Therefore, the purpose of this study was to generate CL in the laboratory to evaluate the toxicity response of C. dubia and perform chronic toxicity identification evaluation (TIE) tests to identify the causes of CL toxicity. Coke was subjected to a 15-d batch leaching process at pH 5.5 and 9.5. Leachates were filtered on day 15 and used for chemical and toxicological characterization. The 7-d median lethal concentration (LC50) was 6.3 and 28.7% (v/v) for pH 5.5 and 9.5 CLs, respectively. Trace element characterization of the CLs showed Ni and V levels to be well above their respective 7-d LC50s for C. dubia. Addition of ethylenediaminetetraacetic acid significantly (p ≤ 0.05) improved survival and reproduction in pH 5.5 CL, but not in pH 9.5 CL. Cationic and anionic resins removed toxicity of pH 5.5 CL only. Conversely, the toxicity of pH 9.5 CL was completely removed with an anion resin alone, suggesting that the pH 9.5 CL contained metals that formed oxyanions. Toxicity reappeared when Ni and V were added back to anion resin-treated CLs. The TIE results combined with the trace element chemistry suggest that both Ni and V are the cause of toxicity in pH 5.5 CL, whereas V appears to be the primary cause of toxicity in pH 9.5 CL. Environmental monitoring and risk assessments should therefore focus on the fate and toxicity of metals, especially Ni and V, in coke-amended oil sands reclamation landscapes. Copyright © 2011 SETAC.

[Nephrotoxicity of Aristolochia manshuriensis and aristolochic acids in mice].

PubMed

Ding, Xiao-shuang; Liang, Ai-hua; Wang, Jin-hua; Xiao, Yong-qing; Wu, Zi-lun; Li, Chun-ying; Li, Li; He, Rong; Hui, Lian-qiang; Liu, Bao-yan

2005-07-01

The acute toxic effects of Aristolochia manshuriensis (GMT) and the total aristolochic acids (TA) were compared in mice with aristolochic acid A (AA) as the dose standard. The dose relationship of the renal toxicity induced by Aristolochia manshuriensis was determined. A single dose of GMT extract or TA was given intragastrically to mice at different doses. LD50 values, the blood levels of BUN, Cr and ALT were measured. A histomorphological study was also performed in livers and kidneys of mice. LD50 value of GMT extract was 4.4 g x kg(-1) which was equivalent to 40 mg x kg(-1) as calculated by the content of AA in GMT extract, and this value was comparable with LD50 obtained from TA given intragastrically in mice (equivalent to 33 mg x kg(-1) of AA for male and 37 mg x kg(-1) for female). GMT extract caused a significant increase in blood BUN and Cr and an obvious morphological change in kidney in a dose-dependent manner at doses of AA 4.5 mg x kg(-1) and above. Liver damage, characterized by both an increase in blood level of AST and histomorphological change, was observed at doses of AA 25 mg x kg(-1) and above. All changes were in proportion to the doses of AA. GMT causes both renal and liver toxicity. The dose leading to nephrotoxicity is much lower than that inducing hepatatoxicity. Aristolochic acids existed in GMT are the main toxic components to cause renal toxicity which is a crucial cause to result in death. The lethality and nephrotoxicity of GMT is in proportion to the doses of AA.

Pb Neurotoxicity: Neuropsychological Effects of Lead Toxicity

PubMed Central

Mason, Lisa H.; Harp, Jordan P.; Han, Dong Y.

2014-01-01

Neurotoxicity is a term used to describe neurophysiological changes caused by exposure to toxic agents. Such exposure can result in neurocognitive symptoms and/or psychiatric disturbances. Common toxic agents include heavy metals, drugs, organophosphates, bacterial, and animal neurotoxins. Among heavy metal exposures, lead exposure is one of the most common exposures that can lead to significant neuropsychological and functional decline in humans. In this review, neurotoxic lead exposure's pathophysiology, etiology, and epidemiology are explored. In addition, commonly associated neuropsychological difficulties in intelligence, memory, executive functioning, attention, processing speed, language, visuospatial skills, motor skills, and affect/mood are explored. PMID:24516855

Antifungal Therapy for Systemic Mycosis and the Nanobiotechnology Era: Improving Efficacy, Biodistribution and Toxicity.

PubMed

Souza, Ana C O; Amaral, Andre C

2017-01-01

Fungal diseases have been emerging as an important public health problem worldwide with the increase in host predisposition factors due to immunological dysregulations, immunosuppressive and/or anticancer therapy. Antifungal therapy for systemic mycosis is limited, most of times expensive and causes important toxic effects. Nanotechnology has become an interesting strategy to improve efficacy of traditional antifungal drugs, which allows lower toxicity, better biodistribution, and drug targeting, with promising results in vitro and in vivo . In this review, we provide a discussion about conventional antifungal and nanoantifungal therapies for systemic mycosis.

In vitro and in vivo evidence of the cytotoxic and genotoxic effects of metal ions released by orthodontic appliances: A review.

PubMed

Martín-Cameán, Ana; Jos, Ángeles; Mellado-García, Pilar; Iglesias-Linares, Alejandro; Solano, Enrique; Cameán, Ana M

2015-07-01

Intraoral fixed orthodontic appliances are frequently used in the clinical practice of dentistry. They are made from alloys containing different metals at various percentages. The use of these appliances leads to the long-term exposure of patients to these materials, and the potential toxic effects of this exposure raises concerns about patient safety. Thus, the biocompatibility (corrosion behaviour and toxicity) of these materials has to be evaluated prior to clinical use. In the present report, the most recent studies in the scientific literature examining metal ion release from orthodontic appliances and the toxic effects of these ions have been reviewed with a special focus on cytotoxicity and genotoxicity. Previous studies suggest that a case-by-case safety evaluation is required to take into account the increasing variability of materials, their composition and the manufacturing processes. Moreover, in vivo toxicity studies in regard to metal release, cytotoxicity and genotoxicity are still scarce. Therefore, in vitro and in vivo monitoring studies are needed to establish cause-effect relationships between metal ion release and biomarkers of cytotoxicity and genotoxicity. Further investigations could be performed to elucidate the toxic mechanisms involved in the observed effects with a special emphasis on oxidative damage. Copyright © 2015 Elsevier B.V. All rights reserved.

Early Life Origins of Metabolic Syndrome: The Role of Environmental Toxicants

PubMed Central

Wang, Guoying; Chen, Zhu; Bartell, Tami; Wang, Xiaobin

2014-01-01

Metabolic syndrome (MetS) affects more than 47 million people in the U.S. Even more alarming, MetS, once regarded as an “adult problem”, has become increasingly common in children. To date, most related research and intervention efforts have occurred in the adult medicine arena, with limited understanding of the root causes and lengthy latency of MetS. This review highlights new science on the early life origins of MetS, with a particular focus on exposure to two groups of environmental toxicants: endocrine disrupting chemicals (EDCs) and metals during the prenatal and early postnatal periods, and their specific effects and important differences in the development of MetS. It also summarizes available data on epigenetic effects, including the role of EDCs in the androgen/estrogen pathways. Emerging evidence supports the link between exposures to environmental toxicants during early life and the development of MetS later in life. Additional research is needed to address important research gaps in this area, including prospective birth cohort studies to delineate temporal and dose-response relationships, important differences in the effects of various environmental toxicants and their joint effects on MetS, as well as epigenetic mechanisms underlying the effects of specific toxicants such as EDCs and metals. PMID:24883264

Pre-clinical efficacy assessment of Malva sylvestris on chronic skin inflammation.

PubMed

Prudente, Arthur S; Sponchiado, Graziela; Mendes, Daniel A G B; Soley, Bruna S; Cabrini, Daniela A; Otuki, Michel F

2017-09-01

In the search for improved quality of life, the treatment of skin diseases like psoriasis (hyperproliferative disease) is valid, since it causes huge social discomfort to the patient. In this context, earlier studies showed that Malva sylvestris L. has anti-inflammatory activity demonstrated by acute animal models of skin inflammation, becoming a promising target for further studies. The present investigation aimed to verify the effect of hydroalcoholic extract of M. sylvestris (HEMS) on the chronic inflammatory and hyperproliferative response caused by multiple applications of 12-O-tetradecanoylphorbol-13-acetate (TPA) on mouse ears. Topical application of HEMS reduced oedema, leukocyte migration (mono- and polymorphonuclear cells) and keratinocyte hyperproliferation, confirmed by histology and proliferating cell nuclear antigen (PCNA) immunostaining. It was found that the anti-inflammatory effects of the extract did not involve the glucocorticoid system, and its incubation with HaCaT keratinocytes caused low toxicity and reduced cell proliferation by apoptosis. Thus, HEMS proved to be effective as an anti-psoriatic therapy, with the ability to prevent keratinocyte hyperproliferation and with low toxicity by topical application. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Effects of the fluoride on the central nervous system.

PubMed

Valdez-Jiménez, L; Soria Fregozo, C; Miranda Beltrán, M L; Gutiérrez Coronado, O; Pérez Vega, M I

2011-06-01

Fluoride (F) is a toxic and reactive element, and exposure to it passes almost unnoticed, with the consumption of tea, fish, meat, fruits, etcetera and articles of common use such as: toothpaste additives; dental gels, non-stick pans and razor blades as Teflon. It has also been used with the intention of reducing the dental cares. Fluoride can accumulate in the body, and it has been shown that continuous exposure to it causes damaging effects on body tissues, particularly the nervous system directly without any previous physical malformations. Several clinical and experimental studies have reported that the F induces changes in cerebral morphology and biochemistry that affect the neurological development of individuals as well as cognitive processes, such as learning and memory. F can be toxic by ingesting one part per million (ppm), and the effects they are not immediate, as they can take 20 years or more to become evident. The prolonged ingestion of F may cause significant damage to health and particularly to the nervous system. Therefore, it is important to be aware of this serious problem and avoid the use of toothpaste and items that contain F, particularly in children as they are more susceptible to the toxic effects of F. Copyright © 2010 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Therapeutic effects of date palm (Phoenix dactylifera L.) pollen extract on cadmium-induced testicular toxicity.

PubMed

El-Neweshy, M S; El-Maddawy, Z K; El-Sayed, Y S

2013-12-01

Cadmium (Cd) is a well-known testicular toxicant. This study was designed to explore the long-term effects of a single low dose of Cd on spermatogenesis, and testicular dysfunction and oxidative stress, and the therapeutic potential of date palm pollen extract (DPP) in averting such reproductive damage. Adult male Wistar rats received a single intraperitoneal injection of CdCl2 (0 or 1 mg kg(-1) ). Twenty-four hours later, they started receiving DPP (0 or 40 mg kg(-1) ) orally, once daily for 56 consecutive days. Cd exposure caused significant reproductive damage via reduced weight of the reproductive organs, which includes spermatological damage (decreased sperm count and motility and increased rates of sperm abnormalities), increased oxidative stress (increased malondialdehyde and decreased reduced glutathione levels), histological alterations (necrosis, inefficient to completely arrest spermatogenesis and a reduced Johnsen's score) and decreased serum testosterone level. DPP restored spermatogenesis and attenuated the toxic effects of Cd on the reproductive system to the levels observed in the control animals. These findings support the hypothesis that the testis is particularly sensitive to Cd, which can cause testicular damage and infertility. Treatment with DPP can ameliorate the deleterious effects of Cd, probably by activating testicular endocrine and antioxidant systems. © 2012 Blackwell Verlag GmbH.

Toxic Effects of Silica Nanoparticles on Zebrafish Embryos and Larvae

PubMed Central

Shi, Huiqin; Tian, Linwei; Guo, Caixia; Huang, Peili; Zhou, Xianqing; Peng, Shuangqing; Sun, Zhiwei

2013-01-01

Silica nanoparticles (SiNPs) have been widely used in biomedical and biotechnological applications. Environmental exposure to nanomaterials is inevitable as they become part of our daily life. Therefore, it is necessary to investigate the possible toxic effects of SiNPs exposure. In this study, zebrafish embryos were treated with SiNPs (25, 50, 100, 200 µg/mL) during 4–96 hours post fertilization (hpf). Mortality, hatching rate, malformation and whole-embryo cellular death were detected. We also measured the larval behavior to analyze whether SiNPs had adverse effects on larvae locomotor activity. The results showed that as the exposure dosages increasing, the hatching rate of zebrafish embryos was decreased while the mortality and cell death were increased. Exposure to SiNPs caused embryonic malformations, including pericardial edema, yolk sac edema, tail and head malformation. The larval behavior testing showed that the total swimming distance was decreased in a dose-dependent manner. The lower dose (25 and 50 µg/mL SiNPs) produced substantial hyperactivity while the higher doses (100 and 200 µg/mL SiNPs) elicited remarkably hypoactivity in dark periods. In summary, our data indicated that SiNPs caused embryonic developmental toxicity, resulted in persistent effects on larval behavior. PMID:24058598

CADDIS Volume 2. Sources, Stressors and Responses: Unspecified Toxic Chemicals

EPA Pesticide Factsheets

Intro to the unspecified toxic chemicals module, when to list toxic chemicals as a candidate cause, ways to measure toxic chemicals, simple and detailed conceptual diagrams for toxic chemicals, toxic chemicals module references and literature reviews.

HEALTH CONSEQUENCES OF DIOXIN EXPOSURE

EPA Science Inventory

Abstract TCDD is often called the most toxic man-made chemical because of its potency to cause health effects in a wide variety of vertebrates. Structurally related persistent compounds, known as 'dioxins', have the same plethora of responses. Dioxins have effects in mu...

Hyperbaric Oxygen Therapy in Treating Long-Term Gastrointestinal Adverse Effects Caused by Radiation Therapy in Patients With Pelvic Cancer

ClinicalTrials.gov

2011-07-14

Bladder Cancer; Cervical Cancer; Colorectal Cancer; Endometrial Cancer; Gastrointestinal Complications; Long-term Effects Secondary to Cancer Therapy in Adults; Ovarian Cancer; Prostate Cancer; Radiation Toxicity; Sarcoma; Testicular Germ Cell Tumor; Vaginal Cancer

Modeling the effects of chemical exposure on avian seasonal productivity: Importance of differences in breeding strategies

EPA Science Inventory

Agencies that regulate the use of chemicals are increasingly interested in understanding the magnitude of effects of those chemicals on wildlife populations. While laboratory toxicity tests provide insights into the types of effects caused by chemical exposure, they do not alway...

Effect of test concentration in the ready biodegradability test for chemical substances: Improvement of OECD test guideline 301C.

PubMed

Nabeoka, Ryosuke; Taruki, Masanori; Kayashima, Takakazu; Yoshida, Tomohiko; Kameya, Takashi

2016-01-01

In Japan, understanding the environmental persistence of chemicals is very important for risk assessment, and ready biodegradability tests are mainly conducted according to the Organisation for Economic Co-operation and Development test guideline 301C. However, the highest test concentration specified in test guideline 301C, 100 mg/L, may cause microbial toxicity and incomplete biodegradation. The authors performed test guideline 301C tests at test concentrations of 30 mg/L for 13 substances that were readily biodegradable in ready biodegradability tests but not in test guideline 301C tests. Of the 5 substances with potential to cause microbial toxicity at 100 mg/L, the percentage of biodegradation of sodium dimethyldithiocarbamate, 4-chloro-3-cresol (CC), thymol (THY), and p-tert-butyl-α-methylbenzenepropionaldehyde measured by biochemical oxygen demand (BOD) increased in the test guideline 301C test at 30 mg/L, suggesting a reduction in toxicity effects. Furthermore, CC and THY met the criteria for ready biodegradability, which are more than 60% of biodegradation by BOD and a 10-d window. Of the 8 substances with a low potential for causing microbial toxicity at 100 mg/L, the percentage of biodegradation of only 2-(diethylamino)ethanol increased in the test guideline 301C test at 30 mg/L. Employing a lower test concentration in the standard test guideline 301C test will contribute to improvement of consistency between results of a test guideline 301C test and other ready biodegradability tests. © 2015 SETAC.

Bioavailability Assessment of a Contaminated Field Sediment from Patrick Bayou, Texas, USA: Toxicity Identification Evaluation and Equilibrium Partitioning

EPA Science Inventory

Contaminated sediments are commonly found in urbanized harbors. At sufficiently high contaminant levels, sediments can cause toxicity to aquatic organisms and impair benthic communities. As a result, remediation is necessary and diagnosing the cause of sediment toxicity become...

Causes of toxicity in stormwater runoff from sawmills

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

Bailey, H.C.; Elphick, J.R.; Potter, A.

1999-07-01

Samples of stormwater runoff from nine sawmills in British Columbia, Canada, were tested for acute toxicity with juvenile rainbow trout over a 23-month period. Forty-two of the 58 samples tested exhibited toxicity. Causes of toxicity were investigated using toxicity identification evaluation techniques. Toxicity was attributed to divalent cations, particularly zinc, in 32 of the samples. The low hardness associated with most of the samples increased the potential for metal toxicity. For example, the LC50 of zinc was 14 {micro}g/L at a hardness of 5 mg/L. Toxicity in the remaining samples was largely attributed to tannins and lignins and was associatedmore » with areas of bulk log handling. No evidence was found to indicate that antisapstain chemicals applied to freshly cut wood contributed to toxicity.« less

Risks, risk assessment and risk competence in toxicology.

PubMed

Stahlmann, Ralf; Horvath, Aniko

2015-01-01

Understanding the toxic effects of xenobiotics requires sound knowledge of physiology and biochemistry. The often described lack of understanding pharmacology/toxicology is therefore primarily caused by the general absence of the necessary fundamental knowledge. Since toxic effects depend on exposure (or dosage) assessing the risks arising from toxic substances also requires quantitative reasoning. Typically public discussions nearly always neglect quantitative aspects and laypersons tend to disregard dose-effect-relationships. One of the main reasons for such disregard is the fact that exposures often occur at extremely low concentrations that can only be perceived intellectually but not by the human senses. However, thresholds in the low exposure range are often scientifically disputed. At the same time, ignorance towards known dangers is wide-spread. Thus, enhancing the risk competence of laypersons will have to be initially restricted to increasing the awareness of existing problems.

Characterization of the dinophysistoxin-2 acute oral toxicity in mice to define the Toxicity Equivalency Factor.

PubMed

Abal, Paula; Louzao, M Carmen; Cifuentes, José Manuel; Vilariño, Natalia; Rodriguez, Ines; Alfonso, Amparo; Vieytes, Mercedes R; Botana, Luis M

2017-04-01

Ingestion of shellfish with dinophysistoxin-2 (DTX2) can lead to diarrheic shellfish poisoning (DSP). The official control method of DSP toxins in seafood is the liquid chromatography-mass spectrometry analysis (LC-MS). However in order to calculate the total toxicity of shellfish, the concentration of each compound must be multiplied by individual Toxicity Equivalency Factor (TEF). Considering that TEFs caused some controversy and the scarce information about DTX2 toxicity, the aim of this study was to characterize the oral toxicity of DTX2 in mice. A 4-Level Up and Down Procedure allowed the characterization of DTX2 effects and the estimation of DTX2 oral TEF based on determination of the lethal dose 50 (LD50). DTX2 passed the gastrointestinal barrier and was detected in urine and feces. Acute toxicity symptoms include diarrhea and motionless, however anatomopathology study and ultrastructural images restricted the toxin effects to the gastrointestinal tract. Nevertheless enterocytes microvilli and tight junctions were not altered, disconnecting DTX2 diarrheic effects from paracellular epithelial permeability. This is the first report of DTX2 oral LD 50 (2262 μg/kg BW) indicating that its TEF is about 0.4. This result suggests reevaluation of the present TEFs for the DSP toxins to better determine the actual risk to seafood consumers. Copyright © 2017 Elsevier Ltd. All rights reserved.

Inhibitory effects of toxic compounds on nitrification process for cokes wastewater treatment.

PubMed

Kim, Young Mo; Park, Donghee; Lee, Dae Sung; Park, Jong Moon

2008-04-15

Cokes wastewater is one of the most toxic industrial effluents since it contains high concentrations of toxic compounds such as phenols, cyanides and thiocyanate. Although activated sludge process has been adapted to treat this wastewater, nitrification process has been occasionally upset by serious inhibitory effects of toxic compounds. In this study, therefore, we examined inhibitory effects of ammonia, thiocyanate, free cyanide, ferric cyanide, phenol and p-cresol on nitrification in an activated sludge system, and then correlated their threshold concentrations with the full-scale pre-denitrification process for treating cokes wastewater. Ammonia below 350 mg/L did not cause substrate inhibition for nitrifying bacteria. Thiocyanate above 200mg/L seemed to inhibit nitrification, but it was due to the increased loading of ammonia produced from its biodegradation. Free cyanide above 0.2mg/L seriously inhibited nitrification, but ferric cyanide below 100mg/L did not. Phenol and p-cresol significantly inhibited nitrification above 200 mg/L and 100mg/L, respectively. Meantime, activated carbon was added to reduce inhibitory effects of phenol and free cyanide.

Toxic effects of imidacloprid on adult loach (Misgurnus anguillicaudatus).

PubMed

Xia, Xiaohua; Xia, Xiaopei; Huo, Weiran; Dong, Hui; Zhang, Linxia; Chang, Zhongjie

2016-07-01

The present investigation was aimed to assess the effects of imidacloprid on the survival, genetic materials, hepatic transaminase activity and histopathology of loach (Misgurnus anguillicaudatus). The values of LC50 (24, 48, 72 and 96h) of imidacloprid were 167.7, 158.6, 147.9 and 145.8mg/L, respectively, and the safety concentration was 42.55mg/L. The erythrocyte micronuclei assays and the comet assay results showed that imidacloprid had genetic toxic effect on the loach erythrocytes. To assess the physiological and biochemical damage caused by imidacloprid, the activities of hepatic glutamic-pyruvic transaminase (GPT) and glutamic-oxalacetic transaminase (GOT) were measured and their values declined in treatment groups. Histological examination of testis revealed that imidacloprid treatment resulted in disorganized lobules and cysts structures. In the present work, we also investigated the joint toxicity of pesticides commonly used in paddy fields (imidacloprid and lambda-cyhalothrin) on M. anguillicaudatus, and confirmed that a synergistic effect existing in the binary mixtures. The results of our study provide relevant and comparable toxicity information that are useful for safety application of pesticides. Copyright © 2016. Published by Elsevier B.V.

Toxic metal(loid)-based pollutants and their possible role in autism spectrum disorder.

PubMed

Bjørklund, Geir; Skalny, Anatoly V; Rahman, Md Mostafizur; Dadar, Maryam; Yassa, Heba A; Aaseth, Jan; Chirumbolo, Salvatore; Skalnaya, Margarita G; Tinkov, Alexey A

2018-06-11

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social interaction, verbal and non-verbal communication, and stereotypic behaviors. Many studies support a significant relationship between many different environmental factors in ASD etiology. These factors include increased daily exposure to various toxic metal-based environmental pollutants, which represent a cause for concern in public health. This article reviews the most relevant toxic metals, commonly found, environmental pollutants, i.e., lead (Pb), mercury (Hg), aluminum (Al), and the metalloid arsenic (As). Additionally, it discusses how pollutants can be a possible pathogenetic cause of ASD through various mechanisms including neuroinflammation in different regions of the brain, fundamentally occurring through elevation of the proinflammatory profile of cytokines and aberrant expression of nuclear factor kappa B (NF-κB). Due to the worldwide increase in toxic environmental pollution, studies on the role of pollutants in neurodevelopmental disorders, including direct effects on the developing brain and the subjects' genetic susceptibility and polymorphism, are of utmost importance to achieve the best therapeutic approach and preventive strategies. Copyright © 2018 Elsevier Inc. All rights reserved.

Repeated dose 90-day oral toxicity test of G-7% NANA in rats: An application of new criterion for toxicity determination to test article-induced changes.

PubMed

Heo, Hye Seon; An, MinJi; Lee, Ji Sun; Kim, Hee Kyong; Park, Yeong-Chul

2018-06-01

G-7% NANA is N-acetylneuraminic acid(NANA) containing 7% sialic acid isolated from glycomacropeptide (GMP), a compound of milk. Since NANA is likely to have immunotoxicity, the need to ensure safety for long-term administration has been raised. In this study, a 90-day repeated oral dose toxicity test was performed in rats using G-7% NANA in the dosages of 0, 1250, 2500 and 5000 mg/kg/day.A toxicity determination criterion based on the significant change caused by the administration of the substancewas developed for estimating NOEL, NOAEL and LOAELapplied to this study. When analyzing the immunological markers, no significant changes were observed, even if other significant changes were observed in the high dose group. In accordance with the toxicity determination criterion developed, the NOEL in male and female has been determined as 2500 mg/kg/day, and the NOAEL in females has been determined as 5000 mg/kg/day. The toxicity determination criterion, applied for the first time in the repeated dose toxicity tests, could provide a basis for distinguishing NOEL and NOAEL more clearly; nevertheless, the toxicity determination criterion needs to be supplemented by adding differentiating adverse effects and non-adverse effects based on more experiences of the repeated dose toxicity tests. Copyright © 2018 Elsevier Inc. All rights reserved.

CADDIS Volume 2. Sources, Stressors and Responses: Unspecified Toxic Chemicals - Simple Conceptual Diagram

EPA Pesticide Factsheets

Intro to the unspecified toxic chemicals module, when to list toxic chemicals as a candidate cause, ways to measure toxic chemicals, simple and detailed conceptual diagrams for toxic chemicals, toxic chemicals module references and literature reviews.

CADDIS Volume 2. Sources, Stressors and Responses: Unspecified Toxic Chemicals - Detailed Conceptual Diagram

EPA Pesticide Factsheets

Intro to the unspecified toxic chemicals module, when to list toxic chemicals as a candidate cause, ways to measure toxic chemicals, simple and detailed conceptual diagrams for toxic chemicals, toxic chemicals module references and literature reviews.

Selenomethionine incorporation into amyloid sequences regulates fibrillogenesis and toxicity.

PubMed

Martínez, Javier; Lisa, Silvia; Sánchez, Rosa; Kowalczyk, Wioleta; Zurita, Esther; Teixidó, Meritxell; Giralt, Ernest; Andreu, David; Avila, Jesús; Gasset, María

2011-01-01

The capacity of a polypeptide chain to engage in an amyloid formation process and cause a conformational disease is contained in its sequence. Some of the sequences undergoing fibrillation contain critical methionine (Met) residues which in vivo can be synthetically substituted by selenomethionine (SeM) and alter their properties. Using peptide synthesis, biophysical techniques and cell viability determinations we have studied the effect of the substitution of methionine (Met) by selenomethionine (SeM) on the fibrillogenesis and toxic properties of Aβ40 and HuPrP(106-140). We have found that the effects display site-specificity and vary from inhibition of fibrillation and decreased toxicity ([SeM(35)]Aβ40, [SeM(129)]HuPrP(106-140) and [SeM(134)]HuPrP(106-140)), retarded assembly, modulation of polymer shape and retention of toxicity ([SeM(112)]HuPrP(106-140) to absence of effects ([SeM(109)]HuPrP(106-140)). This work provides direct evidence that the substitution of Met by SeM in proamyloid sequences has a major impact on their self-assembly and toxic properties, suggesting that the SeM pool can play a major role in dictating the allowance and efficiency of a polypeptide chain to undergo toxic polymerization.

Toxic effects of two essential oils and their constituents on the mealworm beetle, Tenebrio molitor.

PubMed

Martínez, L C; Plata-Rueda, A; Colares, H C; Campos, J M; Dos Santos, M H; Fernandes, F L; Serrão, J E; Zanuncio, J C

2017-12-14

The study identified insecticidal effects from the cinnamon and clove essential oils in Tenebrio molitor L. (Coleoptera: Tenebrionidae). The lethal concentrations (LC50 and LC90), lethal time, and repellent effect on larvae, pupae, and adults of T. molitor after exposure to six concentrations of each essential oil and toxic compounds were evaluated. The chemical composition of the cinnamon oil was also determined and primary compounds were eugenol (10.19%), trans-3-caren-2-ol (9.92%), benzyl benzoate (9.68%), caryophyllene (9.05%), eugenyl acetate (7.47%), α-phellandrene (7.18%), and α-pinene (6.92%). In clove essential oil, the primary compounds were eugenol (26.64%), caryophyllene (23.73%), caryophyllene oxide (17.74%), 2-propenoic acid (11.84%), α-humulene (10.48%), γ-cadinene (4.85%), and humulene oxide (4.69%). Cinnamon and clove essential oils were toxic to T. molitor. In toxic chemical compounds, eugenol have stronger contact toxicity in larvae, pupae, and adult than caryophyllene oxide, followed by α-pinene, α-phellandrene, and α-humulene. In general, the two essential oils were toxic and repellent to adult T. molitor. Cinnamon and clove essential oils and their compounds caused higher mortality and repellency on T. molitor and, therefore, have the potential for integrated management programs of this insect.

Birds and Dutch elm disease control

USGS Publications Warehouse

DeWitt, J.B.

1958-01-01

Brief, factual review of information on effect of DDT and other insecticides on birds. One program for control of elm disease caused 22% decrease in number of adult birds and 56% mortality of nestlings. Quail fed 3 oz. of DDT per ton of food had 16% reduction in young hatched and 500% increase in defective chicks. Quail fed same dosage during winter and breeding seasons had 30% decrease in fertile eggs and 800% increase in defective chicks. More than 90% of their chicks died in first 6 weeks although fed no insecticide. Almost equally bad results came from feeding Pheasants diets with about 1 oz. DDT per ton. Other common insecticides (chlorinated hydrocarbons) also caused lowered chick survival and higher percentages of crippled chicks. From field data we know that 2 lbs. DDT/acre can affect birds and has even worse effects on cold-blooded animals. Efforts to control elm disease have left as much as 196 lbs. DDT/acre in top 3 inches of soil. Earthworms concentrate DDT in their tissues. Thus the treated areas can be traps for birds and other animals. What can be done? 1) In control of elm disease, use minimum effective amount of insecticide; mist blowers use less than sprayers. 2) Avoid applications during migration and nesting seasons. It has been reported that adequate control can be obtained with dormant sprays and that foliar applications may not be required. Tables of this paper show effects of DDT on reproduction of Quail, relative toxicity to quail of 8 insecticides, and amounts of 7 insecticides required to cause 40% or more decrease in Quail reproduction. These comparisons demonstrate that Aldrin, Endrin, and Dieldrin are 20 to 200 times as toxic as DDT and that Heptachlor and Chlordane are only slightly less toxic than Dieldrin. Methoxychlor and Strobane are less toxic to Quail than is DDT.

A Hemorrhagic Factor (Apicidin) Produced by Toxic Fusarium Isolates from Soybean Seeds

PubMed Central

Park, Jun-Suk; Lee, Kyung-Rim; Kim, Jin-Cheol; Lim, Sun-Hee; Seo, Jeong-Ah; Lee, Yin-Won

1999-01-01

Fifty-two isolates of Fusarium species were obtained from soybean seeds from various parts of Korea and identified as Fusarium oxysporum, F. moniliforme, F. semitectum, F. solani, F. graminearum, or F. lateritium. These isolates were grown on autoclaved wheat grains and examined for toxicity in a rat-feeding test. Nine cultures were toxic to rats. One of these, a culture of Fusarium sp. strain KCTC 16677, produced apicidin, an antiprotozoal agent that caused toxic effects in rats (including body weight loss; hemorrhage in the stomach, intestines, and bladder; and finally death) when rats were fed diets supplemented with 0.05 and 0.1% apicidin. The toxin was toxic to brine shrimp (the 50% lethal concentration was 40 μg/ml) and was weakly cytotoxic to human and mouse tumor cell lines. PMID:9872769

Vitamin E (α tocopherol) attenuates toxicity and oxidative stress induced by aflatoxin in rats.

PubMed

Yılmaz, Seval; Kaya, Emre; Comakli, Selim

2017-09-01

Aflatoxins are toxic metabolites produced by Aspergillus flavus and Aspergillus parasiticus and are classified as group I carcinogens by the International Agency for Research on Cancer (IARC). The purpose of this study was to investigate the possible preventive role of vitamin E (Vit E) on aflatoxin (AF) induced toxicity by using biochemical and histopathological approaches. Wistar-Albino rats were divided into 4 groups as follows: control group, Vit E group (Vit E was administered), AFB1 group (a single dose of AFB1 was administered), AF + Vit E group (AF and Vit E were administered). The effects of Vit E on AFB1 induced tissue toxicity were evaluated by using malondialdehyde (MDA), reduced glutathione (GSH) levels, antioxidant enzyme activities, and histopathological examination in tissues. AF caused the oxidative stress by the increased MDA level and the reduced GSH level, glutathioneS-transferase (GST), catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and glucose-6-phosphate dehydrogenase (G6PD) activities in tissues. Plasma aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) activities, creatinine, and urea concentrations significantly increased; whereas, chloride, phosphorus, and magnesium concentrations were insignificantly affected. Plasma glucose, protein and sodium concentrations significantly decreased. Administration of AF caused hepatotoxicity, cardiotoxicity, and nephrotoxicity. As far as histopathological changes are concerned, a statistically significant difference was found in AFB1 group compared to the control group. Vit E considerably reduced plasma AST, ALT, ALP, LDH activities, and urea concentration and ameliorated the deleterious effects of AF on oxidative stress markers and pathological changes. This data indicated that the natural antioxidant Vit E might have a protective effect against AF-induced toxicity and oxidative stress.

Ovario-protective effects of genistein against cyclophosphamide toxicity in rats: Role of anti-müllerian hormone and oestradiol.

PubMed

Saleh, Dalia O; Mansour, Dina F

2016-10-15

Cyclophosphamide (CP), the commonly used chemotherapeutic agent in cancer treatment, is proven to cause ovarian toxicity and infertility in women. In the present study, we investigated the protective effect of genistein (GEN), a phytoestrogen found in the soy protein, against CP-induced ovarian toxicity in rats. Forty female adult rats were allocated into five groups. A normal control group received the vehicle; another group was injected with a single acute intraperitoneal dose of CP (200mg/kg). Three other groups were pretreated with GEN (0.5, 1 or 2mg/kg; s.c.) for 14 days. Sera and ovaries were obtained 48h after CP treatment. Serum levels of anti-müllerian hormone (AMH) and oestradiol (E2) were detected as well as the ovarian level of reduced glutathione (GSH), activity of superoxide dismutase (SOD), level of malondialdehyde (MDA) and interleukin 1β (IL-1β) were evaluated. Histopathological examination and immunohistochemical detection of inducible nitric oxide synthetase (iNOS) were conducted. Results of the present study revealed that CP-induced severe ovarian toxicity via decreasing serum levels of AMH and E2 and elevating oxidative stress and inflammation in ovarian tissues. Histologically, CP caused increase in primordial follicles with less graafian follicles and corpora lutea in ovarian tissues as well as severe induction of iNOS. GEN inhibited the severe decrease in serum AMH and E2 with alleviation of oxidative stress and inflammation significantly compared to CP-treated group. GEN improved ovarian histology and immunostaining of ovarian iNOS disrupted by CP. Finally, it can be concluded that GEN exerted protective effects against CP-induced ovarian toxicity. Copyright © 2016 Elsevier B.V. All rights reserved.

Surface modifications on InAs decrease indium and arsenic leaching under physiological conditions

NASA Astrophysics Data System (ADS)

Jewett, Scott A.; Yoder, Jeffrey A.; Ivanisevic, Albena

2012-11-01

Devices containing III-V semiconductors such as InAs are increasingly being used in the electronic industry for a variety of optoelectronic applications. Furthermore, the attractive chemical, material, electronic properties make such materials appealing for use in devices designed for biological applications, such as biosensors. However, in biological applications the leaching of toxic materials from these devices could cause harm to cells or tissue. Additionally, after disposal, toxic inorganic materials can leach from devices and buildup in the environment, causing long-term ecological harm. Therefore, the toxicity of these materials along with their stability in physiological conditions are important factors to consider. Surface modifications are one common method of stabilizing semiconductor materials in order to chemically and electronically passivate them. Such surface modifications could also prevent the leaching of toxic materials by preventing the regrowth of the unstable surface oxide layer and by creating an effective barrier between the semiconductor surface and the surrounding environment. In this study, various surface modifications on InAs are developed with the goal of decreasing the leaching of indium and arsenic. The leaching of indium and arsenic from modified substrates was assessed in physiological conditions using inductively coupled plasma mass spectrometry (ICP-MS). Substrates modified with 11-mercapto-1-undecanol (MU) and graft polymerized with poly(ethylene) glycol (PEG) were most effective at preventing indium and arsenic leaching. These surfaces were characterized using contact angle analysis, ellipsometry, atomic force microscopy (AFM), and X-ray photoelectron spectroscopy (XPS). Substrates modified with collagen and synthetic polyelectrolytes were least effective, due to the destructive nature of acidic environments on InAs. The toxicity of modified and unmodified InAs, along with raw indium, arsenic, and PEG components was assessed using zebrafish embryos.

Environmental interactions with the toxicity of plant essential oils to the poultry red mite Dermanyssus gallinae.

PubMed

George, D R; Sparagano, O A E; Port, G; Okello, E; Shiel, R S; Guy, J H

2010-03-01

The toxicity of a range of plant essential oils to the poultry red mite, Dermanyssus gallinae (De Geer) (Acari: Dermanyssidae), a serious ectoparasitic pest of laying hens throughout Europe and elsewhere, was assessed in the laboratory. Dermanyssus gallinae may cause losses in egg production, anaemia and, in extreme cases, death of hens. With changes in legislation and consumer demand, alternatives to synthetic acaricides are needed to manage this pest. Fifty plant essential oils were selected for their toxicity to arthropods reported in the literature. Twenty-four of these essential oils were found to kill > 75% of adult D. gallinae in contact toxicity tests over a 24-h period at a rate of 0.21 mg/cm(2). Subsequent testing at lower rates showed that the essential oils of cade, manuka and thyme were especially toxic to adult D. gallinae. The toxicity of the seven most acaricidal essential oils was found to be stable at different temperatures likely to be encountered in commercial poultry housing (15 degrees C, 22 degrees C and 29 degrees C), although results suggest that humidity and dust might influence the toxicity of some of the oils tested. The toxicity of clove bud essential oil to D. gallinae, for example, was increased at high humidity and dust levels compared with ambient levels. The results suggest that certain essential oils may make effective botanical pesticides for use against D. gallinae, although it is likely that issues relating to the consistency of the toxic effect of some oils will determine which oils will be most effective in practice.

Neurotoxic effects of indocyanine green -cerebellar granule cell culture viability study

PubMed Central

Toczylowska, Beata; Zieminska, Elzbieta; Goch, Grazyna; Milej, Daniel; Gerega, Anna; Liebert, Adam

2014-01-01

The aim of this study was to examine neurotoxicity indocyanine green (ICG). We assessed viability of primary cerebellar granule cell culture (CGC) exposed to ICG to test two mechanisms that could be the first triggers causing neuronal toxicity: imbalance in calcium homeostasis and the degree of oligomerization of ICG molecules. We have observed this imbalance in CGC after exposure to 75-125μΜ ICG and dose and application sequence dependent protective effect of Gadovist on surviving neurons in vitro when used with ICG. Spectroscopic studies suggest the major cause of toxicity of the ICG is connected with oligomers formation. ICG at concentration of 25 μM (which is about 4 times higher than the highest concentration of ICG in the brain applied in in-vivo human studies) is not neurotoxic in the cell culture. PMID:24688815

NMR shielding and a thermodynamic study of the effect of environmental exposure to petrochemical solvent on DPPC, an important component of lung surfactant

NASA Astrophysics Data System (ADS)

Monajjemi, M.; Afsharnezhad, S.; Jaafari, M. R.; Abdolahi, T.; Nikosade, A.; Monajemi, H.

2007-12-01

The chemical and petrochemical industries are the major air polluters. Millions of workers are exposed to toxic chemicals on the job, and it is becoming more toxic, causing much damage to respiratory system, today. One of the main components of lung alveoli is a surfactant. DPPC (Dipalmitolphosphatidylcholine) is the predominant lipid component in the lung surfactant, which is responsible for lowering surface tension in alveoli. In this article, we used an approximate model and ab initio computations to describe interactions between DPPC and some chemical solvents, such as benzene, toluene, heptane, acetone, chloroform, ether, and ethanol, which cause lung injuries and lead to respiratory distress such as ARDS. The effect of these solvents on the conformation and disordering of the DPPC head group was investigated by calculations at the Hatree-Fock level using the 6-31G basis set with the Onsager continuum solvation, GAIO, and frequency models. The simulation model was confirmed by accurate NMR measurements as concerns conformational energy. Water can be the most suitable solvent for DPPC. Furthermore, this study shows that ethanol has the most destructive effect on the conformation and lipid disorder of the DPPC head group of the lung surfactant in our model. Our finding will be useful for detecting the dysfunction of DPPC in the lung surfactant caused by acute or chronic exposures to air toxics from petrochemical organic solvent emission source and chronic alcohol consumption, which may lead to ARDS.

Zebrafish embryo toxicity of anaerobic biotransformation products from the insensitive munitions compound 2,4-dinitroanisole.

PubMed

Olivares, Christopher I; Sierra-Alvarez, Reyes; Abrell, Leif; Chorover, Jon; Simonich, Michael; Tanguay, Robert L; Field, Jim A

2016-11-01

2,4-Dinitroanisole (DNAN) is an emerging insensitive munitions compound that readily undergoes anaerobic nitro-group reduction to 2-methoxy-5-nitroaniline (MENA) and 2,4-diaminoanisole (DAAN), followed by formation of unique azo dimers. Currently there is little knowledge on the ecotoxicity of DNAN (bio)transformation products. In the present study, mortality, development, and behavioral effects of DNAN (bio)transformation products were assessed using zebrafish (Danio rerio) embryos. The authors tested individual products, MENA and DAAN, as well as dimer and trimer surrogates. As pure compounds, 3-nitro-4-methoxyaniline and 2,2'-dimethoxy-4,4'-azodianiline caused statistically significant effects, with lowest-observable-adverse effect levels (LOAEL) at 6.4 μM on 1 or 2 developmental endpoints, respectively. The latter had 6 additional statistically significant developmental endpoints with LOAELs of 64 μM. Based on light-to-dark swimming behavioral tests, DAAN (640 μM) caused reduction in swimming, suggestive of neurotoxicity. No statistically significant mortality occurred (≤64 μM) for any of the individual compounds. However, metabolite mixtures formed during different stages of MENA (bio)transformation in soil were characterized using high-resolution mass spectrometry in parallel with zebrafish embryo toxicity assays, which demonstrated statistically significant mortality during the onset of azo-dimer formation. Overall the results indicate that several DNAN (bio)transformation products cause different types of toxicity to zebrafish embryos. Environ Toxicol Chem 2016;35:2774-2781. © 2016 SETAC. © 2016 SETAC.

Combined Non-Target Effects of Insecticide and High Temperature on the Parasitoid Bracon nigricans

PubMed Central

Abbes, Khaled; Biondi, Antonio; Kurtulus, Alican; Ricupero, Michele; Russo, Agatino; Siscaro, Gaetano; Chermiti, Brahim; Zappalà, Lucia

2015-01-01

We studied the acute toxicity and the sublethal effects, on reproduction and host-killing activity, of four widely used insecticides on the generalist parasitoid Bracon nigricans (Hymenoptera: Braconidae), a natural enemy of the invasive tomato pest, Tuta absoluta (Lepidoptera: Gelechiidae). Laboratory bioassays were conducted applying maximum insecticide label rates at three constant temperatures, 25, 35 and 40°C, considered as regular, high and very high, respectively. Data on female survival and offspring production were used to calculate population growth indexes as a measure of population recovery after pesticide exposure. Spinetoram caused 80% mortality at 25°C and 100% at higher temperatures, while spinosad caused 100% mortality under all temperature regimes. Cyantraniliprole was slightly toxic to B. nigricans adults in terms of acute toxicity at the three temperatures, while it did not cause any sublethal effects in egg-laying and host-killing activities. The interaction between the two tested factors (insecticide and temperature) significantly influenced the number of eggs laid by the parasitoid, which was the lowest in the case of females exposed to chlorantraniliprole at 35°C. Furthermore, significantly lower B. nigricans demographic growth indexes were estimated for all the insecticides under all temperature conditions, with the exception of chlorantraniliprole at 25°C. Our findings highlight an interaction between high temperatures and insecticide exposure, which suggests a need for including natural stressors, such as temperature, in pesticide risk assessments procedures. PMID:26382245

Nanoparticles: health effects--pros and cons.

PubMed

Gwinn, Maureen R; Vallyathan, Val

2006-12-01

With the advent of nanotechnology, the prospects for using engineered nanomaterials with diameters of < 100 nm in industrial applications, medical imaging, disease diagnoses, drug delivery, cancer treatment, gene therapy, and other areas have progressed rapidly. The potential for nanoparticles (NPs) in these areas is infinite, with novel new applications constantly being explored. The possible toxic health effects of these NPs associated with human exposure are unknown. Many fine particles generally considered "nuisance dusts" are likely to acquire unique surface properties when engineered to nanosize and may exhibit toxic biological effects. Consequently, the nuisance dust may be transported to distant sites and could induce adverse health effects. In addition the beneficial uses of NPs in drug delivery, cancer treatment, and gene therapy may cause unintentional human exposure. Because of our lack of knowledge about the health effects associated with NP exposure, we have an ethical duty to take precautionary measures regarding their use. In this review we highlight the possible toxic human health effects that can result from exposure to ultrafine particles (UFPs) generated by anthropogenic activities and their cardiopulmonary outcomes. The comparability of engineered NPs to UFPs suggests that the human health effects are likely to be similar. Therefore, it is prudent to elucidate their toxicologic effect to minimize occupational and environmental exposure. Highlighting the human health outcomes caused by UFPs is not intended to give a lesser importance to either the unprecedented technologic and industrial rewards of the nanotechnology or their beneficial human uses.

Toxic C17-Sphinganine Analogue Mycotoxin, Contaminating Tunisian Mussels, Causes Flaccid Paralysis in Rodents

PubMed Central

Marrouchi, Riadh; Benoit, Evelyne; Le Caer, Jean-Pierre; Belayouni, Nawel; Belghith, Hafedh; Molgó, Jordi; Kharrat, Riadh

2013-01-01

Severe toxicity was detected in mussels from Bizerte Lagoon (Northern Tunisia) using routine mouse bioassays for detecting diarrheic and paralytic toxins not associated to classical phytoplankton blooming. The atypical toxicity was characterized by rapid mouse death. The aim of the present work was to understand the basis of such toxicity. Bioassay-guided chromatographic separation and mass spectrometry were used to detect and characterize the fraction responsible for mussels’ toxicity. Only a C17-sphinganine analog mycotoxin (C17-SAMT), with a molecular mass of 287.289 Da, was found in contaminated shellfish. The doses of C17-SAMT that were lethal to 50% of mice were 750 and 150 μg/kg following intraperitoneal and intracerebroventricular injections, respectively, and 900 μg/kg following oral administration. The macroscopic general aspect of cultures and the morphological characteristics of the strains isolated from mussels revealed that the toxicity episodes were associated to the presence of marine microfungi (Fusarium sp., Aspergillus sp. and Trichoderma sp.) in contaminated samples. The major in vivo effect of C17-SAMT on the mouse neuromuscular system was a dose- and time-dependent decrease of compound muscle action potential amplitude and an increased excitability threshold. In vitro, C17-SAMT caused a dose- and time-dependent block of directly- and indirectly-elicited isometric contraction of isolated mouse hemidiaphragms. PMID:24287956

Aquatic toxicity of nine aircraft deicer and anti-icer formulations and relative toxicity of additive package ingredients alkylphenol ethoxylates and 4,5-methyl-1H-henzotriazoles.

PubMed

Corsi, Steven R; Geis, Steven W; Loyo-Rosales, Jorge E; Rice, Clifford P

2006-12-01

Characterization of the effects of aircraft deicer and anti-icer fluid (ADAF) runoff on aquatic organisms in receiving streams is a complex issue because the identities of numerous toxic additives are proprietary and not publicly available. Most potentially toxic and endocrine disrupting effects caused by ADAF are due to the numerous additive package ingredients which vary among manufacturers and types of ADAF formulation. Toxicity investigations of nine ADAF formulations indicate that endpoint concentrations for formulations of different manufacturers are widely variable. Type IV ADAF (anti-icers) are more toxic than Type I (deicers) for the four organisms tested (Vibrio fischeri, Pimephales promelas, Ceriodaphnia dubia, and Selenastrum capricornutum). Acute toxicity endpoint concentrations ranged from 347 to 7700 mg/L as ADAF for Type IV and from 1550 to 45,100 mg/L for Type I formulations. Chronic endpoint concentrations ranged from 70 to 1300 mg/L for Type IV and from 37 to 18,400 mg/L for Type I formulations. Alkylphenol ethoxylates and tolyltriazoles are two known classes of additives. Nonylphenol, nonylphenol ethoxylates, octylphenol, octylphenol ethoxylates, and 4,5-methyl-1H-benzotriazoles were quantified in the nine ADAF formulations, and toxicity tests were conducted with nonylphenol ethoxylates and 4,5-methyl-1H-benzotriazoles. Toxicity units computed for glycol and these additives, with respect to toxicity of the ADAF formulations, indicate that a portion of ADAF toxicity can be explained by the known additives and glycols, but much of the toxicity is due to unidentified additives.

Toxicity of the organophosphate chemical warfare agents GA, GB, and VX: Implications for public protection

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

Munro, N.B.; Ambrose, K.R.; Watson, A.P.

1994-01-01

The nerve agents, GA, GB, and VX are organophosphorus esters that form a major portion of the total agent volume contained in the U.S. stockpile of unitary chemical munitions. Congress has mandated the destruction of these agents, which is currently slated for completion in 2004. The acute, chronic, and delayed toxicity of these agents is reviewed in this analysis. The largely negative results from studies of genotoxicity, carcinogenicity, developmental, and reproductive toxicity are also presented. Nerve agents show few or delayed effects. At supralethal doses, GB can cause delayed neuropathy in antidote-protected chickens, but there is not evidence that itmore » causes this syndrome in humans at any dose. Agent VX shows no potential for inducing delayed neuropathy in any species. In view of their lack of genotoxicity, the nerve agent exposure is the extraordinarily high acute toxicity of these substances. Futhermore, acute effects of moderate exposure such as nausea, diarrhea, inability to perform simple mental tasks, and respiratory effects may render the public unable to respond adequately to emergency instructions in the unlikely event of agent release, making early warning and exposure avoidance important. Likewise, exposure or self-contamination of first responders and medical personnel must be avoided. Control limits for exposure via surface contact of drinking water are needed, as are detection methods for low levels in water or foodstuffs. 187 refs., 3 figs., 7 tabs.« less

Toxicity of the Organophosphate Chemical Warfare Agents GA, GB, and VX: Implications for Public Protection.

PubMed Central

Munro, N

1994-01-01

The nerve agents, GA, GB, and VX are organophosphorus esters that form a major portion of the total agent volume contained in the U.S. stockpile of unitary chemical munitions. Congress has mandated the destruction of these agents, which is currently slated for completion in 2004. The acute, chronic, and delayed toxicity of these agents is reviewed in this analysis. The largely negative results from studies of genotoxicity, carcinogenicity, developmental, and reproductive toxicity are also presented. Nerve agents show few or delayed effects. At supralethal doses, GB can cause delayed neuropathy in antidote-protected chickens, but there is no evidence that it causes this syndrome in humans at any dose. Agent VX shows no potential for inducing delayed neuropathy in any species. In view of their lack of genotoxcity, the nerve agents are not likely to be carcinogens. The overreaching concern with regard to nerve agent exposure is the extraordinarily high acute toxicity of these substances. Furthermore, acute effects of moderate exposure such as nausea, diarrhea, inability to perform simple mental tasks, and respiratory effects may render the public unable to respond adequately to emergency instructions in the unlikely event of agent releaase, making early warning and exposure avoidance important. Likewise, exposure or self-contamination of first responders and medical personnel must be avoided. Control limits for exposure via surface contact of drinking water are needed, as are detection methods for low levels in water or foodstuffs. Images Figure 2. PMID:9719666

Evaluation of antimicrobial activity of glycerol monolaurate nanocapsules against American foulbrood disease agent and toxicity on bees.

PubMed

Lopes, Leonardo Q S; Santos, Cayane G; de Almeida Vaucher, Rodrigo; Gende, Liesel; Raffin, Renata P; Santos, Roberto C V

2016-08-01

The American Foulbrood Disease (AFB) is a fatal larval bee infection. The etiologic agent is the bacterium Paenibacillus larvae. The treatment involves incineration of all contaminated materials, leading to high losses. The Glycerol Monolaurate (GML) is a known antimicrobial potential compound, however its use is reduced due to its low solubility in water and high melting point. The nanoencapsulation of some drugs offers several advantages like improved stability and solubility in water. The present study aimed to evaluate the antimicrobial activity against P. larvae and the toxicity in bees of GML nanoparticles. The nanocapsules were produced and presented mean diameter of 210 nm, polydispersity index of 0.044, and zeta potential of -23.4 mV demonstrating the acceptable values to predict a stable system. The microdilution assay showed that it is necessary 142 and 285 μg/mL of GML nanocapsules to obtain a bacteriostatic and bactericidal effect respectively. The time-kill curve showed the controlled release of compound, exterminating the microorganism after 24 h. The GML nanocapsules were able to kill the spore form of Paenibacillus larvae while the GML do not cause any effect. The assay in bees showed that the GML has a high toxicity while the GML nanoparticles showed a decrease on toxic effects. Concluding, the formulation shows positive results in the action to combat AFB besides not causing damage to bees. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Pharmacogenetic Discovery: Cystamine Protects Against Haloperidol-Induced Toxicity and Ischemic Brain Injury.

PubMed

Zhang, Haili; Zheng, Ming; Wu, Manhong; Xu, Dan; Nishimura, Toshihiko; Nishimura, Yuki; Giffard, Rona; Xiong, Xiaoxing; Xu, Li Jun; Clark, J David; Sahbaie, Peyman; Dill, David L; Peltz, Gary

2016-05-01

Haloperidol is an effective antipsychotic agent, but it causes Parkinsonian-like extrapyramidal symptoms in the majority of treated subjects. To address this treatment-limiting toxicity, we analyzed a murine genetic model of haloperidol-induced toxicity (HIT). Analysis of a panel of consomic strains indicated that a genetic factor on chromosome 10 had a significant effect on susceptibility to HIT. We analyzed a whole-genome SNP database to identify allelic variants that were uniquely present on chromosome 10 in the strain that was previously shown to exhibit the highest level of susceptibility to HIT. This analysis implicated allelic variation within pantetheinase genes (Vnn1 and Vnn3), which we propose impaired the biosynthesis of cysteamine, could affect susceptibility to HIT. We demonstrate that administration of cystamine, which is rapidly metabolized to cysteamine, could completely prevent HIT in the murine model. Many of the haloperidol-induced gene expression changes in the striatum of the susceptible strain were reversed by cystamine coadministration. Since cystamine administration has previously been shown to have other neuroprotective actions, we investigated whether cystamine administration could have a broader neuroprotective effect. Cystamine administration caused a 23% reduction in infarct volume after experimentally induced cerebral ischemia. Characterization of this novel pharmacogenetic factor for HIT has identified a new approach for preventing the treatment-limiting toxicity of an antipsychotic agent, which could also be used to reduce the extent of brain damage after stroke. Copyright © 2016 by the Genetics Society of America.

A Pharmacogenetic Discovery: Cystamine Protects Against Haloperidol-Induced Toxicity and Ischemic Brain Injury

PubMed Central

Zhang, Haili; Zheng, Ming; Wu, Manhong; Xu, Dan; Nishimura, Toshihiko; Nishimura, Yuki; Giffard, Rona; Xiong, Xiaoxing; Xu, Li Jun; Clark, J. David; Sahbaie, Peyman; Dill, David L.; Peltz, Gary

2016-01-01

Haloperidol is an effective antipsychotic agent, but it causes Parkinsonian-like extrapyramidal symptoms in the majority of treated subjects. To address this treatment-limiting toxicity, we analyzed a murine genetic model of haloperidol-induced toxicity (HIT). Analysis of a panel of consomic strains indicated that a genetic factor on chromosome 10 had a significant effect on susceptibility to HIT. We analyzed a whole-genome SNP database to identify allelic variants that were uniquely present on chromosome 10 in the strain that was previously shown to exhibit the highest level of susceptibility to HIT. This analysis implicated allelic variation within pantetheinase genes (Vnn1 and Vnn3), which we propose impaired the biosynthesis of cysteamine, could affect susceptibility to HIT. We demonstrate that administration of cystamine, which is rapidly metabolized to cysteamine, could completely prevent HIT in the murine model. Many of the haloperidol-induced gene expression changes in the striatum of the susceptible strain were reversed by cystamine coadministration. Since cystamine administration has previously been shown to have other neuroprotective actions, we investigated whether cystamine administration could have a broader neuroprotective effect. Cystamine administration caused a 23% reduction in infarct volume after experimentally induced cerebral ischemia. Characterization of this novel pharmacogenetic factor for HIT has identified a new approach for preventing the treatment-limiting toxicity of an antipsychotic agent, which could also be used to reduce the extent of brain damage after stroke. PMID:26993135

Toxic effects of three strobilurins (trifloxystrobin, azoxystrobin and kresoxim-methyl) on mRNA expression and antioxidant enzymes in grass carp (Ctenopharyngodon idella) juveniles.

PubMed

Liu, Lei; Jiang, Chao; Wu, Zhuo-Qi; Gong, Yu-Xin; Wang, Gao-Xue

2013-12-01

The strobilurins are used widely in the world as effective fungicidal agents to control Asian soybean rust. In this study, the early life stage of grass carp (Ctenopharyngodon idella), which is one of the most important aquaculture species in China, was chosen to measure the acute toxicity of three common strobilurin-derived fungicides (trifloxystrobin (TFS), azoxystrobin (AZ) and kresoxim-methyl (KM)). As endpoints, normal developmental parameters (lethal concentration (LC₅₀) and average heart rate), expression of relative genes, and three antioxidant enzyme activities in the developing juveniles were recorded during a 48 h exposure. The results revealed that values of LC₅₀ were TFS 0.051 (0.046-0.058) mg L⁻¹, AZ 0.549 (0.419-0.771) mg L⁻¹ and KM 0.338 (0.284-0.407) mg L⁻¹ for juveniles. For the potential toxicity mechanisms, these three fungicides increased catalase (CAT) and peroxidase (POD) activity and decreased superoxide dismutase (SOD) activity, significantly inhibited expressions of three growth-related genes (IGF-1, IGF-2 and GHR) and two energy-related-genes (CCK and PYY), and caused pronounced up-regulation a stress-gene (HSP70). The present study demonstrated potential toxic effects of TFS, AZ and KM on the early development of C. idella. Overall, three strobilurins (TFS, AZ and KM) might cause serious damages to the aquatic species; therefore, their pollution supervision in water ecological environment should be strengthened.

Selenium Administration Alleviates Toxicity of Chromium(VI) in the Chicken Brain.

PubMed

Hao, Pan; Zhu, Yiran; Wang, Shenghua; Wan, Huiyu; Chen, Peng; Wang, Yang; Cheng, Ziqiang; Liu, Yongxia; Liu, Jianzhu

2017-07-01

Selenium (Se) can play a protective role against heavy metal toxicity. This experiment aims to evaluate the effect of Se supplementation at different doses on the chicken brains. Oxidative stress was induced in the chicken brains by chromium(VI). A total of 105 Hyland brown male chickens were randomly divided into seven groups, including the control group, poisoned group [6%LD 50 K 2 Cr 2 O 7 body weight (B.W.)], and detoxification groups K 2 Cr 2 O 7 (6%LD 50 ) + Se (0.31, 0.63, 1.25, 2.50, and 5.00 Na 2 SeO 3 mg/kg B.W.) orally in water for 42 days. The chickens were detected by the activities of mitochondrial membrane potential, 2'-benzoyloxycinnamaldehyde, superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), and Ca 2+ -ATPase. Cr(VI) administration caused histopathological damage. In addition, changes in oxidative stress indicators were observed in the chicken's brains. Se supplement increased the levels of GSH, mitochondrial membrane potential (MMP), and Ca 2+ -ATPase and reduced MDA activity in the detoxification groups. However, the high-dose Se supplementation groups of 2.50 and 5.00 mg/kg reduced the activities of GSH, MMP, and Ca 2+ -ATPase; increased the brain-body ratio; and increased SOD activity. In conclusion, Cr(VI) exposure caused oxidative stress. Se exerted a remission effect on toxic responses in the chicken brains. However, a high Se concentration was synergistic to the toxic effect of Cr(VI).

Human alcohol-related neuropathology

PubMed Central

Kril, Jillian J.

2015-01-01

Alcohol-related diseases of the nervous system are caused by excessive exposures to alcohol, with or without co-existing nutritional or vitamin deficiencies. Toxic and metabolic effects of alcohol (ethanol) vary with brain region, age/developmental stage, dose, and duration of exposures. In the mature brain, heavy chronic or binge alcohol exposures can cause severe debilitating diseases of the central and peripheral nervous systems, and skeletal muscle. Most commonly, long-standing heavy alcohol abuse leads to disproportionate loss of cerebral white matter and impairments in executive function. The cerebellum (especially the vermis), cortical-limbic circuits, skeletal muscle, and peripheral nerves are also important targets of chronic alcohol-related metabolic injury and degeneration. Although all cell types within the nervous system are vulnerable to the toxic, metabolic, and degenerative effects of alcohol, astrocytes, oligodendrocytes, and synaptic terminals are major targets, accounting for the white matter atrophy, neural inflammation and toxicity, and impairments in synaptogenesis. Besides chronic degenerative neuropathology, alcoholics are predisposed to develop severe potentially life-threatening acute or subacute symmetrical hemorrhagic injury in the diencephalon and brainstem due to thiamine deficiency, which exerts toxic/metabolic effects on glia, myelin, and the microvasculature. Alcohol also has devastating neurotoxic and teratogenic effects on the developing brain in association with fetal alcohol spectrum disorder/fetal alcohol syndrome. Alcohol impairs function of neurons and glia, disrupting a broad array of functions including neuronal survival, cell migration, and glial cell (astrocytes and oligodendrocytes) differentiation. Further progress is needed to better understand the pathophysiology of this exposure-related constellation of nervous system diseases and better correlate the underlying pathology with in vivo imaging and biochemical lesions. PMID:24370929

Short and long-term effects of three neurotoxic insecticides on biological and behavioural attributes of the orb-web spider Alpaida veniliae (Araneae, Araneidae): implications for IPM programs.

PubMed

Benamú, Marco A; Schneider, Marcela I; González, Alda; Sánchez, Norma E

2013-09-01

Soybean pest control in Argentina is done just by chemical control using broad-spectrum pesticides. Alpaida veniliae (Araneae, Araneidae) is one of the most abundant spider species of the orb web weaver guild in soybean, and it is considered a very important polyphagous predator, attacking different insects' families. The objective of this study was to determine if neurotoxic insecticides commonly used in soybean crops and a new active ingredient registered in Argentina (spinosad) adversely affected survival, prey consumption, mating behaviour, web building and reproductive capacity of A. veniliae females, under standard laboratory conditions. Spinosad was the most harmful insecticide due to high acute toxicity, even at lower concentrations than those registered for its field use and for its sublethal effects also. Cypermethrin caused several sublethal effects although its acute toxicity on spider was lower than other insecticides. It reduced prey consumption, affected web building, caused abnormalities in eggs sacs and decreased drastically the fecundity and fertility at sublethal concentrations. Endosulfan did not reduce prey consumption but it affected web building, caused abnormalities in eggs sacs and egg masses, and decreased the fecundity and fertility. Spinosad was also the compound with the most drastic effect on web building, it did not reduce prey consumption and fecundity, but fertility was reduced and abnormalities in egg sacs and egg masses were observed. The use of these insecticides in IPM programs according to their potential toxicity on spider communities is discussed.

[Advance in studies on TRPV1 and analgesic effect of traditional Chinese medicines].

PubMed

Liu, Xiao-Li; Lv, Cui; Zhang, Wen-Sheng

2014-05-01

Transient receptor potential vanilloid 1 (TRPV1) is a non-selective positive ion channel that is mainly expressed in sensory neurons and a member of transient receptor potential (TRP) family. The receptor could be activated by mechanical irritation, chemical irritation or endogenous ligand to mediate pains and cause injury to body functions. Traditional Chinese medicine believes that the mechanism of pain is that "stagnation leads to pain". Specifically, both of the contracture and tautness caused by cold and the blood stasis could result in blood impassability and pain. Most of traditional Chinese medicines for clearing heat and removing toxicity have the anti-inflammatory effect, while those for warming interior, and promoting blood circulation to remove blood stasis have the effect in smoothening blood vessels. Therefore, either with the anti-inflammatory effect or the effect in smoothening blood vessels, traditional Chinese medicines for clearing heat and removing toxicity, warming interior, and promoting blood circulation have the analgesic effect In this paper, the authors summarize the analgesic effect of the above three traditional Chinese medicines, with TRPV1 as the target.

Stormwater-related transport of the insecticides bifenthrin, fipronil, imidacloprid, and chlorpyrifos into a tidal wetland, San Francisco Bay, California.

PubMed

Weston, Donald P; Chen, Da; Lydy, Michael J

2015-09-15

Suisun Marsh, in northern San Francisco Bay, is the largest brackish marsh in California, and provides critical habitat for many fish species. Storm runoff enters the marsh through many creeks that drain agricultural uplands and the urban areas of Fairfield and Suisun City. Five creeks were sampled throughout a major storm event in February 2014, and analyzed for representatives of several major insecticide classes. Concentrations were greatest in creeks with urban influence, though sampling was done outside of the primary season for agricultural pesticide use. Urban creek waters reached maximum concentrations of 9.9 ng/l bifenthrin, 27.4 ng/l fipronil, 11.9 ng/l fipronil sulfone, 1462 ng/l imidacloprid, and 4.0 ng/l chlorpyrifos. Water samples were tested for toxicity to Hyalella azteca and Chironomus dilutus, and while few samples caused mortality, 70% of the urban creek samples caused paralysis of either or both species. Toxic unit analysis indicated that bifenthrin was likely responsible for effects to H. azteca, and fipronil and its sulfone degradate were responsible for effects to C. dilutus. These results demonstrate the potential for co-occurrence of multiple insecticides in urban runoff, each with the potential for toxicity to particular species, and the value of toxicity monitoring using multiple species. In the channels of Suisun Marsh farther downstream, insecticide concentrations and toxicity diminished as creek waters mixed with brackish waters entering from San Francisco Bay. Only fipronil and its degradates remained measurable at 1-10 ng/l. These concentrations are not known to present a risk based on existing data, but toxicity data for estuarine and marine invertebrates, particularly for fipronil's degradates, are extremely limited. Copyright © 2015 Elsevier B.V. All rights reserved.

Factors influencing methionine toxicity in young bobwhite quail

USGS Publications Warehouse

Serafin, J.A.

1981-01-01

Young Bobwhite quail (Colinus virginianus) were fed low and adequate protein purified diets with and without excess methionine to evaluate factors affecting methionine toxicity. Growth of quail fed an adequate protein (27%) diet, without supplemental glycine, was depressed by 1.75% and 2.25% excess methionine. Supplemental glycine (.3%) alleviated growth depression caused by 2.25% excess methionine. Quail fed 1.75% and 2.25% excess methionine developed signs of toxicity characterized by weakness, a lowered, outstretched neck when moving, and ataxia. In addition, quail would fall on their sides when disturbed and spin with their heads retracted. These conditions were transient in nature. Growth of quail fed a low protein (18.9%) diet was depressed by 1% and 1.5% excess methionine and DL-homocystine. Quail fed 1% and 1.5% excess methionine in this diet also developed signs of toxicity, the incidence of which was greater and the duration longer than occurred with quail fed adequate protein. Supplementing a low protein (20.15%) diet with .3% or .6% glycine or threonine or a combination of these amino acids did not alleviate growth depression caused by 1.5% excess methionine; however, 2% and 3% supplemental glycine were somewhat effective. Supplements of glycine (2%, 3%) and threonine (1%) completely reversed growth depression from 1% excess methionine but did not influence growth of controls, indicating that both amino acids counteract methionine toxicity. Both glycine and threonine alone improved growth by about the same extent in diets with 1% or 1.5% excess methionine; however, these amino acids alleviated less than 30% of the growth depression resulting from 1.5% excess methionine. The effectiveness of glycine in alleviating methionine toxicity in a low protein diet was decreased, and hemoglobin levels were depressed with 1.5% excess methionine compared to less amounts.

The Simplest Flowchart Stating the Mechanisms for Organic Xenobiotics-induced Toxicity: Can it Possibly be Accepted as a “Central Dogma” for Toxic Mechanisms?

PubMed Central

Lee, Sundong; Cho, Myung-Haing

2014-01-01

Xenobiotics causing a variety of toxicity in biological systems could be classified as two types, inorganic and organic chemicals. It is estimated that the organic xenobiotics are responsible for approximately 80~90% of chemical-induced toxicity in human population. In the class for toxicology, we have encountered some difficulties in explaining the mechanisms of toxicity caused especially by organic chemicals. Here, a simple flowchart was introduced for explaining the mechanism of toxicity caused by organic xenobiotics, as the central dogma of molecular biology. This flowchart, referred to as a central dogma, was described based on a view of various aspects as follows: direct-acting chemicals vs. indirect-acting chemicals, cytochrome P450-dependent vs. cytochrome P450-independent biotransformation, reactive intermediates, reactivation, toxicokinetics vs. toxicodynamics, and reversibility vs. irreversibility. Thus, the primary objective of this flowchart is to help better understanding of the organic xenobiotics-induced toxic mechanisms, providing a major pathway for toxicity occurring in biological systems. PMID:25343011

Zebrafish as a Vertebrate Model System to Evaluate Effects of Environmental Toxicants on Cardiac Development and Function.

PubMed

Sarmah, Swapnalee; Marrs, James A

2016-12-16

Environmental pollution is a serious problem of the modern world that possesses a major threat to public health. Exposure to environmental pollutants during embryonic development is particularly risky. Although many pollutants have been verified as potential toxicants, there are new chemicals in the environment that need assessment. Heart development is an extremely sensitive process, which can be affected by environmentally toxic molecule exposure during embryonic development. Congenital heart defects are the most common life-threatening global health problems, and the etiology is mostly unknown. The zebrafish has emerged as an invaluable model to examine substance toxicity on vertebrate development, particularly on cardiac development. The zebrafish offers numerous advantages for toxicology research not found in other model systems. Many laboratories have used the zebrafish to study the effects of widespread chemicals in the environment on heart development, including pesticides, nanoparticles, and various organic pollutants. Here, we review the uses of the zebrafish in examining effects of exposure to external molecules during embryonic development in causing cardiac defects, including chemicals ubiquitous in the environment and illicit drugs. Known or potential mechanisms of toxicity and how zebrafish research can be used to provide mechanistic understanding of cardiac defects are discussed.

Mixture toxicity of six sulfonamides and their two transformation products to green algae Scenedesmus vacuolatus and duckweed Lemna minor.

PubMed

Białk-Bielińska, Anna; Caban, Magda; Pieczyńska, Aleksandra; Stepnowski, Piotr; Stolte, Stefan

2017-04-01

Since humans and ecosystems are continually exposed to a very complex and permanently changing mixture of chemicals, there is increasing concern in the general public about the potential adverse effects they may cause. Among all "emerging pollutants", pharmaceuticals in particular have raised great environmental concern. For these reasons the aim of our study was to evaluate the mixture toxicity of six antimicrobial sulfonamides (SAs) and their two most commonly identified degradation products - sulfanilic acid (SNA) and sulfanilamide (SN) - to limnic green algae Scenedesmus vacuolatus and duckweed Lemna minor. The ecotoxicological data for the single toxicity of SNA and SN towards selected organisms are presented. The concept of Concentration Addition (CA) was applied to estimate the effects, and less than additive effects were observed. In general terms, it seems sufficiently precautionary for the aquatic environment to consider the toxicity of a sulfonamide mixture as additive. The Concentration Addition model proves to be a reasonable worst-case estimation. Such a comparative study on the mixture toxicity of sulfonamides and their transformation products has been presented for the first time. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cell-based approaches for screening and prioritization of chemicals that may cause developmental neurotoxicity

EPA Science Inventory

The National Academies report on Toxicity Testing in the 21st Century envisioned the use of in vitro toxicity tests using cells of human origin to predict the ability of chemicals to cause toxicity in vivo. Successful implementation of this strategy will ultimately result in fast...

Effects of Chinese Medicine as Adjunct Medication for Adjuvant Chemotherapy Treatments of Non-Small Cell Lung Cancer Patients

PubMed Central

Jiao, Lijing; Dong, Changsheng; Liu, Jiaxiang; Chen, Zhiwei; Zhang, Lei; Xu, Jianfang; Shen, Xiaoyong; Che, Jiaming; Yang, Yi; Huang, Hai; Li, Hegen; Sun, Jianli; Jiang, Yi; Mao, Zhujun; Chen, Peiqi; Gong, Yabin; Jin, Xiaolin; Xu, Ling

2017-01-01

The aim was to evaluate the effects of traditional Chinese medicine (TCM) as a combination medication with adjuvant chemotherapy on postoperative early stage non-small cell lung cancer (NSCLC) patients. The 314 patients with completely resected stage IB, II or IIIA cancers were assigned into vinorelbine plus cisplatin/carboplatin (NP/NC) (control, n = 158) and NP/NC with additional TCM (intervention, n = 156) groups. The primary endpoint was QOL scores; secondary endpoints were the toxicity and safety of the regimens. The NP/NC regimen caused mild (grade 1 or 2) non-hematologic toxic effects in the patients comprising vomiting (43.6%), fatigue (36.9%), pain (23%), dry mouth (27.6%) and diarrhea (7.9%). The incidence of adverse events was significantly lower in the intervention group than in the control group (0.57% vs 4.02%, P = 0.037). Transient severe (grade 3 or 4) hematological toxic effects occurred less often (hemoglobin reduction (11.9 vs 22.5 percent) and total bilirubin increased (to 42.1 vs 46.2%) in the intervention compared to the control group during the 2nd chemotherapy cycle. When combined with adjuvant chemotherapy, TCM led to partial relief of symptoms in addition to a reduction of side-effects and adverse events caused by the NP/NC regimens. PMID:28436479

Fusarium infection causes genotoxic disorders and antioxidant-based damages in Orobanche spp.

PubMed

Aybeke, Mehmet

2017-08-01

This study aims to evaluate the toxic effects of Fusarium oxysporum on root parasitic weed, Orobanche spp. Comparative genetic and gene expression studies were conducted on uninfected and fungus-infected orobanches. In genetic studies, isolated total DNA was amplified by RAPD PCR. Fragment properties were analysed by GTS test. According to the results, the fragment properties of control and Fusarium infected (experimental) groups varied widely; and it has been observed that Fusarium has genotoxic effects on the DNA of orobanches. In gene expression studies, the expression levels of genes encoding enzymes or proteins were associated with ROS damage and toxic effects, therefore, gene expressions of Mn-superoxide dismutase (SOD), Zn-superoxide dismutase (=SOD2, mitochondrial), glutamine synthetase (GS), heat shock protein gene (HSP70), BAX, Caspase-3 and BCL2 were significantly higher in the experimental group. In the light of obtained data, it was concluded that F. oxysporum (1) caused heavy ROS damage in Orobanche (2) induced significant irrevocable genotoxic effects on the DNA of Orobanche, (3) degraded protein metabolism and synthesis, and finally (4) triggered apoptosis. The results of this study can be a ground for further research on reducing the toxic effects of Fusarium on agricultural products, so that advancements in bio-herbicide technology may provide a sustainable agricultural production. Copyright © 2017 Elsevier GmbH. All rights reserved.

Evaluating the toxic effects of three priority hazardous and noxious substances (HNS) to rotifer Brachionus plicatilis.

PubMed

Zheng, Lei; Pan, Luqing; Lin, Pengfei; Miao, Jingjing; Wang, Xiufen; Lin, Yufei; Wu, Jiangyue

2017-12-01

Hazardous and noxious substances (HNS) spill in the marine environment is an issue of growing concern, and it will mostly continue to do so in the future owing to the increase of high chemical traffic. Nevertheless, the effects of HNS spill on marine environment, especially on aquatic organisms are unclear. Consequently, it is emergent to provide valuable information for the toxicities to marine biota caused by HNS spill. Accordingly, the acute toxicity of three preferential HNS and sub-lethal effects of acrylonitrile on Brachionus plicatilis were evaluated. The median lethal concentration (LC 50 ) at 24 h were 47.2 mg acrylonitrile L -1 , 276.9 mg styrene L -1 , and 488.3 mg p-xylene L -1 , respectively. Sub-lethal toxicity effects of acrylonitrile on feeding behavior, development, and reproduction parameters of B. plicatilis were also evaluated. Results demonstrated that rates of filtration and ingestion were significantly reduced at 2.0, 4.0, and 8.0 mg L -1 of acrylonitrile. Additionally, reproductive period, fecundity, and life span were significantly decreased at high acrylonitrile concentrations. Conversely, juvenile period was significantly increased at the highest two doses and no effects were observed on embryonic development and post-reproductive period. Meanwhile, we found that ingestion rate decline could be a good predictor of reproduction toxicity in B. plicatilis and ecologically relevant endpoint for toxicity assessment. These data will be useful to assess and deal with marine HNS spillages.

Triclosan persistence through wastewater treatment plants and its potential toxic effects on river biofilms.

PubMed

Ricart, Marta; Guasch, Helena; Alberch, Mireia; Barceló, Damià; Bonnineau, Chloé; Geiszinger, Anita; Farré, Marinel la; Ferrer, Josep; Ricciardi, Francesco; Romaní, Anna M; Morin, Soizic; Proia, Lorenzo; Sala, Lluís; Sureda, David; Sabater, Sergi

2010-11-15

Triclosan is a commonly used bactericide that survives several degradation steps in WWTP (wastewater treatment plants) and potentially reaches fluvial ecosystems. In Mediterranean areas, where water scarcity results in low dilution capacity, the potential environmental risk of triclosan is high. A set of experimental channels was used to examine the short-term effects of triclosan (from 0.05 to 500μgL⁻¹) on biofilm algae and bacteria. Environmentally relevant concentrations of triclosan caused an increase of bacterial mortality with a no effect concentration (NEC) of 0.21μgL⁻¹. Dead bacteria accounted for up to 85% of the total bacterial population at the highest concentration tested. The toxicity of triclosan was higher for bacteria than algae. Photosynthetic efficiency was inhibited with increasing triclosan concentrations (NEC=0.42μgL⁻¹), and non-photochemical quenching mechanisms decreased. Diatom cell viability was also affected with increasing concentrations of triclosan. Algal toxicity may be a result of indirect effects on the biofilm toxicity, but the clear and progressive reduction observed in all the algal-related endpoints suggest the existence of direct effects of the bactericide. The toxicity detected on the co-occurring non-target components of the biofilm community, the capacity of triclosan to survive through WWTP processes and the low dilution capacity that characterizes Mediterranean systems extend the relevance of triclosan toxicity beyond bacteria in aquatic habitats. Copyright © 2010 Elsevier B.V. All rights reserved.

The repellent and persistent toxic effects of essential oils against the poultry red mite, Dermanyssus gallinae.

PubMed

Nechita, I S; Poirel, M T; Cozma, V; Zenner, L

2015-12-15

The economic impact of the poultry red mite, Dermanyssus gallinae, the lack of new acaricides, the occurrence of resistance and tighter legislation have all led to the need to find new ways to control this pest. One promising alternative method of control focuses on employing repellent and/or toxic effects of selected plant essential oils against D. gallinae. Ten essential oils (basil, thyme, coriander, eucalyptus, lavender, lemon, fir tree, oregano, mint, and juniper) were tested for the persistence of toxic and repellent effects. In filter-paper toxicity bioassays against D. gallinae, the best results were observed for lavender (more than 97% mortality after 48 and 72 h) and thyme (84% at 72 h) at a dose of 0.12 mg/cm(2). In addition, two oils showed significant persistent toxic effects 15 and 30 days post application to filter papers. Thyme was the most effective (100% mortality at 72 h), followed by lavender (nearly 80% mortality after 72 h). Out of the ten oils tested for their repellent effect, thyme was the strongest, with nearly 80% of the tested area avoided by mites; oregano caused a 60% avoidance and lavender exhibited an effect close to 40%. All other oils exhibited a repellent effect of less than 30%. None of the experiments showed a repellent effect for HM (commercial alimentary oil) or negative controls. We found that the thyme and lavender essential oils exhibited promising results when tested in vitro for toxic and repellent effects against D. gallinae; thus, we suggest that future experiments focus on in vivo tests using these oils in farm units. Copyright © 2015 Elsevier B.V. All rights reserved.

In vitro toxicity analysis of nanoscale aluminum: Particle size and shape effects

NASA Astrophysics Data System (ADS)

Palazuelos Jorganes, Maria

2007-12-01

Nanostructured materials promise to revolutionize many key areas of science and technology. As our ability to manipulate matter at the nanoscale increases, there is a need to assess the effects of these materials on human health and the environment. Materials at the nanoscale are interesting and useful because they possess properties that are different from the equivalent bulk or molecular scale. These same properties can make toxicological profiles very different from those of the same materials on a different scale. There is a rising consensus that toxicity analysis of nanomaterials should start from a thorough physicochemical characterization of the materials under investigation in order to be able to establish a proper correlation between the nanoparticles characteristics and their effects and behavior in physiological environments. This research is a clear example of the necessity of comprehensive studies when investigating the toxicity of nanomaterials. Aluminum nanoparticles are being extensively used for their very unique energetic properties. These materials offer a very promising market that is fostering many startup companies which are expected to consolidate on strong technological positions. Aluminum is generally recognized as a non-toxic material to humans and it is widely used for applications which imply direct human contact. The effect of aluminum nanoparticles in human health is still an unknown. My research consisted of an in vitro toxicity screening of aluminum materials from nano to micron size, including spherical irregularly shaped particles. Several issues relating to size, shape, detection and characterization of nanoparticles in the different environments relevant to in vitro toxicity analysis were addressed and suitable protocols were developed. Lung human epithelial cells were exposed to different concentrations of these materials and the effects were analyzed by means of various toxicity tests. Some of the materials investigated caused elevated in vitro toxicity. Cells endocytosed the particles and a clear correlation between the particle size, shape and the effects observed was established. The hypothesized toxicity mechanism was explored using different analytical techniques. The detected toxicity of aluminum nanoparticles was demonstrated to be a direct effect of their reactivity inside the cells.

What ailed Goya?

PubMed

Ravin, J G; Ravin, T B

1999-01-01

At age 46, Francisco de Goya (1746-1828) suffered from a severe illness that lasted several months. It caused loss of vision and hearing, tinnitus, disorientation, weakness, abdominal distress, and general malaise. After a few months he recuperated but was left deaf forever. In addition to the physical effects, his emotional health and artwork were affected. The precise cause of this illness has long been debated. One early, but unlikely, hypothesis was that he had syphilis. Later conjectures have included Vogt-Koyanagi-Harada disease and lead toxicity. Cogan's syndrome and vasculitis are additional possibilities, although neither is likely to have been Goya's diagnosis. An infectious disease such as meningitis, encephalitis, or malaria is far more likely. Quinine toxicity (cinchonism) may have complicated the illness.

Liposomalization of oxaliplatin induces skin accumulation of it, but negligible skin toxicity.

PubMed

Nishida, Kentaro; Kashiwagi, Misaki; Shiba, Shunsuke; Muroki, Kiwamu; Ohishi, Akihiro; Doi, Yusuke; Ando, Hidenori; Ishida, Tatsuhiro; Nagasawa, Kazuki

2017-12-15

Liposomalization causes alteration of the pharmacokinetics of encapsulated drugs, and allows delivery to tumor tissues through passive targeting via an enhanced permeation and retention (EPR) effect. PEGylated liposomal doxorubicin (Doxil ® , Lipo-DXR), a representative liposomal drug, is well-known to reduce cardiotoxicity and increase the anti-tumor activity of DXR, but to induce the hand-foot syndrome (HFS) as a result of skin DXR accumulation, which is one of its severe adverse effects. We have developed a new liposomal preparation of oxaliplatin (l-OHP), an important anti-tumor drug for treatment of colorectal cancer, using PEGylated liposomes (Lipo-l-OHP), and showed that Lipo-l-OHP exhibits increased anti-tumor activity in tumor-bearing mice compared to the original preparation of l-OHP. However, whether Lipo-l-OHP causes HFS-like skin toxicity similar to Lipo-DXR remains to be determined. Administration of Lipo-l-OHP promoted accumulation of platinum in rat hind paws, however, it caused negligible morphological and histological alterations on the plantar surface of the paws. Administration of DiI-labeled empty PEGylated liposomes gave almost the same distribution profile of dyes into the dermis of hind paws with DXR as in the case of Lipo-DXR. Treatment with Lipo-l-OHP, Lipo-DXR, DiI-labeled empty PEGylated liposomes or empty PEGylated liposomes caused migration of CD68 + macrophages into the dermis of hind paws. These findings suggest that the skin toxicity on administration of liposomalized drugs is reflected in the proinflammatory characteristics of encapsulated drugs, and indicate that Lipo-l-OHP with a higher anti-cancer effect and no HFS may be an outstanding l-OHP preparation leading to an improved quality of life of cancer patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Cross-species extrapolation of toxicity information using the ...

EPA Pesticide Factsheets

In the United States, the Endocrine Disruptor Screening Program (EDSP) was established to identify chemicals that may lead to adverse effects via perturbation of the endocrine system (i.e., estrogen, androgen, and thyroid hormone systems). In the mid-1990s the EDSP adopted a two tiered approach for screening chemicals that applied standardized in vitro and in vivo toxicity tests. The Tier 1 screening assays were designed to identify substances that have the potential of interacting with the endocrine system and Tier 2 testing was developed to identify adverse effects caused by the chemical, with documentation of dose-response relationships. While this tiered approach was effective in identifying possible endocrine disrupting chemicals, the cost and time to screen a single chemical was significant. Therefore, in 2012 the EDSP proposed a transition to make greater use of computational approaches (in silico) and high-throughput screening (HTS; in vitro) assays to more rapidly and cost-efficiently screen chemicals for endocrine activity. This transition from resource intensive, primarily in vivo, screening methods to more pathway-based approaches aligns with the simultaneously occurring transformation in toxicity testing termed “Toxicity Testing in the 21st Century” which shifts the focus to the disturbance of the biological pathway predictive of the observable toxic effects. An example of such screening tools include the US Environmental Protection Agency’s

Assessing Aromatic-Hydrocarbon Toxicity to Fish Early Life Stages Using Passive-Dosing Methods and Target-Lipid and Chemical-Activity Models.

PubMed

Butler, Josh D; Parkerton, Thomas F; Redman, Aaron D; Letinski, Daniel J; Cooper, Keith R

2016-08-02

Aromatic hydrocarbons (AH) are known to impair fish early life stages (ELS). However, poorly defined exposures often confound ELS-test interpretation. Passive dosing (PD) overcomes these challenges by delivering consistent, controlled exposures. The objectives of this study were to apply PD to obtain 5 d acute embryo lethality and developmental data and 30 d chronic embryo-larval survival and growth-effects data using zebrafish with different AHs; to analyze study and literature toxicity data using target-lipid (TLM) and chemical-activity (CA) models; and to extend PD to a mixture and test the assumption of AH additivity. PD maintained targeted exposures over a concentration range of 6 orders of magnitude. AH toxicity increased with log Kow up to pyrene (5.2). Pericardial edema was the most sensitive sublethal effect that often preceded embryo mortality, although some AHs did not produce developmental effects at concentrations causing mortality. Cumulative embryo-larval mortality was more sensitive than larval growth, with acute-to-chronic ratios of <10. More-hydrophobic AHs did not exhibit toxicity at aqueous saturation. The relationship and utility of the TLM-CA models for characterizing fish ELS toxicity is discussed. Application of these models indicated that concentration addition provided a conservative basis for predicting ELS effects for the mixture investigated.

Effect of H+ ion activity and Ca2+ on the toxicity of metals in the environment.

PubMed Central

Hutchinson, T C; Collins, F W

1978-01-01

The role of acidity in determining and restricting plant distribution and performance is discussed. In soils especially, a key effect of H+ ion concentration is on the solubility of potentially toxic heavy metals such as aluminum, managenese, zinc, iron, copper, and nickel. Al has been reported from many studies since the 1920's as the key determining toxic factor in acid soils. Some acid-tolerant species have been shown to be especially tolerant of Al, and mechanisms of tolerance have been suggested. Mn is also a commonly toxic factor at soil pH less than 5.0. Calcium has been shown to alleviate Mn toxicity. Low pH soils are also generally low in Ca, K, Na, and P; all essential major elements for plant growth. In lakes and marine situations acidic waters are uncommon as the waters are buffered. Calcium is again ameliorative of metal toxicities. The pH, redox, and valency state are critical in determining nutrient availability and metal speciation. Recent increases in the H+ ion content of precipitation have caused increased acidities of freshwater lakes in Scandinavia and eastern North America, which have depleted biota, including fish populations. PMID:31277

The Role of Transporters in the Toxicity of Nucleoside and Nucleotide Analogs

PubMed Central

Koczor, Christopher A; Torres, Rebecca A

2013-01-01

Introduction Two families of nucleoside analogs have been developed to treat viral infections and cancer, but these compounds can cause tissue and cell-specific toxicity related to their uptake and subcellular activity which are dictated by host enzymes and transporters. Cellular uptake of these compounds requires nucleoside transporters that share functional similarities but differ in substrate specificity. Tissue-specific cellular expression of these transporters enables nucleoside analogs to produce their tissue specific toxic effects, a limiting factor in the treatment of retroviruses and cancer. Areas Covered This review discusses the families of nucleoside transporters and how they mediate cellular uptake of nucleoside analogs. Specific focus is placed on examples of known cases of transporter-mediated cellular toxicity and classification of the toxicities resulting. Efflux transporters are also explored as a contributor to analog toxicity and cell-specific effects. Expert Opinion Efforts to modulate transporter uptake/clearance remain long-term goals of oncologists and virologists. Accordingly, subcellular approaches that either increase or decrease intracellular nucleoside analog concentrations are eagerly sought and include transporter inhibitors and targeting transporter expression. However, additional understanding of nucleoside transporter kinetics, tissue expression, and genetic polymorphisms are required to design better molecules and better therapies. PMID:22509856

Identification of water soluble and particle bound compounds causing sublethal toxic effects. A field study on sediments affected by a chlor-alkali industry.

PubMed

Bosch, Carme; Olivares, Alba; Faria, Melissa; Navas, Jose M; del Olmo, Iván; Grimalt, Joan O; Piña, Benjamín; Barata, Carlos

2009-08-13

A combination of cost effective sublethal Daphnia magna feeding tests, yeast- and cell culture-based bioassays and Toxicity Identification Evaluation (TIE) procedures was used to characterize toxic compounds within sediments collected in a river area under the influence of the effluents from a chlor-alkali industry (Ebro River, NE Spain). Tests were designed to measure and identify toxic compounds in the particulate and filtered water fractions of sediment elutriates. The combined use of bioassays responding to elutriates and dioxin-like compounds evidenced the existence of three major groups of hazardous contaminants in the most contaminated site: (A) metals such as cadmium and mercury bound to sediment fine particles that could be easily resuspended and moved downstream, (B) soluble compounds (presumably, lye) able to alkalinize water to toxic levels, and (C) organochlorine compounds with high dioxin-like activity. These results provided evidence that elutriate D. magna feeding responses can be used as surrogate assays for more tedious chronic whole sediment tests, and that the incorporation of such tests in sediment TIE procedures may improve the ability to identify the toxicity of particle-bound and water-soluble contaminants in sediments.

Exposure to Cobalt Causes Transcriptomic and Proteomic Changes in Two Rat Liver Derived Cell Lines

PubMed Central

Permenter, Matthew G.; Dennis, William E.; Sutto, Thomas E.; Jackson, David A.; Lewis, John A.; Stallings, Jonathan D.

2013-01-01

Cobalt is a transition group metal present in trace amounts in the human diet, but in larger doses it can be acutely toxic or cause adverse health effects in chronic exposures. Its use in many industrial processes and alloys worldwide presents opportunities for occupational exposures, including military personnel. While the toxic effects of cobalt have been widely studied, the exact mechanisms of toxicity remain unclear. In order to further elucidate these mechanisms and identify potential biomarkers of exposure or effect, we exposed two rat liver-derived cell lines, H4-II-E-C3 and MH1C1, to two concentrations of cobalt chloride. We examined changes in gene expression using DNA microarrays in both cell lines and examined changes in cytoplasmic protein abundance in MH1C1 cells using mass spectrometry. We chose to closely examine differentially expressed genes and proteins changing in abundance in both cell lines in order to remove cell line specific effects. We identified enriched pathways, networks, and biological functions using commercial bioinformatic tools and manual annotation. Many of the genes, proteins, and pathways modulated by exposure to cobalt appear to be due to an induction of a hypoxic-like response and oxidative stress. Genes that may be differentially expressed due to a hypoxic-like response are involved in Hif-1α signaling, glycolysis, gluconeogenesis, and other energy metabolism related processes. Gene expression changes linked to oxidative stress are also known to be involved in the NRF2-mediated response, protein degradation, and glutathione production. Using microarray and mass spectrometry analysis, we were able to identify modulated genes and proteins, further elucidate the mechanisms of toxicity of cobalt, and identify biomarkers of exposure and effect in vitro, thus providing targets for focused in vivo studies. PMID:24386269

Involvement of the histamine H{sub 4} receptor in clozapine-induced hematopoietic toxicity: Vulnerability under granulocytic differentiation of HL-60 cells

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

Goto, Aya; Mouri, Akihiro; Nagai, Tomoko

Clozapine is an effective antipsychotic for treatment-resistant schizophrenia, but can cause fatal hematopoietic toxicity as agranulocytosis. To elucidate the mechanism of hematopoietic toxicity induced by clozapine, we developed an in vitro assay system using HL-60 cells, and investigated the effect on hematopoiesis. HL-60 cells were differentiated by all-trans retinoic acid (ATRA) into three states according to the following hematopoietic process: undifferentiated HL-60 cells, those undergoing granulocytic ATRA-differentiation, and ATRA-differentiated granulocytic cells. Hematopoietic toxicity was evaluated by analyzing cell survival, cell proliferation, granulocytic differentiation, apoptosis, and necrosis. In undifferentiated HL-60 cells and ATRA-differentiated granulocytic cells, both clozapine (50 and 100 μM)more » and doxorubicin (0.2 µM) decreased the cell survival rate, but olanzapine (1–100 µM) did not. Under granulocytic differentiation for 5 days, clozapine, even at a concentration of 25 μM, decreased survival without affecting granulocytic differentiation, increased caspase activity, and caused apoptosis rather than necrosis. Histamine H{sub 4} receptor mRNA was expressed in HL-60 cells, whereas the expression decreased under granulocytic ATRA-differentiation little by little. Both thioperamide, a histamine H{sub 4} receptor antagonist, and DEVD-FMK, a caspase-3 inhibitor, exerted protection against clozapine-induced survival rate reduction, but not of live cell counts. 4-Methylhistamine, a histamine H{sub 4} receptor agonist, decreased the survival rate and live cell counts, as did clozapine. HL-60 cells under granulocytic differentiation are vulnerable under in vitro assay conditions to hematopoietic toxicity induced by clozapine. Histamine H{sub 4} receptor is involved in the development of clozapine-induced hematopoietic toxicity through apoptosis, and may be a potential target for preventing its occurrence through granulocytic differentiation. - Highlights: • HL-60 cells under granulocytic differentiation were vulnerable for clozapine. • HL-60 cells would be in vitro assay systems for hematopoietic toxicity by clozapine. • Histamine H{sub 4} receptor was involved in hematopoietic toxicity with apoptosis. • Histamine H{sub 4} receptor may be therapeutic target to prevent hematopoietic toxicity.« less

Nanoparticles: Health Effects—Pros and Cons

PubMed Central

Gwinn, Maureen R.; Vallyathan, Val

2006-01-01

With the advent of nanotechnology, the prospects for using engineered nanomaterials with diameters of < 100 nm in industrial applications, medical imaging, disease diagnoses, drug delivery, cancer treatment, gene therapy, and other areas have progressed rapidly. The potential for nanoparticles (NPs) in these areas is infinite, with novel new applications constantly being explored. The possible toxic health effects of these NPs associated with human exposure are unknown. Many fine particles generally considered “nuisance dusts” are likely to acquire unique surface properties when engineered to nanosize and may exhibit toxic biological effects. Consequently, the nuisance dust may be transported to distant sites and could induce adverse health effects. In addition the beneficial uses of NPs in drug delivery, cancer treatment, and gene therapy may cause unintentional human exposure. Because of our lack of knowledge about the health effects associated with NP exposure, we have an ethical duty to take precautionary measures regarding their use. In this review we highlight the possible toxic human health effects that can result from exposure to ultrafine particles (UFPs) generated by anthropogenic activities and their cardiopulmonary outcomes. The comparability of engineered NPs to UFPs suggests that the human health effects are likely to be similar. Therefore, it is prudent to elucidate their toxicologic effect to minimize occupational and environmental exposure. Highlighting the human health outcomes caused by UFPs is not intended to give a lesser importance to either the unprecedented technologic and industrial rewards of the nanotechnology or their beneficial human uses. PMID:17185269

Environmentally relevant levels of λ-cyhalothrin, fenvalerate, and permethrin cause developmental toxicity and disrupt endocrine system in zebrafish (Danio rerio) embryo.

PubMed

Zhang, Quan; Zhang, Yi; Du, Jie; Zhao, Meirong

2017-10-01

Synthetic pyrethroids (SPs) are one of the most widely used pesticides and frequently detected in the aquatic environment. Previous studies have shown that SPs posed high aquatic toxicity, but information on the developmental toxicity and endocrine disruption on zebrafish (Danio rerio) at environmentally relevant concentrations is limited. In this study, zebrafish embryos were employed to examine the adverse effects of λ-cyhalothrin (LCT), fenvalerate (FEN), and permethrin (PM) at 2.5, 10, 25, 125, 500 nM for 96 h. The results showed these 3 SPs caused dose-dependent mortality, malformation rate, and hatching rate. Thyroid hormone triiodothyronine (T 3 ) levels were significantly decreased after exposure to LCT and FEN. Quantitative real-time PCR analysis was then performed on a series of nuclear receptors (NRs) genes involved in the hypothalamic-pituitary-gonadal (HPG), hypothalamic-pituitary-thyroid (HPT), hypothalamic-pituitary-adrenocortical (HPA) axes, and oxidative-stress-related system. Our results showed that LCT, FEN, and PM downregulated AR expression while upregulated ER1 expression, and caused alteration to ER2a and ER2b expression. As for the expression of TRα and TRβ, they were both decreased following exposure to the 3 SPs. LCT and PM downregulated the MR expression and FEN induced MR expression. In addition, the expression of GR was increased after treating with LCT, while it was suppressed after exposure to FEN and PM. The 3 SPs also caused various alterations to the expression of genes including AhRs, PPARα, and PXR. These findings suggest that these 3 SPs may cause developmental toxicity to zebrafish larvae by disrupting endocrine signaling at environmentally relevant concentrations. Copyright © 2017. Published by Elsevier Ltd.

Preventive effects of fructose and N-acetyl-L-cysteine against cytotoxicity induced by the psychoactive compounds N-methyl-5-(2-aminopropyl)benzofuran and 3,4-methylenedioxy-N-methamphetamine in isolated rat hepatocytes.

PubMed

Nakagawa, Yoshio; Suzuki, Toshinari; Inomata, Akiko

2018-02-01

Psychoactive compounds, N-methyl-5-(2-aminopropyl)benzofuran (5-MAPB) and 3,4-methylenedioxy-N-methamphetamine (MDMA), are known to be hepatotoxic in humans and/or experimental animals. As previous studies suggested that these compounds elicited cytotoxicity via mitochondrial dysfunction and/or oxidative stress in rat hepatocytes, the protective effects of fructose and N-acetyl-l-cysteine (NAC) on 5-MAPB- and MDMA-induced toxicity were studied in rat hepatocytes. These drugs caused not only concentration-dependent (0-4 mm) and time-dependent (0-3 hours) cell death accompanied by the depletion of cellular levels of adenosine triphosphate (ATP) and glutathione (reduced form; GSH) but also an increase in the oxidized form of GSH. The toxic effects of 5-MAPB were greater than those of MDMA. Pretreatment of hepatocytes with either fructose at a concentration of 10 mm or NAC at a concentration of 2.5 mm prevented 5-MAPB-/MDMA-induced cytotoxicity. In addition, the exposure of hepatocytes to 5-MAPB/MDMA caused the loss of mitochondrial membrane potential, although the preventive effect of fructose was weaker than that of NAC. These results suggest that: (1) 5-MAPB-/MDMA-induced cytotoxicity is linked to mitochondrial failure and depletion of cellular GSH; (2) insufficient cellular ATP levels derived from mitochondrial dysfunction were ameliorated, at least in part, by the addition of fructose; and (3) GSH loss via oxidative stress was prevented by NAC. Taken collectively, these results indicate that the onset of toxic effects caused by 5-MAPB/MDMA may be partially attributable to cellular energy stress as well as oxidative stress. Copyright © 2017 John Wiley & Sons, Ltd.

Are insect repellents toxic to freshwater insects? A case study using caddisflies exposed to DEET.

PubMed

Campos, Diana; Gravato, Carlos; Quintaneiro, Carla; Koba, Olga; Randak, Tomas; Soares, Amadeu M V M; Pestana, João L T

2016-04-01

Stream ecosystems face ever-increasing pressures by the presence of emergent contaminants, such as, personal care products. N, N-diethyl-3-methylbenzamide (DEET) is a synthetic insect repellent that is being found in surface waters environments in concentrations up to 33.4 μg/L. Information concerning DEET's toxicity in the aquatic environment is still limited and focused only on its acute effects on model species. Our main objective was to assess the effects of DEET exposure to a caddisfly non-target species using sub-lethal endpoints. For that, we chose Sericostoma vittatum, an important shredder in Portuguese freshwaters that has been already used in different ecotoxicological assays. Besides acute tests, S. vittatum were exposed during 6 days to a gradient of DEET concentrations (8, 18 and 40.5 mg/L) to assess effects on feeding behaviour and biochemical responses, such as, lipid peroxidation levels (LPO), catalase and acetylcholinesterase (AChE) activities, and also assess effects on energy reserves and consumption. Acute tests revealed a 48 h-LC50 of 80.12 mg/L and DEET exposure caused feeding inhibition with a LOEC of 36.80 mg/L. Concerning the biochemical responses, DEET caused no effects in LPO nor on catalase activity. A non-significant decrease in AChE activity was observed. Regarding energetic reserves, exposure to DEET caused a significant reduction in S. vittatum carbohydrates levels. These results add important information for the risk assessment of insect repellents in the aquatic environment and suggest that reported environmental concentrations of DEET are not toxic to non-target freshwater insects. Copyright © 2016 Elsevier Ltd. All rights reserved.

Transport, fate, and long-term impacts of metal oxide nanoparticles on the stability of an anaerobic methanogenic system with anaerobic granular sludge.

PubMed

Li, Huiting; Cui, Fuyi; Liu, Zhiquan; Li, Dapeng

2017-06-01

The fate and long-term effect of different metal oxide (TiO 2 , CuO and ZnO) nanoparticles (NPs) on anaerobic granular sludge (AGS) was evaluated in an anaerobic methanogenic system. Operation stability and structural characteristics of the granules were compared, the metabolism changes in the microbial community were quantified, and NPs fate were investigated. CuO NPs had greatest toxic effect on AGS after extended exposure, whereas ZnO NPs benefited methanogenesis temporarily (no more than 5d). The inhibition on AGS caused by NPs varied due to the unique structure of AGS and different toxic mechanism. Structural changes of AGS provided new evidence that tested NPs have different toxicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of soil organic matter content on cadmium toxicity in Eisenia fetida: implications for the use of biomarkers and standard toxicity tests.

PubMed

Irizar, A; Rodríguez, M P; Izquierdo, A; Cancio, I; Marigómez, I; Soto, M

2015-01-01

Bioavailability is affected by soil physicochemical characteristics such as pH and organic matter (OM) content. In addition, OM constitutes the energy source of Eisenia fetida, a well established model species for soil toxicity assessment. The present work aimed at assessing the effects of changes in OM content on the toxicity of Cd in E. fetida through the measurement of neutral red uptake (NRU) and mortality, growth, and reproduction (Organisation for Economic Co-operation and Development [OECD] Nos. 207 and 222). Complementarily, metallothionein (MT) and catalase transcription levels were measured. To decrease variability inherent to natural soils, artificial soils (Organization for Economic Cooperation and Development 1984) with different OM content (6, 10, and 14%) and spiked with Cd solutions at increasing concentrations were used. Low OM in soil decreased soil ingestion and Cd bioaccumulation but also increased Cd toxicity causing lower NRU of coelomocytes, 100 % mortality, and stronger reproduction impairment, probably due to the lack of energy to maintain protection mechanisms (production of MT).Cd bioaccumulation did not reflect toxicity, and OM played a pivotal role in Cd toxicity. Thus, OM content should be taken into account when using E. fetida in in vivo exposures for soil health assessment.

ToxCast Phase I

EPA Pesticide Factsheets

Background: Chemical toxicity testing is being transformed by advances in biology and computer modeling, concerns over animal use and the thousands of environmental chemicals lacking toxicity data. EPA's ToxCast program aims to address these concerns by screening and prioritizing chemicals for potential human toxicity using in vitro assays and in silico approaches. Objectives: This project aims to evaluate the use of in vitro assays for understanding the types of molecular and pathway perturbations caused by environmental chemicals and to build initial prioritization models of in vivo toxicity. Methods: We tested 309 mostly pesticide active chemicals in 467 assays across 9 technologies, including high-throughput cell-free assays and cell-based assays in multiple human primary cells and cell lines, plus rat primary hepatocytes. Both individual and composite scores for effects on genes and pathways were analyzed. Results: Chemicals display a broad spectrum of activity at the molecular and pathway levels. Many expected interactions are seen, including endocrine and xenobiotic metabolism enzyme activity. Chemicals range in promiscuity across pathways, from no activity to affecting dozens of pathways. We find a statistically significant inverse association between the number of pathways perturbed by a chemical at low in vitro concentrations and the lowest in vivo dose at which a chemical causes toxicity. We also find associations between a small set in vitro ass

Impacts of low-molecular-weight organic acids on aquatic behavior of graphene nanoplatelets and their induced algal toxicity and antioxidant capacity.

PubMed

Wang, Zhuang; Gao, Yucheng; Wang, Se; Fang, Hao; Xu, Defu; Zhang, Fan

2016-06-01

Knowledge of the interaction between graphene-based materials and low-molecular-weight organic acids (LOAs) is essential to understand fate and effects of graphene-based materials in the aquatic environment, but this interaction remains poorly elucidated. In this study, the effects of LOAs on the physicochemical properties of graphene nanoplatelets (GNPs) in an aqueous medium and on the GNP toxicity to algae were studied. The unicellular green alga Scenedesmus obliquus was exposed to GNP suspensions in the presence of benzoic acid or gallic acid at various concentrations. The GNPs had smaller hydrodynamic sizes and the GNP suspensions were more stable and had higher or lower surface zeta potentials in the presence of LOAs than when LOAs were not present. The toxic effects in S. obliquus cultures incubated with GNP suspensions containing LOAs were related to the LOA concentration, and the presence of LOAs caused three effects: stimulation, alleviation, and synergistic inhibition. The intensities of the effects mainly correlated with the LOA concentration, the extent of agglomeration, and particle-induced oxidative stress. The results indicate that the environmental fates and toxicities of GNPs are strongly affected by the binding of GNPs to LOAs.

Differential cardiac effects in rats exposed to atmospheric smog generated from isoprene versus toluene

EPA Science Inventory

The results of this study demonstrate that atmospheric smog generated from both isoprene and toluene cause cardiac effects in rats. In addition, it appears that smog from toluene is more toxic in terms of cardiac arrhythmogenicity. Smog, which is a comple...

Effects of ToxCast Phase I Chemicals on Steroidogenesis in H295R Human Adrenocortical Carcinoma cells (SOT)

EPA Science Inventory

Steroid hormones are essential for proper development and reproduction. Disruption of steroidogenesis by environmental toxicants results in altered hormone levels causing adverse reproductive and developmental effects. H295R human adrenocortical carcinoma cells were used to evalu...

Vegetable Oils and Animal Fats

EPA Pesticide Factsheets

non-petroleum oils are also regulated under CFR 112. Like petroleum oils, they can cause devastating physical effects, be toxic, destroy food supplies and habitats, produce rancid odors, foul shorelines and treatment plants, be flammable, and linger.

Hazardous and toxic waste management in Botswana: practices and challenges.

PubMed

Mmereki, Daniel; Li, Baizhan; Meng, Liu

2014-12-01

Hazardous and toxic waste is a complex waste category because of its inherent chemical and physical characteristics. It demands for environmentally sound technologies and know-how as well as clean technologies that simultaneously manage and dispose it in an environmentally friendly way. Nevertheless, Botswana lacks a system covering all the critical steps from importation to final disposal or processing of hazardous and toxic waste owing to limited follow-up of the sources and types of hazardous and toxic waste, lack of modern and specialised treatment/disposal facilities, technical know-how, technically skilled manpower, funds and capabilities of local institutions to take lead in waste management. Therefore, because of a lack of an integrated system, there are challenges such as lack of cooperation among all the stakeholders about the safe management of hazardous and toxic waste. Furthermore, Botswana does not have a systematic regulatory framework regarding monitoring and hazardous and toxic waste management. In addition to the absence of a systematic regulatory framework, inadequate public awareness and dissemination of information about hazardous and toxic waste management, slower progress to phase-out persistent and bio-accumulative waste, and lack of reliable and accurate information on hazardous and toxic waste generation, sources and composition have caused critical challenges to effective hazardous and toxic waste management. It is, therefore, important to examine the status of hazardous and toxic waste as a waste stream in Botswana. By default; this mini-review article presents an overview of the current status of hazardous and toxic waste management and introduces the main challenges in hazardous and toxic waste management. Moreover, the article proposes the best applicable strategies to achieve effective hazardous and toxic waste management in the future. © The Author(s) 2014.

Toxicity of sediment cores collected from the Ashtabula River in northeastern Ohio, USA, to the amphipod Hyalella azteca

USGS Publications Warehouse

Ingersoll, C.G.; Kemble, N.E.; Kunz, J.L.; Brumbaugh, W.G.; MacDonald, D.D.; Smorong, D.

2009-01-01

This study was conducted to support a Natural Resource Damage Assessment and Restoration project associated with the Ashtabula River in Ohio. The objective of the study was to evaluate the chemistry and toxicity of 50 sediment samples obtained from five cores collected from the Ashtabula River (10 samples/core, with each 10-cm-diameter core collected to a total depth of about 150 cm). Effects of chemicals of potential concern (COPCs) measured in the sediment samples were evaluated by measuring whole-sediment chemistry and whole-sediment toxicity in the sediment samples (including polycyclic aromatic hydrocarbons [PAHs], polychlorinated biphenyls [PCBs], organochlorine pesticides, and metals). Effects on the amphipod Hyalella azteca at the end of a 28-day sediment toxicity test were determined by comparing survival or length of amphipods in individual sediment samples in the cores to the range of responses of amphipods exposed to selected reference sediments that were also collected from the cores. Mean survival or length of amphipods was below the lower limit of the reference envelope in 56% of the sediment samples. Concentrations of total PCBs alone in some samples or concentrations of total PAHs alone in other samples were likely high enough to have caused the reduced survival or length of amphipods (i.e., concentrations of PAHs or PCBs exceeded mechanistically based and empirically based sediment quality guidelines). While elevated concentrations of ammonia in pore water may have contributed to the reduced length of amphipods, it is unlikely that the reduced length was caused solely by elevated ammonia (i.e., concentrations of ammonia were not significantly correlated with the concentrations of PCBs or PAHs and concentrations of ammonia were elevated both in the reference sediments and in the test sediments). Results of this study show that PAHs, PCBs, and ammonia are the primary COPCs that are likely causing or substantially contributing to the toxicity to sediment-dwelling organisms. ?? 2009 US Government.

Development of a toxicity identification evaluation procedure for characterizing metal toxicity in marine sediments

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

Burgess, R.M.; Cantwell, M.G.; Pelletier, M.C.

2000-04-01

A multiagency effort is underway to develop whole sediment toxicity identification evaluation (TIE) methods. Whole sediment TIE methods will be critical tools for characterizing toxicity at hazardous waste sites and in the conduct of environmental risk assessments. The research approach is based on the predominance of three classes of toxicants in sediments: ammonia, nonpolar organic chemicals, and metals. Here the authors describe a procedure for characterizing acute toxicity caused by metals in whole marine sediments. The procedure involves adding a chelating resin to sediments, resulting in the sequestration of bioavailable metal while not stressing testing organisms. Within the testing chambers,more » the presence of resin resulted in statistically significant reductions in the overlying and interstitial water concentrations of five metals (cadmium, copper, nickel, lead, and zinc) generally by factors of 40 and 200. Toxicity to both the amphipod Ampelisca abdita and mysid Americamysis bahia (formerly Mysidopsis bahia) of sediments spiked with the five metals was decreased by approximately a factor of four when resin was present. While very effective at reducing the concentrations and toxicity of metals, the resin has only minor ameliorative effects on the toxicity of ammonia and a representative nonpolar toxicant (Endosulfan). Resin and accumulated metal were easily isolated from the testing system following exposures allowing for the initiation of phase II TIE (identification) procedures. This procedure using the addition of a chelating resin provides an approach for determining the importance of metals to the toxicity of marine sediments. Work is continuing to validate the method with environmentally contaminated sediments.« less

Mechanisms of cadmium-caused eye hypoplasia and hypopigmentation in zebrafish embryos.

PubMed

Zhang, Ting; Zhou, Xin-Ying; Ma, Xu-Fa; Liu, Jing-Xia

2015-10-01

Cadmium-caused head and eye hypoplasia and hypopigmentation has been recognized for a long time, but knowledge of the underlying mechanisms is limited. In this study, we found that high mortality occurred in exposed embryos after 24 hpf, when cadmium (Cd) dosage was above 17.8 μM. Using high-throughput in situ hybridization screening, we found that genes labelling the neural crest and its derivative pigment cells exhibited obviously reduced expression in Cd-exposed embryos from 24 hpf, 2 days earlier than head and eye hypoplasia and hypopigmentation occurred. Moreover, based on expression of crestin, a neural crest marker, we found that embryos before the gastrula stage were more sensitive to cadmium toxicity and that damage caused by Cd on embryogenesis was dosage dependent. In addition, by phenotype observation and detection of neural crest and pigment cell markers, we found that BIO and retinoic acid (RA) could neutralize the toxic effects of Cd on zebrafish embryogenesis. In this study, we first determined that Cd blocked the formation of the neural crest and inhibited specification of pigment cells, which might contribute to the molecular mechanisms underlying the phenotype defects of head and eye hypoplasia and hypopigmentation in Cd-exposed embryos. Moreover, we found that compounds BIO or RA could neutralize the toxic effects of Cd. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

The impact of Staphylococcus aureus-associated molecular patterns on staphylococcal superantigen-induced toxic shock syndrome and pneumonia.

PubMed

Tilahun, Ashenafi Y; Karau, Melissa; Ballard, Alessandro; Gunaratna, Miluka P; Thapa, Anusa; David, Chella S; Patel, Robin; Rajagopalan, Govindarajan

2014-01-01

Staphylococcus aureus is capable of causing a spectrum of human illnesses. During serious S. aureus infections, the staphylococcal pathogen-associated molecular patterns (PAMPs) such as peptidoglycan, lipoteichoic acid, and lipoproteins and even intact S. aureus, are believed to act in conjunction with the staphylococcal superantigens (SSAg) to activate the innate and adaptive immune system, respectively, and cause immunopathology. However, recent studies have shown that staphylococcal PAMPs could suppress inflammation by several mechanisms and protect from staphylococcal toxic shock syndrome, a life-threatening systemic disease caused by toxigenic S. aureus. Given the contradictory pro- and anti-inflammatory roles of staphylococcal PAMPs, we examined the effects of S. aureus-derived molecular patterns on immune responses driven by SSAg in vivo using HLA-DR3 and HLA-DQ8 transgenic mice. Our study showed that neither S. aureus-derived peptidoglycans (PGN), lipoteichoic acid (LTA), nor heat-killed Staphylococcus aureus (HKSA) inhibited SSAg-induced T cell proliferation in vitro. They failed to antagonize the immunostimulatory effects of SSAg in vivo as determined by their inability to attenuate systemic cytokine/chemokine response and reduce SSAg-induced T cell expansion. These staphylococcal PAMPs also failed to protect HLA-DR3 as well as HLA-DQ8 transgenic mice from either SSAg-induced toxic shock or pneumonia induced by a SSAg-producing strain of S. aureus.

Putrescine as indicator of manganese neurotoxicity: Dose-response study in human SH-SY5Y cells.

PubMed

Fernandes, Jolyn; Chandler, Joshua D; Liu, Ken H; Uppal, Karan; Go, Young-Mi; Jones, Dean P

2018-06-01

Disrupted polyamine metabolism with elevated putrescine is associated with neuronal dysfunction. Manganese (Mn) is an essential nutrient that causes neurotoxicity in excess, but methods to evaluate biochemical responses to high Mn are limited. No information is available on dose-response effects of Mn on putrescine abundance and related polyamine metabolism. The present research was to test the hypothesis that Mn causes putrescine accumulation over a physiologically adequate to toxic concentration range in a neuronal cell line. We used human SH-SY5Y neuroblastoma cells treated with MnCl 2 under conditions that resulted in cell death or no cell death after 48 h. Putrescine and other metabolites were analyzed by liquid chromatography-ultra high-resolution mass spectrometry. Putrescine-related pathway changes were identified with metabolome-wide association study (MWAS). Results show that Mn caused a dose-dependent increase in putrescine over a non-toxic to toxic concentration range. MWAS of putrescine showed positive correlations with the polyamine metabolite N8-acetylspermidine, methionine-related precursors, and arginine-associated urea cycle metabolites, while putrescine was negatively correlated with γ-aminobutyric acid (GABA)-related and succinate-related metabolites (P < 0.001, FDR < 0.01). These data suggest that measurement of putrescine and correlated metabolites may be useful to study effects of Mn intake in the high adequate to UL range. Copyright © 2018. Published by Elsevier Ltd.

The use of bacteria for detecting toxic effects of pollutants in soil and water

NASA Astrophysics Data System (ADS)

Obiakor, Maximilian; Wilson, Susan; Tighe, Matthew; Pereg, Lily

2017-04-01

Microbial abundance and diversity are essential for sustaining soil structure and function and have been strongly linked to human health and wellbeing. Antimony (Sb) in the environment can present an ecological hazard and depending on concentration can be lethal. The toxic effects of Sb(III) and Sb(V) on the model soil bacterium Azospirillum brasilense Sp7 were assessed in exposure-dose-response assays and water samples from an Sb contaminated creek were analyzed for bacterial mortality. In both cases, Sb(III) and Sb(V) greatly affected the survival of A. brasilense Sp7 cells. The Sb(III) had a greater toxic effect than Sb(V) at all concentrations tested. Critical concentrations of Sb also caused variant colonies to appear, indicating both acute and sub-lethal effects, which were dose and time dependent. This work demonstrates the usefulness of A. brasilense as an indicator species to detect harmful effects of an environmental pollutant of emerging concern.

Risks, risk assessment and risk competence in toxicology

PubMed Central

Stahlmann, Ralf; Horvath, Aniko

2015-01-01

Understanding the toxic effects of xenobiotics requires sound knowledge of physiology and biochemistry. The often described lack of understanding pharmacology/toxicology is therefore primarily caused by the general absence of the necessary fundamental knowledge. Since toxic effects depend on exposure (or dosage) assessing the risks arising from toxic substances also requires quantitative reasoning. Typically public discussions nearly always neglect quantitative aspects and laypersons tend to disregard dose-effect-relationships. One of the main reasons for such disregard is the fact that exposures often occur at extremely low concentrations that can only be perceived intellectually but not by the human senses. However, thresholds in the low exposure range are often scientifically disputed. At the same time, ignorance towards known dangers is wide-spread. Thus, enhancing the risk competence of laypersons will have to be initially restricted to increasing the awareness of existing problems. PMID:26195922

Stimulation of Diethylnitrosamine Metabolism Reduces Its General Toxic and Hepatocarcinogenic Effects.

PubMed

Il'nitskaya, S I; Kaledin, V I; Bogdanova, L A; Morozkova, T S; Kapustina, V I; Perepechaeva, M L; Grishanova, A Yu

2016-11-01

The general toxic and hepatocarcinogenic effects of diethylnitrosamine after stimulation of its metabolism with 1,4-bis[2-(3,5-dichloropyridyloxy)]-benzene (TCPOBOP) were studied. The hydroxylating activity of liver microsomes of C57Bl/6Mv mice towards p-nitrophenol increased more than 4-fold 3 days after injection of TCPOBOP. Injection of diethylnitrosamine 3 days after TCPOBOP caused a lesser body weight loss and decrease of food consumption in C57Bl/6Mv mice than in response to diethylnitrosamine without preinduction. Injection of diethylnitrosamine to suckling ICR mice after TCPOBOP induction of cytochrome P450 2e1 activity led to development of 2-fold lesser number of tumors and pretumorous nodes in the liver in comparison with animals injected with diethylnitrosamine without induction. These data indicated that metabolism stimulation reduced the general toxic and hepatocarcinogenic effects of diethylnitrosamine.

Pentachlorophenol-Treated Materials

DTIC Science & Technology

1991-09-30

C SOLUBILITY IN WATER [g/lOOg H20 at 20 °C (68 OF)]: 0.002 MELTING POINT: 182 - 190 ’C (360 - 374 °F) APPEARANCE AND ODOR : Light brown solid with a...pungent odor when hot. INCOMPATIBILITY: Contact with strong oxidizers may cause fires and explosions. HAZARDOUS DECOMPOSITION PRODUCTS: Toxic gases and...FR) 11798). The rule, which became effective on September 25, 1990, adds 25 new organic compounds to the list of toxic constituents that may render a

Conference summary & recent advances: The 8th Conference on Metal Toxicity and Carcinogenesis

PubMed Central

Zhou, Xixi; Burchiel, Scott W.; Hudson, Laurie G.; Liu, Ke Jian

2015-01-01

Diseases caused by occupational and environmental exposure to metals are a public health concern. The underlying molecular mechanisms of metal toxicity and carcinogenicity remain largely unknown. Over 130 scientists attended the 8th Conference on Metal Toxicity and Carcinogenesis, presenting their various research concerns and recent findings to stimulate interactions and collaborations among scientists in the field. Several major areas were emphasized, including human & population studies, molecular & cellular mechanisms, biological targets, epigenetic effects, metabolism, and metal mixtures. Here we summarize presentations at the conference sessions and highlight the attendees’ latest work published in this special issue of Biological Trace Element Research. PMID:25975949

Synergistic interactions between a variety of insecticides and an ergosterol biosynthesis inhibitor fungicide in dietary exposures of bumble bees (Bombus terrestris L.).

PubMed

Raimets, Risto; Karise, Reet; Mänd, Marika; Kaart, Tanel; Ponting, Sally; Song, Jimao; Cresswell, James E

2018-03-01

In recent years, concern has been raised over honey bee colony losses, and also among wild bees there is evidence for extinctions and range contractions in Europe and North America. Pesticides have been proposed as a potential cause of this decline. Bees are exposed simultaneously to a variety of agrochemicals, which may cause synergistically detrimental impacts, which are incompletely understood. We investigated the toxicity of the fungicide imazalil in mixture with four common insecticides: fipronil (phenylpyrazoid), cypermethrin (pyrethroid), thiamethoxam, and imidacloprid (neonicotinoids). Ergosterol biosynthesis inhibitor (EBI) fungicides like imazalil can inhibit P450 detoxification systems in insects and therefore fungicide - insecticide co-occurrence might produce synergistic toxicity in bees. We assessed the impact of dietary fungicide - insecticide mixtures on the mortality and feeding rates of laboratory bumble bees (Bombus terrestris L.). Regarding mortality, imazalil synergised the toxicity of fipronil, cypermethrin and thiamethoxam, but not imidacloprid. We found no synergistic effects on feeding rates. Our findings suggest that P450-based detoxification processes are differentially important in mitigating the toxicity of certain insecticides, even those of the same chemical class. Our evidence that cocktail effects can arise in bumble bees should extend concern about the potential impacts of agrochemical mixtures to include wild bee species in farmland. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Effects of bisphenol A and its analogs bisphenol F and S on life parameters, antioxidant system, and response of defensome in the marine rotifer Brachionus koreanus.

PubMed

Park, Jun Chul; Lee, Min-Chul; Yoon, Deok-Seo; Han, Jeonghoon; Kim, Moonkoo; Hwang, Un-Ki; Jung, Jee-Hyun; Lee, Jae-Seong

2018-06-01

To understand the adverse outcome in response to bisphenol A and its analogs bisphenol F and S (BPA, BPF, and BPS), we examined acute toxicity, life parameter, and defensome in the marine rotifer Brachionus koreanus. Among the bisphenol analogs, BPA showed the highest acute toxicity and then BPF and BPS, accordingly in the view of descending magnitude of toxicity. In life parameters including life span and reproduction, BPA, BPF, and BPS were found to cause adverse effect. Both intracellular ROS level and GST activity were significantly increased (P < 0.05) in response to each dosage of bisphenol analogs exposures. In response to bisphenol analogs, defensomes of phase I, II, and III detoxification mechanism demonstrated inverse relationship between the lipophilicity of bisphenol analogs and the expression patterns of defensomes. BPA and BPF were found to have significant modulation (P < 0.05) in the expression of cytochrome P450 (CYP) and GST genes. In phase III, BPS with comparatively lower lipophilicity demonstrated highly diversified expressional pattern, suggesting that BPS is likely caused less toxicity compared to BPA and BPF. In this study, via phase I, II, and III detoxification mechanism, bisphenol A and its analogs F and S demonstrated specific detoxification mechanism in rotifer. Copyright © 2018 Elsevier B.V. All rights reserved.

Simultaneous quantification of twelve compounds in ethyl acetate extracts of Euphorbia kansui before and after fry-baked with vinegar by UPLC-MS/MS and its toxic effect on zebrafish.

PubMed

Zhang, Qiao; Zhang, Kai-Cheng; Lou, Jian-Wei; Guo, Shu-Chen; Zhang, Yi; Yao, Wei-Feng; Tang, Yu-Ping; Wu, Jian-Hua; Zhang, Li

2018-06-05

The dried roots of Euphorbia kansui T.N. Liou ex T.P. Wang have been traditionally used for edema in China. However, the severe toxicity caused by Euphorbia kansui has seriously restricted its clinical application. Therefore, in order to study the material basis of the toxicity attenuation effect of processing with vinegar, a rapid, sensitive, validated and reliable UPLC-MS/MS method was developed to determine twelve compounds in ethyl acetate extracts of Euphorbia kansui before and after fry-baked with vinegar simultaneously. Meanwhile, the study of their toxic effect on zebrafish was conducted. Chromatographic separation was accomplished on Waters BEH C 18 UPLC column. 0.3% formic acid in water and acetonitrile were used as mobile phase with a flow rate of 0.40 mL/min and a temperature at 30 °C. The analysis was performed in multiple reaction monitoring (MRM) mode using positive electrospray ionization (ESI). Furthermore, the toxic research results indicated that the toxicity of Euphorbia kansui was decreased after vinegar-processed, which might because of the increase in the content of 5-O-benzoyl-20-deoxyingenol and the decrease in the contents of the remaining terpenoids in ethyl acetate extracts of Euphorbia kansui fry-baked with vinegar. This study demonstrated that the method used is a powerful approach to determine the content of twelve compounds that responsible for the toxic effect of Euphorbia kansui at the same instant. And provided the experimental evidence for the rationale behind the reduction of toxicity. Copyright © 2018 Elsevier B.V. All rights reserved.

Liver Necrosis and Lipid Peroxidation in the Rat as the Result of Paraquat and Diquat Administration

PubMed Central

Burk, Raymond F.; Lawrence, Richard A.; Lane, James M.

1980-01-01

Paraquat and diquat facilitate formation of superoxide anion in biological systems, and lipid peroxidation has been postulated to be their mechanism of toxicity. Paraquat has been shown to be more toxic to selenium-deficient mice than to controls, presumably as the result of decreased activity of the selenoenzyme glutathione peroxidase. The present study was designed to measure lipid peroxidation and to assess toxicity in control and selenium-deficient rats given paraquat and diquat. Lipid peroxidation was measured by determining ethane production rates of intact animals; toxicity was assessed by survival and by histological and serum enzyme evidence of liver and kidney necrosis. Paraquat and diquat were both much more toxic to selenium-deficient rats than to control rats. Diquat (19.5 μmol/kg) caused rapid and massive liver and kidney necrosis and very high ethane production rates in selenium-deficient rats. The effect of paraquat (78 μmol/kg) was similar to that of diquat but was not as severe. Acutely lethal doses of paraquat (390 μmol/kg) and diquat (230 μmol/kg) in control rats caused very little ethane production and no evidence of liver necrosis. These findings suggest that paraquat and diquat exert their acute toxicity largely through lipid peroxidation in selenium-deficient rats. Selenium deficiency had no effect on superoxide dismutase activity in erythrocytes or in 105,000 g supernate of liver or kidney. Glutathione peroxidase, which represents the only well-characterized biochemical function of selenium in animals, was dissociated from the protective effect of selenium against diquat-induced lipid peroxidation and toxicity by a time-course study in which selenium-deficient rats were injected with 50 μg of selenium and later given diquat (19.5 μmol/kg). Within 10 h, the selenium injection provided significant protection against diquat-induced lipid peroxidation and mortality even though this treatment resulted in no rise in glutathione peroxidase activity of liver, kidney, lung, or plasma at 10 h. This suggests that a selenium-dependent factor in addition to glutathione peroxidase exists that protects against lipid peroxidation. Images PMID:7364936

Failure of ATP supply to match ATP demand: the mechanism of toxicity of the lampricide, 3-trifluoromethyl-4-nitrophenol (TFM), used to control sea lamprey (Petromyzon marinus) populations in the Great Lakes.

PubMed

Birceanu, Oana; McClelland, Grant B; Wang, Yuxiang S; Wilkie, Michael P

2009-10-04

Although the pesticide, 3-trifluoromethyl-4-nitrophenol (TFM), has been extensively used to control invasive sea lamprey (Petromyzon marinus) populations in the Great Lakes, it is surprising that its mechanism(s) of toxicity is unresolved. A better knowledge of the mode of toxicity of this pesticide is needed for predicting and improving the effectiveness of TFM treatments on lamprey, and for risk assessments regarding potential adverse effects on invertebrate and vertebrate non-target organisms. We investigated two hypotheses of TFM toxicity in larval sea lamprey. The first was that TFM interferes with oxidative ATP production by mitochondria, causing rapid depletion of energy stores in vital, metabolically active tissues such as the liver and brain. The second was that TFM toxicity resulted from disruption of gill-ion uptake, adversely affecting ion homeostasis. Exposure of larval sea lamprey to 4.6 m gl(-1) TFM (12-h LC50) caused glycogen concentrations in the brain to decrease by 80% after 12h, suggesting that the animals increased their reliance on glycolysis to generate ATP due to a shortfall in ATP supply. This conclusion was reinforced by a 9-fold increase in brain lactate concentration, a 30% decrease in brain ATP concentration, and an 80% decrease in phosphocreatine (PCr) concentration after 9 and 12h. A more pronounced trend was noted in the liver, where glycogen decreased by 85% and ATP was no longer detected after 9 and 12h. TFM led to marginal changes in whole body Na(+), Cl(-), Ca(2+) and K(+), as well as in plasma Na(+) and Cl(-), which were unlikely to have contributed to toxicity. TFM had no adverse effect on Na(+) uptake rates or gill Na(+)/K(+)-ATPase activity. We conclude that TFM toxicity in the sea lamprey is due to a mismatch between ATP consumption and ATP production rates, leading to a depletion of glycogen in the liver and brain, which ultimately leads to neural arrest and death.

Ligand-Specific Transcriptional Mechanisms Underlie Aryl Hydrocarbon Receptor-Mediated Developmental Toxicity of Oxygenated PAHs

PubMed Central

Goodale, B. C.; La Du, J.; Tilton, S. C.; Sullivan, C. M.; Bisson, W. H.; Waters, K. M.; Tanguay, R. L.

2015-01-01

Polycyclic aromatic hydrocarbons (PAHs) are priority environmental contaminants that exhibit mutagenic, carcinogenic, proinflammatory, and teratogenic properties. Oxygen-substituted PAHs (OPAHs) are formed during combustion processes and via phototoxidation and biological degradation of parent (unsubstituted) PAHs. Despite their prevalence both in contaminated industrial sites and in urban air, OPAH mechanisms of action in biological systems are relatively understudied. Like parent PAHs, OPAHs exert structure-dependent mutagenic activities and activation of the aryl hydrocarbon receptor (AHR) and cytochrome p450 metabolic pathway. Four-ring OPAHs 1,9-benz-10-anthrone (BEZO) and benz(a)anthracene-7,12-dione (7,12-B[a]AQ) cause morphological aberrations and induce markers of oxidative stress in developing zebrafish with similar potency, but only 7,12-B[a]AQ induces robust Cyp1a protein expression. We investigated the role of the AHR in mediating the toxicity of BEZO and 7,12-B[a]AQ, and found that knockdown of AHR2 rescued developmental effects caused by both compounds. Using RNA-seq and molecular docking, we identified transcriptional responses that precede developmental toxicity induced via differential interaction with AHR2. Redox-homeostasis genes were affected similarly by these OPAHs, while 7,12-B[a]AQ preferentially activated phase 1 metabolism and BEZO uniquely decreased visual system genes. Analysis of biological functions and upstream regulators suggests that BEZO is a weak AHR agonist, but interacts with other transcriptional regulators to cause developmental toxicity in an AHR-dependent manner. Identifying ligand-dependent AHR interactions and signaling pathways is essential for understanding toxicity of this class of environmentally relevant compounds. PMID:26141390

Allergy and "toxic mold syndrome".

PubMed

Edmondson, David A; Nordness, Mark E; Zacharisen, Michael C; Kurup, Viswanath P; Fink, Jordan N

2005-02-01

"Toxic mold syndrome" is a controversial diagnosis associated with exposure to mold-contaminated environments. Molds are known to induce asthma and allergic rhinitis through IgE-mediated mechanisms, to cause hypersensitivity pneumonitis through other immune mechanisms, and to cause life-threatening primary and secondary infections in immunocompromised patients. Mold metabolites may be irritants and may be involved in "sick building syndrome." Patients with environmental mold exposure have presented with atypical constitutional and systemic symptoms, associating those symptoms with the contaminated environment. To characterize the clinical features and possible etiology of symptoms in patients with chief complaints related to mold exposure. Review of patients presenting to an allergy and asthma center with the chief complaint of toxic mold exposure. Symptoms were recorded, and physical examinations, skin prick/puncture tests, and intracutaneous tests were performed. A total of 65 individuals aged 1 1/2 to 52 years were studied. Symptoms included rhinitis (62%), cough (52%), headache (34%), respiratory symptoms (34%), central nervous system symptoms (25%), and fatigue (23%). Physical examination revealed pale nasal mucosa, pharyngeal "cobblestoning," and rhinorrhea. Fifty-three percent (33/62) of the patients had skin reactions to molds. Mold-exposed patients can present with a variety of IgE- and non-IgE-mediated symptoms. Mycotoxins, irritation by spores, or metabolites may be culprits in non-IgE presentations; environmental assays have not been perfected. Symptoms attributable to the toxic effects of molds and not attributable to IgE or other immune mechanisms need further evaluation as to pathogenesis. Allergic, rather than toxic, responses seemed to be the major cause of symptoms in the studied group.

Sediment Toxicity Identification Evaluation

EPA Science Inventory

Approach combining chemical manipulations and aquatic toxicity testing, generally with whole organisms, to systematically characterize, identify and confirm toxic substances causing toxicity in whole sediments and sediment interstitial waters. The approach is divided into thre...

Agrochemical synergism imposes higher risk to Neotropical bees than to honeybees

PubMed Central

Tomé, Hudson V. V.; Ramos, Gabryele S.; Araújo, Micaele F.; Santana, Weyder C.; Santos, Gil R.; Guedes, Raul Narciso C.; Maciel, Carlos D.; Newland, Philip L.

2017-01-01

Bees are key pollinators whose population numbers are declining, in part, owing to the effects of different stressors such as insecticides and fungicides. We have analysed the susceptibility of the Africanized honeybee, Apis mellifera, and the stingless bee, Partamona helleri, to commercial formulations of the insecticides deltamethrin and imidacloprid. The toxicity of fungicides based on thiophanate-methyl and chlorothalonil were investigated individually and in combination, and with the insecticides. Results showed that stingless bees were more susceptible to insecticides than honeybees. The commercial fungicides thiophanate-methyl or chlorothalonil caused low mortality, regardless of concentration; however, their combination was as toxic as imidacloprid to both species, and over 400-fold more toxic than deltamethrin for A. mellifera. There were highly synergistic effects on mortality caused by interactions in the mixture of imidacloprid and the fungicides thiophanate-methyl, chlorothalonil and the combined fungicide formulation in A. mellifera, and also to a lesser extent in P. helleri. By contrast, mixtures of the deltamethrin and the combined fungicide formulation induced high synergy in P. helleri, but had little effect on the mortality of A. mellifera. Differences in physiology and modes of action of agrochemicals are discussed as key factors underlying the differences in susceptibility to agrochemicals. PMID:28280585

PROTECTIVE EFFECT OF MORINGA PEREGRINA LEAVES EXTRACT ON ACETAMINOPHEN -INDUCED LIVER TOXICITY IN ALBINO RATS.

PubMed

Azim, Samy Abdelfatah Abdel; Abdelrahem, Mohamed Taha; Said, Mostafa Mohamed; Khattab, Alshaimaa

2017-01-01

Acetaminophen is a common antipyretic drug but at overdose can cause severe hepatotoxicity that may further develop into liver failure and hepatic centrilobular necrosis in experimental animals and humans. This study was undertaken to assess the ameliorative role of Moringa peregrina leaves extract against acetaminophen toxicity in rats. Induction of hepatotoxicity was done by chronic oral administration of acetaminophen (750 mg/kg bwt) for 4 weeks. To study the possible hepatoprotective effect, Moringa peregrina leaves extract (200 mg/kg bwt) or Silymarin (50 mg/kg bwt) was administered orally, for 4 weeks, along with acetaminophen. acetaminophen significantly increased serum liver enzymes and caused oxidative stress, evidenced by significantly increased tissue malondialdehyde, glutathione peroxidase, hepatic DNA fragmentation, and significant decrease of glutathione and antioxidant enzymes in liver, blood and brain. On the other hand, administration of Moringa peregrina leaves extract reversed acetaminophen-related toxic effects through: powerful malondialdehyde suppression, glutathione peroxidase normalization and stimulation of the cellular antioxidants synthesis represented by significant increase of glutathione, catalase and superoxide dismutase in liver, blood and brain, besides, DNA fragmentation was significantly decreased in the liver tissue. acetaminophen induced oxidative damage can be improved by Moringa peregrina leaves extract-treatment, due to its antioxidant potential.

Long-term protective effects of methamphetamine preconditioning against single-day methamphetamine toxic challenges.

PubMed

Hodges, A B; Ladenheim, B; McCoy, M T; Beauvais, G; Cai, N; Krasnova, I N; Cadet, J L

2011-03-01

Methamphetamine (METH) use is associated with neurotoxic effects which include decreased levels of dopamine (DA), serotonin (5-HT) and their metabolites in the brain. We have shown that escalating METH dosing can protect against METH induced neurotoxicity in rats sacrificed within 24 hours after a toxic METH challenge. The purpose of the current study was to investigate if the protective effects of METH persisted for a long period of time. We also tested if a second challenge with a toxic dose of METH would cause further damage to monoaminergic terminals. Saline-pretreated rats showed significant METH-induced decreases in striatal DA and 5-HT levels in rats sacrificed 2 weeks after the challenge. Rats that received two METH challenges showed no further decreases in striatal DA or 5-HT levels in comparison to the single METH challenge. In contrast, METH-pretreated rats showed significant protection against METH-induced striatal DA and 5-HT depletion. In addition, the METH challenge causes substantial decreases in cortical 5-HT levels which were not further potentiated by a second drug challenge. METH preconditioning provided almost complete protection against METH -induced 5-HT depletion. These results are consistent with the idea that METH pretreatment renders the brain refractory to METH-induced degeneration of brain monoaminergic systems.

PROTECTIVE EFFECT OF MORINGA PEREGRINA LEAVES EXTRACT ON ACETAMINOPHEN -INDUCED LIVER TOXICITY IN ALBINO RATS

PubMed Central

Azim, Samy Abdelfatah Abdel; Abdelrahem, Mohamed Taha; Said, Mostafa Mohamed; khattab, Alshaimaa

2017-01-01

Background: Acetaminophen is a common antipyretic drug but at overdose can cause severe hepatotoxicity that may further develop into liver failure and hepatic centrilobular necrosis in experimental animals and humans. This study was undertaken to assess the ameliorative role of Moringa peregrina leaves extract against acetaminophen toxicity in rats. Materials and methods: Induction of hepatotoxicity was done by chronic oral administration of acetaminophen (750 mg/kg bwt) for 4 weeks. To study the possible hepatoprotective effect, Moringa peregrina leaves extract (200 mg/kg bwt) or Silymarin (50 mg/kg bwt) was administered orally, for 4 weeks, along with acetaminophen. Results: acetaminophen significantly increased serum liver enzymes and caused oxidative stress, evidenced by significantly increased tissue malondialdehyde, glutathione peroxidase, hepatic DNA fragmentation, and significant decrease of glutathione and antioxidant enzymes in liver, blood and brain. On the other hand, administration of Moringa peregrina leaves extract reversed acetaminophen-related toxic effects through: powerful malondialdehyde suppression, glutathione peroxidase normalization and stimulation of the cellular antioxidants synthesis represented by significant increase of glutathione, catalase and superoxide dismutase in liver, blood and brain, besides, DNA fragmentation was significantly decreased in the liver tissue. Conclusion: acetaminophen induced oxidative damage can be improved by Moringa peregrina leaves extract-treatment, due to its antioxidant potential. PMID:28573237

Toxicological characterization of a novel wastewater treatment process using EDTA-Na2Zn as draw solution (DS) for the efficient treatment of MBR-treated landfill leachate.

PubMed

Niu, Aping; Ren, Yi-Wei; Yang, Li; Xie, Shao-Lin; Jia, Pan-Pan; Zhang, Jing-Hui; Wang, Xiao; Li, Jing; Pei, De-Sheng

2016-07-01

Landfill leachate has become an important source of environmental pollution in past decades, due to the increase of waste volume. Acute toxic and genotoxic hazards to organisms can be caused by landfill leachate. Thus, how to efficiently recover water from landfill leachate and effectively eliminate combined toxicity of landfill leachate are the most pressing issues in waste management. In this study, EDTA-Na2Zn as draw solution (DS) was used to remove the toxicity of membrane bioreactor-treated landfill leachate (MBR-treated landfill leachate) in forward osmosis (FO) process, and nanofiltration (NF) was designed for recovering the diluted DS. Zebrafish and human cells were used for toxicity assay after the novel wastewater treatment process using EDTA-Na2Zn as DS. Results showed that the water recovery rate of MBR-treated landfill leachate (M-LL) in FO membrane system could achieve 66.5% and 71.2% in the PRO and FO mode respectively, and the diluted DS could be efficiently recovered by NF. Toxicity tests performed by using zebrafish and human cells showed that M-LL treated by EDTA-Na2Zn had no toxicity effect on zebrafish larvae and human cells, but it had very slight effect on zebrafish embryos. In conclusion, all results indicated that EDTA-Na2Zn as DS can effectively eliminate toxicity of landfill leachate and this method is economical and eco-friendly for treatment of different types of landfill leachate. Copyright © 2016 Elsevier Ltd. All rights reserved.

The interactive effects of essential ions and salinity on the survival of Mysidopsis bahia in 96-H acute toxicity tests of effluents discharged to marine and estuarine receiving waters

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

Douglas, W.S.; Horne, M.T.

1997-10-01

The importance of salinity in whole effluent toxicity tests using marine organisms has been acknowledged in most testing protocols. However, little if any attention has been given to the specific effects of alteration of the ionic composition of seawater solutions to the test organism. The presence of persistent toxicity in effluents with no apparent toxic agents prompted examination of the potential influence of essential ions on the survival of the opossum shrimp, Mysidopsis bahia, a common effluent toxicity indicator organism. Through stepwise additions of ionic salts to deionized water, the minimum complement of salts to maintain survival of M. bahiamore » during 96-h exposures was determined to be Ca, Mg, K, Br, Na, and Cl. The toxicity curves for Ca, Mg, K, and Br were then determined across test salinity ranging from 10 to 35 parts per thousand. These curves for Ca, Mg, and K revealed that there are significant negative effects on survival when the essential ions are present in either low or high concentrations relative to the levels in natural seawater. Although there were no statistically detectable effects of Br on organism survival over the concentration range tested (5--480 mg/L). Br toxicity at concentrations less than 5 mg/L and greater than 700 mg/L have been shown in other studies. In addition, the tolerance ranges for K, Ca, and Mg were shown to shift significantly with changes in salinity, with lower salinity causing an apparent decrease in tolerance to an excess of essential ions. Tests with toxic effluents from five industrial and municipal sources revealed that adjustment of the ionic balance prior to testing reduced or eliminated toxicity in four of the five whole effluents tested. Suggestions for integrating this information into biomonitoring programs and toxicity identification evaluations are presented.« less

Aluminum stress signaling in plants

PubMed Central

Baluska, Frantisek; Matsumoto, Hideaki

2009-01-01

Aluminum (Al) toxicity is a major constraint for crop production in acidic soil worldwide. When the soil pH is lower than 5, Al3+ is released to the soil and enters into root tip cell ceases root development of plant. In acid soil with high mineral content, Al is the major cause of phytotoxicity. The target of Al toxicity is the root tip, in which Al exposure causes inhibition of cell elongation and cell division, leading to root stunting accompanied by reduced water and nutrient uptake. A variety of genes have been identified that are induced or repressed upon Al exposure. At tissue level, the distal part of the transition zone is the most sensitive to Al. At cellular and molecular level, many cell components are implicated in the Al toxicity including DNA in nucleus, numerous cytoplastic compounds, mitochondria, the plasma membrane and the cell wall. Although it is difficult to distinguish the primary targets from the secondary effects so far, understanding of the target sites of the Al toxicity is helpful for elucidating the mechanisms by which Al exerts its deleterious effects on root growth. To develop high tolerance against Al stress is the major goal of plant sciences. This review examines our current understanding of the Al signaling with the physiological, genetic and molecular approaches to improve the crop performance under the Al toxicity. New discoveries will open up new avenues of molecular/physiological inquiry that should greatly advance our understanding of Al tolerance mechanisms. Additionally, these breakthroughs will provide new molecular resources for improving the crop Al tolerance via molecular-assisted breeding and biotechnology. PMID:19820334

Direct toxicity assessment - Methods, evaluation, interpretation.

PubMed

Gruiz, Katalin; Fekete-Kertész, Ildikó; Kunglné-Nagy, Zsuzsanna; Hajdu, Csilla; Feigl, Viktória; Vaszita, Emese; Molnár, Mónika

2016-09-01

Direct toxicity assessment (DTA) results provide the scale of the actual adverse effect of contaminated environmental samples. DTA results are used in environmental risk management of contaminated water, soil and waste, without explicitly translating the results into chemical concentration. The end points are the same as in environmental toxicology in general, i.e. inhibition rate, decrease in the growth rate or in yield and the 'no effect' or the 'lowest effect' measurement points of the sample dilution-response curve. The measurement unit cannot be a concentration, since the contaminants and their content in the sample is unknown. Thus toxicity is expressed as the sample proportion causing a certain scale of inhibition or no inhibition. Another option for characterizing the scale of toxicity of an environmental sample is equivalencing. Toxicity equivalencing represents an interpretation tool which enables toxicity of unknown mixtures of chemicals be converted into the concentration of an equivalently toxic reference substance. Toxicity equivalencing, (i.e. expressing the toxicity of unknown contaminants as the concentration of the reference) makes DTA results better understandable for non-ecotoxicologists and other professionals educated and thinking based on the chemical model. This paper describes and discusses the role, the principles, the methodology and the interpretation of direct toxicity assessment (DTA) with the aim to contribute to the understanding of the necessity to integrate DTA results into environmental management of contaminated soil and water. The paper also introduces the benefits of the toxicity equivalency method. The use of DTA is illustrated through two case studies. The first case study focuses on DTA of treated wastewater with the aim to characterize the treatment efficacy of a biological wastewater treatment plant by frequent bioassaying. The second case study applied DTA to investigate the cover layers of two bauxite residue (red mud) reservoirs. Based on the DTA results the necessary toxicity attenuation rate of the cover layers was estimated. Copyright © 2016 Elsevier B.V. All rights reserved.

Stronger effects of Roundup than its active ingredient glyphosate in damselfly larvae.

PubMed

Janssens, Lizanne; Stoks, Robby

2017-12-01

Pesticides are causing strong decreases in aquatic biodiversity at concentrations assumed safe by legislation. One reason for the failing risk assessment may be strong differences in the toxicity of the active ingredient of pesticides and their commercial formulations. Sublethal effects, especially those on behaviour, have been largely ignored in this context, yet can be equally important as lethal effects at the population and ecosystem levels. Here, we compared the toxicity of the herbicide Roundup and its active ingredient glyphosate on survival, but also on ecologically relevant sublethal traits (life history, behaviour and physiology) in damselfly larvae. Roundup was more toxic than glyphosate with negative effects on survival, behaviour and most of the physiological traits being present at lower concentrations (food intake, escape swimming speed) or even only present (survival, sugar and total energy content and muscle mass) following Roundup exposure. This confirms the toxicity of the surfactant POEA. Notably, also glyphosate was not harmless: a realistic concentration of 2mg/l resulted in reduced growth rate, escape swimming speed and fat content. Our results therefore indicate that the toxicity of Roundup cannot be fully attributed to its surfactant, thereby suggesting that also the new generation of glyphosate-based herbicides with other mixtures of surfactants likely will have adverse effects on non-target aquatic organisms. Ecotoxicological studies comparing the toxicity of active ingredients and their commercial formulations typically ignore behaviour while the here observed differential effects on behaviour likely will negatively impact damselfly populations. Our data highlight that risk assessment of pesticides ignoring sublethal effects may contribute to the negative effects of pesticides on aquatic biodiversity. Copyright © 2017 Elsevier B.V. All rights reserved.

Competitive interaction between Ditylum Brightwellii and Skeletonema Costatum by toxic metabolites

NASA Astrophysics Data System (ADS)

Rijstenbil, J. W.

Comparative growth experiments were carried out in order to examine the role of toxic metabolites in the competition between two marine diatom species. Ditylum brightwellii and Skeletonema costatum exhibited mutual inhibition and auto-inhibition. Charcoal filtration did not entirely remove the toxicity. Algal extracts were more toxic than algal filtrates. Cell lysis induced by osmotic-shock treatment caused auto-inhibition in a dense culture of D. brightwellii; cells of this species recovered from a low salinity treatment after addition of charcoal to a culture. In mixed cultures the growth of both species may be affected by mutual inhibition. Toxicity of media depends on the growth phase of the competitors. In dense cultures, comparable with algal blooms in eutrophic waters, exocrines may be more effective than in diluted cultures ( cf. mesotrophic waters.) Substances excreted in dense blooms of S. costatum may inhibit competing species.

Effect of borax on immune cell proliferation and sister chromatid exchange in human chromosomes

PubMed Central

Pongsavee, Malinee

2009-01-01

Background Borax is used as a food additive. It becomes toxic when accumulated in the body. It causes vomiting, fatigue and renal failure. Methods The heparinized blood samples from 40 healthy men were studied for the impact of borax toxicity on immune cell proliferation (lymphocyte proliferation) and sister chromatid exchange in human chromosomes. The MTT assay and Sister Chromatid Exchange (SCE) technic were used in this experiment with the borax concentrations of 0.1, 0.15, 0.2, 0.3 and 0.6 mg/ml. Results It showed that the immune cell proliferation (lymphocyte proliferation) was decreased when the concentrations of borax increased. The borax concentration of 0.6 mg/ml had the most effectiveness to the lymphocyte proliferation and had the highest cytotoxicity index (CI). The borax concentrations of 0.15, 0.2, 0.3 and 0.6 mg/ml significantly induced sister chromatid exchange in human chromosomes (P < 0.05). Conclusion Borax had effects on immune cell proliferation (lymphocyte proliferation) and induced sister chromatid exchange in human chromosomes. Toxicity of borax may lead to cellular toxicity and genetic defect in human. PMID:19878537

Toxicity prediction of compounds from turmeric (Curcuma longa L).

PubMed

Balaji, S; Chempakam, B

2010-10-01

Turmeric belongs to the ginger family Zingiberaceae. Currently, cheminformatics approaches are not employed in any of the spices to study the medicinal properties traditionally attributed to them. The aim of this study is to find the most efficacious molecule which does not have any toxic effects. In the present study, toxicity of 200 chemical compounds from turmeric were predicted (includes bacterial mutagenicity, rodent carcinogenicity and human hepatotoxicity). The study shows out of 200 compounds, 184 compounds were predicted as toxigenic, 136 compounds are mutagenic, 153 compounds are carcinogenic and 64 compounds are hepatotoxic. To cross validate our results, we have chosen the popular curcumin and found that curcumin and its derivatives may cause dose dependent hepatotoxicity. The results of these studies indicate that, in contrast to curcumin, few other compounds in turmeric which are non-mutagenic, non-carcinogenic, non-hepatotoxic, and do not have any side-effects. Hence, the cost-effective approach presented in this paper could be used to filter toxic compounds from the drug discovery lifecycle. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Lethal and Sublethal Impacts of Acaricides on Tamarixia radiata (Hemiptera: Eulophidae), an Important Ectoparasitoid of Diaphorina citri (Hemiptera: Liviidae).

PubMed

Lira, A C S; Zanardi, O Z; Beloti, V H; Bordini, G P; Yamamoto, P T; Parra, J R P; Carvalho, G A

2015-10-01

The use of synthetic acaricides for management of pest mites may alter the efficacy of the ectoparasitoid Tamarixia radiata (Waterston) in biological control of Diaphorina citri Kuwayama, the vector of the bacteria associated with huanglongbing (HLB) in citrus orchards. We evaluated the toxicity of 16 acaricides that are recommended for the control of citrus-pest mites to T. radiata. Acrinathrin, bifenthrin, carbosulfan, and fenpropathrin caused high acute toxicity and were considered harmful (mortality >77%) to T. radiata. Abamectin, diflubenzuron, etoxazole, fenbutatin oxide, fenpyroximate, flufenoxuron, hexythiazox, propargite, spirodiclofen, and sulfur caused low acute toxicity and affected the parasitism rate and emergence rate of adults (F1 generation), and were considered slightly harmful to T. radiata. Dicofol and pyridaben did not affect the survival and action of the ectoparasitoid, and were considered harmless. In addition to its acute toxicity, carbosulfan caused mortality higher than 25% for >30 d after application, and was considered persistent. Acrinathrin, bifenthrin, fenpropathrin, fenpyroximate, propargite, and sulfur caused mortalities over 25% until 24 d after application and were considered moderately persistent; abamectin was slightly persistent, and fenbutatin oxide was short lived. Our results suggest that most acaricides used to control pest mites in citrus affect the density and efficacy of T. radiata in the biological control of D. citri. However, further evaluations are needed in order to determine the effect of these products on this ectoparasitoid under field conditions. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Staphylococcal toxic shock syndrome: superantigen-mediated enhancement of endotoxin shock and adaptive immune suppression.

PubMed

Kulhankova, Katarina; King, Jessica; Salgado-Pabón, Wilmara

2014-08-01

Infectious diseases caused by Staphylococcus aureus present a significant clinical and public health problem. S. aureus causes some of the most severe hospital-associated and community-acquired illnesses. Specifically, it is the leading cause of infective endocarditis and osteomyelitis, and the second leading cause of sepsis in the USA. While pathogenesis of S. aureus infections is at the center of current research, many questions remain about the mechanisms underlying staphylococcal toxic shock syndrome (TSS) and associated adaptive immune suppression. Both conditions are mediated by staphylococcal superantigens (SAgs)-secreted staphylococcal toxins that are major S. aureus virulence factors. Toxic shock syndrome toxin-1 (TSST-1) is the SAg responsible for almost all menstrual TSS cases in the USA. TSST-1, staphylococcal enterotoxin B and C are also responsible for most cases of non-menstrual TSS. While SAgs mediate all of the hallmark features of TSS, such as fever, rash, hypotension, and multi-organ dysfunction, they are also capable of enhancing the toxic effects of endogenous endotoxin. This interaction appears to be critical in mediating the severity of TSS and related mortality. In addition, interaction between SAgs and the host immune system has been recognized to result in a unique form of adaptive immune suppression, contributing to poor outcomes of S. aureus infections. Utilizing rabbit models of S. aureus infective endocarditis, pneumonia and sepsis, and molecular genetics techniques, we aim to elucidate the mechanisms of SAg and endotoxin synergism in the pathogenesis of TSS, and examine the cellular and molecular mechanisms underlying SAg-mediated immune dysfunction.

Prevention and treatment of Nitrite toxicity in juvenile steelhead trout (Salmo gairdneri)

USGS Publications Warehouse

Wedemeyer, Gary A.; Yasutake, W.T.

1978-01-01

The efficacy of mineral salts, pH, and tetramethylthianine (methylene blue) treatment in reducing the acute toxicity of nitrite to fingerling steelhead trout (Salmo gairdneri) was determined using a static bioassay system at 10 °C. The acute toxicity (96-h LC50) was reduced by a factor of about 24 for 5-g steelhead and 13 for 10-g fish when the total water hardness was increased from 25 to 300 mg/L (as CaCO3). NaCl or CaCl2 additions (0–200 mg/L) reduced toxicity by a factor of up to 3 for NaCl and 50 for CaCl2. Increasing the pH from 6.0 to 8.0 decreased toxicity by a factor of about 8 for the smaller and 3 for the larger fish. Methylene blue at 0.1 or 1.0 mg/L was effective in decreasing acute toxicity. For alleviating methemoglobinemia, removing the fish to freshwater for 48 h was about as effective as 1.0 mg/L methylene blue. Chronic exposure in soft water to 0.03 mg/L NO2-N for 6 mo caused no significant growth reduction, gill histological changes, hematological dyscrasias, or impaired ability of the smolts to adapt to 30‰ seawater and grow for an additional 2 mo. Key words: nitrite, toxicity, fish, methylene blue, pH, salts, acute toxicity, chronic toxicity

Accelerated hematopoietic toxicity by high energy (56)Fe radiation.

PubMed

Datta, Kamal; Suman, Shubhankar; Trani, Daniela; Doiron, Kathryn; Rotolo, Jimmy A; Kallakury, Bhaskar V S; Kolesnick, Richard; Cole, Michael F; Fornace, Albert J

2012-03-01

There is little information on the relative toxicity of highly charged (Z) high-energy (HZE) radiation in animal models compared to γ or X-rays, and the general assumption based on in vitro studies has been that acute toxicity is substantially greater. C57BL/6J mice were irradiated with (56)Fe ions (1 GeV/nucleon), and acute (within 30 d) toxicity compared to that of γ rays or protons (1 GeV). To assess relative hematopoietic and gastrointestinal toxicity, the effects of (56)Fe ions were compared to γ rays using complete blood count (CBC), bone marrow granulocyte-macrophage colony forming unit (GM-CFU), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay for apoptosis in bone marrow, and intestinal crypt survival. Although onset was more rapid, (56)Fe ions were only slightly more toxic than γ rays or protons with lethal dose (LD)(50/30) (a radiation dose at which 50% lethality occurs at 30-day) values of 5.8, 7.25, and 6.8 Gy, respectively, with relative biologic effectiveness for (56)Fe ions of 1.25 and 1.06 for protons. (56)Fe radiation caused accelerated and more severe hematopoietic toxicity. Early mortality correlated with more profound leukopenia and subsequent sepsis. Results indicate that there is selective enhanced toxicity to bone marrow progenitor cells, which are typically resistant to γ rays, and bone marrow stem cells, because intestinal crypt cells did not show increased HZE toxicity.

Accelerated Hematopoietic Toxicity by High Energy 56Fe Radiation

PubMed Central

Datta, Kamal; Suman, Shubhankar; Trani, Daniela; Doiron, Kathryn; Rotolo, Jimmy A.; Kallakury, Bhaskar V. S.; Kolesnick, Richard; Cole, Michael F.; Fornace, Albert J.

2013-01-01

Purpose There is little information on the relative toxicity of highly charged (Z) high-energy (HZE) radiation in animal models compared to γ or x-rays, and the general assumption based on in vitro studies has been that acute toxicity is substantially greater. Methods C57BL/6J mice were irradiated with 56Fe ions (1 GeV/nucleon), and acute (within 30 d) toxicity compared to that of γ rays or protons (1 GeV). To assess relative hematopoietic and gastrointestinal toxicity, the effects of 56Fe ions were compared to γ rays using complete blood count (CBC), bone marrow granulocyte-macrophage colony forming unit (GM-CFU), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay for apoptosis in bone marrow, and intestinal crypt survival. Results Although onset was more rapid, 56Fe ions were only slightly more toxic than γ rays or protons with lethal dose (LD)50/30 (a radiation dose at which 50% lethality occurs at 30-day) values of 5.8, 7.25, and 6.8 Gy respectively with relative biologic effectiveness for 56Fe ions of 1.25 and 1.06 for protons. Conclusions 56Fe radiation caused accelerated and more severe hematopoietic toxicity. Early mortality correlated with more profound leukopenia and subsequent sepsis. Results indicate that there is selective enhanced toxicity to bone marrow progenitor cells, which are typically resistant to γ rays, and bone marrow stem cells, because intestinal crypt cells did not show increased HZE toxicity. PMID:22077279

Ketamine induces toxicity in human neurons differentiated from embryonic stem cells via mitochondrial apoptosis pathway

PubMed Central

Bosnjak, Zeljko J.; Yan, Yasheng; Canfield, Scott; Muravyeva, Maria Y.; Kikuchi, Chika; Wells, Clive; Corbett, John; Bai, Xiaowen

2013-01-01

Ketamine is widely used for anesthesia in pediatric patients. Growing evidence indicates that ketamine causes neurotoxicity in a variety of developing animal models. Our understanding of anesthesia neurotoxicity in humans is currently limited by difficulties in obtaining neurons and performing developmental toxicity studies in fetal and pediatric populations. It may be possible to overcome these challenges by obtaining neurons from human embryonic stem cells (hESCs) in vitro. hESCs are able to replicate indefinitely and differentiate into every cell type. In this study, we investigated the toxic effect of ketamine on neurons differentiated from hESCs. Two-week-old neurons were treated with different doses and durations of ketamine with or without the reactive oxygen species (ROS) scavenger, Trolox. Cell viability, ultrastructure, mitochondrial membrane potential (ΔΨm), cytochrome c distribution within cells, apoptosis, and ROS production were evaluated. Here we show that ketamine induced ultrastructural abnormalities and dose- and time-dependently caused cell death. In addition, ketamine decreased ΔΨm and increased cytochrome c release from mitochondria. Ketamine also increased ROS production and induced differential expression of oxidative stress-related genes. Specifically, abnormal ultrastructural and ΔΨm changes occurred earlier than cell death in the ketamine-induced toxicity process. Furthermore, Trolox significantly decreased ROS generation and attenuated cell death caused by ketamine in a dose-dependent manner. In conclusion, this study illustrates that ketamine time- and dose-dependently induces human neurotoxicity via ROS-mediated mitochondrial apoptosis pathway and that these side effects can be prevented by the antioxidant agent Trolox. Thus, hESC-derived neurons might provide a promising tool for studying anesthetic-induced developmental neurotoxicity and prevention strategies. PMID:22873495

Acute exposure to offshore produced water has an effect on stress- and secondary stress responses in three-spined stickleback Gasterosteus aculeatus.

PubMed

Knag, Anne Christine; Taugbøl, Annette

2013-09-01

Pollution is one of today's greatest problems, and the release of contaminants into the environment can cause adverse changes in vitally important biological pathways. In this study, we exposed three-spined stickleback Gasterosteus aculeatus to produced water (PW), i.e. wastewater from offshore petroleum production. PW contains substances such as alkylphenols (APs) and aromatic hydrocarbons (PAHs) known to induce toxicant stress and endocrine disruption in a variety of organisms. Following exposure to PW, a standardized confinement treatment was applied as a second stressor (PW-stress), testing how fish already under stress from the pollutant would respond to an additional stressor. The endpoint for analysis was a combination of blood levels of cortisol and glucose, in addition to transcribed levels of a set of genes related to toxicant stress, endocrine disruption and general stress. The findings of this study indicate that low doses of PW do not induce vitellogenin in immature female stickleback, but do cause an upregulation of cytochrome (CYP1A) and UDP-glucuronsyltransferase (UDP-GT), two biomarkers related to toxicant stress. However, when the second stressor was applied, both genes were downregulated, indicating that the confinement exposure had a suppressive effect on the expression of toxicant biomarkers (CYP1A and UDP-GT). Further, two of the stress related genes, heat shock protein 90 (HSP90) and stress-induced phosphoprotein (STIP), were upregulated in both PW- and PW-stress-treatment, but not in the water control confinement treatment, indicating that PW posed as a larger stress-factor than confinement for these genes. The confinement stressor caused an increased level of glucose in both control and PW-treated fish, indicating hyperglycemia, a commonly reported stress response in fish. © 2013.

Toxic effects of environmental rare earth elements on delayed outward potassium channels and their mechanisms from a microscopic perspective.

PubMed

Wang, Lihong; He, Jingfang; Xia, Ao; Cheng, Mengzhu; Yang, Qing; Du, Chunlei; Wei, Haiyan; Huang, Xiaohua; Zhou, Qing

2017-08-01

The wide applications cause a large amount of rare earth elements (REEs) to be released into the environment, and ultimately into the human body through food chain. Toxic effects of REEs on humans have been extensively studied, but their toxic effects and binding targets in cells are not understood. Delayed outward potassium channels (K + channels) are good targets for exogenous substances or clinical drugs. To evaluate cellular toxicities of REEs and clarify toxic mechanisms, the toxicities of REEs on the K + channel and their structural basis were investigated. The results showed that delayed outward potassium channels on the plasma membrane are the targets of REEs acting on living organisms, and the changes in the thermodynamic and kinetic characteristics of the K + channel are the reasons of diseases induced by REEs. Two types of REEs, a light REE La 3+ and a heavy REE Tb 3+ , displayed different intensity of toxicities on the K + channel, in which the toxicity of Tb 3+ was stronger than that of La 3+ . More interestingly, in comparison with that of heavy metal Cd 2+ , the cytotoxicities of the light and heavy REEs showed discriminative differences, and the cytotoxicity of Tb 3+ was higher than that of Cd 2+ , while the cytotoxicity of La 3+ was lower than that of Cd 2+ . These different cytotoxicities of La 3+ , Tb 3+ and Cd 2+ on human resulted from the varying binding abilities of the metals to this channel protein. Copyright © 2017 Elsevier Ltd. All rights reserved.

Incomplete transfer of accessory loci influencing SbMATE expression underlies genetic background effects for aluminum tolerance in sorghum

USDA-ARS?s Scientific Manuscript database

Impaired root development caused by aluminum (Al) toxicity is a major cause for grain yield reduction for crops cultivated on acid soils which are widespread worldwide. In sorghum, the major Al tolerance locus, AltSB, is due to the function of SbMATE, which is an Al-activated root citrate transporte...

Ecotoxicological effect of ketamine: Evidence of acute, chronic and photolysis toxicity to Daphnia magna.

PubMed

Li, Shih-Wei; Wang, Yu-Hsiang; Lin, Angela Yu-Chen

2017-09-01

Ketamine has been increasingly used in medicine and has the potential for abuse or illicit use around the world. Ketamine cannot be removed by conventional wastewater treatment plants. Although ketamine and its metabolite norketamine have been detected to a significant degree in effluents and aquatic environments, their ecotoxicity effects in aquatic organisms remain undefined. In this study, we investigated the acute toxicity of ketamine and its metabolite, along with the chronic reproductive toxicity of ketamine (5-100μg/L) to Daphnia magna. Multiple environmental scenarios were also evaluated, including drug mixtures and sunlight irradiation toxicity. Ketamine and norketamine caused acute toxicity to D. magna, with half lethal concentration (LC 50 ) values of 30.93 and 25.35mg/L, respectively, after 48h of exposure. Irradiated solutions of ketamine (20mg/L) significantly increased the mortality of D. magna; pre-irradiation durations up to 2h rapidly increased the death rate to 100%. A new photolysis byproduct (M.W. 241) of norketamine that accumulates during irradiation was identified for the first time. The relevant environmental concentration of ketamine produced significant reproductive toxicity effects in D. magna, as revealed by the reduction of the number of total live offspring by 33.6-49.8% (p < 0.05). The toxicity results indicate that the environmental hazardous risks of the relevant ketamine concentration cannot be ignored and warrant further examination. Copyright © 2017 Elsevier Inc. All rights reserved.

Investigation of olive mill wastewater (OMW) ozonation efficiency with the use of a battery of selected ecotoxicity and human toxicity assays.

PubMed

Siorou, Sofia; Vgenis, Theodoros T; Dareioti, Margarita A; Vidali, Maria-Sophia; Efthimiou, Ioanna; Kornaros, Michael; Vlastos, Dimitris; Dailianis, Stefanos

2015-07-01

The effects of olive mill wastewater (OMW) on a battery of biological assays, before and during the ozonation process, were investigated in order to assess ozone's efficiency in removing phenolic compounds from OMW and decreasing the concomitant OMW toxicity. Specifically, ozonated-OMW held for 0, 60, 120, 300, 420, 540min in a glass bubble reactor, showed a drastic reduction of OMW total phenols (almost 50%) after 300min of ozonation with a concomitant decrease of OMW toxicity. In particular, the acute toxicity test primarily performed in the fairy shrimp Thamnocephalus platyurus (Thamnotoxkit F™ screening toxicity test) showed a significant attenuation of OMW-induced toxic effects, after ozonation for a period of 120 and in a lesser extent 300min, while further treatment resulted in a significant enhancement of ozonated-OMW toxic effects. Furthermore, ozonated-OMW-treated mussel hemocytes showed a significant attenuation of the ability of OMW to cause cytotoxic (obtained by the use of NRRT assay) effects already after an ozonation period of 120 and to a lesser extent 300min. In accordance with the latter, OMW-mediated oxidative (enhanced levels of superoxide anions and lipid peroxidation by-products) and genotoxic (induction of DNA damage) effects were diminished after OMW ozonation for the aforementioned periods of time. The latter was also revealed by the use of cytokinesis block micronucleus (CBMN) assay in human lymphocytes exposed to different concentrations of both raw- and ozonated-OMW for 60, 120 and 300min. Those findings revealed for a first time the existence of a critical time point during the OMW ozonation process that could be fundamentally used for evaluating OMW ozonation as a pretreatment method of OMW. Copyright © 2015 Elsevier B.V. All rights reserved.

The underlying toxicological mechanism of chemical mixtures: A case study on mixture toxicity of cyanogenic toxicants and aldehydes to Photobacterium phosphoreum

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

Tian, Dayong; Department of Chemical and Environmental Engineering, Anyang Institute of Technology, Anyang 455000; Lin, Zhifen, E-mail: lzhifen@tongji.edu.cn

Intracellular chemical reaction of chemical mixtures is one of the main reasons that cause synergistic or antagonistic effects. However, it still remains unclear what the influencing factors on the intracellular chemical reaction are, and how they influence on the toxicological mechanism of chemical mixtures. To reveal this underlying toxicological mechanism of chemical mixtures, a case study on mixture toxicity of cyanogenic toxicants and aldehydes to Photobacterium phosphoreum was employed, and both their joint effects and mixture toxicity were observed. Then series of two-step linear regressions were performed to describe the relationships between joint effects, the expected additive toxicities and descriptorsmore » of individual chemicals (including concentrations, binding affinity to receptors, octanol/water partition coefficients). Based on the quantitative relationships, the underlying joint toxicological mechanisms were revealed. The result shows that, for mixtures with their joint effects resulting from intracellular chemical reaction, their underlying toxicological mechanism depends on not only their interaction with target proteins, but also their transmembrane actions and their concentrations. In addition, two generic points of toxicological mechanism were proposed including the influencing factors on intracellular chemical reaction and the difference of the toxicological mechanism between single reactive chemicals and their mixtures. This study provided an insight into the understanding of the underlying toxicological mechanism for chemical mixtures with intracellular chemical reaction. - Highlights: • Joint effects of nitriles and aldehydes at non-equitoxic ratios were determined. • A novel descriptor, ligand–receptor interaction energy (E{sub binding}), was employed. • Quantitative relationships for mixtures were developed based on a novel descriptor. • The underlying toxic mechanism was revealed based on quantitative relationships. • Two generic points of toxicological mechanism were elucidated.« less

Interaction of the carbon monoxide-releasing molecule Ru(CO)3Cl(glycinate) (CORM-3) with Salmonella enterica serovar Typhimurium: in situ measurements of carbon monoxide binding by integrating cavity dual-beam spectrophotometry.

PubMed

Rana, Namrata; McLean, Samantha; Mann, Brian E; Poole, Robert K

2014-12-01

Carbon monoxide (CO) is a toxic gas that binds to haems, but also plays critical signalling and cytoprotective roles in mammalian systems; despite problems associated with systemic delivery by inhalation of the gas, it may be employed therapeutically. CO delivered to cells and tissues by CO-releasing molecules (CO-RMs) has beneficial and toxic effects not mimicked by CO gas; CO-RMs are also attractive candidates as novel antimicrobial agents. Salmonella enterica serovar Typhimurium is an enteropathogen causing gastroenteritis in humans. Recent studies have implicated haem oxygenase-1 (HO-1), the protein that catalyses the degradation of haem into biliverdin, free iron and CO, in the host immune response to Salmonella infection. In several studies, CO administration via CO-RMs elicited many of the protective roles of HO-1 induction and so we investigated the effects of a well-characterized water-soluble CO-RM, Ru(CO)3Cl(glycinate) (CORM-3), on Salmonella. CORM-3 exhibits toxic effects at concentrations significantly lower than those reported to cause toxicity to RAW 264.7 macrophages. We demonstrated here, through oxyhaemoglobin assays, that CORM-3 did not release CO spontaneously in phosphate buffer, buffered minimal medium or very rich medium. CORM-3 was, however, accumulated to high levels intracellularly (as shown by inductively coupled plasma MS) and released CO inside cells. Using growing Salmonella cultures without prior concentration, we showed for the first time that sensitive dual-beam integrating cavity absorption spectrophotometry can detect directly the CO released from CORM-3 binding in real-time to haems of the bacterial electron transport chain. The toxic effects of CO-RMs suggested potential applications as adjuvants to antibiotics in antimicrobial therapy. © 2014 The Authors.

Effects of harmful cyanobacteria on the freshwater pathogenic free-living amoeba Acanthamoeba castellanii.

PubMed

Urrutia-Cordero, Pablo; Agha, Ramsy; Cirés, Samuel; Lezcano, María Ángeles; Sánchez-Contreras, María; Waara, Karl-Otto; Utkilen, Hans; Quesada, Antonio

2013-04-15

Grazing is a major regulating factor in cyanobacterial population dynamics and, subsequently, considerable effort has been spent on investigating the effects of cyanotoxins on major metazoan grazers. However, protozoan grazers such as free-living amoebae can also feed efficiently on cyanobacteria, while simultaneously posing a major threat for public health as parasites of humans and potential reservoirs of opportunistic pathogens. In this study, we conducted several experiments in which the freshwater amoeba Acanthamoeba castellanii was exposed to pure microcystin-LR (MC-LR) and six cyanobacterial strains, three MC-producing strains (MC-LR, MC-RR, MC-YR, MC-WR, [Dha7] MC-RR) and three strains containing other oligopeptides such as anabaenopeptins and cyanopeptolins. Although the exposure to high concentrations of pure MC-LR yielded no effects on amoeba, all MC-producing strains inflicted high mortality rates on amoeba populations, suggesting that toxic effects must be mediated through the ingestion of toxic cells. Interestingly, an anabaenopeptin-producing strain caused the greatest inhibition of amoeba growth, indicating that toxic bioactive compounds other than MCs are of great importance for amoebae grazers. Confocal scanning microscopy revealed different alterations in amoeba cytoskeleton integrity and as such, the observed declines in amoeba densities could have indeed been caused via a cascade of cellular events primarily triggered by oligopeptides with protein-phosphatase inhibition capabilities such as MCs or anabaenopeptins. Moreover, inducible-defense mechanisms such as the egestion of toxic, MC-producing cyanobacterial cells and the increase of resting stages (encystation) in amoebae co-cultivated with all cyanobacterial strains were observed in our experiments. Consequently, cyanobacterial strains showed different susceptibilities to amoeba grazing which were possibly influenced by the potentiality of their toxic secondary metabolites. Hence, this study shows the importance of cyanobacterial toxicity against amoeba grazing and, that cyanobacteria may contain a wide range of chemical compounds capable of negatively affect free-living, herbivorous amoebae. Moreover, this is of high importance for understanding the interactions and population dynamics of such organisms in aquatic ecosystems. Copyright © 2012 Elsevier B.V. All rights reserved.

Toxicity of Superparamagnetic Iron Oxide Nanoparticles on Green Alga Chlorella vulgaris

PubMed Central

Barhoumi, Lotfi

2013-01-01

Toxicity of superparamagnetic iron oxide nanoparticles (SPION) was investigated on Chlorella vulgaris cells exposed during 72 hours to Fe3O4 (SPION-1), Co0.2Zn0.8Fe2O4 (SPION-2), or Co0.5Zn0.5Fe2O4 (SPION-3) to a range of concentrations from 12.5 to 400 μg mL−1. Under these treatments, toxicity impact was indicated by the deterioration of photochemical activities of photosynthesis, the induction of oxidative stress, and the inhibition of cell division rate. In comparison to SPION-2 and -3, exposure to SPION-1 caused the highest toxic effects on cellular division due to a stronger production of reactive oxygen species and deterioration of photochemical activity of Photosystem II. This study showed the potential source of toxicity for three SPION suspensions, having different chemical compositions, estimated by the change of different biomarkers. In this toxicological investigation, algal model C. vulgaris demonstrated to be a valuable bioindicator of SPION toxicity. PMID:24369015

Albendazole Induced Recurrent Acute Toxic Hepatitis: A Case Report.

PubMed

Bilgic, Yilmaz; Yilmaz, Cengiz; Cagin, Yasir Furkan; Atayan, Yahya; Karadag, Nese; Harputluoglu, Murat Muhsin Muhip

2017-01-01

Drug induced acute toxic hepatitis can be idiosyncratic. Albendazole, a widely used broad spectrum antiparasitic drug is generally accepted as a safe drug. It may cause asymptomatic transient liver enzyme abnormalities but acute toxic hepatitis is very rare. Case Report : Herein, we present the case of 47 year old woman with recurrent acute toxic hepatitis after a single intake of albendazole in 2010 and 2014. The patient was presented with symptoms and findings of anorexia, vomiting and jaundice. For diagnosis, other acute hepatitis etiologies were excluded. Roussel Uclaf Causality Assessment Method (RUCAM) score was calculated and found to be 10, which meant highly probable drug hepatotoxicity. Within 2 months, all pathological findings came to normal. There are a few reported cases of albendazole induced toxic hepatitis, but at adults, there is no known recurrent acute toxic hepatitis due to albendazole at this certainty according to RUCAM score. Physicians should be aware of this rare and potentially fatal adverse effect of albendazole. © Acta Gastro-Enterologica Belgica.

Ion toxicity and the development of a salinity toxicity relationship (STR) model for marine species

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

Tietge, J.E.; Mount, D.R.

1994-12-31

Salinity in effluents can cause acute toxicity to marine organisms. The toxicity of the water can be due to an excess or deficiency of common ions, which usually are not thought of as toxicants. In order to develop an understanding of this phenomenon, laboratory toxicity tests were conducted to determine the effects of single ion deficiency, single ion excess, multiple ion deficiency, multiple ion excess, and total salinity on survival of three common marine test organisms (Mysidopsis bahia, Cyprinidon variegatus, and Menidia beryllina). The ions which were manipulated in these studies were Na{sup +}, K{sup +}, Ca{sup ++}, Mg{sup ++},more » Sr{sup ++}, Cl{sup {minus}}, Br{sup {minus}}, SO{sub 4}{sup {minus}{minus}}, HCO{sub 3}{sup {minus}}, and B{sub 4}O{sub 7}{sup {minus}{minus}}. Results indicate that Ca{sup ++} and K{sup +} are essential ions at normal salinities, since the deficiency of these two ions causes mortality. In contrast, the complete deficiency of Mg{sup ++}, Sr{sup ++}, B{sub 4}O{sub 7}{sup {minus}{minus}}, and HCO{sub 3}{sup {minus}} did not affect survival. The single ion excess studies demonstrated that K{sup +}, Ca{sup ++}, Mg{sup ++}, and B{sub 4}O{sub 7}{sup {minus}} were acutely toxic in excess at normal salinities. Total salinity studies determined the salinity tolerance range for each species, with upper and lower LC{sub 50}s for Mysidopsis bahia at 44 g/L and 8 g/L, for Cyprinidon variegatus at 73 g/L and < 0 g/L, and for Menidia beryllina at 45 g/L and < 0 g/L. These data will be used to develop a model to predict toxicity due to common ions.« less

Citizens' perceptions of the presence and health risks of synthetic chemicals in food: results of an online survey in Spain.

PubMed

Pumarega, José; Larrea, Cristina; Muñoz, Araceli; Pallarès, Natàlia; Gasull, Magda; Rodríguez, Giselle; Jariod, Manel; Porta, Miquel

To explore factors influencing perceptions and viewpoints on the responsibility for the presence of toxic substances in food, on enforcement of laws and regulations that control human exposure to toxic substances in food, and on the effectiveness of such regulations. An online survey was completed by 740 individuals from several parts of Spain (median age, 47 years; 67% were women; 70% had completed university studies). Over 87% of respondents said that it was possible that throughout their lives they could have accumulated in their body toxic substances potentially dangerous to their health. The attribution of the responsibility for toxic substances in food to a larger number of social groups was more frequent among respondents who consulted information about the problem more often (odds ratio [OR]: 1.92), who correctly identified factors that increase the likelihood of toxic substances in food being harmful to human health (OR: 2.86), who better knew the health problems that may be caused by such substances (OR: 2.48), and who recognised more food groups that tend to have concentrations of toxic substances potentially harmful to health (OR: 2.92) (all p values <0.001). Women were 65% less likely than men to answer that regulations on toxic substances in food are effective (p<0.001); and so were participants who identified more food groups with potentially toxic concentrations. Among study participants there was a widespread scepticism and distrust towards the enforcement and effectiveness of laws and regulations that in Spain aim to control human exposure to toxic substances in food. Copyright © 2017 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

Selenium-Induced Toxicity Is Counteracted by Sulfur in Broccoli (Brassica oleracea L. var. italica).

PubMed

Tian, Ming; Hui, Maixia; Thannhauser, Theodore W; Pan, Siyi; Li, Li

2017-01-01

Selenium (Se) is an essential micronutrient for humans. Increasing Se content in food crops offers an effective approach to enhance the consumption of Se in human diets. A thoroughly understanding of the effects of Se on plant growth is important for Se biofortification in food crops. Given that Se is an analog of sulfur (S) and can be toxic to plants, its effect on plant growth is expected to be greatly affected by S nutrition. However, this remains to be further understood. Here, we evaluated the influence of Se treatments on broccoli ( Brassica oleracea L. var. italica ) growth when S was withheld from the growth nutrient solution. We found that Se was highly toxic to plants when S nutrition was poor. In contrast to Se treatments with adequate S nutrition that slightly reduced broccoli growth, the same concentration of Se treatments without S supplementation dramatically reduced plant sizes. Higher Se toxicity was observed with selenate than selenite under low S nutrition. We examined the bases underlying the toxicity. We discovered that the high Se toxicity in low S nutrition was specifically associated with an increased ratio of Se in proteins verse total Se level, enhanced generation of reactive oxygen species, elevated lipid peroxidation causing increased cell membrane damage, and reduced antioxidant enzyme activities. Se toxicity could be counteracted with increased supplementation of S, which is likely through decreasing non-specific integration of Se into proteins and altering the redox system. The present study provides information for better understanding of Se toxicity and shows that adequate S nutrition is important to prevent Se toxicity during biofortification of crops by Se fertilization.

Effect of hardness on acute toxicity of metal mixtures using Daphnia magna: prediction of acid mine drainage toxicity.

PubMed

Yim, Jin Hee; Kim, Kyoung W; Kim, Sang D

2006-11-02

In this study, the effect of hardness on the combined outcome of metal mixtures was investigated using Daphnia magna. The toxic unit (TU) was calculated using modified LC(50) values based on the hardness (i.e., LC(50-soft) and LC(50-hard)). From a bioassay test, the degree of sensitivity to hardness on the toxicity changes was in the order: Cd

Medicinal plants combating against cancer--a green anticancer approach.

PubMed

Sultana, Sabira; Asif, Hafiz Muhammad; Nazar, Hafiz Muhammad Irfan; Akhtar, Naveed; Rehman, Jalil Ur; Rehman, Riaz Ur

2014-01-01

Cancer is the most deadly disease that causes the serious health problems, physical disabilities, mortalities, and morbidities around the world. It is the second leading cause of death all over the world. Although great advancement have been made in the treatment of cancer progression, still significant deficiencies and room for improvement remain. Chemotherapy produced a number of undesired and toxic side effects. Natural therapies, such as the use of plant-derived products in the treatment of cancer, may reduce adverse and toxic side effects. However, many plants exist that have shown very promising anticancer activities in vitro and in vivo but their active anticancer principle have yet to be evaluated. Combined efforts of botanist, pharmacologist and chemists are required to find new lead anticancer constituent to fight disease. This review will help researchers in the finding of new bioactive molecules as it will focus on various plants evaluated for anticancer properties in vitro and in vivo.

Evaluation of cytotoxic, genotoxic and inflammatory responses of micro- and nano-particles of granite on human lung fibroblast cell IMR-90.

PubMed

Ahmad, Iqbal; Khan, Mohd Imran; Patil, Govil; Chauhan, L K S

2012-02-05

Occupational exposure of granite workers is well known to cause lung impairment and silicosis. Toxicological profiles of different size particles of granite dust, however, are not yet understood. Present evaluation of micro- and nano-particles of granite dust as on human lung fibroblast cells IMR-90, revealed that their toxic effects were dose-dependent, and nanoparticles in general were more toxic. In this study we first demonstrated that nanoparticles caused oxidative stress, inflammatory response and genotoxicity, as seen by nearly 2 fold induction of ROS and LPO, mRNA levels of TNF-α and IL-1β, and induction in micronuclei formation. All these were significantly higher when compared with the effect of micro particles. Thus, the study suggests that separate health safety standards would be required for granite particles of different sizes. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Effect of cadmium on the bioelement composition of Nostoc UAM208: Interaction with calcium

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

Fernandez-Pinas, F.; Mateo, P.; Bonilla, I.

1997-04-01

Heavy metals may cause effects on the cyanobacterial cell including possible damage to the membranes and leakage from cells resulting in the loss or reduction of essential bioelements. There are many reports in the literature concerning morphological, biochemical and physiological changes caused by cadmium in cyanobacteria, but data on the influence of cadmium on the ion balance of the cell dealing with the interactive effect of cadmium and calcium are limited. Calcium has been found to exert a protective role against heavy metal toxicity in a variety of organisms, We previously reported that calcium is able to counteract the toxicmore » effect of cadmium towards growth, photosynthesis, nitrogenase activity and pigment content of the cyanobacterium Nostoc UAM208. In the present study, we analyzed the content of essential ions, as affected by cadmium treatment, to search for possible mechanisms of heavy metal damage and toxicity in Nostoc. We also studied whether calcium enrichment (1.1 mM final concentration) has any influence on the heavy metal effect on those ionic contents. 13 refs., 2 figs.« less

Interactive effects of pesticide mixtures, predators, and environmental regimes on the toxicity of two pesticides to red-eyed tree frog larvae.

PubMed

Johnson, Laura A; Welch, Bill; Whitfield, Steven M

2013-10-01

Global amphibian declines have many corroborative causes, and the use of pesticides in agriculture is a likely contributor. In places with high pesticide usage, such as Costa Rica, agrochemical pesticides may interact with other factors to contribute to rapid species losses. Classical ecotoxicological studies rarely address the effects of a pesticide in combination with other stressors. The present study investigated the synergistic roles of 2 pesticides (chlorothalonil and endosulfan), predator stress, and environmental regimes (controlled laboratory environments versus ambient conditions) on the survival of red-eyed tree frog larvae (Agalychnis callidryas). No synergistic effects of pesticide mixtures or predator stress were found on the toxicity of either chlorothalonil or endosulfan. Both pesticides, however, were considerably more toxic under realistic ambient temperature regimes than in a climate-controlled laboratory. Overall, endosulfan displayed the highest toxicity to tadpoles, although chlorothalonil was also highly toxic. The median lethal concentration estimated to kill 50% of a tested population (LC50) for endosulfan treatments under ambient temperatures was less than one-half of that for laboratory treatments (3.26 µg/L and 8.39 µg/L, respectively). Studies commonly performed in stable temperature-controlled laboratories may significantly underestimate toxicity compared with more realistic environmental regimes. Furthermore, global climatic changes are leading to warmer and more variable climates and may increase impacts of pesticides on amphibians. © 2013 SETAC.

In vitro inflammatory effects of hard metal (WC-Co) nanoparticle exposure.

PubMed

Armstead, Andrea L; Li, Bingyun

Identifying the toxicity of nanoparticles (NPs) is an important area of research as the number of nanomaterial-based consumer and industrial products continually rises. In addition, the potential inflammatory effects resulting from pulmonary NP exposure are emerging as an important aspect of nanotoxicity. In this study, the toxicity and inflammatory state resulting from tungsten carbide-cobalt (WC-Co) NP exposure in macrophages and a coculture (CC) of lung epithelial cells (BEAS-2B) and macrophages (THP-1) at a 3:1 ratio were examined. It was found that the toxicity of nano-WC-Co was cell dependent; significantly less toxicity was observed in THP-1 cells compared to BEAS-2B cells. It was demonstrated that nano-WC-Co caused reduced toxicity in the CC model compared to lung epithelial cell monoculture, which suggested that macrophages may play a protective role against nano-WC-Co-mediated toxicity in CCs. Nano-WC-Co exposure in macrophages resulted in increased levels of interleukin (IL)-1β and IL-12 secretion and decreased levels of tumor necrosis factor alpha (TNFα). In addition, the polarizing effects of nano-WC-Co exposure toward the M1 (pro-inflammatory) and M2 (anti-inflammatory) macrophage phenotypes were investigated. The results of this study indicated that nano-WC-Co exposure stimulated the M1 phenotype, marked by high expression of CD40 M1 macrophage surface markers.

Cancer risks in naval divers with multiple exposures to carcinogens.

PubMed Central

Richter, Elihu D; Friedman, Lee S; Tamir, Yuval; Berman, Tamar; Levy, Or; Westin, Jerome B; Peretz, Tamar

2003-01-01

We investigated risks for cancer and the case for a cause-effect relationship in five successive cohorts of naval commando divers (n = 682) with prolonged underwater exposures (skin, gastrointestinal tract, and airways) to many toxic compounds in the Kishon River, Israel's most polluted waterway, from 1948 to 1995. Releases of industrial, ship, and agricultural effluents in the river increased substantially, fish yields decreased, and toxic damage to marine organisms increased. Among the divers (16,343 person-years follow-up from 18 years of age to year 2000), the observed/expected ratio for all tumors was 2.29 (p<0.01). Risks increased in cohorts first diving after 1960 compared to risks in earlier cohorts, notably for hematolymphopoietic, central nervous system, gastrointestinal, and skin cancer; induction periods were often brief. The findings suggest that the increases in risk for cancer and short induction periods resulted from direct contact with and absorption of multiple toxic compounds. Early toxic effects in marine life predicted later risks for cancer in divers. PMID:12676624

In vitro approaches to evaluate toxicity induced by organotin compounds tributyltin (TBT), dibutyltin (DBT), and monobutyltin (MBT) in neuroblastoma cells.

PubMed

Ferreira, Martiña; Blanco, Lucía; Garrido, Alejandro; Vieites, Juan M; Cabado, Ana G

2013-05-01

The toxic effects of the organotin compounds (OTCs) monobutyltin (MBT), dibutyltin (DBT), and tributyltin (TBT) were evaluated in vitro in a neuroblastoma human cell line. Mechanisms of cell death, apoptosis versus necrosis, were studied by using several markers: inhibition of cell viability and proliferation, F-actin, and mitochondrial membrane potential changes as well as reactive oxygen species (ROS) production and DNA fragmentation. The most toxic effects were detected with DBT and TBT even at very low concentrations (0.1-1 μM). In contrast, MBT induced lighter cytotoxic changes at the higher doses tested. None of the studied compounds stimulated propidium iodide uptake, although the most toxic chemical, TBT, caused lactate dehydrogenase release at the higher concentrations tested. These findings suggest that in neuroblastoma, OTC-induced cytotoxicity involves different pathways depending on the compound, concentration, and incubation time. A screening method for DBT and TBT quantification based on cell viability loss was developed, allowing a fast detection alternative to complex methodology.

Ecotoxic effect of photocatalytic active nanoparticles (TiO2) on algae and daphnids.

PubMed

Hund-Rinke, Kerstin; Simon, Markus

2006-07-01

Due to their large potential for manifold applications, the use of nanoparticles is of increasing importance. As large amounts of nanoparticles may reach the environment voluntarily or by accident, attention should be paid on the potential impacts on the environment. First studies on potential environmental effects of photocatalytic TiO2 nanoparticles have been performed on the basis of widely accepted, standardized test systems which originally had been developed for the characterization of chemicals. The methods were adapted to the special requirements of testing photocatalytic nanoparticles. Suspensions of two different nanoparticles were illuminated to induce their photocatalytic activity. For testing, the growth inhibition test with the green alga Desmodesmus subspicatus and the immobilization test with the daphnid Daphnia magna were selected and performed following the relevant guidelines (algae: ISO 8692, OECD 201, DIN 38412-33; daphnids: ISO 6341, OECD 202, DIN 38412-30). The guidelines were adapted to meet the special requirements for testing photocatalytic nanoparticles. The results indicate that it is principally possible to determine the ecotoxicity of nanoparticles. It was shown that nanoparticles may have ecotoxicological effects which depend on the nature of the particles. Both products tested differ in their toxicity. Product 1 shows a clear concentration-effect curve in the test with algae (EC50: 44 mg/L). It could be proven that the observed toxicity was not caused by accompanying contaminants, since the toxic effect was comparable for the cleaned and the commercially available product. For product 2, no toxic effects were determined (maximum concentration: 50 mg/L). In the tests with daphnids, toxicity was observed for both products, although the concentration effect-curves were less pronounced. The two products differed in their toxicity; moreover, there was a difference in the toxicity of illuminated and non-illuminated products. Both products differ in size and crystalline form, so that these parameters are assumed to contribute to the different toxicities. The concentration-effect curves for daphnids, which are less-pronounced than the curves obtained for algae, may be due to the different test organisms and/or the differing test designs. The increased toxicity of pre-illuminated particles in the tests with daphnids demonstrates that the photocatalytic activity of nanoparticles lasts for a period of time. The following conclusions can be drawn from the test results: (I) It is principally possible to determine the ecotoxicity of (photocatalytic) nanoparticles. Therefore, they can be assessed using methods comparable to the procedures applied for assessing soluble chemicals. (II) Nanoparticles may exert ecotoxicological effects, which depend on the specific nanoparticle. (III) Comparable to traditional chemicals, the ecotoxicity depends on the test organisms and their physiology. (IV) The photocatalytic activity of nanoparticles lasts for a relevant period of time. Therefore, pre-illumination may be sufficient to detect a photocatalytic activity even by using test organisms which are not suitable for application in the pre-illumination-phase. First results are presented which indicate that the topic 'ecotoxicity and environmental effects of nanoparticles' should not be neglected. In testing photocatalytic nanoparticles, there are still many topics that need clarification or improvement, such as the cause for an observed toxicity, the improvement of the test design, the elaboration of a test battery and an assessment strategy. On the basis of optimized test systems, it will be possible to test nanoparticles systematically. If a potential risk by specific photocatalytic particles is known, a risk-benefit analysis can be performed and, if required, risk reducing measures can be taken.

Developmental toxicity of CdTe QDs in zebrafish embryos and larvae

NASA Astrophysics Data System (ADS)

Duan, Junchao; Yu, Yongbo; Li, Yang; Yu, Yang; Li, Yanbo; Huang, Peili; Zhou, Xianqing; Peng, Shuangqing; Sun, Zhiwei

2013-07-01

Quantum dots (QDs) have widely been used in biomedical and biotechnological applications. However, few studies focus on the assessing toxicity of QDs exposure in vivo. In this study, zebrafish embryos were treated with CdTe QDs (4 nm) during 4-96 h post-fertilization (hpf). Mortality, hatching rate, malformation, heart rate, and QDs uptake were detected. We also measured the larval behavior to analyze whether QDs had persistent effects on larvae locomotor activity at 144 hpf. The results showed that as the exposure dosages increased, the hatching rate and heart rate of zebrafish embryos were decreased, while the mortality increased. Exposure to QDs caused embryonic malformations, including head malformation, pericardial edema, yolk sac edema, bent spine, and yolk not depleted. QDs fluorescence was mainly localized in the intestines region. The larval behavior testing showed that the total swimming distance was decreased in a dose-dependent manner. The lowest dose (2.5 nM QDs) produced substantial hyperactivity while the higher doses groups (5, 10, and 20 nM QDs) elicited remarkably hypoactivity in dark periods. In summary, the data of this article indicated that QDs caused embryonic developmental toxicity, resulted in persistent effects on larval behavior.

Assessing protein oxidation by inorganic nanoparticles with enzyme-linked immunosorbent assay (ELISA).

PubMed

Sun, Wenjie; Luna-Velasco, Antonia; Sierra-Alvarez, Reyes; Field, Jim A

2013-03-01

Growth in the nanotechnology industry is leading to increased production of engineered nanoparticles (NPs). This has given rise to concerns about the potential adverse and toxic effects to biological system and the environment. An important mechanism of NP toxicity is oxidative stress caused by the formation of reactive oxygen species (ROS) or via direct oxidation of biomolecules. In this study, a protein oxidation assay was developed as an indicator of biomolecule oxidation by NPs. The oxidation of the protein, bovine serum albumin (BSA) was evaluated with an enzyme-linked immunosorbent assay (ELISA) to measure the protein carbonyl derivatives formed from protein oxidation. The results showed that some NPs such as Cu(0), CuO, Mn(2)O(3), and Fe(0) caused oxidation of BSA; whereas, many of the other NPs tested were not reactive or very slowly reactive with BSA. The mechanisms involved in the oxidation of BSA protein by the reactive NPs could be attributed to the combined effects of ROS-dependent and direct protein oxidation mechanisms. The ELISA assay is a promising method for the assessment of protein oxidation by NPs, which can provide insights on NP toxicity mechanisms. Copyright © 2012 Wiley Periodicals, Inc.

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.

Novel toxic shock syndrome toxin-1 amino acids required for biological activity.

PubMed

Brosnahan, Amanda J; Schaefers, Matthew M; Amundson, William H; Mantz, Mary J; Squier, Christopher A; Peterson, Marnie L; Schlievert, Patrick M

2008-12-09

Superantigens interact with T lymphocytes and macrophages to cause T lymphocyte proliferation and overwhelming cytokine production, which lead to toxic shock syndrome. Staphylococcus aureus superantigen toxic shock syndrome toxin-1 is a major cause of menstrual toxic shock syndrome. In general, superantigen-secreting S. aureus remains localized at the vaginal surface, and the superantigen must therefore penetrate the vaginal mucosa to interact with underlying immune cells to cause toxic shock syndrome. A dodecapeptide region (toxic shock syndrome toxin-1 amino acids F119-D130), relatively conserved among superantigens, has been implicated in superantigen penetration of the epithelium. The purpose of this study was to determine amino acids within this dodecapeptide region that are required for interaction with vaginal epithelium. Alanine mutations were constructed in S. aureus toxic shock syndrome toxin-1 amino acids D120 to D130. All mutants maintained superantigenicity, and selected mutants were lethal when given intravenously to rabbits. Toxic shock syndrome toxin-1 induces interleukin-8 from immortalized human vaginal epithelial cells; however, three toxin mutants (S127A, T128A, and D130A) induced low levels of interleukin-8 compared to wild type toxin. When carboxy-terminal mutants (S127A to D130A) were administered vaginally to rabbits, D130A was nonlethal, while S127A and T128A demonstrated delayed lethality compared to wild type toxin. In a porcine ex vivo permeability model, mutant D130A penetrated the vaginal mucosa more quickly than wild type toxin. Toxic shock syndrome toxin-1 residue D130 may contribute to binding an epithelial receptor, which allows it to penetrate the vaginal mucosa, induce interleukin-8, and cause toxic shock syndrome.

Effects of industrial effluents, heavy metals, and organic solvents on mallard embryo development.

PubMed

Hoffman, D J; Eastin, W C

1981-09-01

Mallard eggs were externally exposed at 3 and 8 days of incubation to 7 different industrial effluents and to 7 different heavy metal, organic solvent, and petroleum solutions to screen for potential embryo-toxic effects. This route of exposure was chosen in order to simulate the transfer of pollutant from the plumage of aquatic birds to their eggs. Five of the effluents including mineral pigment, scouring effluent, sludge, and tannery effluent resulted in small but significant reductions in embryonic growth. Treatment with methyl mercury chloride solution of 50 ppm (Hg) impaired embryonic growth but much higher concentrations were required to affect survival and cause teratogenic effects. Oil used to suppress road dust was the most toxic of the pollutants tested and only 0.5 microliter/egg caused 60% mortality by 18 days of development. These findings, in combination with other studies suggest that petroleum pollutants, or effluents in combination with petroleum, may pose a hazard to birds' eggs when exposure is by this route.

Biogenic silver nanoparticles based on trichoderma harzianum: synthesis, characterization, toxicity evaluation and biological activity

NASA Astrophysics Data System (ADS)

Guilger, Mariana; Pasquoto-Stigliani, Tatiane; Bilesky-Jose, Natália; Grillo, Renato; Abhilash, P. C.; Fraceto, Leonardo Fernandes; Lima, Renata De

2017-03-01

White mold is an agricultural disease caused by the fungus Sclerotinia sclerotiorum, which affects important crops. There are different ways of controlling this organism, but none provides inhibition of its resistance structures (sclerotia). Nanotechnology offers promising applications in agricultural area. Here, silver nanoparticles were biogenically synthesized using the fungus Trichoderma harzianum and characterized. Cytotoxicity and genotoxicity were evaluated, and the nanoparticles were initially tested against white mold sclerotia. Their effects on soybean were also investigated with no effects observed. The nanoparticles showed potential against S. sclerotiorum, inhibiting sclerotia germination and mycelial growth. Nanoparticle characterization data indicated spherical morphology, satisfactory polydispersity and size distribution. Cytotoxicity and genotoxicity assays showed that the nanoparticles caused both the effects, although, the most toxic concentrations were above those applied for white mold control. Given the potential of the nanoparticles against S. sclerotiorum, we conclude that this study presents a first step for a new alternative in white mold control.

Effects of industrial effluents, heavy metals, and organic solvents on mallard embryo development

USGS Publications Warehouse

Hoffman, D.J.; Eastin, W.C.

1981-01-01

Mallard eggs were externally exposed at 3 and 8 days of incubation to 7 different industrial effluents and to 7 different heavy metal, organic solvent, and petroleum solutions to screen for potential embryo-toxic effects. This route of exposure was chosen in order to simulate the transfer of pollutant from the plumage of aquatic birds to their eggs. Five of the effluents including mineral pigment, scouring effluent, sludge, and tannery effluent resulted in small but significant reductions in embryonic growth. Treatment with methyl mercury chloride solution of 50 ppm (Hg) impaired embryonic growth but much higher concentrations were required to affect survival and cause teratogenic effects. Oil used to suppress road dust was the most toxic of the pollutants tested and only 0.5 microliter/egg caused 60% mortality by 18 days of development. These findings, in combination with other studies suggest that petroleum pollutants, or effluents in combination with petroleum, may pose a hazard to birds' eggs when exposure is by this route.

Lysergic acid diethylamide causes photoreceptor cell damage through inducing inflammatory response and oxidative stress.

PubMed

Hu, Qi-Di; Xu, Ling-Li; Gong, Yan; Wu, Guo-Hai; Wang, Yu-Wen; Wu, Shan-Jun; Zhang, Zhe; Mao, Wei; Zhou, Yu-Sheng; Li, Qin-Bo; Yuan, Jian-Shu

2018-01-19

Lysergic acid diethylamide (LSD), a classical hallucinogen, was used as a popular and notorious substance of abuse in various parts of the world. Its abuse could result in long-lasting abnormalities in retina and little is known about the exact mechanism. This study was to investigate the effect of LSD on macrophage activation state at non-toxic concentration and its resultant toxicity to photoreceptor cells. Results showed that cytotoxicity was caused by LSD on 661 W cells after co-culturing with RAW264.7 cells. Treatment with LSD-induced RAW264.7 cells to the M1 phenotype, releasing more pro-inflammatory cytokines, and increasing the M1-related gene expression. Moreover, after co-culturing with RAW264.7 cells, significant oxidative stress in 661 W cells treated with LSD was observed, by increasing the level of malondialdehyde (MDA) and reactive oxygen species (ROS), and decreasing the level of glutathione (GSH) and the activity of superoxide dismutase (SOD). Our study demonstrated that LSD caused photoreceptor cell damage by inducing inflammatory response and resultant oxidative stress, providing the scientific rationale for the toxicity of LSD to retina.

Interactions of aquaculture and waste disposal in the coastal zone

NASA Astrophysics Data System (ADS)

Zhai, Xuemei; Hawkins, S. J.

2002-04-01

Throughout the world, the coastal zones of many countries are used increasingly for aquaculture in addition to other activities such as waste disposal. These activities can cause environmental problems and health problems where they overlap. The interaction between aquaculture and waste disposal, and their relationship with eutrophication are the subjects of this paper. Sewage discharge without adequate dispersion can lead to nutrient elevation and hence eutrophication which has clearly negative effects on aquaculture with the potential for toxic blooms. Blooms may be either toxic or anoxia-causing through the decay process or simply clog the gills of filter-feeding animals in some cases. With the development of aquaculture, especially intensive aquaculture, many environmental problems appeared, and have resulted in eutrophication in some areas. Eutrophication may destroy the health of whole ecosystem which is important for sustainable aquaculture. Sewage discharge may also cause serious public health problems. Filter-feeding shellfish growing in sewage-polluted waters accumulate micro-organims, including human pathogenic bacteria and viruses, and heavy metal ion, presenting a significant health risk. Some farmed animals may also accumulate heavy metals from sewage. Bivalves growing in areas affected by toxic algae blooms may accumulate toxins (such as PSP, DSP) which can be harmful to human beings.

The toxicity of rifampicin polylactic acid nanoparticles against Mycobacterium bovis BCG and human macrophage THP-1 cell line

NASA Astrophysics Data System (ADS)

Erokhina, M.; Rybalkina, E.; Barsegyan, G.; Onishchenko, G.; Lepekha, L.

2015-11-01

Tuberculosis is rapidly becoming a major health problem. The rise in tuberculosis incidence stimulates efforts to develop more effective delivery systems for the existing antituberculous drugs while decreasing the side effects. The nanotechnology may provide novel drug delivery tools allowing controlled drug release. Rifampicin is one of the main antituberculous drugs, characterized by high toxicity, and Poly (L-lactic acid) (PLLA) is a biodegradable polymer used for the preparation of encapsulated drugs. The aim of our work was to evaluate the toxicity of rifampicin-PLLA nanoparticles against Mycobacterium bovis BCG using human macrophage THP-1 cell line. Our data demonstrate that rifampicin-PLLA is effective against M. bovis BCG in the infected macrophages. The drug is inducing the dysfunction of mitochondria and apoptosis in the macrophages and is acting as a potential substrate of Pgp thereby modulating cell chemosensitivity. The severity of the toxic effects of the rifampicin-PLLA nanoparticles is increasing in a dose-dependent manner. We suggest that free rifampicin induces death of M. bovis BCG after PLLA degradation and diffusion from phago-lysosomes to cytoplasm causing mitochondria dysfunction and affecting the Pgp activity.

Inhibition of the in vitro growth of Babesia bigemina, Babesia caballi and Theileria equi parasites by trifluralin analogues.

PubMed

G Silva, Marta; Knowles, Donald P; Antunes, Sandra; Domingos, Ana; Esteves, Maria A; Suarez, Carlos E

2017-06-01

Bovine and equine babesiosis caused by Babesia bovis, Babesia bigemina and Babesia caballi, along with equine theileriosis caused by Theileria equi are global tick-borne hemoprotozoan diseases characterized by fever, anemia, weight losses and abortions. A common feature of these diseases are transition from acute to chronic phases, in which parasites may persist in the hosts for life. Antiprotozoal drugs are important for managing infection and disease. Previous research demonstrated that trifluralin analogues, designated (TFLAs) 1-15, which specifically bind to regions of alpha-tubulin protein in plants and protozoan parasites, have the ability to inhibit the in vitro growth of B. bovis. The inhibitory activity of TFLAs 1-15 minus TFLA 5 was tested in vitro against cultured B. bigemina, B. caballi and T. equi. The four TFLAs with greatest inhibitory activity were then analyzed for hemolytic activity and toxicity against erythrocytes. All TFLAs tested in the study showed inhibitory effects against the three parasite species. TFLA 2, TFLA 11, TFLA 13 and TFLA 14 were the most effective inhibitors for the three species tested, with estimated IC 50 between 5.1 and 10.1μM at 72h. The drug's solvent (DMSO/ethanol) did not statistically affect the growth of the parasites nor cause hemolysis. Also, TFLA 2, 13 and 14 did not cause statistically significant hemolytic activity on bovine and equine erythrocytes at 15μM, and TFLA 2, 11 and 13 had no detectable toxic effects on bovine and equine erythrocytes at 15μM, suggesting that these drugs do not compromise erythrocyte viability. The demonstrated ability of the trifluralin analogues to inhibit in vitro growth of Babesia spp. and Theileria equi, and their lack of toxic effects on erythrocytes supports further in vivo testing and eventually their development as novel alternatives for the treatment of babesiosis and theileriosis. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

Retardation of biodegradation of linear alkyl benzene sulphonate by a sublethal concentration of mercuric chloride

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

Misra, V.; Pandey, S.D.; Viswanathan, P.N.

1991-10-01

Environmental xenobiotics are usually classified into persistent and biodegradable ones. However, this may not be universally true, since biochemical capacity of ecosystems species may vary with species diversity and versatility. This may differ in different locations decided by geoclimatic factors. Prolonged exposure of organisms causing primary degradation to the toxic xenobiotics may lead to metabolic adaptation to survive the chemical stress. Also under multiple toxicant stress, the normal biodegrading capacity may be impaired by the effect of one toxicant on the organisms per se or on the enzymes causing degradation. If such inhibition of biodegradation occurs in ecosystems, even normallymore » biodegradable chemicals may tend to accumulate. To test this view, model experiments were conducted with LAS (Linear alkyl benzene sulphonate) a biodegradable surfactant and mercuric chloride. Since the purpose of the study was to test the degradation under natural conditions, no attempt was made to identify the micro-organisms involved.« less

Modification of Susceptible and Toxic Herbs on Grassland Disease.

PubMed

Yao, Xiang; Fan, Yubing; Chai, Qing; Johnson, Richard D; Nan, Zhibiao; Li, Chunjie

2016-09-16

Recent research shows that continuous overgrazing not only causes grassland biodiversity to decline, but also causes light fungal disease. Achnatherum inebrians is susceptible to fungal diseases and increases in prevalence during over grazing due its toxicity to livestock. This study aimed to examine the effects of A. inebrians on biological control organisms and levels of plant diseases in overgrazed grasslands in northwestern China. The results showed that A. inebrians plants were seriously infected by fungal diseases and that this led to a high incidence of the mycoparasitic species Ampelomyces quisqualis and Sphaerellopsis filum. In addition, the fungivore, Aleocharinae, was found only in the soil growing A. inebrians rather than in the overgrazed area without A. inebrians. Overall, in an overgrazed grassland fenced for one year, disease levels in blocks without A. inebrians were significantly higher than those in blocks with A. inebrians. Our findings indicated that the disease susceptible, toxic A. inebrians can help control plant disease levels in overgrazed grasslands.

Modification of Susceptible and Toxic Herbs on Grassland Disease

PubMed Central

Yao, Xiang; Fan, Yubing; Chai, Qing; Johnson, Richard D.; Nan, Zhibiao; Li, Chunjie

2016-01-01

Recent research shows that continuous overgrazing not only causes grassland biodiversity to decline, but also causes light fungal disease. Achnatherum inebrians is susceptible to fungal diseases and increases in prevalence during over grazing due its toxicity to livestock. This study aimed to examine the effects of A. inebrians on biological control organisms and levels of plant diseases in overgrazed grasslands in northwestern China. The results showed that A. inebrians plants were seriously infected by fungal diseases and that this led to a high incidence of the mycoparasitic species Ampelomyces quisqualis and Sphaerellopsis filum. In addition, the fungivore, Aleocharinae, was found only in the soil growing A. inebrians rather than in the overgrazed area without A. inebrians. Overall, in an overgrazed grassland fenced for one year, disease levels in blocks without A. inebrians were significantly higher than those in blocks with A. inebrians. Our findings indicated that the disease susceptible, toxic A. inebrians can help control plant disease levels in overgrazed grasslands. PMID:27633060

Transient protein-protein interactions perturb E. coli metabolome and cause gene dosage toxicity

PubMed Central

Bhattacharyya, Sanchari; Bershtein, Shimon; Yan, Jin; Argun, Tijda; Gilson, Amy I; Trauger, Sunia A; Shakhnovich, Eugene I

2016-01-01

Gene dosage toxicity (GDT) is an important factor that determines optimal levels of protein abundances, yet its molecular underpinnings remain unknown. Here, we demonstrate that overexpression of DHFR in E. coli causes a toxic metabolic imbalance triggered by interactions with several functionally related enzymes. Though deleterious in the overexpression regime, surprisingly, these interactions are beneficial at physiological concentrations, implying their functional significance in vivo. Moreover, we found that overexpression of orthologous DHFR proteins had minimal effect on all levels of cellular organization – molecular, systems, and phenotypic, in sharp contrast to E. coli DHFR. Dramatic difference of GDT between ‘E. coli’s self’ and ‘foreign’ proteins suggests the crucial role of evolutionary selection in shaping protein-protein interaction (PPI) networks at the whole proteome level. This study shows how protein overexpression perturbs a dynamic metabolon of weak yet potentially functional PPI, with consequences for the metabolic state of cells and their fitness. DOI: http://dx.doi.org/10.7554/eLife.20309.001 PMID:27938662

Biological Mechanism of Silver Nanoparticle Toxicity

NASA Astrophysics Data System (ADS)

Armstrong, Najealicka Nicole

Silver nanoparticles (AgNPs), like almost all nanoparticles, are potentially toxic beyond a certain concentration because the survival of the organism is compromised due to scores of pathophysiological abnormalities above that concentration. However, the mechanism of AgNP toxicity remains undetermined. Instead of applying a toxic dose, these investigations were attempted to monitor the effects of AgNPs at a non-lethal concentration on wild type Drosophila melanogaster by exposing them to nanoparticles throughout their development. All adult flies raised in AgNP doped food indicated that of not more than 50 mg/L had no negative influence on median survival; however, these flies appeared uniformly lighter in body color due to the loss of melanin pigments in their cuticle. Additionally, fertility and vertical movement ability were compromised after AgNP feeding. The determination of the amount of free ionic silver (Ag+) indicated that the observed biological effects had resulted from the AgNPs and not from Ag+. Biochemical analysis suggests that the activity of copper dependent enzymes, namely tyrosinase and Cu-Zn superoxide dismutase, were decreased significantly following the consumption of AgNPs, despite the constant level of copper present in the tissue. Furthermore, copper supplementation restored the loss of AgNP induced demelanization, and the reduction of functional Ctr1 in Ctr1 heterozygous mutants caused the flies to be resistant to demelanization. Consequently, these studies proposed a mechanism whereby consumption of excess AgNPs in association with membrane bound copper transporter proteins cause sequestration of copper, thus creating a condition that resembles copper starvation. This model also explained the cuticular demelanization effect resulting from AgNP since tyrosinase activity is essential for melanin biosynthesis. Finally, these investigations demonstrated that Drosophila, an established genetic model system, can be well utilized for further characterizing the biological effects of nanoparticles.

Effect-directed analysis supporting monitoring of aquatic environments--An in-depth overview.

PubMed

Brack, Werner; Ait-Aissa, Selim; Burgess, Robert M; Busch, Wibke; Creusot, Nicolas; Di Paolo, Carolina; Escher, Beate I; Mark Hewitt, L; Hilscherova, Klara; Hollender, Juliane; Hollert, Henner; Jonker, Willem; Kool, Jeroen; Lamoree, Marja; Muschket, Matthias; Neumann, Steffen; Rostkowski, Pawel; Ruttkies, Christoph; Schollee, Jennifer; Schymanski, Emma L; Schulze, Tobias; Seiler, Thomas-Benjamin; Tindall, Andrew J; De Aragão Umbuzeiro, Gisela; Vrana, Branislav; Krauss, Martin

2016-02-15

Aquatic environments are often contaminated with complex mixtures of chemicals that may pose a risk to ecosystems and human health. This contamination cannot be addressed with target analysis alone but tools are required to reduce this complexity and identify those chemicals that might cause adverse effects. Effect-directed analysis (EDA) is designed to meet this challenge and faces increasing interest in water and sediment quality monitoring. Thus, the present paper summarizes current experience with the EDA approach and the tools required, and provides practical advice on their application. The paper highlights the need for proper problem formulation and gives general advice for study design. As the EDA approach is directed by toxicity, basic principles for the selection of bioassays are given as well as a comprehensive compilation of appropriate assays, including their strengths and weaknesses. A specific focus is given to strategies for sampling, extraction and bioassay dosing since they strongly impact prioritization of toxicants in EDA. Reduction of sample complexity mainly relies on fractionation procedures, which are discussed in this paper, including quality assurance and quality control. Automated combinations of fractionation, biotesting and chemical analysis using so-called hyphenated tools can enhance the throughput and might reduce the risk of artifacts in laboratory work. The key to determining the chemical structures causing effects is analytical toxicant identification. The latest approaches, tools, software and databases for target-, suspect and non-target screening as well as unknown identification are discussed together with analytical and toxicological confirmation approaches. A better understanding of optimal use and combination of EDA tools will help to design efficient and successful toxicant identification studies in the context of quality monitoring in multiply stressed environments. Copyright © 2015 Elsevier B.V. All rights reserved.

JV Task 96 - Phase 2 - Investigating the Importance of the Mercury-Selenium Interaction

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

Nicholas Ralston; Laura Raymond

2008-03-01

In order to improve the understanding of the mercury issue, it is vital to study mercury's effects on selenium physiology. While mercury present in the environment or food sources may pose health risks, the protective effects of selenium have not been adequately considered in establishing regulatory policy. Numerous studies report that vulnerability to mercury toxicity is inversely proportional to selenium status or level. However, selenium status has not been considered in the development of the reference dosage levels for mercury exposure. Experimental animals fed low-selenium diets are far more vulnerable to mercury toxicity than animals fed normal selenium, and animalsmore » fed selenium-rich diets are even more resistant. Selenium-dependent enzymes in brain and endocrine tissues can be impaired by excessive mercury exposure, apparently because mercury has an extremely high binding affinity for selenium. When selenium becomes bound to mercury, it is unable to participate in the metabolic cycling of selenoprotein synthesis. Because of mercury-dependent impairments of selenoprotein synthesis, various antioxidant and regulatory functions in brain biochemistry are compromised. This report details a 2-year multiclient-funded research program designed to examine the interactions between mercury and selenium in animal models. The studies explored the effects of dietary intakes of toxic amounts of methylmercury and the protective effects of the normal dietary range of selenium in counteracting mercury toxicity. This study finds that the amounts of selenium present in ocean fish are sufficient to protect against far larger quantities of methylmercury than those present in typical seafoods. Toxic effects of methylmercury exposure were not directly proportional to mercury concentrations in blood, brain, or any other tissues. Instead, mercury toxicity was proportional to molar ratios of mercury relative to selenium. In order to accurately assess risk associated with methylmercury or mercury exposures, mercury-selenium ratios appear to be far more accurate and effective in identifying risk and protecting human and environmental health. This study also finds that methylmercury toxicity can be effectively treated by dietary selenium, preventing the death and progressive disabilities that otherwise occur in methylmercury-treated subjects. Remarkably, the positive response to selenium therapy was essentially equivalent regardless of whether or not toxic amounts of methylmercury were still administered. The findings of the Physiologically Oriented Integration of Nutrients and Toxins (POINT) models of the effects of mercury and selenium developed in this project are consistent with the hypothesis that mercury toxicity arises because of mercury-dependent inhibition of selenium availability in brain and endocrine tissues. This appears to occur through synergistic effects of mercury-dependent inhibition of selenium transport to these tissues and selective sequestration of the selenium present in the tissues. Compromised transport of selenium to the brain and endocrine tissues would be particularly hazardous to the developing fetus because the rapidly growing tissues of the child have no selenium reserves. Therefore, maternal consumption of foods with high mercury-selenium ratios is hazardous. In summation, methylmercury exposure is unlikely to cause harm in populations that eat selenium-rich diets but may cause harm among populations that consume certain foods that have methylmercury present in excess of selenium.« less

Sequestration of Sup35 by aggregates of huntingtin fragments causes toxicity of [PSI+] yeast.

PubMed

Zhao, Xiaohong; Park, Yang-Nim; Todor, Horia; Moomau, Christine; Masison, Daniel; Eisenberg, Evan; Greene, Lois E

2012-07-06

Expression of huntingtin fragments with 103 glutamines (HttQ103) is toxic in yeast containing either the [PIN(+)] prion, which is the amyloid form of Rnq1, or [PSI(+)] prion, which is the amyloid form of Sup35. We find that HttQP103, which has a polyproline region at the C-terminal end of the polyQ repeat region, is significantly more toxic in [PSI(+)] yeast than in [PIN(+)], even though HttQP103 formed multiple aggregates in both [PSI(+)] and [PIN(+)] yeast. This toxicity was only observed in the strong [PSI(+)] variant, not the weak [PSI(+)] variant, which has more soluble Sup35 present than the strong variant. Furthermore, expression of the MC domains of Sup35, which retains the C-terminal domain of Sup35, but lacks the N-terminal prion domain, almost completely rescued HttQP103 toxicity, but was less effective in rescuing HttQ103 toxicity. Therefore, the toxicity of HttQP103 in yeast containing the [PSI(+)] prion is primarily due to sequestration of the essential protein, Sup35.

Mercury Exposure and Heart Diseases

PubMed Central

Genchi, Giuseppe; Sinicropi, Maria Stefania; Carocci, Alessia; Lauria, Graziantonio; Catalano, Alessia

2017-01-01

Environmental contamination has exposed humans to various metal agents, including mercury. It has been determined that mercury is not only harmful to the health of vulnerable populations such as pregnant women and children, but is also toxic to ordinary adults in various ways. For many years, mercury was used in a wide variety of human activities. Nowadays, the exposure to this metal from both natural and artificial sources is significantly increasing. Recent studies suggest that chronic exposure, even to low concentration levels of mercury, can cause cardiovascular, reproductive, and developmental toxicity, neurotoxicity, nephrotoxicity, immunotoxicity, and carcinogenicity. Possible biological effects of mercury, including the relationship between mercury toxicity and diseases of the cardiovascular system, such as hypertension, coronary heart disease, and myocardial infarction, are being studied. As heart rhythm and function are under autonomic nervous system control, it has been hypothesized that the neurotoxic effects of mercury might also impact cardiac autonomic function. Mercury exposure could have a long-lasting effect on cardiac parasympathetic activity and some evidence has shown that mercury exposure might affect heart rate variability, particularly early exposures in children. The mechanism by which mercury produces toxic effects on the cardiovascular system is not fully elucidated, but this mechanism is believed to involve an increase in oxidative stress. The exposure to mercury increases the production of free radicals, potentially because of the role of mercury in the Fenton reaction and a reduction in the activity of antioxidant enzymes, such as glutathione peroxidase. In this review we report an overview on the toxicity of mercury and focus our attention on the toxic effects on the cardiovascular system. PMID:28085104

Mercury Exposure and Heart Diseases.

PubMed

Genchi, Giuseppe; Sinicropi, Maria Stefania; Carocci, Alessia; Lauria, Graziantonio; Catalano, Alessia

2017-01-12

Environmental contamination has exposed humans to various metal agents, including mercury. It has been determined that mercury is not only harmful to the health of vulnerable populations such as pregnant women and children, but is also toxic to ordinary adults in various ways. For many years, mercury was used in a wide variety of human activities. Nowadays, the exposure to this metal from both natural and artificial sources is significantly increasing. Recent studies suggest that chronic exposure, even to low concentration levels of mercury, can cause cardiovascular, reproductive, and developmental toxicity, neurotoxicity, nephrotoxicity, immunotoxicity, and carcinogenicity. Possible biological effects of mercury, including the relationship between mercury toxicity and diseases of the cardiovascular system, such as hypertension, coronary heart disease, and myocardial infarction, are being studied. As heart rhythm and function are under autonomic nervous system control, it has been hypothesized that the neurotoxic effects of mercury might also impact cardiac autonomic function. Mercury exposure could have a long-lasting effect on cardiac parasympathetic activity and some evidence has shown that mercury exposure might affect heart rate variability, particularly early exposures in children. The mechanism by which mercury produces toxic effects on the cardiovascular system is not fully elucidated, but this mechanism is believed to involve an increase in oxidative stress. The exposure to mercury increases the production of free radicals, potentially because of the role of mercury in the Fenton reaction and a reduction in the activity of antioxidant enzymes, such as glutathione peroxidase. In this review we report an overview on the toxicity of mercury and focus our attention on the toxic effects on the cardiovascular system.

Toxic effects of arsenic on semen and hormonal profile and their amelioration with vitamin E in Teddy goat bucks.

PubMed

Zubair, M; Ahmad, M; Jamil, H; Deeba, F

2016-12-01

The present environmental study has been planned to investigate the toxic effects of arsenic on reproductive functions of Teddy bucks as well as to examine whether these toxic effects are ameliorated by vitamin E. Sixteen adult Teddy bucks were divided randomly into four equal groups A, B, C and D with following treatment: A (control), B (sodium arsenite 5 mg kg -1 BW day -1 ), C (vit E 200 mg kg -1 BW day -1  + Arsenic 5 mg kg -1 BW day -1 ) and D (vit E 200 mg kg -1 BW day -1 ). This treatment was continued for 84 days. Semen quality parameters were evaluated weekly. Male testosterone, luteinising hormone (LH), follicle-stimulating hormone (FSH) and cortisol levels were measured through enzyme-linked immunosorbent assay (ELISA) after every 2 weeks. The data were subjected to two-way analysis of variance followed by Duncan test for multiple comparisons. Semen evaluation parameters were reduced significantly (P < 0.05) in arsenic-treated animals. The serum hormonal profile of testosterone, LH and FSH was reduced significantly (P < 0.05) in arsenic group, while the serum level of cortisol was increased. Vitamin E alleviated the toxic effects of arsenic on semen and hormonal parameters. It may be concluded from this study that sodium arsenite causes major toxicity changes in semen and hormonal profile in Teddy goat bucks and vitamin E has ameliorative effects on these toxic changes. © 2016 Blackwell Verlag GmbH.

A high throughput passive dosing format for the Fish Embryo Acute Toxicity test.

PubMed

Vergauwen, Lucia; Schmidt, Stine N; Stinckens, Evelyn; Maho, Walid; Blust, Ronny; Mayer, Philipp; Covaci, Adrian; Knapen, Dries

2015-11-01

High throughput testing according to the Fish Embryo Acute Toxicity (FET) test (OECD Testing Guideline 236) is usually conducted in well plates. In the case of hydrophobic test substances, sorptive and evaporative losses often result in declining and poorly controlled exposure conditions. Therefore, our objective was to improve exposure conditions in FET tests by evaluating a passive dosing format using silicone O-rings in standard 24-well polystyrene plates. We exposed zebrafish embryos to a series of phenanthrene concentrations until 120h post fertilization (hpf), and obtained a linear dilution series. We report effect values for both mortality and sublethal morphological effects based on (1) measured exposure concentrations, (2) (lipid normalized) body residues and (3) chemical activity. The LC50 for 120hpf was 310μg/L, CBR50 (critical body residue) was 2.72mmol/kg fresh wt and La50 (lethal chemical activity) was 0.047. All values were within ranges expected for baseline toxicity. Impaired swim bladder inflation was the most pronounced morphological effect and swimming activity was reduced in all exposure concentrations. Further analysis showed that the effect on swimming activity was not attributed to impaired swim bladder inflation, but rather to baseline toxicity. We conclude that silicone O-rings (1) produce a linear dilution series of phenanthrene in the 120hpf FET test, (2) generate and maintain aqueous concentrations for reliable determination of effect concentrations, and allow for obtaining mechanistic toxicity information, and (3) cause no toxicity, demonstrating its potential as an extension of the FET test when testing hydrophobic chemicals. Copyright © 2015 Elsevier Ltd. All rights reserved.

The zerovalent iron nanoparticle causes higher developmental toxicity than its oxidation products in early life stages of medaka fish.

PubMed

Chen, Pei-Jen; Wu, Wan-Lin; Wu, Kevin Chia-Wen

2013-08-01

Nanoscale zerovalent iron (nZVI)-mediated oxidation reaction is increasingly being used for enhanced treatment of water or wastewater processes; however, the fate and eco-toxicological effects of nZVI in the surface aquifer remain unclear. We investigated bioaccumulation and lethal-to-sublethal toxic effects on early life development of Japanese medaka (Oryzias latipes) with 7-day exposure to 25-200 mg/L of well-characterized solutions containing carboxymethyl cellulose (CMC)-stabilized nZVI (CMC-nZVI), nanoscale iron oxide (nFe3O4) or ferrous ion [Fe(II)aq]. The CMC-nZVI solution had the greatest acute mortality and developmental toxic effects in embryos, with lesser and the least effects with Fe(II)aq and nFe3O4. The toxicity of CMC-nZVI was ascribed to its high reactivity in the oxygenic solution, which led to a combination of hypoxia and production of reactive oxygen species (ROS) and Fe(II)aq. nFe3O4 (50-100 mg/L) was more bioavailable to embryos and bioaccmulative in hatchlings than suspended CMC-nZVI. The antioxidant balance was differentially altered by induced intracellular ROS in hatchlings with all 3 iron species. We revealed causal toxic effects of nZVI and its oxidized products in early life stages of medaka fish using different organizational levels of biomarker assays. The toxicity results implicate a potential eco-toxicological impact of nZVI on the aquatic environment. Copyright © 2013 Elsevier Ltd. All rights reserved.