Acute and Subchronic Toxic Effects of the Fruits of Physalis peruviana L.

PubMed Central

Perk, Basak Ozlem; Ilgin, Sinem; Atli, Ozlem; Duymus, Hale Gamze; Sirmagul, Basar

2013-01-01

The fruit of Physalis peruviana L. (PPL) has been traditionally used as antispasmodic, diuretic, antiseptic, sedative, and analgesic all over the world. We aimed to perform qualitative content analysis of the fruits of PPL and to clarify the in vitro genotoxicity and in vivo acute and subchronic toxicity of the fruit. Lyophilized fruit juice does not induce genetic damage. In the acute toxicity studies, LD50 value of the fruit was found to be more than 5000 mg kg−1 for both sexes. According to the subchronic toxicity studies, hepatic, renal, and hematological toxic effects were not induced in both sexes. Plasma troponin I (only in the group treated with 5000 mg kg−1 of lyophilized fruit juice) and troponin T levels were significantly increased in male groups treated with lyophilized fruit juice compared to the control group. Furthermore, potassium level was significantly increased in the male group treated with 5000 mg kg−1 of lyophilized fruit juice. These findings were considered to indicate the myocardial damage particularly in the male group treated with 5000 mg kg−1 of lyophilized fruit juice. In conclusion, lyophilized fruit juice of PPL is shown to induce cardiac toxicity only at high doses and in male gender. PMID:24369482

Acute toxicity and genotoxic activity of avocado seed extract (Persea americana Mill., c.v. Hass).

PubMed

Padilla-Camberos, Eduardo; Martínez-Velázquez, Moisés; Flores-Fernández, José Miguel; Villanueva-Rodríguez, Socorro

2013-01-01

The use of vegetal extracts requires toxicological and genotoxic evaluations to establish and verify safety before being added to human cosmetic, pharmaceutical medicine, or alimentary products. Persea americana seeds have been used in traditional medicine as treatment for several diseases. In this work, the ethanolic seed extract of Persea americana was evaluated with respect to its genotoxic potential through micronucleus assay in rodents. The frequency of micronuclei in groups of animals treated with avocado seed extract showed no differences compared to the negative control (vehicle); therefore, it is considered that the avocado seed extract showed no genotoxic activity in the micronucleus test.

Uranium mining wastes: The use of the Fish Embryo Acute Toxicity Test (FET) test to evaluate toxicity and risk of environmental discharge.

PubMed

Lourenço, J; Marques, S; Carvalho, F P; Oliveira, J; Malta, M; Santos, M; Gonçalves, F; Pereira, R; Mendo, S

2017-12-15

Active and abandoned uranium mining sites often create environmentally problematic situations, since they cause the contamination of all environmental matrices (air, soil and water) with stable metals and radionuclides. Due to their cytotoxic, genotoxic and teratogenic properties, the exposure to these contaminants may cause several harmful effects in living organisms. The Fish Embryo Acute Toxicity Test (FET) test was employed to evaluate the genotoxic and teratogenic potential of mine liquid effluents and sludge elutriates from a deactivated uranium mine. The aims were: a) to determine the risk of discharge of such wastes in the environment; b) the effectiveness of the chemical treatment applied to the uranium mine water, which is a standard procedure generally applied to liquid effluents from uranium mines and mills, to reduce its toxicological potential; c) the suitability of the FET test for the evaluation the toxicity of such wastes and the added value of including the evaluation of genotoxicity. Results showed that through the FET test it was possible to determine that both elutriates and effluents are genotoxic and also that the mine effluent is teratogenic at low concentrations. Additionally, liquid effluents and sludge elutriates affect other parameters namely, growth and hatching and that water pH alone played an important role in the hatching process. The inclusion of genotoxicity evaluation in the FET test was crucial to prevent the underestimation of the risks posed by some of the tested effluents/elutriates. Finally, it was possible to conclude that care should be taken when using benchmark values calculated for specific stressors to evaluate the risk posed by uranium mining wastes to freshwater ecosystems, due to their chemical complexity. Copyright © 2017 Elsevier B.V. All rights reserved.

Acute Toxicity and Genotoxic Activity of Avocado Seed Extract (Persea americana Mill., c.v. Hass)

PubMed Central

Padilla-Camberos, Eduardo; Martínez-Velázquez, Moisés; Flores-Fernández, José Miguel; Villanueva-Rodríguez, Socorro

2013-01-01

The use of vegetal extracts requires toxicological and genotoxic evaluations to establish and verify safety before being added to human cosmetic, pharmaceutical medicine, or alimentary products. Persea americana seeds have been used in traditional medicine as treatment for several diseases. In this work, the ethanolic seed extract of Persea americana was evaluated with respect to its genotoxic potential through micronucleus assay in rodents. The frequency of micronuclei in groups of animals treated with avocado seed extract showed no differences compared to the negative control (vehicle); therefore, it is considered that the avocado seed extract showed no genotoxic activity in the micronucleus test. PMID:24298206

Toxicity and genotoxicity of hospital laundry wastewaters treated with photocatalytic ozonation.

PubMed

Kern, Deivid I; Schwaickhardt, Rômulo de O; Mohr, Geane; Lobo, Eduardo A; Kist, Lourdes T; Machado, Ênio L

2013-01-15

The aim of the present study was to assess the efficiency of advanced oxidative processes based on photocatalytic ozonation (O(3), UV, UV/O(3), UV/O(3)/Fe(2+) 50 mg L(-1) and 150 mg L(-1)) in the treatment of hospital laundry wastewaters. The analysis of the investigated wastewater revealed high chemical oxygen demand (COD - 3343.8 mg L(-1)), biochemical oxygen demand (BOD(5) - 1906.4 mg L(-1)), total Kjeldahl nitrogen (TKN - 79.8 mg L(-1)) and Daphnia magna toxicity (EC50=1.73). Genotoxic effects were also detected for Allium cepa. Reductions of some parameters occurred after photocatalytic ozonation. The UV/O(3)/Fe(2+) 150 mg L(-1) method was more efficient in reducing COD (59.1%), BOD(5) (50.3%) and TKN (86.8%). There was significant reduction (p<0.05) in D. magna toxicity, O(3) (EC50=47.3%), UV (EC50=50.6%) and UV/O(3)/Fe(2+) 150 mg L(-1) (EC50=45.4%) processes. Normalization of the mitotic index and reduction of micronucleated cells were observed in A. cepa after the treatments. Results demonstrate that these methods were efficient in the degradation of hospital laundry wastewaters, representing a thriving alternative for the removal of pollutants that cause toxicity and genotoxicity. Copyright © 2012 Elsevier B.V. All rights reserved.

Cholesterol reduction and lack of genotoxic or toxic effects in mice after repeated 21-day oral intake of lemongrass (Cymbopogon citratus) essential oil.

PubMed

Costa, Celso A R A; Bidinotto, Lucas T; Takahira, Regina K; Salvadori, Daisy M F; Barbisan, Luís F; Costa, Mirtes

2011-09-01

Cymbopogon citratus (lemongrass) is currently used in traditional folk medicine. Although this species presents widespread use, there are no scientific data on its efficacy or safety after repeated treatments. Therefore, this work investigated the toxicity and genotoxicity of this lemongrass's essential oil (EO) in male Swiss mice. The single LD(50) based on a 24h acute oral toxicity study was found to be around 3500 mg/kg. In a repeated-dose 21-day oral toxicity study, mice were randomly assigned to two control groups, saline- or Tween 80 0.01%-treated groups, or one of the three experimental groups receiving lemongrass EO (1, 10 or 100mg/kg). No significant changes in gross pathology, body weight, absolute or relative organ weights, histology (brain, heart, kidneys, liver, lungs, stomach, spleen and urinary bladder), urinalysis or clinical biochemistry were observed in EO-treated mice relative to the control groups. Additionally, blood cholesterol was reduced after EO-treatment at the highest dose tested. Similarly, data from the comet assay in peripheral blood cells showed no genotoxic effect from the EO. In conclusion, our findings verified the safety of lemongrass intake at the doses used in folk medicine and indicated the beneficial effect of reducing the blood cholesterol level. Copyright © 2011 Elsevier Ltd. All rights reserved.

Evaluation of Hypoglycemic and Genotoxic Effect of Polyphenolic Bark Extract from Quercus sideroxyla

PubMed Central

Soto-García, Marcela; Rosales-Castro, Martha; Escalona-Cardoso, Gerardo N.

2016-01-01

Quercus sideroxyla is a wood species whose bark has phenolic compound and should be considered to be bioactive; the hypoglycemic and genotoxic properties of Q. sideroxyla bark were evaluated in this study. Total phenolic compound was determined in crude extract (CE) and organic extract (OE). The OE has the highest amount of phenols (724.1 ± 12.0 GAE/g). Besides, both CE and OE demonstrated effect over the inhibition of α-amylase in vitro. Hypoglycemic activity was assessed by glucose tolerance curve and the area under curve (UAC); OE showed the highest hypoglycemic activity. In addition, diabetes was induced by streptozotocin (65 mg/kg) and the extracts (50 mg/kg) were administered for 10 days; OE showed hypoglycemic effect compared with diabetic control and decreased hepatic lipid peroxidation. Acute toxicity and genotoxicity were evaluated in CE; results of acute toxicity did not show any mortality. Besides, the comet assay showed that CE at a dose of 100 mg/kg did not show any genotoxic effect when evaluated at 24 h, whereas it induced slight damage at 200 mg/kg, with the formation of type 1 comets. PMID:27867402

Evaluation of toxicity and genotoxicity of 2-chlorophenol on bacteria, fish and human cells.

PubMed

Vlastos, Dimitris; Antonopoulou, Maria; Konstantinou, Ioannis

2016-05-01

Due to the extensive use of chlorophenols (CPs) in anthropogenic activities, 2-Chlorophenol (2-CP), among other CPs, can enter aquatic ecosystems and can be harmful to a variety of organisms, including bacteria, fish and humans, that are exposed directly and/or indirectly to such contaminated environments. Based on the existing knowledge and in order to move a step forward, the purpose of this study is to investigate the toxic and mainly the genotoxic effects of 2-CP using a combination of bioassays. The tests include the marine bacterium Vibrio fischeri and micronuclei induction in the erythrocytes of Carassius auratus as well as in cultured human lymphocytes. The results obtained reveal that 2-CP is able to induce dose-dependent toxic and genotoxic effects on the selected tested concentrations under the specific experimental conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

Sensitivity or artifact? -- IQ Toxicity Test -- effluent values

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

Hayes, K.R.; Novotny, A.N.; Batista, N.

1995-12-31

Several complex effluents were DAPHNIA MAGNA IQ TOXICITY TESTED -- (1.25 hours) and conventionally tested with Daphnia magna (48 hours). In many samples the IQ Technology yielded low EC50 values while the 48 hour exposures yielded no acute toxicity. Possible explanations have been suggested for this occurrence such as: genotoxicity, mutagenicity, substrate interference, and enzyme satiation. To identify the causative agent(s) of this response a Toxicity Identification Evaluation was performed on one of the samples. To define the nature of the response, THE SOS-CHROMOTEST KIT and THE MUTA-CHROMOPLATE KIT were utilized to characterize genotoxicity and mutagenicity respectively. The sample didmore » not test positive for genotoxicity but tested positive for mutagenicity only after activation with S9 enzymes, suggesting the presence of promutagens. Additional work needs to be performed to correlate IQ TOXICITY TEST sensitivity with positive MUTA-CHROMOPLATE response.« less

Effect of Boron Toxicity on Oxidative Stress and Genotoxicity in Wheat (Triticum aestivum L.).

PubMed

Çatav, Şükrü Serter; Genç, Tuncer Okan; Kesik Oktay, Müjgan; Küçükakyüz, Köksal

2018-04-01

Boron (B) toxicity, which occurs in semi-arid and arid environments, can adversely affect the growth and yield of many plants. The aim of this study was to determine the effects of different concentrations of boric acid (3, 6, 9 and 12 mM) on growth, oxidative stress and genotoxicity parameters in root and shoot tissues of wheat seedlings. Our results indicate that B stress inhibits root and shoot growth of wheat in a concentration-dependent manner, and leads to increases in TBARS and H 2 O 2 contents in shoot tissue. Moreover, our findings suggest that high concentrations of B may exert a genotoxic effect on wheat. To the best of our knowledge, this is the first report to evaluate the effect of B stress on genotoxicity in both root and shoot tissues of wheat.

Nonclinical Safety Assessment of Morus alba L. Fruits: Study of 90-D Toxicity in Sprague Dawley Rats and Genotoxicity in Salmonella.

PubMed

Chang, Bo Yoon; Kim, Seon Beom; Lee, Mi Kyeong; Park, Hyun; Kim, Sung Yeon

2016-05-01

Morus alba L. is a traditional herb with a long history of consumption, both as an edible fruit and as medicine. However, its safety evaluation has not yet been established. The objective of this study was to evaluate subchronic oral toxicity and genotoxicity of M. alba L. fruits (MFE). The subchronic toxicity after daily oral administration of MFE at 0, 40, 200, and 1000 mg/kg for 90 d was examined in Sprague Dawley (SD) rats. MFE administration did not lead to death, adverse effects, change in food and water consumption, and body weight gain. Significant toxic effects were not found within the parameters of organ weight, biochemical values, and hematological and urine analysis between the control and the MFE group. The genotoxicity of MFE was assayed by Ames test in Salmonella typhimurium strains TA98, TA102, and TA1535. No genotoxicity was found in all the tested strains. Thus in this study, a no-observed-adverse-effect level for MFE in 90 d repeated oral toxicity study in rats was determined to be greater than 1000 mg/kg regardless of gender. The results also suggested that MFE does not have a genotoxicity potential. © 2016 Institute of Food Technologists®

Cytotoxicity and genotoxicity of polyethylenimine and nickel chloride in red sea bream ( Pagrosomus major) fin cell line RSBF

NASA Astrophysics Data System (ADS)

Guo, Hua-Rong; Zhang, Shi-Cui

2002-12-01

A continuous marine fish cell line RSBF (i. c. Red Sea Bream Fin) was utilized to screen the cytotoxicity and genotoxicity of polyethylenimine (PEI) and nickel chloride (NiCl2) in this study on the deleterious effects of aquatic genotoxins on fish. At the 0.01 to 1 μg/ml concentration tested, PEI had acute toxicity to the treated RSBF cells (IC50=1.12, 0.92, 0.88 and 0.64 μg/ml PEI for time 0 h, 24 h, 48 h and 72 h after treatment, respectively) and markedly inhibited their proliferation in a dose-dependent manner. At the 0.001 to 5 μmol/L concentration tested, NiCl2 posed no acute toxicity but significantly stimulated their growth (107% 214% of control). Random amplified polymorphic DNA (RAPD) technique was used to detect the genotoxic effects of PEI and NiCl2 by comparing the RAPD banding patterns of the control and treated cells. RAPD analysis indicated that at the concentrations tested, PEI was more genotoxic than NiCl2 to RSBF cells; that there was a slight dose-dependent response in the genotoxic effect of PEI but not NiCl2; and that RAPD technique might provide a sensitive, non-specific genotoxic endpoint. And the potent cytotoxicity and genotoxicity of PEI on fish cells showed that we should be cautious in utilizing it as gene, vector in fish gene transfer and human gene therapy.

Acute and long-term in vitro effects of zinc oxide nanoparticles.

PubMed

Annangi, Balasubramanyam; Rubio, Laura; Alaraby, Mohamed; Bach, Jordi; Marcos, Ricard; Hernández, Alba

2016-09-01

Since most of the toxic studies of zinc oxide nanoparticles (ZnO NPs) focused on acute and high-dose exposure conditions, the aim of the present study was to fill the existing knowledge gap of long-term effects of ZnO NPs at sub-toxic doses. To overcome this point, we have evaluated the toxic, genotoxic, and carcinogenic effects of ZnO NPs under long-term treatments (12 weeks), using a sub-toxic dose (1 µg/mL) according to acute 48-h exposure. Preliminarily, oxidative stress and genotoxic/oxidative DNA damage were determined under acute exposure and high-dose conditions. To determine the role of oxidative DNA damage, a wild-type mouse embryonic fibroblast (MEF Ogg1 (+/+)) and its isogenic 8-oxo-guanine DNA glycosylase 1 (Ogg1) knockout partner (MEF Ogg1 (-/-)) cell lines were used. Although short-term exposure (24-h) experiments demonstrated that ZnO NPs were able to induce ROS, genotoxicity, and oxidative DNA damage in both cell lines, no effects were obtained under long-term exposure scenario. Thus, 1 µg/mL exposure over 12 weeks was unable to induce genotoxicity as well as cellular transformation in both cell types, as indicated by the lack of observed morphological cell changes, variations in the secretion of matrix metalloproteinases, and anchorage-independent cell growth ability, regarded as cancer-like phenotypic hallmarks. Our results indicate that short-term effects of ZnO NP exposure are not replicated under long-term and sub-toxic dose conditions. All together, the lack of genotoxic/carcinogenic effects after chronic treatments seem to indicate a reduced risk associated with ZnO NP exposure.

Ecotoxicological and genotoxic assessment of hospital laundry wastewaters.

PubMed

Kern, Deivid Ismael; Schwaickhardt, Rômulo de Oliveira; Lutterbeck, Carlos Alexandre; Kist, Lourdes Teresinha; Alcayaga, Eduardo Alexis Lobo; Machado, Ênio Leandro

2015-01-01

The aim of the present study was to assess the ecotoxicity and genotoxicity of hospital laundry wastewaters generated from a regional hospital located in Rio Pardo Valley in the state of Rio Grande do Sul, Brazil. Physicochemical, microbiological, ecotoxicological, and genotoxic analyses were performed, and the results indicate that some parameters were not in accordance with the limit concentrations established by Brazilian and international guidelines for urban wastewaters. Daphnia magna (EC50 2.01%) and Danio rerio (LC50 29.25%) acute toxicity was detected, and sublethal effects were identified in Lactuca sativa (IC25 12.50%) and Allium cepa (IC25 51.25%). Cytotoxicity was observed at the five wastewater concentrations used yielding statistically significant differences (p < 0.05) in the meristematic cells of A. cepa compared with the negative control. The results obtained here warn about the necessity to develop treatment methods that can mitigate the environmental impacts caused by the ecotoxicity and genotoxicity of hospital laundry wastewaters.

Toxicity evaluation of the photoprotective compound LQFM048: Eye irritation, skin toxicity and genotoxic endpoints.

PubMed

de Ávila, Renato Ivan; de Sousa Vieira, Marcelo; Gaeti, Marilisa Pedroso Nogueira; Moreira, Larissa Cleres; de Brito Rodrigues, Laís; de Oliveira, Gisele Augusto Rodrigues; Batista, Aline Carvalho; Vinhal, Daniela Cristina; Menegatti, Ricardo; Valadares, Marize Campos

2017-02-01

A new molecule, LQFM048, originally designed through molecular hybridization using green chemistry approach, is in development as a photoprotective agent. Eye irritation, skin toxicity and genotoxicity evaluations are mandatory for predicting health risks. In this context, the purpose of this study was to investigate the eye irritation potential of LQFM048 by combining Short Time Exposure (STE), Bovine Corneal Opacity and Permeability (BCOP) associated with corneal histomorphometry and Hen's Egg Test-Chorioallantoic Membrane (HET-CAM). Additionally, skin toxicity was evaluated by interleukin-18 production in the HaCaT keratinocyte, Local Lymph Node Assay (LLNA:BrdU-ELISA) method, 3T3 Neutral red uptake (NRU) assay and in vivo phototoxicity test. Genotoxic potential of LQFM048 was also analyzed by cytokinesis-block micronucleus assay (MNvit test-cytoB) in HepG2 cells. Our results showed that LQFM048 did not induce eye irritation and it was classified as UN GHS No Category for both STE and BCOP assays and non-irritating for HET-CAM test. LQFM048 showed non-potential skin sensitization with stimulation index (SI=0.7) in the LLNA:BrdU-ELISA method. Corroborating in vivo tests, it did not promote significant cytotoxicity in HaCaT cells and it showed similar levels of IL-18 when compared to control. Furthermore, LQFM048 induced non-phototoxic potential with photo-irritation factor (PIF) and mean photo effect (MPE) of 1 and -0.138, respectively, for 3T3 cells. Similarly, it was not phototoxic for in vivo testing with or without exposure to UVA, showing SI values of 1 and 1.2, respectively. The micronucleus test showed that LQFM048 was not genotoxic, under the conditions tested.In conclusion, LQFM048, a heterocyclic compound obtained through an environmentally acceptable simple synthetic route, seems to be safe for human use, especially for the development of a new sunscreen product, since it is neither an eye irritant, nor a contact allergen, nor mutagenic and nor

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

PubMed

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

2018-02-01

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

Aerobic Bioremediation of PAH Contaminated Soil Results in Increased Genotoxicity and Developmental Toxicity.

PubMed

Chibwe, Leah; Geier, Mitra C; Nakamura, Jun; Tanguay, Robert L; Aitken, Michael D; Simonich, Staci L Massey

2015-12-01

The formation of more polar and toxic polycyclic aromatic hydrocarbon (PAH) transformation products is one of the concerns associated with the bioremediation of PAH-contaminated soils. Soil contaminated with coal tar (prebioremediation) from a former manufactured gas plant (MGP) site was treated in a laboratory scale bioreactor (postbioremediation) and extracted using pressurized liquid extraction. The soil extracts were fractionated, based on polarity, and analyzed for 88 PAHs (unsubstituted, oxygenated, nitrated, and heterocyclic PAHs). The PAH concentrations in the soil tested, postbioremediation, were lower than their regulatory maximum allowable concentrations (MACs), with the exception of the higher molecular weight PAHs (BaA, BkF, BbF, BaP, and IcdP), most of which did not undergo significant biodegradation. The soil extract fractions were tested for genotoxicity using the DT40 chicken lymphocyte bioassay and developmental toxicity using the embryonic zebrafish (Danio rerio) bioassay. A statistically significant increase in genotoxicity was measured in the unfractionated soil extract, as well as in four polar soil extract fractions, postbioremediation (p < 0.05). In addition, a statistically significant increase in developmental toxicity was measured in one polar soil extract fraction, postbioremediation (p < 0.05). A series of morphological abnormalities, including peculiar caudal fin malformations and hyperpigmentation in the tail, were measured in several soil extract fractions in embryonic zebrafish, both pre- and postbioremediation. The increased toxicity measured postbioremediation is not likely due to the 88 PAHs measured in this study (including quinones), because most were not present in the toxic polar fractions and/or because their concentrations did not increase postbioremediation. However, the increased toxicity measured postbioremediation is likely due to hydroxylated and carboxylated transformation products of the 3- and 4-ring PAHs (PHE, 1

Genotoxicity and toxicity assay of water sampled from a radium production industry storage cell territory by means of Allium-test.

PubMed

Evseeva, Tatiana I; Geras'kin, Stanislav A; Shuktomova, Ida I

2003-01-01

Water from natural reservoirs located near the radium production industry storage cell were analyzed using the anaphase-telophase chromosome aberration assay that was carried out on Allium schoenoprasum L. meristematic root tip cells. (262)Ra, (228)U, (232)Th, (210)Pb and (210)Po concentrations in all samples were found not to exceed the radioactivity concentration guides. The concentrations of 10 heavy metal ions were measured in water samples, but only Zn and Mn levels exceeded the maximum permissible concentration for the natural reservoirs. All water samples caused a significant increase of the chromosome aberration frequency as compared to control. The chromosome aberration spectrum analysis shows that the genotoxic effect was a result of chemical toxicity mainly. Two samples from the brook springhead were found to be toxic. The regression analysis results show that the mitotic index increased in parallel to Zn ion levels, and decreased with higher (238)U concentrations. The water samples genotoxicity positively correlated with the Zn concentration. The present work demonstrates that in order to achieve pollutant screening, it is not sufficient to determine the pollutants concentration only. Adequate conclusions on the risk due to environment contamination need to be based on the additional simultaneous use of toxicity and genotoxicity tests. When bioassays indicate some genotoxic and toxic effects, the determination of the chemical composition of the samples is then required. A combination of these two methods allows the identification of the elements that require constant biological monitoring. In the study reported here, those elements are Zn and (238)U.

Aerobic Bioremediation of PAH Contaminated Soil Results in Increased Genotoxicity and Developmental Toxicity

PubMed Central

Chibwe, Leah; Geier, Mitra C.; Nakamura, Jun; Tanguay, Robert L.; Aitken, Michael D.; Simonich, Staci L. Massey

2015-01-01

The formation of more polar and toxic polycyclic aromatic hydrocarbon (PAH) transformation products is one of the concerns associated with the bioremediation of PAH-contaminated soils. Soil contaminated with coal tar (pre-bioremediation) from a former manufactured gas plant (MGP) site was treated in a laboratory scale bioreactor (post-bioremediation) and extracted using pressurized liquid extraction. The soil extracts were fractionated, based on polarity, and analyzed for 88 PAHs (unsubstituted, oxygenated, nitrated, and heterocyclic PAHs). The PAH concentrations in the soil tested, post-bioremediation, were lower than their regulatory maximum allowable concentrations (MACs), with the exception of the higher molecular weight PAHs (BaA, BkF, BbF, BaP, and IcdP), most of which did not undergo significant biodegradation. The soil extract fractions were tested for genotoxicity using the DT40 chicken lymphocyte bioassay and developmental to xicity using the embryonic zebrafish (Danio rerio) bioassay. A statistically significant increase in genotoxicity was measured in the unfractionated soil extract, as well as in four polar soil extract fractions, post-bioremediation (p < 0.05). In addition, a statistically significant increase in developmental toxicity was measured in one polar soil extract fraction, post-bioremediation (p < 0.05). A series of morphological abnormalities, including peculiar caudal fin malformations and hyperpigmentation in the tail, were measured in several soil extract fractions in embryonic zebrafish, both pre- and post-bioremediation. The increased toxicity measured post-bioremediation is not likely due to the 88 PAHs measured in this study (including quinones), because most were not present in the toxic polar fractions and/or because their concentrations did not increase post-bioremediation. However, the increased toxicity measured post-bioremediation is likely due to hydroxylated and carboxylated transformation products of the 3- and 4-ring PAHs

Safety evaluation of phytosterol esters. Part 8. Lack of genotoxicity and subchronic toxicity with phytosterol oxides.

PubMed

Lea, L J; Hepburn, P A; Wolfreys, A M; Baldrick, P

2004-05-01

Vegetable oil spreads containing phytosterol-esters are marketed as a cholesterol-lowering functional food in more than 20 countries worldwide. An extensive package of safety data has shown phytosterol-esters to be safe for human use. However, even though phytosterols are very stable molecules, oxidation may occur at low levels under extreme heating conditions, resulting in phytosterol oxides. As there is some suggestion of adverse biological effects in the literature for the related cholesterol oxidation products, safety data have been generated for phytosterol oxides. A phytosterol oxide concentrate (POC) was generated by prolonged heating of phytosterol-esters in the presence of oxygen. The genotoxicity and subchronic toxicity of this mixture was assessed in a series of in vitro genotoxicity assays (bacterial mutation, chromosome aberration and micronucleus) and a subchronic feeding study in the rat. Results showed that a phytosterol oxide concentrate containing approximately 30% phytosterol oxides did not possess genotoxic potential and no obvious evidence of toxicity when administered in the diet of the rat for 90 consecutive days. In the latter study, a NOEL was established at an estimated dietary level of phytosterol oxides of 128 mg/kg/day for males and 144 mg/kg/day for females. In conclusion, these materials have been shown to raise no obvious concerns for human safety.

Interrelationships among carcinogenicity, mutagenicity, acute toxicity, and chemical structure in a genotoxicity data base

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

Benigni, R.; Andreoli, C.; Giuliani, A.

1989-01-01

The interrelationships among carcinogenicity, mutagenicity, acute toxicity (LD50), and a number of molecular descriptors were studied by computerized data analysis methods on the data base generated by the International Program for the Evaluation of Short-Term Test for Carcinogens (IPESTTC). With the use of statistical regression methods, three main associations were evidenced: (1) the well-known correlation between carcinogenicity and mutagenicity; (2) a correlation between mutagenicity and toxicity (LD50 ip in mice); and (3) a correlation between toxicity and a recently introduced estimator of the free energy of binding of the molecules to biological receptors. As expected on the basis of themore » large variety of chemical classes represented in the IPESTTC data base, no simple relationship between mutagenicity or carcinogenicity and chemical descriptors was found. To overcome this problem, a new pattern recognition method (REPAD), developed by us for structure-activity studies of noncongeneric chemicals, has been used. This allowed us to highlight a significant difference between the whole patterns of relationships among chemicophysical variables in the two groups to active (mutagenicity and/or carcinogenic) and inactive chemicals. This approach generated a classification rule able to correctly assign about 80% of carcinogens or mutagens.« less

Acute toxic nephropathies: clinical pathologic correlations.

PubMed

Muehrcke, R C; Volini, F I; Morris, A M; Moles, J B; Lawrence, A G

1976-01-01

Man's ever increasing exposure to numerous drugs and chemicals, which are the results of medical and industrial progress, produces a by-product of acute toxic nephropathies. These include acute toxic renal failure, drug-induced acute oliguric renal failure, acute hemorrhagic glomerulonephritis, nephrotic syndrome, tubular disturbances and potassium deficiency. In depth information is provided for the previously mentioned disorders.

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.

Toxicity hazard of organophosphate insecticide malathion identified by in vitro methods.

PubMed

Jira, David; Janousek, Stanislav; Pikula, Jiri; Vitula, Frantisek; Kejlova, Kristina

2012-01-01

Malathion is generally not classified as toxic. However, the toxicity seems to be species-dependent. Local and systemic toxicity data for birds are rare, but a decrease of wild bird densities in areas where malathion was applied was reported. Aim of the study was to extend knowledge on malathion toxicity on cellular and organ level and to evaluate embryotoxicity and genotoxicity for birds using the chick embryo model HET-CAM. Skin and eye irritation was determined using reconstructed skin and eye cornea tissues and the chorioallantoic membrane of chick embryo to simulate conjunctiva. Cytotoxicity in 3T3 Balb/c fibroblast culture was determined to estimate acute systemic toxicity. Chick embryo model was further employed to evaluate acute embryotoxicity for birds (mortality and genotoxicity). Data were analysed by means of general linear models. Malathion is not a skin and eye irritant. Cytotoxicity in vitro test provided LD50 value of 616 mg/kg suggesting higher toxic potential than is generally published based on in vivo tests on laboratory rodents. Embryotoxicity studies revealed dose and age dependent mortality of chick embryos. Genotoxicity was identified by means of micronucleus test in erythroid cells isolated from chorioallantois vascular system of chick embryos. Using in vitro alternative toxicological methods, a higher toxic potential of malathion was demonstrated than is generally declared. An increased health and environmental hazard may occur in areas with intensive agricultural production. The environmental consequences of delayed effects and embryotoxicity for bird populations in areas exposed to organophosphate insecticides, such as malathion, are obvious.

Evaluation of Genotoxicity and 28-day Oral Dose Toxicity on Freeze-dried Powder of Tenebrio molitor Larvae (Yellow Mealworm).

PubMed

Han, So-Ri; Yun, Eun-Young; Kim, Ji-Young; Hwang, Jae Sam; Jeong, Eun Ju; Moon, Kyoung-Sik

2014-06-01

The larval form of Tenebrio molitor (T. molitor) has been eaten in many countries and provides benefits as a new food source of protein for humans. However, no information exists regarding its safety for humans. The objective of the present study was to evaluate the genotoxicity and repeated dose oral toxicity of the freeze-dried powder of T. molitor larvae. The genotoxic potential was evaluated by a standard battery testing: bacterial reverse mutation test, in vitro chromosome aberration test, and in vivo micronucleus test. To assess the repeated dose toxicity, the powder was administered once daily by oral gavage to Sprague-Dawley (SD) rats at dose levels of 0, 300, 1000 and 3000 mg/kg/day for 28 days. The parameters which were applied to the study were mortality, clinical signs, body and organ weights, food consumption, ophthalmology, urinalysis, hematology, serum chemistry, gross findings and histopathologic examination. The freezedried powder of T. molitor larvae was not mutagenic or clastogenic based on results of in vitro and in vivo genotoxicity assays. Furthermore, no treatment-related changes or findings were observed in any parameters in rats after 28 days oral administration. In conclusion, the freeze-dried powder of T. molitor larvae was considered to be non-genotoxic and the NOAEL (No Observed Adverse Effect Level) was determined to be 3000 mg/kg/day in both sexes of SD rats under our experimental conditions.

The genotoxic effect of oxcarbazepine on mice blood lymphocytes.

PubMed

Akbar, Huma; Khan, Ajmal; Mohammadzai, Imdadullah; Khisroon, Muhammad; Begum, Ilham

2018-04-01

This study was conducted to assess the amount of DNA damage caused by Oxcarbazepine (OXC) through single cell gel electrophoresis (SCGE) technique/comet assay. OXC derived from dibenzazepine series is an effective second generation antiepileptic drug (AED) for both children and adults. Side effects like genotoxic effects of AEDs are of prime importance resulting from toxic metabolites, free radicals and reactive oxygen species (ROS). Forty Eight adult male Bagg's albino mice (BALB/c) were randomly classified into eight groups, each comprising of six animals. Two of these groups were control and six were tested groups. Control groups were injected with 1% tween 80 while tested groups were injected with 10, 20, and 40 mg/kg-day OXC for seven days (acute therapy) and 28 days (subchronic therapy) in peritoneal cavity. Blood samples were collected by cardiac puncture and subjected to comet assay for the analysis of DNA damage. Per sample 100 cells were scored and classified according to comet tail length. The results showed that OXC in acute and long term therapies had significantly higher (p < 0.05) genotoxicity in treated groups as compared to control groups. Our study suggests that OXC may cause significant DNA damage in both acute as well as in subchronic therapies.

Acute and subchronic toxicity as well as mutagenic evaluation of essential oil from turmeric (Curcuma longa L).

PubMed

Liju, Vijayasteltar B; Jeena, Kottarapat; Kuttan, Ramadasan

2013-03-01

The present study investigated the acute, subchronic and genotoxicity of turmeric essential oil (TEO) from Curcuma longa L. Acute administration of TEO was done as single dose up to 5 g of TEO per kg body weight and subchronic toxicity study for thirteen weeks was done by daily oral administration of TEO at doses 0.1, 0.25 and 0.5 g/kg b.wt. in Wistar rats. There were no mortality, adverse clinical signs or changes in body weight; water and food consumption during acute as well as subchronic toxicity studies. Indicators of hepatic function such as aspartate aminotransferase (AST), alanine amino transferase (ALT) and alkaline phosphatase (ALP) were unchanged in treated animals compared to untreated animals. Oral administration of TEO for 13 weeks did not alter total cholesterol, triglycerides, markers of renal function, serum electrolyte parameters and histopathology of tissues. TEO did not produce any mutagenicity to Salmonella typhimurium TA-98, TA-100, TA-102 and TA-1535 with or without metabolic activation. Administration of TEO to rats (1 g/kg b.wt.) for 14 days did not produce any chromosome aberration or micronuclei in rat bone marrow cells and did not produce any DNA damage as seen by comet assay confirming the non toxicity of TEO. Copyright © 2012 Elsevier Ltd. All rights reserved.

Acute toxicity and primary irritancy of alkylalkanolamines.

PubMed

Ballantyne, B; Leung, H W

1996-12-01

The acute handling hazards of several alkylalkanolamines were determined by investigating their potential acute toxicity and primary irritancy. Materials studied were N-methylethanolamine (MEA), N, N, -dimethylethanolamine (DMEA), N, N, -dimethylisopropanolamine (DMIPA), N-methyldiethanolamine (MDEA), and tertbutyldiethanolamine (BDEA). All these alkylalkanolamines were of comparable acute peroral toxicity in the rat (LD50 range 1.48-2.83 ml/kg). By 24 h occluded epicutaneous contact in the rabbit, MEA, DMEA and DMIPA were of moderate acute percutaneous toxicity (LD50 range 1.13-2.0 ml/kg), MDEA was of slight acute percutaneous toxicity (LD50 male 9.85 ml/kg, female 10.90 ml/kg), and BDEA of intermediate toxicity (LD50 6.4 ml/kg). Due to differences in vapor pressure the acute vapor exposure toxicity of the alkylalkanolamines to rats varied; MEA, MDEA and BDEA were of a low order of acute toxicity, and DMIPA was moderately toxic with an LT50 of 3.2 h for a saturated vapor atmosphere exposure. A 4 h-LC50 (rat combined sex) of 1461 ppm was determined for DMEA. All alkylalkanolamines studied, except MDEA, were moderately to markedly irritating and caused variable degrees of skin corrosivity; MDEA caused only transient minor skin irritation. In accord with the skin irritancy results, the eye irritancy from 0.005 ml MEA, DMEA, DMIPA and BDEA was severe, and that from MDEA was slight. Exposure to these compounds has implications for occupational health procedures.

Cytotoxicity and genotoxicity evaluation of organochalcogens in human leucocytes: a comparative study between ebselen, diphenyl diselenide, and diphenyl ditelluride.

PubMed

Caeran Bueno, Diones; Meinerz, Daiane Francine; Allebrandt, Josiane; Waczuk, Emily Pansera; dos Santos, Danúbia Bonfanti; Mariano, Douglas Oscar Ceolin; Rocha, João Batista Teixeira

2013-01-01

Organochalcogens, particularly ebselen, have been used in experimental and clinical trials with borderline efficacy. (PhSe)2 and (PhTe)2 are the simplest of the diaryl dichalcogenides and share with ebselen pharmacological properties. In view of the concerns with the use of mammals in studies and the great number of new organochalcogens with potential pharmacological properties that have been synthesized, it becomes important to develop screening protocols to select compounds that are worth to be tested in vivo. This study investigated the possible use of isolated human white cells as a preliminary model to test organochalcogen toxicity. Human leucocytes were exposed to 5-50  μM of ebselen, (PhSe)2, or (PhTe)2. All compounds were cytotoxic (Trypan's Blue exclusion) at the highest concentration tested, and Ebselen was the most toxic. Ebselen and (PhSe)2 were genotoxic (Comet Assay) only at 50  μM, and (PhTe)2 at 5-50  μM. Here, the acute cytotoxicity did not correspond with in vivo toxicity of the compounds. But the genotoxicity was in the same order of the in vivo toxicity to mice. These results indicate that in vitro genotoxicity in white blood cells should be considered as an early step in the investigation of potential toxicity of organochalcogens.

Toxic and genotoxic effects of the 2,4-dichlorophenoxyacetic acid (2,4-D)-based herbicide on the Neotropical fish Cnesterodon decemmaculatus.

PubMed

Ruiz de Arcaute, C; Soloneski, S; Larramendy, M L

2016-06-01

Acute toxicity and genotoxicity of the 54.8% 2,4-D-based commercial herbicide DMA® were assayed on Cnesterodon decemmaculatus (Pisces, Poeciliidae). Whereas lethal effect was used as the end point for mortality, frequency of micronuclei (MNs), other nuclear abnormalities and primary DNA damage evaluated by the single cell gel electrophoresis (SCGE) assay were employed as end points for genotoxicity. Mortality studies demonstrated an LC50 96 h value of 1008 mg/L (range, 929-1070) of 2,4-D. Behavioral changes, e.g., gathering at the bottom of the aquarium, slowness in motion, slow reaction and abnormal swimming were observed. Exposure to 2,4-D within the 252-756 mg/L range increased the frequency of MNs in fish exposed for both 48 and 96 h. Whereas blebbed nuclei were induced in treatments lasting for 48 and 96 h, notched nuclei were only induced in fish exposed for 96 h. Regardless of both concentration and exposure time, 2,4-D did not induce lobed nuclei and binucleated erythrocytes. In addition, we found that exposure to 2,4-D within the 252-756 mg/L range increased the genetic damage index in treatments lasting for either 48 and 96 h. The results represent the first experimental evidence of the lethal and several sublethal effects, including behavioral alterations and two genotoxic properties namely the induction of MNs and primary DNA strand breaks, exerted by 2,4-D on an endemic organism as C. decemmaculatus. Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluation of Genotoxicity and 28-day Oral Dose Toxicity on Freeze-dried Powder of Tenebrio molitor Larvae (Yellow Mealworm)

PubMed Central

Han, So-Ri; Yun, Eun-Young; Kim, Ji-Young; Hwang, Jae Sam; Jeong, Eun Ju

2014-01-01

The larval form of Tenebrio molitor (T. molitor) has been eaten in many countries and provides benefits as a new food source of protein for humans. However, no information exists regarding its safety for humans. The objective of the present study was to evaluate the genotoxicity and repeated dose oral toxicity of the freeze-dried powder of T. molitor larvae. The genotoxic potential was evaluated by a standard battery testing: bacterial reverse mutation test, in vitro chromosome aberration test, and in vivo micronucleus test. To assess the repeated dose toxicity, the powder was administered once daily by oral gavage to Sprague-Dawley (SD) rats at dose levels of 0, 300, 1000 and 3000 mg/kg/day for 28 days. The parameters which were applied to the study were mortality, clinical signs, body and organ weights, food consumption, ophthalmology, urinalysis, hematology, serum chemistry, gross findings and histopathologic examination. The freezedried powder of T. molitor larvae was not mutagenic or clastogenic based on results of in vitro and in vivo genotoxicity assays. Furthermore, no treatment-related changes or findings were observed in any parameters in rats after 28 days oral administration. In conclusion, the freeze-dried powder of T. molitor larvae was considered to be non-genotoxic and the NOAEL (No Observed Adverse Effect Level) was determined to be 3000 mg/kg/day in both sexes of SD rats under our experimental conditions. PMID:25071922

Evaluation of ecotoxicological effects of benzophenone UV filters: Luminescent bacteria toxicity, genotoxicity and hormonal activity.

PubMed

Zhang, Qiuya; Ma, Xiaoyan; Dzakpasu, Mawuli; Wang, Xiaochang C

2017-08-01

The widespread use of organic ultraviolet (UV) filters in personal care products raises concerns about their potentially hazardous effects on human and ecosystem health. In this study, the toxicities of four commonly used benzophenones (BPs) UV filters including benzophenone (BP), 2-Hydroxybenzophenone (2HB), 2-Hydroxy-4-methoxybenzophenone (BP3), and 2-Hydroxy-4-methoxybenzophenone-5-sulfonicacid (BP4) in water were assayed in vitro using Vibrio fischeri, SOS/umu assay, and yeast estrogen screen (YES) assay, as well as in vivo using zebrafish larvae. The results showed that the luminescent bacteria toxicity, expressed as logEC 50 , increased with the lipophilicity (logKow) of BPs UV filters. Especially, since 2HB, BP3 and BP4 had different substituent groups, namely -OH, -OCH 3 and -SO 3 H, respectively, these substituent functional groups had a major contribution to the lipophilicity and acute toxicity of these BPs. Similar tendency was observed for the genotoxicity, expressed as the value of induction ratio=1.5. Moreover, all the target BPs UV filters showed estrogenic activity, but no significant influences of lipophilicity on the estrogenicity were observed, with BP3 having the weakest estrogenic efficiency in vitro. Although BP3 displayed no noticeable adverse effects in any in vitro assays, multiple hormonal activities were observed in zebrafish larvae including estrogenicity, anti-estrogenicity and anti-androgenicity by regulating the expression of target genes. The results indicated potential hazardous effects of BPs UV filters and the importance of the combination of toxicological evaluation methods including in vitro and in vivo assays. Copyright © 2017 Elsevier Inc. All rights reserved.

Ecotoxicological and Genotoxic Evaluation of Buenos Aires City (Argentina) Hospital Wastewater

PubMed Central

Juárez, Ángela Beatriz; Dragani, Valeria; Saenz, Magalí Elizabeth; Moretton, Juan

2014-01-01

Hospital wastewater (HWW) constitutes a potential risk to the ecosystems and human health due to the presence of toxic and genotoxic chemical compounds. In the present work we investigated toxicity and genotoxicity of wastewaters from the public hospital of Buenos Aires (Argentina). The effluent from the sewage treatment plant (STP) serving around 10 million inhabitants was also evaluated. The study was carried out between April and September 2012. Toxicity and genotoxicity assessment was performed using the green algae Pseudokirchneriella subcapitata and the Allium cepa test, respectively. Toxicity assay showed that 55% of the samples were toxic to the algae (%I of growth between 23.9 and 54.8). The A. cepa test showed that 40% of the samples were genotoxic. The analysis of chromosome aberrations (CA) and micronucleus (MN) showed no significant differences between days and significant differences between months. The sample from the STP was not genotoxic to A. cepa but toxic to the algae (%I = 41%), showing that sewage treatment was not totally effective. This study highlights the need for environmental control programs and the establishment of advanced and effective effluent treatment plants in the hospitals, which are merely dumping the wastewaters in the municipal sewerage system. PMID:25214834

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

Cyto- and genotoxic profile of groundwater used as drinking water supply before and after disinfection.

PubMed

Pellacani, C; Cassoni, F; Bocchi, C; Martino, A; Pinto, G; Fontana, F; Furlini, M; Buschini, A

2016-12-01

The assessment of the toxicological properties of raw groundwater may be useful to predict the type and quality of tap water. Contaminants in groundwater are known to be able to affect the disinfection process, resulting in the formation of substances that are cytotoxic and/or genotoxic. Though the European directive (98/83/EC, which establishes maximum levels for contaminants in raw water (RW)) provides threshold levels for acute exposure to toxic compounds, the law does not take into account chronic exposure at low doses of pollutants present in complex mixture. The purpose of this study was to evaluate the cyto- and genotoxic load in the groundwater of two water treatment plants in Northern Italy. Water samples induced cytotoxic effects, mainly observed when human cells were treated with RW. Moreover, results indicated that the disinfection process reduced cell toxicity, independent of the biocidal used. The induction of genotoxic effects was found, in particular, when the micronucleus assay was carried out on raw groundwater. These results suggest that it is important to include bio-toxicological assays as additional parameters in water quality monitoring programs, as their use would allow the evaluation of the potential risk of groundwater for humans.

Non-infectious chemotherapy-associated acute toxicities during childhood acute lymphoblastic leukemia therapy

PubMed Central

Schmiegelow, Kjeld; Müller, Klaus; Mogensen, Signe Sloth; Mogensen, Pernille Rudebeck; Wolthers, Benjamin Ole; Stoltze, Ulrik Kristoffer; Tuckuviene, Ruta; Frandsen, Thomas

2017-01-01

During chemotherapy for childhood acute lymphoblastic leukemia, all organs can be affected by severe acute side effects, the most common being opportunistic infections, mucositis, central or peripheral neuropathy (or both), bone toxicities (including osteonecrosis), thromboembolism, sinusoidal obstruction syndrome, endocrinopathies (especially steroid-induced adrenal insufficiency and hyperglycemia), high-dose methotrexate-induced nephrotoxicity, asparaginase-associated hypersensitivity, pancreatitis, and hyperlipidemia. Few of the non-infectious acute toxicities are associated with clinically useful risk factors, and across study groups there has been wide diversity in toxicity definitions, capture strategies, and reporting, thus hampering meaningful comparisons of toxicity incidences for different leukemia protocols. Since treatment of acute lymphoblastic leukemia now yields 5-year overall survival rates above 90%, there is a need for strategies for assessing the burden of toxicities in the overall evaluation of anti-leukemic therapy programs. PMID:28413626

Classification of baseline toxicants for QSAR predictions to replace fish acute toxicity studies.

PubMed

Nendza, Monika; Müller, Martin; Wenzel, Andrea

2017-03-22

Fish acute toxicity studies are required for environmental hazard and risk assessment of chemicals by national and international legislations such as REACH, the regulations of plant protection products and biocidal products, or the GHS (globally harmonised system) for classification and labelling of chemicals. Alternative methods like QSARs (quantitative structure-activity relationships) can replace many ecotoxicity tests. However, complete substitution of in vivo animal tests by in silico methods may not be realistic. For the so-called baseline toxicants, it is possible to predict the fish acute toxicity with sufficient accuracy from log K ow and, hence, valid QSARs can replace in vivo testing. In contrast, excess toxicants and chemicals not reliably classified as baseline toxicants require further in silico, in vitro or in vivo assessments. Thus, the critical task is to discriminate between baseline and excess toxicants. For fish acute toxicity, we derived a scheme based on structural alerts and physicochemical property thresholds to classify chemicals as either baseline toxicants (=predictable by QSARs) or as potential excess toxicants (=not predictable by baseline QSARs). The step-wise approach identifies baseline toxicants (true negatives) in a precautionary way to avoid false negative predictions. Therefore, a certain fraction of false positives can be tolerated, i.e. baseline toxicants without specific effects that may be tested instead of predicted. Application of the classification scheme to a new heterogeneous dataset for diverse fish species results in 40% baseline toxicants, 24% excess toxicants and 36% compounds not classified. Thus, we can conclude that replacing about half of the fish acute toxicity tests by QSAR predictions is realistic to be achieved in the short-term. The long-term goals are classification criteria also for further groups of toxicants and to replace as many in vivo fish acute toxicity tests as possible with valid QSAR

Genotoxicity and antigenotoxicity study of aqueous and hydro-methanol extracts of Spondias mombin L., Nymphaea lotus L. and Luffa cylindrical L. using animal bioassays

PubMed Central

Oyeyemi, Ifeoluwa Temitayo; Yekeen, Olaide Maruf; Odusina, Paul Olayinka; Ologun, Taiwo Mary; Ogbaide, Orezimena Michelle; Olaleye, Olayinka Israel

2015-01-01

Spondias mombin (Linn), Nymphaea lotus (Linn) and Luffa cylindrica (Linn) (syn Luffa aegyptiaca Mill) are plants traditionally used as food ingredients and in the management of diseases, including cancer, in Nigeria. Despite the therapeutic potentials attributed to these plants, reports on their genotoxicity are scanty. In this study, the genotoxicity of the aqueous and hydro-methanol extract of these plants was evaluated using mouse bone marrow micronucleus and sperm morphology assays. Antigenotoxicity was assessed by the bone marrow micronucleus test. The highest attainable dose of 5 000 mg/kg according to OECD guidelines was first used to assess acute toxicity of the aqueous and hydro-methanol extracts in Swiss albino mice. For each extract, there were five groups of mice (n=4/group) treated with different concentrations of the extract as against the negative and positive control group for the genotoxicity study. In the antigenotoxicity study, five groups of mice were exposed to five different concentrations of the extracts along with 60 mg/kg of methyl methane sulfonate (MMS), which was used to induce genotoxicity. The mice were administered 0.2 mL of extract per day for 10 days in the genotoxicity and antigenotoxicity groups. Administration of each of the extracts at the concentration of 5 000 mg/kg did not induce acute toxicity in mice. At the concentrations tested, all the extracts, except aqueous S. mombin, increased micronucleated polychromatic erythrocytes. The aqueous and hydro-methanol extracts of N. lotus increased the frequency of aberrant sperm cells. All the extracts were also able to ameliorate MMS induced genotoxicity in bone marrow cells of the exposed mice. The results showed the potential of the extracts to induce somatic and germ cell mutation in male mice. The extracts also ameliorated the genotoxic effect of MMS. PMID:27486380

Genotoxicity and antigenotoxicity study of aqueous and hydro-methanol extracts of Spondias mombin L., Nymphaea lotus L. and Luffa cylindrical L. using animal bioassays.

PubMed

Oyeyemi, Ifeoluwa Temitayo; Yekeen, Olaide Maruf; Odusina, Paul Olayinka; Ologun, Taiwo Mary; Ogbaide, Orezimena Michelle; Olaleye, Olayinka Israel; Bakare, Adekunle A

2015-12-01

Spondias mombin (Linn), Nymphaea lotus (Linn) and Luffa cylindrica (Linn) (syn Luffa aegyptiaca Mill) are plants traditionally used as food ingredients and in the management of diseases, including cancer, in Nigeria. Despite the therapeutic potentials attributed to these plants, reports on their genotoxicity are scanty. In this study, the genotoxicity of the aqueous and hydro-methanol extract of these plants was evaluated using mouse bone marrow micronucleus and sperm morphology assays. Antigenotoxicity was assessed by the bone marrow micronucleus test. The highest attainable dose of 5 000 mg/kg according to OECD guidelines was first used to assess acute toxicity of the aqueous and hydro-methanol extracts in Swiss albino mice. For each extract, there were five groups of mice (n=4/group) treated with different concentrations of the extract as against the negative and positive control group for the genotoxicity study. In the antigenotoxicity study, five groups of mice were exposed to five different concentrations of the extracts along with 60 mg/kg of methyl methane sulfonate (MMS), which was used to induce genotoxicity. The mice were administered 0.2 mL of extract per day for 10 days in the genotoxicity and antigenotoxicity groups. Administration of each of the extracts at the concentration of 5 000 mg/kg did not induce acute toxicity in mice. At the concentrations tested, all the extracts, except aqueous S. mombin, increased micronucleated polychromatic erythrocytes. The aqueous and hydro-methanol extracts of N. lotus increased the frequency of aberrant sperm cells. All the extracts were also able to ameliorate MMS induced genotoxicity in bone marrow cells of the exposed mice. The results showed the potential of the extracts to induce somatic and germ cell mutation in male mice. The extracts also ameliorated the genotoxic effect of MMS.

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

PubMed

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

2017-04-01

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

Extensive review of fish embryo acute toxicities for the prediction of GHS acute systemic toxicity categories.

PubMed

Scholz, Stefan; Ortmann, Julia; Klüver, Nils; Léonard, Marc

2014-08-01

Distribution and marketing of chemicals require appropriate labelling of health, physical and environmental hazards according to the United Nations global harmonisation system (GHS). Labelling for (human) acute toxicity categories is based on experimental findings usually obtained by oral, dermal or inhalative exposure of rodents. There is a strong societal demand for replacing animal experiments conducted for safety assessment of chemicals. Fish embryos are considered as alternative to animal testing and are proposed as predictive model both for environmental and human health effects. Therefore, we tested whether LC50s of the fish embryo acute toxicity test would allow effectively predicting of acute mammalian toxicity categories. A database of published fish embryo LC50 containing 641 compounds was established. For these compounds corresponding rat oral LD50 were identified resulting in 364 compounds for which both fish embryo LC50 and rat LD50 was available. Only a weak correlation of fish embryo LC50 and rat oral LD50 was obtained. Fish embryos were also not able to effectively predict GHS oral acute toxicity categories. We concluded that due to fundamental exposure protocol differences (single oral dose versus water-borne exposure) a reverse dosimetry approach is needed to explore the predictive capacity of fish embryos. Copyright © 2014 Elsevier Inc. All rights reserved.

Acute aquatic toxicity of biodiesel fuels

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

Wright, B.; Haws, R.; Little, D.

1995-12-31

This study develops data on the acute aquatic toxicity of selected biodiesel fuels which may become subject to environmental effects test regulations under the US Toxic Substances Control Act (TSCA). The test substances are Rape Methyl Ester (RME), Rape Ethyl Ester (REE), Methyl Soyate (MS), a biodiesel mixture of 20% REE and 80% Diesel, a biodiesel mixture of 50% REE and diesel, and a reference substance of Phillips D-2 Reference Diesel. The test procedure follows the Daphnid Acute Toxicity Test outlined in 40 CFR {section} 797.1300 of the TSCA regulations. Daphnia Magna are exposed to the test substance in amore » flow-through system consisting of a mixing chamber, a proportional diluter, and duplicate test chambers. Novel system modifications are described that accommodate the testing of oil-based test substances with Daphnia. The acute aquatic toxicity is estimated by an EC50, an effective concentration producing immobility in 50% of the test specimen.« less

Acute toxicity of commercial atrazine in Piaractus mesopotamicus: Histopathological, ultrastructural, molecular, and genotoxic evaluation

PubMed Central

de Paiva, Paula Pereira; Delcorso, Mariana Cruz; Matheus, Valquíria Aparecida; de Queiroz, Sonia Claudia do Nascimento; Collares-Buzato, Carla Beatriz; Arana, Sarah

2017-01-01

Aim: The aim of this work was to evaluate the sensitivity of Pacu fingerlings (Piaractus mesopotamicus) by measuring the effects of median lethal concentration (LC50) of atrazine (ATZ - 28.58 mg/L) after acute exposure (up to 96 h). Materials and Methods: The fish were exposed to the LC50 of ATZ for 96 h (28.58 mg/L) in a static system. During the experiment, the fingerlings were randomly distributed in four glass tanks (50 L) containing dechlorinated water. Four glass tanks were for the control group, and four were for the ATZ-exposed group (n=4 per glass tank), given a total number of 16 animals tested per group. The genotoxicity was evaluated by micronucleus (MN) test in erythrocytes from peripheral blood. Qualitative and semi-quantitative histopathological analyses, and also ultrastructural study, were applied in liver and kidney samples. Finally, the content of heat shock protein (Hsp70) in the liver was evaluated by the western blotting method. Results: The morphological alterations in the liver, which was associated with increased expression of Hsp70, included nuclear and cytoplasmic vacuolization, cytoplasmic hyaline inclusions, and necrosis. The kidney presented edema and tubular cell degeneration with cytoplasmic hyaline inclusion. The semi-quantitative histopathological analyses indicated that the liver was more sensitive than kidney to ATZ-induced damage. Ultrastructural analysis showed that ATZ caused membrane alterations in several organelles and increased the number of lysosomes in hepatocytes and kidney proximal tubular cells. Nevertheless, no significant difference was observed in MN frequency in erythrocytes comparing treated and control groups., Conclusion: These results indicated that ATZ-induced damage to the kidney and liver function, ATZ at the concentration tested did not induce a significant difference in MN frequency in Pacu erythrocytes comparing treated and control groups, and also that Pacu fingerlings may be a good bioindicator for

Acute oral toxicity test of chemical compounds in silkworms.

PubMed

Usui, Kimihito; Nishida, Satoshi; Sugita, Takuya; Ueki, Takuro; Matsumoto, Yasuhiko; Okumura, Hidenobu; Sekimizu, Kazuhisa

2016-02-01

This study performed an acute oral toxicity test of 59 compounds in silkworms. These compounds are listed in OECD guidelines as standard substances for a cytotoxicity test, and median lethal dose (LD(50)) werecalculated for each compound. Acute oral LD(50) values in mammals are listed in OECD guidelines and acute oral LD(50) values in silkworms were determined in this study. R(2) for the correlation between LD(50) values in mammals and LD(50) values in silkworms was 0.66. In addition, the acute oral toxicity test in silkworms was performed by two different facilities, and test results from the facilities were highly reproducible. These findings suggest that an acute oral toxicity test in silkworms is a useful way to evaluate the toxicity of compounds in mammals.

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.

Studies on fate and toxicity of nanoalumina in male albino rats: Lethality, bioaccumulation and genotoxicity.

PubMed

Morsy, Gamal M; El-Ala, Kawther S Abou; Ali, Atef A

2016-02-01

The purpose of this study is to follow-up the distribution, lethality percentile doses (LDs) and bioaccumulation of aluminium oxide nanoparticles (Al2O3-NPs, average diameter 9.83 ± 1.61 nm) in some tissues of male albino rats, and to evaluate its genotoxicity to the brain tissues, during acute and sublethal experiments. The LDs of Al2O3-NPs, including median lethal dose (LD50), were estimated after intraperitoneal injection. The computed LD50 at 24 and 48 h were 15.10 and 12.88 g/kg body weight (b.w.), respectively. For acute experiments, the bioaccumulation of aluminium (Al) in the brain, liver, kidneys, intestine and spleen was estimated after 48 h of injection with a single acute dose (3.9, 6.4 and 8.5 g/kg b.w.), while for sublethal experiments it was after 1, 3, 7, 14 and 28 days of injection with 1.3 g/kg b.w. once in 2 days. Multi-way analysis of variance affirmed that Al uptake, in acute experiments, was significantly affected by the injected doses, organs (brain, liver, kidneys, intestine and spleen) and their interactions, while for sublethal experiments an altogether effect based on time (1, 3, 7, 14, 28 days), doses (0 and 1.3 g), organs and their interactions was reported. In addition, Al accumulated in the brain, liver, kidney, intestine and spleen of rats administered with Al2O3-NPs were significantly higher than the corresponding controls, during acute and sublethal experiments. The uptake of Al by the spleen of rats injected with acute doses was greater than that accumulated by kidney>brain>intestine>liver, whereas the brain of rats injected with sublethal dose accumulated lesser amount of Al followed by the kidneyacute term) and the experimental periods (in sublethal term). In the acute and sublethal experiments, comet assay parameters such as the tail intensity (i.e. DNA percentage), tail extent moment and olive tail

Oxidative stress and genotoxicity induced by ketorolac on the common carp Cyprinus carpio.

PubMed

Galar-Martínez, M; García-Medina, S; Gómez-Olivan, L M; Pérez-Coyotl, I; Mendoza-Monroy, D J; Arrazola-Morgain, R E

2016-09-01

The nonsteroidal anti-inflammatory drug ketorolac is extensively used in the treatment of acute postoperative pain. This pharmaceutical has been found at concentrations of 0.2-60 µg/L in diverse water bodies around the world; however, its effects on aquatic organisms remain unknown. The present study, evaluated the oxidative stress and genotoxicity induced by sublethal concentrations of ketorolac (1 and 60 µg/L) on liver, brain, and blood of the common carp Cyprinus carpio. This toxicant induced oxidative damage (increased lipid peroxidation, hydroperoxide content, and protein carbonyl content) as well as changes in antioxidant status (superoxide dismutase, catalase, and glutathione peroxidase activity) in liver and brain of carp. In blood, ketorolac increased the frequency of micronuclei and is therefore genotoxic for the test species. The effects observed were time and concentration dependent. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1035-1043, 2016. © 2015 Wiley Periodicals, Inc.

The influence of organic solvents on estimates of genotoxicity and antigenotoxicity in the SOS chromotest.

PubMed

Quintero, Nathalia; Stashenko, Elena E; Fuentes, Jorge Luis

2012-04-01

In this work, the toxicity and genotoxicity of organic solvents (acetone, carbon tetrachloride, dichloromethane, dimethylsulfoxide, ethanol, ether and methanol) were studied using the SOS chromotest. The influence of these solvents on the direct genotoxicity induced by the mutagens mitomycin C (MMC) and 4-nitroquinoline-1-oxide (4-NQO) were also investigated. None of the solvents were genotoxic in Escherichia coli PQ37. However, based on the inhibition of protein synthesis assessed by constitutive alkaline phosphatase activity, some solvents (carbon tetrachloride, dimethylsulfoxide, ethanol and ether) were toxic and incompatible with the SOS chromotest. Solvents that were neither toxic nor genotoxic to E. coli (acetone, dichloromethane and methanol) significantly reduced the genotoxicity of MMC and 4-NQO. When these solvents were used to dissolve vitamin E they increased the antigenotoxic activity of this compound, possibly through additive or synergistic effects. The relevance of these results is discussed in relation to antigenotoxic studies. These data indicate the need for careful selection of an appropriate diluent for the SOS chromotest since some solvents can modulate genotoxicity and antigenotoxicity.

Genotoxicity of metal nanoparticles.

PubMed

Xie, Hong; Mason, Michael M; Wise, John Pierce

2011-01-01

Nanotechnology is currently used in industry, medicine, and military applications, as well as in more than 300 commercial products. Yet, the same properties that make these particles exciting for technology also make them daunting public health concerns because their toxicity is unknown and relatively unexplored. Increased attention is being placed on the study of metal particle genotoxicity; however, a lot of unknowns remain about their effects and the mechanisms. In this article, we highlight some metal and metal oxide nanoparticles of interest and discuss the current in vivo and in vitro studies of genotoxic effects. Many metal nanoparticles were found to cause chromosomal aberrations, DNA strand breaks, oxidative DNA damage, and mutations. Inconsistencies are found in the literature, however, thus drawing conclusions is difficult due to a variety of factors. Therefore, the areas requiring further attention are highlighted and recommendations to improve our understanding of the genotoxic potential are addressed.

The cytotoxicity and genotoxicity of soluble and particulate cobalt in human lung fibroblast cells

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

Smith, Leah J.; Holmes, Amie L.; Maine Center for Environmental Toxicology and Health, University of Southern Maine, 96 Falmouth St., P.O. Box 9300, Portland, ME 04101-9300

Cobalt exposure is increasing as cobalt demand rises worldwide due to its use in enhancing rechargeable battery efficiency, super-alloys, and magnetic products. Cobalt is considered a possible human carcinogen with the lung being a primary target. However, few studies have considered cobalt-induced toxicity in human lung cells. Therefore, in this study, we sought to determine the cytotoxicity and genotoxicity of particulate and soluble cobalt in human lung cells. Cobalt oxide and cobalt chloride were used as representative particulate and soluble cobalt compounds, respectively. Exposure to both particulate and soluble cobalt induced a concentration-dependent increase in cytotoxicity, genotoxicity, and intracellular cobaltmore » ion levels. Based on intracellular cobalt ion levels, we found that soluble cobalt was more cytotoxic than particulate cobalt while particulate and soluble cobalt induced similar levels of genotoxicity. However, soluble cobalt induced cell cycle arrest indicated by the lack of metaphases at much lower intracellular cobalt concentrations compared to cobalt oxide. Accordingly, we investigated the role of particle internalization in cobalt oxide-induced toxicity and found that particle-cell contact was necessary to induce cytotoxicity and genotoxicity after cobalt exposure. These data indicate that cobalt compounds are cytotoxic and genotoxic to human lung fibroblasts, and solubility plays a key role in cobalt-induced lung toxicity. - Highlights: • Particulate and soluble cobalt are cytotoxic and genotoxic to human lung cells. • Soluble cobalt induces more cytotoxicity compared to particulate cobalt. • Soluble and particulate cobalt induce similar levels of genotoxicity. • Particle-cell contact is required for particulate cobalt-induced toxicity.« less

Acute aquatic toxicity and biodegradation potential of biodiesel fuels

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

Haws, R.A.; Zhang, X.; Marshall, E.A.

1995-12-31

Recent studies on the biodegradation potential and aquatic toxicity of biodiesel fuels are reviewed. Biodegradation data were obtained using the shaker flask method observing the appearance of CO{sub 2} and by observing the disappearance of test substance with gas chromatography. Additional BOD{sub 5} and COD data were obtained. The results indicate the ready biodegradability of biodiesel fuels as well as the enhanced co-metabolic biodegradation of biodiesel and petroleum diesel fuel mixtures. The study examined reference diesel, neat soy oil, neat rape oil, and the methyl and ethyl esters of these vegetable oils as well as various fuel blends. Acute toxicitymore » tests on biodiesel fuels and blends were performed using Oncorhynchus mykiss (Rainbow Trout) in a static non-renewal system and in a proportional dilution flow replacement system. The study is intended to develop data on the acute aquatic toxicity of biodiesel fuels and blends under US EPA Good Laboratory Practice Standards. The test procedure is designed from the guidelines outlined in Methods for Measuring the Acute Toxicity of Effluents and Receiving Waters to Freshwater and Marine Organisms and the Fish Acute Aquatic Toxicity Test guideline used to develop aquatic toxicity data for substances subject to environmental effects test regulations under TSCA. The acute aquatic toxicity is estimated by an LC50, a lethal concentration effecting mortality in 50% of the test population.« less

THE GENOTOXICITY OF PRIORITY POLYCYCLIC AROMATIC HYDROCARBONS IN COMPLEX MIXTURES

EPA Science Inventory

Risk assessment of complex environmental samples suffers from difficulty in identifying toxic components, inadequacy of available toxicity data, and a paucity of knowledge about the behavior of geno(toxic) substances in complex mixtures. Lack of information about the behavior of ...

Acute Oral Toxicity Up-And-Down-Procedure

EPA Pesticide Factsheets

The Up-and-Down Procedure is an alternative acute toxicity test that provides a way to determine the toxicity of chemicals with fewer test animals by using sequential dosing steps. Find out about this test procedure.

Acute recreational drug toxicity

PubMed Central

Liakoni, Evangelia; Yates, Christopher; Dines, Alison M.; Dargan, Paul I.; Heyerdahl, Fridtjof; Hovda, Knut Erik; Wood, David M.; Eyer, Florian; Liechti, Matthias E.

2018-01-01

Abstract The aim of the study was to compare self-reported and analytically confirmed substance use in cases of acute recreational drug toxicity. We performed a retrospective analysis of emergency department presentations of acute recreational drug toxicity over 2 years (October 2013 to September 2015) within the European Drug Emergencies Network Plus project. Among the 10,956 cases of acute recreational drug toxicity during the study period, 831 could be included. Between the self-reported substance use and the toxicological results, the highest agreement was found for heroin (86.1%) and cocaine (74.1%), whereas inhalants, poppers, and magic mushrooms were self-reported but not analytically detected. Cathinones and other new psychoactive substances (NPS) could be detected using additional analytical methods. Among cases with both immunoassay (IA) and confirmation with mass spectrometry (MS), the results were consistent for methadone (100%) and cocaine (95.5%) and less consistent for amphetamines (81.8%). In cases with a positive IA for amphetamines (n = 54), MS confirmed the presence of 3,4-methylenedioxymethamphetamine (MDMA), amphetamine, methamphetamine, and NPS in 37, 20, 10, and 6 cases, respectively, also revealing use of more than 1 substance in some cases. MS yielded positive results in 21 cases with a negative IA for amphetamines, including amphetamine, MDMA, methamphetamine, and NPS, in 14, 7, 2, and 2 cases, respectively. In conclusion, the highest agreement was found between self-reports and analytical findings for heroin and cocaine. The diagnosis of NPS use was mainly based on self-report. The IAs accurately identified methadone and cocaine, and MS had advantages for the detection of NPS and amphetamine derivatives. PMID:29384873

Detection of genotoxic and non-genotoxic carcinogens in Xpc(-/-)p53(+/-) mice.

PubMed

Melis, Joost P M; Speksnijder, Ewoud N; Kuiper, Raoul V; Salvatori, Daniela C F; Schaap, Mirjam M; Maas, Saskia; Robinson, Joke; Verhoef, Aart; van Benthem, Jan; Luijten, Mirjam; van Steeg, Harry

2013-01-15

An accurate assessment of the carcinogenic potential of chemicals and pharmaceutical drugs is essential to protect humans and the environment. Therefore, substances are extensively tested before they are marketed to the public. Currently, the rodent two-year bioassay is still routinely used to assess the carcinogenic potential of substances. However, over time it has become clear that this assay yields false positive results and also has several economic and ethical drawbacks including the use of large numbers of animals, the long duration, and the high cost. The need for a suitable alternative assay is therefore high. Previously, we have proposed the Xpa*p53 mouse model as a very suitable alternative to the two-year bioassay. We now show that the Xpc*p53 mouse model preserves all the beneficial traits of the Xpa*p53 model for sub-chronic carcinogen identification and can identify both genotoxic and non-genotoxic carcinogens. Moreover, Xpc*p53 mice appear to be more responsive than Xpa*p53 mice towards several genotoxic and non-genotoxic carcinogens. Furthermore, Xpc*p53 mice are far less sensitive than Xpa*p53 mice for the toxic activity of DNA damaging agents and as such clearly respond in a similar way as wild type mice do. These advantageous traits of the Xpc*p53 model make it a better alternative for in vivo carcinogen testing than Xpa*p53. This pilot study suggests that Xpc*p53 mice are suited for routine sub-chronic testing of both genotoxic and non-genotoxic carcinogens and as such represent a suitable alternative to possibly replace the murine life time cancer bioassay. Copyright © 2012 Elsevier Inc. All rights reserved.

Biochemical and genotoxic effect of triclosan on earthworms (Eisenia fetida) using contact and soil tests.

PubMed

Lin, Dasong; Xie, Xiujie; Zhou, Qixing; Liu, Yao

2012-07-01

Triclosan (TCS) is a broad-spectrum bactericide that is used for a variety of antimicrobial functions. TCS is frequently detected in the terrestrial environment due to application of sewage sludge to agricultural land. In the present study, 48-h paper contact and 28-day spiked soil tests were conducted to examine the toxic effects of TCS on the antioxidative and genetic indices of earthworms (Eisenia fetida). The activity of antioxidative enzymes (superoxide dismutase, SOD; catalase, CAT) and the content of the lipid peroxidation product (malondialdehyde, MDA) were determined as biomarkers of oxidative stress in E. fetida. Moreover, single cell gel electrophoresis (SCGE) was used as a biomarker of genotoxicity. The results showed that triclosan induced a significant increase (P < 0.05) in antioxidative enzyme activities and MDA content. Of all of the biomarkers examined, CAT activity was most sensitive to TCS, and the CAT activity increased significantly (P < 0.05) at bactericidal concentrations of 7.86 ng cm⁻² in the contact test and 10 mg kg⁻¹ in the spiked soil test. The comet assay showed that TCS treatments significantly induced (P < 0.05) DNA damage in E. fetida, and that 78.6 ng cm⁻² caused significant genotoxic effects in the acute test (48 h). Clear dose-dependent DNA damage to E. fetida was observed both in contact and spiked soil tests. These results imply that TCS may have potential biochemical and genetic toxicity toward earthworms (E. fetida). A battery of biomarkers covering multiple molecular targets of acute toxicity can be combined to better understand the impacts of TCS on E. fetida. Copyright © 2010 Wiley Periodicals, Inc.

Acute toxicity of gasoline and some additives.

PubMed Central

Reese, E; Kimbrough, R D

1993-01-01

The acute toxicity of gasoline; its components benzene, toluene, and xylene; and the additives ethanol, methanol, and methyl tertiary butyl ether are reviewed. All of these chemicals are only moderately to mildly toxic at acute doses. Because of their volatility, these compounds are not extensively absorbed dermally unless the exposed skin is occluded. Absorption through the lungs and the gastrointestinal tract is quite efficient. After ingestion, the principal danger for a number of these chemicals, particularly gasoline, is aspiration pneumonia, which occurs mainly in children. It is currently not clear whether aspiration pneumonia would still be a problem if gasoline were diluted with ethanol or methanol. During the normal use of gasoline or mixtures of gasoline and the other solvents as a fuel, exposures would be much lower than the doses that have resulted in poisoning. No acute toxic health effects would occur during the normal course of using automotive fuels. PMID:8020435

Differential genotoxicity of diphenyl diselenide (PhSe)2 and diphenyl ditelluride (PhTe)2

PubMed Central

Meinerz, Daiane Francine; Allebrandt, Josiane; Mariano, Douglas O.C.; Waczuk, Emily P.; Soares, Felix Antunes

2014-01-01

Organoselenium compounds have been pointed out as therapeutic agents. In contrast, the potential therapeutic aspects of tellurides have not yet been demonstrated. The present study evaluated the comparative toxicological effects of diphenyl diselenide (PhSe)2 and diphenyl ditelluride (PhTe)2 in mice after in vivo administration. Genotoxicity (as determined by comet assay) and mutagenicicity were used as end-points of toxicity. Subcutaneous administration of high doses of (PhSe)2 or (PhTe)2 (500 µmol/kg) caused distinct genotoxicity in mice. (PhSe)2 significantly decreased the DNA damage index after 48 and 96 h of its injection (p < 0.05). In contrast, (PhTe) caused a significant increase in DNA damage (p < 0.05) after 48 and 96 h of intoxication. (PhSe)2 did not cause mutagenicity but (PhTe)2 increased the micronuclei frequency, indicating its mutagenic potential. The present study demonstrated that acute in vivo exposure to ditelluride caused genotoxicity in mice, which may be associated with pro-oxidant effects of diphenyl ditelluride. In addition, the use of this compound and possibly other related tellurides must be carefully controlled. PMID:24711962

Genotoxicity of tetracycline as an emerging pollutant on root meristem cells of wheat (Triticum aestivum L.).

PubMed

Xie, Xiujie; Zhou, Qixing; Bao, Qiuhua; He, Zhangchun; Bao, Yanyu

2011-08-01

Increasing attention has been paid to antibiotic contamination as an increasingly serious environmental issue. Tetracycline has been widely used for decades in human and veterinary medicines, with incremental residues in the environment and adverse influences on living organisms. In the present study, the genetic toxicity of tetracycline was investigated using a bioassay method with wheat (Triticum aestivum L.) root-meristem cells at a concentration range of 0.25-300 mg L(-1) and exposure times of 24, 48, and 72 h. The results indicated that tetracycline at lower concentrations (0.25-1 mg L(-1) ) stimulated cell mitotic division, whereas at 50-300 mg L(-1) concentration caused a concentration-related decrease in mitotic index (MI). The lower tetracycline concentrations induced a slight increase in the frequency of micronucleus (MN), chromosomal aberration (CA), and sister chromatid exchange (SCE) in wheat root tips. However, there were significant increases in these indices at higher concentrations in concentration- and time-dependent manners, including the frequencies of MN (25-200 mg L(-1) ), CA (10-200 mg L(-1) ), and SCE (5-200 mg L(-1) ), respectively. The inducement of MN, CA, and SCE decreased at 250 and 300 mg L(-1) due to acute cell toxicity for all tested times. Comparatively, SCE was the most sensitive, followed by CA, with MN the least sensitive to the genotoxicity of tetracycline in wheat. These results imply that tetracycline may be genotoxic to plant cells, and exposure to tetracycline may pose a genotoxic risk to living organisms. The results also suggest that the wheat bioassay was efficient, simple, and reproducible in monitoring the genotoxicity of tetracycline in the environment. Copyright © 2010 Wiley Periodicals, Inc.

Acute toxicity of some nerve agents and pesticides in rats.

PubMed

Misik, Jan; Pavlikova, Ruzena; Cabal, Jiri; Kuca, Kamil

2015-01-01

Highly toxic organophosphorus compounds (V- and G-nerve agents) were originally synthesized for warfare or as agricultural pesticides. Data on their acute toxicity are rare and patchy. Therefore, there is a need for integrated summary comparing acute toxicity of organophosphates using different administration routes in the same animal model with the same methodology. Based on original data, a summary of in vivo acute toxicity of selected V- and G-nerve agents (tabun, sarin, soman, VX, Russian VX) and organophosphates paraoxon (POX) and diisopropyl fluorophosphate (DFP) in rats has been investigated. Male Wistar rats were exposed to organophosphates in several administration routes (i.m., i.p., p.o, s.c., p.c.). The acute toxicity was evaluated by the assessment of median lethal dose (LD50, mg kg(-1)) 2, 4, and 24 hours post exposure. V-agents were the most toxic presented with LD50 ranged from 0.0082 mg kg(-1) (VX, i.m.) to 1.402 mg kg(-1) (Russian VX, p.o.), followed by G-agents (LD50 = 0.069 mg kg(-1)/soman, i.m./ - 117.9 mg kg(-1)/sarin, p.c./), organophosphate POX and DFP (LD50 = 0.321 mg kg(-1)/POX, i.m./ - 420 mg kg(-1)/DFP, p.c./). Generally, i.m. administration was the most toxic throughout all tested agents and ways of administration (LD50 = 0.0082 mg kg(-1)/VX/ - 1.399 mg kg(-1)/DFP/) whereas p.c. way was responsible for lowest acute toxicity (LD50 = 0.085 mg kg(-1)/VX/ - 420 mg kg(-1)/DFP/). The acute toxicity of selected organophosphorus compounds is summarized throughout this study. Although the data assessed in rats are rather illustrative prediction for human, it presents a valuable contribution, indicating the toxic potential and harmfulness of organophosphates.

Predictive acute toxicity tests with pesticides.

PubMed

Brown, V K

1983-01-01

By definition pesticides are biocidal products and this implies a probability that pesticides may be acutely toxic to species other than the designated target species. The ways in which pesticides are manufactured, formulated, packaged, distributed and used necessitates a potential for the exposure of non-target species although the technology exists to minimize adventitious exposure. The occurrence of deliberate exposure of non-target species due to the misuse of pesticides is known to happen. The array of predictive acute toxicity tests carried out on pesticides and involving the use of laboratory animals can be justified as providing data on which hazard assessment can be based. This paper addresses the justification and rationale of this statement.

Genotoxicity profile of fexinidazole--a drug candidate in clinical development for human African trypanomiasis (sleeping sickness).

PubMed

Tweats, David; Bourdin Trunz, Bernadette; Torreele, Els

2012-09-01

The parasitic disease human African trypanomiasis (HAT), also known as sleeping sickness, is a highly neglected fatal condition endemic in sub-Saharan Africa, which is poorly treated with medicines that are toxic, no longer effective or very difficult to administer. New, safe, effective and easy-to-use treatments are urgently needed. Many nitroimidazoles possess antibacterial and antiprotozoal activity and examples such as tinidazole are used to treat trichomoniasis and guardiasis, but concerns about toxicity including genotoxicity limit their usefulness. Fexinidazole, a 2-substituted 5-nitroimidazole rediscovered by the Drugs for Neglected Diseases initiative (DNDi) after extensive compound mining of public and pharmaceutical company databases, has the potential to become a short-course, safe and effective oral treatment, curing both acute and chronic HAT. This paper describes the genotoxicity profile of fexinidazole and its two active metabolites, the sulfoxide and sulfone derivatives. All the three compounds are mutagenic in the Salmonella/Ames test; however, mutagenicity is either attenuated or lost in Ames Salmonella strains that lack one or more nitroreductase(s). It is known that these enzymes can nitroreduce compounds with low redox potentials, whereas their mammalian cell counterparts cannot, under normal conditions. Fexinidazole and its metabolites have low redox potentials and all mammalian cell assays to detect genetic toxicity, conducted for this study either in vitro (micronucleus test in human lymphocytes) or in vivo (ex vivo unscheduled DNA synthesis in rats; bone marrow micronucleus test in mice), were negative. Thus, fexinidazole does not pose a genotoxic hazard to patients and represents a promising drug candidate for HAT. Fexinidazole is expected to enter Phase II clinical trials in 2012.

Acute Toxicity of Tributyltins and Tributyltin Leachates from Marine Antibiofouling Paints.

DTIC Science & Technology

1982-09-10

RO-0184 224 ACUTE TOXICITY OF TRIBUTYLTINS AND TRIBUTYLTIN i/I LEACHATES FROM MARINE ANTIBIOFOULING PAINTS(U) CALIFORNIA UNIV OAKLAND NAVAL...Classification) (U) ACUTE TOXICITY OF TRIBUTYLTINS AND TRIBUTYLTIN LEACHATES FROM MARINE ANTIBIOFOULING PAINTS 12, PERSO A UHR Laugin, Koy"., Linden, Olof and...xins causing acute toxicity or two amphipou species at concentrations as low as 10 g/L . Orchestia traskiana was exposed to bis ( tributyltin ) oxide

Acute and subacute toxicity of Schinus terebinthifolius bark extract.

PubMed

Lima, L B; Vasconcelos, C F B; Maranhão, H M L; Leite, V R; Ferreira, P A; Andrade, B A; Araújo, E L; Xavier, H S; Lafayette, S S L; Wanderley, A G

2009-12-10

Schinus terebinthifolius Raddi (Anacardiaceae) has long been used in traditional Brazilian medicine, especially to treat inflammatory and haemostatic diseases. The objective of this study was to evaluate the acute and subacute toxicity (45 days) of Schinus terebinthifolius via the oral route in Wistar rats of both sexes. For the acute toxicity test, the dried extract of Schinus terebinthifolius bark was administered in doses from 0.625 to 5.0 g/kg (n=5/group/sex) and in the subacute toxicity test the following doses were used: 0.25, 0.625 and 1.5625 g/kg/day (n=13/group/sex), for 45 consecutive days. In the acute toxicity test, Schinus terebinthifolius did not produce any toxic signs or deaths. The subacute treatment with Schinus terebinthifolius did not alter either the body weight gain or the food and water consumption. The hematological and biochemical analysis did not show significant differences in any of the parameters examined in female or male groups, except in two male groups, in which the treatment with Schinus terebinthifolius (0.25 and 0.625 g/kg) induced an increase of mean corpuscular volume values (2.9 and 2.6%, respectively). These variations are within the physiological limits described for the specie and does not have clinical relevance. The acute and subacute administration of the dried extract of Schinus terebinthifolius bark did not produced toxic effects in Wistar rats.

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.

Evaluating the Effects of Bioremediation on Genotoxicity of Polycyclic Aromatic Hydrocarbon-Contaminated Soil Using Genetically Engineered, Higher Eukaryotic Cell Lines

PubMed Central

Hu, Jing; Nakamura, Jun; Richardson, Stephen D.; Aitken, Michael D.

2012-01-01

Bioremediation is one of the commonly applied remediation strategies at sites contaminated with polycyclic aromatic hydrocarbons (PAHs). However, remediation goals are typically based on removal of the target contaminants rather than on broader measures related to health risks. We investigated changes in the toxicity and genotoxicity of PAH-contaminated soil from a former manufactured-gas plant site before and after two simulated bioremediation processes: a sequencing batch bioreactor system and a continuous-flow column system. Toxicity and genotoxicity of the residues from solvent extracts of the soil were determined by the chicken DT40 B-lymphocyte isogenic cell line and its DNA-repair-deficient mutants. Although both bioremediation processes significantly removed PAHs from the contaminated soil (bioreactor 69% removal; column 84% removal), bioreactor treatment resulted in an increase in toxicity and genotoxicity over the course of a treatment cycle, whereas long-term column treatment resulted in a decrease in toxicity and genotoxicity. However, when screening with a battery of DT40 mutants for genotoxicity profiling, we found that column treatment induced DNA damage types that were not observed in untreated soil. Toxicity and genotoxicity bioassays can supplement chemical analysis-based risk assessment for contaminated soil when evaluating the efficacy of bioremediation. PMID:22443351

Fish embryo toxicity test: identification of compounds with weak toxicity and analysis of behavioral effects to improve prediction of acute toxicity for neurotoxic compounds.

PubMed

Klüver, Nils; König, Maria; Ortmann, Julia; Massei, Riccardo; Paschke, Albrecht; Kühne, Ralph; Scholz, Stefan

2015-06-02

The fish embryo toxicity test has been proposed as an alternative for the acute fish toxicity test, but concerns have been raised for its predictivity given that a few compounds have been shown to exhibit a weak acute toxicity in the fish embryo. In order to better define the applicability domain and improve the predictive capacity of the fish embryo test, we performed a systematic analysis of existing fish embryo and acute fish toxicity data. A correlation analysis of a total of 153 compounds identified 28 compounds with a weaker or no toxicity in the fish embryo test. Eleven of these compounds exhibited a neurotoxic mode of action. We selected a subset of eight compounds with weaker or no embryo toxicity (cyanazine, picloram, aldicarb, azinphos-methyl, dieldrin, diquat dibromide, endosulfan, and esfenvalerate) to study toxicokinetics and a neurotoxic mode of action as potential reasons for the deviating fish embryo toxicity. Published fish embryo LC50 values were confirmed by experimental analysis of zebrafish embryo LC50 according to OECD guideline 236. Except for diquat dibromide, internal concentration analysis did not indicate a potential relation of the low sensitivity of fish embryos to a limited uptake of the compounds. Analysis of locomotor activity of diquat dibromide and the neurotoxic compounds in 98 hpf embryos (exposed for 96 h) indicated a specific effect on behavior (embryonic movement) for the neurotoxic compounds. The EC50s of behavior for neurotoxic compounds were close to the acute fish toxicity LC50. Our data provided the first evidence that the applicability domain of the fish embryo test (LC50s determination) may exclude neurotoxic compounds. However, neurotoxic compounds could be identified by changes in embryonic locomotion. Although a quantitative prediction of acute fish toxicity LC50 using behavioral assays in fish embryos may not yet be possible, the identification of neurotoxicity could trigger the conduction of a conventional fish

Acute and sub-chronic toxicity studies of honokiol microemulsion.

PubMed

Zhang, Qianqian; Li, Jianguo; Zhang, Wei; An, Quan; Wen, Jianhua; Wang, Aiping; Jin, Hongtao; Chen, Shizhong

2015-04-01

The purpose of this study was to investigate the acute and sub-chronic toxicity of honokiol microemulsion. In the acute toxicity tests, the mice were intravenously injected graded doses of honokiol microemulsion and were observed for toxic symptoms and mortality daily for 14 days. In the sub-chronic toxicity study, rats were injected honokiol microemulsion at doses of 100, 500, 2500 μg/kg body weight (BW) for 30 days. After 30 days treatment and 14 days recovery, the rats were sacrificed for hematological, biochemical and histological examination. In the acute toxicity tests, the estimated median lethal dosage (LD50) was 50.5mg/kg body weight in mice. In the sub-chronic toxicity tests, the non-toxic reaction dose was 500 μg/kg body weight. In each treatment group, degeneration or/and necrosis in vascular endothelial cells and structure change of vessel wall can be observed in the injection site (cauda vein) of a few animals while there were no changes in the vessels of other organs. The overall findings of this study indicate that the honokiol microemulsion is non-toxic up to 500 μg/kg body weight, and it has irritation to the vascular of the injection site which should be paid attention to in clinical medication. Copyright © 2015. Published by Elsevier Inc.

Glutathione-S-transferase A3 knockout mice are sensitive to acute cytotoxic and genotoxic effects of aflatoxin B1

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

Ilic, Zoran, E-mail: zxi01@health.state.ny.u; Crawford, Dana, E-mail: crawfod@mail.amc.ed; Egner, Patricia A., E-mail: pegner@jhsph.ed

Aflatoxin B1 (AFB1) is a major risk factor for hepatocellular carcinoma (HCC) in humans. However, mice, a major animal model for the study of AFB1 carcinogenesis, are resistant, due to high constitutive expression, in the mouse liver, of glutathione S-transferase A3 subunit (mGSTA3) that is lacking in humans. Our objective was to establish that a mouse model for AFB1 toxicity could be used to study mechanisms of toxicity that are relevant for human disease, i.e., an mGSTA3 knockout (KO) mouse that responds to toxicants such as AFB1 in a manner similar to humans. Exons 3-6 of the mGSTA3 were replacedmore » with a neomycin cassette by homologous recombination. Southern blotting, RT-PCR, Western blotting, and measurement of AFB1-N{sup 7}-DNA adduct formation were used to evaluate the mGSTA3 KO mice. The KO mice have deletion of exons 3-6 of the mGSTA3 gene, as expected, as well as a lack of mGSTA3 expression at the mRNA and protein levels. Three hours after injection of 5 mg/kg AFB1, mGSTA3 KO mice have more than 100-fold more AFB1-N{sup 7}-DNA adducts in their livers than do similarly treated wild-type (WT) mice. In addition, the mGSTA3 KO mice die of massive hepatic necrosis, at AFB1 doses that have minimal toxic effects in WT mice. We conclude that mGSTA3 KO mice are sensitive to the acute cytotoxic and genotoxic effects of AFB1, confirming the crucial role of GSTA3 subunit in protection of normal mice against AFB1 toxicity. We propose the mGSTA3 KO mouse as a useful model with which to study the interplay of risk factors leading to HCC development in humans, as well as for testing of additional possible functions of mGSTA3.« less

40 CFR 799.9135 - TSCA acute inhalation toxicity with histopathology.

Code of Federal Regulations, 2013 CFR

2013-07-01

... TESTING REQUIREMENTS Health Effects Test Guidelines § 799.9135 TSCA acute inhalation toxicity with... Substances Control Act (TSCA). In the assessment and evaluation of the potential human health effects of chemical substances, it is appropriate to test for acute inhalation toxic effects. The goals of this test...

40 CFR 799.9135 - TSCA acute inhalation toxicity with histopathology.

Code of Federal Regulations, 2012 CFR

2012-07-01

... TESTING REQUIREMENTS Health Effects Test Guidelines § 799.9135 TSCA acute inhalation toxicity with... Substances Control Act (TSCA). In the assessment and evaluation of the potential human health effects of chemical substances, it is appropriate to test for acute inhalation toxic effects. The goals of this test...

40 CFR 799.9135 - TSCA acute inhalation toxicity with histopathology.

Code of Federal Regulations, 2014 CFR

2014-07-01

... TESTING REQUIREMENTS Health Effects Test Guidelines § 799.9135 TSCA acute inhalation toxicity with... Substances Control Act (TSCA). In the assessment and evaluation of the potential human health effects of chemical substances, it is appropriate to test for acute inhalation toxic effects. The goals of this test...

Effects of individual and combined toxicity of bisphenol A, dibutyl phthalate and cadmium on oxidative stress and genotoxicity in HepG 2 cells.

PubMed

Li, Xiaohui; Yin, Pinghe; Zhao, Ling

2017-07-01

Bisphenol A, dibutyl phthalate and cadmium can be found in environment simultaneously. Several studies suggested that they had genotoxic effect. In this study, mono-exposure and co-exposure treatments, designed by 3 × 3 full factorial, were established to determine the individual toxicity and binary mixtures' combined effects on the oxidative stress and genotoxicity in HepG 2 cells. The highest oxidative damage was observed in the Cd treatments groups. Compared with control groups, the maximum level of reactive oxygen species and malondialdehyde were ∼1.4 fold and ∼2.22 fold respectively. And a minimum level of superoxide dismutase activity was found with the decrease of 43%. The mechanism that excessive oxidative stress led to the DNA damage was inferred. However, cells treated with BPA showed the worst DNA damage rather than Cd, which may because Cd mainly damages DNA repairing mechanism. For the joint effect, different interactions can be found in different biological endpoints for different combinations since different mechanisms have been clarified in mixture toxicity studies. It is sure that the co-exposure groups enhanced cytotoxicity, oxidative stress and genotoxicity compared to the mono-exposures. Synergistic and additive interactions were considered, which means greater threat to organisms when exposed to multiple estrogenic endocrine disruptors. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed

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

2018-02-05

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

Genotoxicity, acute and subchronic toxicity studies in rats of a rooster comb extract rich in sodium hyaluronate.

PubMed

Canut, Lourdes; Zapatero, Jorge; López, Sílvia; Torrent, Anna; Ruhí, Ramon; Vicente, Laura

2012-04-01

The toxicity of a rooster comb extract (IB0004) that contains mainly sodium hyaluronate was assessed in acute and subchronic studies and in a bacterial reverse mutation assay. In a single dose acute study, male and female rats were administered 2000 mg/kg body weight (bw) of the product and observed for 14 days. No mortality was recorded, thus it was considered that the minimum lethal dose for rats by oral route was greater than 2000 mg/kg bw. A 90-day subchronic study (5, 55 and 600 mg/kg bw/day, oral gavage) with 50 male and 50 female Wistar-Hannover rats produced no significant adverse effects on food consumption, body weight, mortality, clinical biochemistry, hematology, gross pathology, and histopathology. Although some differences were observed between the treated and control animals in body weight gain (%) and some hematological parameters, these changes were generally minor in nature and, are considered to be of no toxicological significance. The no-observable-adverse-effects level was established at 600 mg/kg bw/day. There was no evidence of mutagenic activity in Salmonella typhimurium TA98, TA100, TA1535 and TA1537 or in Escherichia coli WP2 uvra pkM101. In conclusion, the results from these safety studies support the safety of rooster comb extract IB0004 in food. Copyright © 2011 Elsevier Inc. All rights reserved.

Biochemical and genotoxic response of naphthalene to fingerlings of milkfish Chanos chanos.

PubMed

Palanikumar, L; Kumaraguru, A K; Ramakritinan, C M

2013-09-01

The present study investigated the acute toxicity, sub-lethal toxicity and biochemical response of naphthalene in fingerlings of milkfish Chanos chanos. The 96 h acute toxicity LC50 values for C. chanos exposed to naphthalene was 5.18 μg l(-1). The estimated no observed effect concentration and lowest observed effect concentration values for naphthalene in C. chanos were 0.42 and 0.69 μg l(-1) respectively for 30 days. The estimated maximum allowable toxicant concentration for naphthalene was 0.53 μg l(-1). Biochemical enzyme markers such as lipid peroxidation, catalase, glutathione S transferase and reduced glutathione were measured in gills and liver tissues of C. chanos exposed to sub-lethal concentrations of naphthalene. Fluctuation in lipid peroxidation and catalase level suggests that naphthalene concentrations play a vital role in induction of oxidative stress in fish. Induction of reduced glutathione level and inhibition of glutathione S-transferase level was observed in naphthalene exposed C. chanos suggesting that there may be enhanced oxidative damage due to free radicals. Increasing concentration increases in number of nuclear abnormalities. The formation of micronuclei and binucleated micronuclei induction by naphthalene confirm its genotoxic potential. The highest levels of DNA damage (% tail length) were observed at 1.24 μg l(-1) of naphthalene. The study suggests that biochemical enzymes, nuclear abnormalities and DNA damage index can serve as a biological marker for naphthalene contamination.

GENOTOXICITY RISK ASSESSMENT: A PROPOSED CLASSIFICATION STRATEGY

EPA Science Inventory

Recent advances in genetic toxicity (mutagenicity) testing methods and in approaches to performing risk assessment are prompting a renewed effort to harmonize genotoxicity risk assessment across the world. The US Environmental Protection Agency (EPA) first published Guidelines fo...

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

Acute and Subacute Toxicity Evaluation of Corn Silk Extract

PubMed Central

Ha, Ae Wha; Kang, Hyeon Jung; Kim, Sun Lim; Kim, Myung Hwan

2018-01-01

Many studies have reported therapeutic efficacy of corn silk extract. However, research on its toxicity and safe dose range is limited. Thus, the objective of this study was to determine the acute and subacute toxicity of corn silk extract in ICR mice. To determine acute toxicity, corn silk extract containing high levels of maysin was orally administered to mice at a dose of 0 or 2,000 mg/kg. Clinical symptoms, mortality, and body weight changes were recorded for 14 days. To determine subacute toxicity, corn silk extract was orally administered to mice over a 4-week period, and then body weight, water and food consumption, and organ weight were determined. In addition, urine and serum analyses were performed. In the acute toxicity study, no death or abnormal symptoms was observed in all treatment groups during the study period. Body weights did not show any significant change compared to those of the control group. Lethal dose of corn silk extract was estimated to be more than 2,000 mg/kg. In the 4-week subacute toxicity study, there was no corn silk extract related toxic effect on body weight, water intake, food consumption, urine parameters, clinical chemistry, or organ weight. Histopathological examination showed no abnormality related to the administration of corn silk extract at 500 mg/kg. The maximum non-toxic dose of corn silk extract containing high levels of maysin was found to be more than 500 mg/kg. PMID:29662850

Acute and Subacute Toxicity Evaluation of Corn Silk Extract.

PubMed

Ha, Ae Wha; Kang, Hyeon Jung; Kim, Sun Lim; Kim, Myung Hwan; Kim, Woo Kyoung

2018-03-01

Many studies have reported therapeutic efficacy of corn silk extract. However, research on its toxicity and safe dose range is limited. Thus, the objective of this study was to determine the acute and subacute toxicity of corn silk extract in ICR mice. To determine acute toxicity, corn silk extract containing high levels of maysin was orally administered to mice at a dose of 0 or 2,000 mg/kg. Clinical symptoms, mortality, and body weight changes were recorded for 14 days. To determine subacute toxicity, corn silk extract was orally administered to mice over a 4-week period, and then body weight, water and food consumption, and organ weight were determined. In addition, urine and serum analyses were performed. In the acute toxicity study, no death or abnormal symptoms was observed in all treatment groups during the study period. Body weights did not show any significant change compared to those of the control group. Lethal dose of corn silk extract was estimated to be more than 2,000 mg/kg. In the 4-week subacute toxicity study, there was no corn silk extract related toxic effect on body weight, water intake, food consumption, urine parameters, clinical chemistry, or organ weight. Histopathological examination showed no abnormality related to the administration of corn silk extract at 500 mg/kg. The maximum non-toxic dose of corn silk extract containing high levels of maysin was found to be more than 500 mg/kg.

In vitro genotoxicity and cytotoxicity of polydopamine-coated magnetic nanostructures.

PubMed

Woźniak, Anna; Walawender, Magdalena; Tempka, Dominika; Coy, Emerson; Załęski, Karol; Grześkowiak, Bartosz F; Mrówczyński, Radosław

2017-10-01

Synthesis of magnetic nanoparticles and magnetic nanoclusters was performed by the co-precipitation method or solvothermal synthesis, respectively, followed by oxidative polymerization of dopamine, resulting in a polydopamine (PDA) shell. The nanomaterials obtained were described using TEM, FTIR and magnetic measurements. For the first time, cyto- and genotoxicity studies of polydopamine-coated nanostructures were performed on cancer and normal cell lines, providing in-depth insight into the toxicity of such materials. The tests conducted, e.g. ROS, apoptosis and DNA double-break of the nanomaterials obtained revealed the low toxicity of these structures. Thus, these results prove the biocompatibility and low genotoxicity of these materials and provide new data on the toxicity of PDA-coated materials, which is of great importance for their biomedical application. Copyright © 2017 Elsevier Ltd. All rights reserved.

Acute and chronic toxicity studies with monochlorobenzene in rainbow trout

USGS Publications Warehouse

Dahlich, G.M.; Larson, R.E.; Gingerich, W.H.

1982-01-01

The toxicity of monochlorobenzene (CB) was investigated in rainbow trout following acute intraperitoneal (i.p.) administration and chronic exposure via the water in a continuously flowing system for 15 or 30 days. In the acute study overt toxicity and hepatotoxicity were monitored over a 96-h time period. Variables measured to assess toxicity included weight changes, liver weight to body weight ratios, behavioral changes, alanine aminotransferase activity (GPT), sulfobromophthalein (BSP) retention, total plasma protein concentration and liver histopathology. In the chronic study the same measures of toxicity were followed as well as food consumption and alkaline phosphatase (AP) activity. Upon acute i.p. exposure the toxicant (9.8 mmol/kg) caused behavioral changes in the fish which were consistent with the known anesthetic properties of CB in mammals. Elevations in BSP retention and GPT activity, and histopathology indicated that CB was hepatotoxic in fish. The LC50 of CB in trout exposed via the water for 96 h was 4.7 mg/l. Chronic exposure of trout to 2 or 3 mg/l CB resulted in similar behavioral changes as seen in the acute study. Liver toxicity was evident from elevations in GPT activity. BSP retention and AP activity appeared to be affected by the nutritional status of the trout as much as by the CB treatment. After 30 days of exposure to 3 mg/l CB, trout appeared to have developed some tolerance to the toxic effects.

In vivo genotoxicity assessment in rats exposed to Prestige-like oil by inhalation.

PubMed

Valdiglesias, Vanessa; Kiliç, Gözde; Costa, Carla; Amor-Carro, Óscar; Mariñas-Pardo, Luis; Ramos-Barbón, David; Méndez, Josefina; Pásaro, Eduardo; Laffon, Blanca

2012-01-01

One of the largest oil spill disasters in recent times was the accident of the oil tanker Prestige in front of the Galician coast in 2002. Thousands of people participated in the cleanup of the contaminated areas, being exposed to a complex mixture of toxic substances. Acute and prolonged respiratory symptoms and genotoxic effects were reported, although environmental exposure measurements were restricted to current determinations, such that attribution of effects observed to oil exposure is difficult to establish. The aim of this study was to analyze peripheral blood leukocytes (PBL) harvested from a rat model of subchronic exposure to a fuel oil with similar characteristics to that spilled by the Prestige tanker, in order to determine potential genotoxic effects under strictly controlled, in vivo exposure. Wistar Han and Brown Norway rats were exposed to the oil for 3 wk, and micronucleus test (MN) and comet assay, standard and modified with 8-oxoguanine DNA glycosylase (OGG1) enzyme, were employed to assess genotoxicity 72 h and 15 d after the last exposure. In addition, the potential effects of oil exposure on DNA repair capacity were determined by means of mutagen sensitivity assay. Results obtained from this study showed that inhalation oil exposure induced DNA damage in both Brown Norway and Wistar Han rats, especially in those animals evaluated 15 d after exposure. Although alterations in the DNA repair responses were noted, the sensitivity to oil substances varied depending on rat strain. Data support previous positive genotoxicity results reported in humans exposed to Prestige oil during cleanup tasks.

Molecular Mechanisms of Zinc Oxide Nanoparticle-Induced Genotoxicity Short Running Title: Genotoxicity of ZnO NPs

PubMed Central

Scherzad, Agmal; Meyer, Till; Kleinsasser, Norbert

2017-01-01

Background: Zinc oxide nanoparticles (ZnO NPs) are among the most frequently applied nanomaterials in consumer products. Evidence exists regarding the cytotoxic effects of ZnO NPs in mammalian cells; however, knowledge about the potential genotoxicity of ZnO NPs is rare, and results presented in the current literature are inconsistent. Objectives: The aim of this review is to summarize the existing data regarding the DNA damage that ZnO NPs induce, and focus on the possible molecular mechanisms underlying genotoxic events. Methods: Electronic literature databases were systematically searched for studies that report on the genotoxicity of ZnO NPs. Results: Several methods and different endpoints demonstrate the genotoxic potential of ZnO NPs. Most publications describe in vitro assessments of the oxidative DNA damage triggered by dissoluted Zn2+ ions. Most genotoxicological investigations of ZnO NPs address acute exposure situations. Conclusion: Existing evidence indicates that ZnO NPs possibly have the potential to damage DNA. However, there is a lack of long-term exposure experiments that clarify the intracellular bioaccumulation of ZnO NPs and the possible mechanisms of DNA repair and cell survival. PMID:29240707

Prediction of acute inhalation toxicity using in vitro lung surfactant inhibition.

PubMed

Sørli, Jorid B; Huang, Yishi; Da Silva, Emilie; Hansen, Jitka S; Zuo, Yi Y; Frederiksen, Marie; Nørgaard, Asger W; Ebbehøj, Niels E; Larsen, Søren T; Hougaard, Karin S

2018-01-01

Private consumers and professionals may experience acute inhalation toxicity after inhaling aerosolized impregnation products. The distinction between toxic and non-toxic products is difficult to make for producers and product users alike, as there is no clearly described relationship between the chemical composition of the products and induction of toxicity. The currently accepted method for determination of acute inhalation toxicity is based on experiments on animals; it is time-consuming, expensive and causes stress for the animals. Impregnation products are present on the market in large numbers and amounts and exhibit great variety. Therefore, an alternative method to screen for acute inhalation toxicity is needed. The aim of our study was to determine if inhibition of lung surfactant by impregnation products in vitro could accurately predict toxicity in vivo in mice. We tested 21 impregnation products using the constant flow through set-up of the constrained drop surfactometer to determine if the products inhibited surfactant function or not. The same products were tested in a mouse inhalation bioassay to determine their toxicity in vivo. The sensitivity was 100%, i.e., the in vitro method predicted all the products that were toxic for mice to inhale. The specificity of the in vitro test was 63%, i.e., the in vitro method found three false positives in the 21 tested products. Six of the products had been involved in accidental human inhalation where they caused acute inhalation toxicity. All of these six products inhibited lung surfactant function in vitro and were toxic to mice.

Acute toxicity and effects analysis of endosulfan sulfate to freshwater fish species.

PubMed

Carriger, John F; Hoang, Tham C; Rand, Gary M; Gardinali, Piero R; Castro, Joffre

2011-02-01

Endosulfan sulfate is a persistent environmental metabolite of endosulfan, an organochlorine insecticide-acaricide presently registered by the United States Environmental Protection Agency. There is, however, limited acute fish toxicity data for endosulfan sulfate. This study determines the acute toxicity (LC₅₀s and LC₁₀s) of endosulfan sulfate to three inland Florida native fish species (mosquitofish [Gambusia affinis]; least killifish [Heterandria formosa]; and sailfin mollies [Poecilia latipinna]) as well as fathead minnows (Pimephales promelas). Ninety-six-h acute toxicity tests were conducted with each fish species under flow-through conditions. For all of the above-mentioned fish species, 96-h LC₅₀ estimates ranged from 2.1 to 3.5 μg/L endosulfan sulfate. The 96-h LC₁₀ estimates ranged from 0.8 to 2.1 μg/L endosulfan sulfate. Of all of the fish tested, the least killifish appeared to be the most sensitive to endosulfan sulfate exposure. The above-mentioned data were combined with previous acute toxicity data for endosulfan sulfate and freshwater fish for an effects analysis. The effects analysis estimated hazardous concentrations expected to exceed 5, 10, and 50% of the fish species' acute LC₅₀ or LC₁₀ values (HC₅, HC₁₀, and HC₅₀). The endosulfan sulfate freshwater-fish acute tests were also compared with the available freshwater-fish acute toxicity data for technical endosulfan. Technical endosulfan is a mixture of α- and β-endosulfan. The LC₅₀s had a wider range for technical endosulfan, and their distribution produced a lower HC₁₀ than for endosulfan sulfate. The number of freshwater-fish LC₅₀s for endosulfan sulfate is much smaller than the number available for technical endosulfan, reflecting priorities in examining the toxicity of the parent compounds of pesticides. The toxicity test results and effects analyses provided acute effect values for endosulfan sulfate and freshwater fish that might be applied

Behavioral and genotoxic evaluation of rosmarinic and caffeic acid in acute seizure models induced by pentylenetetrazole and pilocarpine in mice.

PubMed

Coelho, Vanessa Rodrigues; Vieira, Caroline Gonçalves; de Souza, Luana Pereira; da Silva, Lucas Lima; Pflüger, Pricila; Regner, Gabriela Gregory; Papke, Débora Kuck Mausolff; Picada, Jaqueline Nascimento; Pereira, Patrícia

2016-11-01

The goal of this study was to investigate the effects of rosmarinic acid (RA) and caffeic acid (CA) in the acute pentylenetetrazole (PTZ) and pilocarpine (PIL) seizure models. We also evaluated the effect of RA and CA on the diazepam (DZP)-induced sleeping time test and its possible neuroprotective effect against the genotoxic damage induced by PTZ and PIL. Mice were treated intraperitoneally (i.p.) with saline, RA (2 or 4 mg/kg), or CA (4 or 8 mg/kg) alone or associated to low-dose DZP. After, mice received a single dose of PTZ (88 mg/kg) or PIL (250 mg/kg) and were monitored for the percentage of seizures and the latency to first seizure (LFS) >3 s. Vigabatrin and DZP were used as positive controls. In the DZP-induced sleeping time test, mice were treated with RA and CA and 30 min after receiving DZP (25 mg/kg, i.p.). The alkaline comet assay was performed after acute seizure tests to evaluate the antigenotoxic profiles of RA and CA. The doses of RA and CA tested alone did not reduce the occurrence of seizures induced by PTZ or PIL. The association of 4 mg/kg RA + low-dose DZP was shown to increase LFS in the PTZ model, compared to the group that received only the DZP. In the DZP-induced sleeping time test, the latency to sleep was reduced by 4 mg/kg RA and 8 mg/kg CA. The PTZ-induced genotoxic damage was not prevented by RA or CA, but the PIL-induced genotoxic damage was decreased by pretreatment with 4 mg/kg RA (in cortex) and 4 mg/kg CA (in hippocampus). In conclusion, RA and CA presented neuroprotective effect against PIL-induced genotoxic damage and reduced the latency to DZP-induced sleep. Of the rosmarinic acid, 4 mg/kg enhanced the DZP effect in the increase of latency to clonic PTZ-induced seizures.

Eco- and genotoxicity profiling of a rapeseed biodiesel using a battery of bioassays.

PubMed

Eck-Varanka, Bettina; Kováts, Nora; Horváth, Eszter; Ferincz, Árpád; Kakasi, Balázs; Nagy, Szabolcs Tamás; Imre, Kornélia; Paulovits, Gábor

2018-04-30

Biodiesel is considered an important renewable energy source but still there is some controversy about its environmental toxicity, especially to aquatic life. In our study, the toxicity of water soluble fraction of biodiesel was evaluated in relatively low concentrations using a battery of bioassays: Vibrio fischeri bioluminescence inhibition, Sinapis alba root growth inhibition, Daphnia magna immobilization, boar semen live/dead ratio and DNA fragmentation and Unio pictorum micronucleus test. While the S. alba test indicated nutritive (stimulating) effect of the sample, the biodiesel exerted toxic effect in the aquatic tests. D. magna was the most sensitive with EC 50 value of 0.0226%. For genotoxicity assessment, the mussel micronucleus test (MNT) was applied, detecting considerable genotoxic potential of the biodiesel sample: it elucidated micronuclei formation already at low concentration of 3.3%. Although this test has never been employed in biodiesel eco/genotoxicity assessments, it seems a promising tool, based on its appropriate sensitivity, and representativity. Copyright © 2018 Elsevier Inc. All rights reserved.

Genotoxicity and growth inhibition effects of aniline on wheat.

PubMed

Tao, Nan; Liu, Guanyi; Bai, Lu; Tang, Lu; Guo, Changhong

2017-02-01

Aniline is a synthetic compound widely used in industrial and pesticide production, which can lead to environmental pollution. Its high concentration in rivers and lakes is hazardous to aquatic species. Although the mechanism of aniline toxicity has been studied extensively in animals and algae, little is known about its genotoxicity in plants. In this study, we investigated the genotoxicity effects of aniline on wheat root tip cells. The mitotic index of wheat root tip cells decreased when the aniline test concentration was higher than 10 mg L -1 . The frequency of micronucleus and chromosomal aberrations increased at aniline concentrations ranging between 5 and 100 mg L -1 , and reached 23.3‰ ± 0.3‰ and 8.9‰ ± 0.68‰, respectively, at an aniline concentration of 100 mg L -1 . These values were sevenfold higher than those in the control group. The wheat seedlings showed various growth toxicity effects under different concentrations of aniline. The shoot height, root length, fresh weight, and dry weight of wheat seedlings decreased at aniline test concentrations ranging between 25 and 200 mg L -1 . At 200 mg L -1 aniline, the dry weight was only one-third that of the control group. Overall, the findings of this study provide evidence that aniline is a serious environmental pollutant causing deleterious genotoxic effects on wheat root tip cells and growth toxic effects on wheat seedlings. However, understanding the mechanisms that underlie aniline genotoxicity in plants needs further study. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hematopoietic Acute Radiation Syndrome (Bone marrow syndrome, Aplastic Anemia): Molecular Mechanisms of Radiation Toxicity.

NASA Astrophysics Data System (ADS)

Popov, Dmitri

Key Words: Aplastic Anemia (AA), Pluripotential Stem Cells (PSC) Introduction: Aplastic Anemia (AA) is a disorder of the pluripotential stem cells involve a decrease in the number of cells of myeloid, erythroid and megakaryotic lineage [Segel et al. 2000 ]. The etiology of AA include idiopathic cases and secondary aplastic anemia after exposure to drugs, toxins, chemicals, viral infections, lympho-proliferative diseases, radiation, genetic causes, myelodisplastic syndromes and hypoplastic anemias, thymomas, lymphomas. [Brodskyet al. 2005.,Modan et al. 1975., Szklo et al. 1975]. Hematopoietic Acute Radiation Syndrome (or Bone marrow syndrome, or Radiation-Acquired Aplastic Anemia) is the acute toxic syndrome which usually occurs with a dose of irradiation between 0.7 and 10 Gy (70- 1000 rads), depending on the species irradiated. [Waselenko et al., 2004]. The etiology of bone morrow damage from high-level radiation exposure results depends on the radiosensitivity of certain bone marrow cell lines. [Waselenko et al. 2004] Aplastic anemia after radiation exposure is a clinical syndrome that results from a marked disorder of bone marrow blood cell production. [Waselenko et al. 2004] Radiation hematotoxicity is mediated via genotoxic and other specific toxic mechanisms, leading to aplasia, cell apoptosis or necrosis, initiation via genetic mechanisms of clonal disorders, in cases such as the acute radiation-acquired form of AA. AA results from radiation injury to pluripotential and multipotential stem cells in the bone marrow. The clinical signs displayed in reticulocytopenia, anemia, granulocytopenia, monocytopenia, and thrombocytopenia. The number of marrow CD34+ cells (multipotential hematopoietic progenitors) and their derivative colony-forming unit{granulocyte-macrophage (CFU-GM) and burst forming unit {erythroid (BFU{E) are reduced markedly in patients with AA. [Guinan 2011, Brodski et al. 2005, Beutler et al.,2000] Cells expressing CD34 (CD34+ cell) are normally

Accuracy of Chronic Aquatic Toxicity Estimates Determined from Acute Toxicity Data and Two Time–Response Models.

EPA Science Inventory

Traditionally, chronic toxicity in aquatic organisms and wildlife has been determined from either toxicity test data, acute to chronic ratios, or application of safety factors. A more recent alternative approach has been to estimate chronic toxicity by modeling the time course of...

Comparative acute toxicity of shale and petroleum derived distillates.

PubMed

Clark, C R; Ferguson, P W; Katchen, M A; Dennis, M W; Craig, D K

1989-12-01

In anticipation of the commercialization of its shale oil retorting and upgrading process, Unocal Corp. conducted a testing program aimed at better defining potential health impacts of a shale industry. Acute toxicity studies using rats and rabbits compared the effects of naphtha, Jet-A, JP-4, diesel and "residual" distillate fractions of both petroleum derived crude oils and hydrotreated shale oil. No differences in the acute oral (greater than 5 g/kg LD50) and dermal (greater than 2 g/kg LD50) toxicities were noted between the shale and petroleum derived distillates and none of the samples were more than mildly irritating to the eyes. Shale and petroleum products caused similar degrees of mild to moderate skin irritation. None of the materials produced sensitization reactions. The LC50 after acute inhalation exposure to Jet-A, shale naphtha, (greater than 5 mg/L) and JP-4 distillate fractions of petroleum and shale oils was greater than 5 mg/L. The LC50 of petroleum naphtha (greater than 4.8 mg/L) and raw shale oil (greater than 3.95 mg/L) also indicated low toxicity. Results demonstrate that shale oil products are of low acute toxicity, mild to moderately irritating and similar to their petroleum counterparts. The results further demonstrate that hydrotreatment reduces the irritancy of raw shale oil.

Chlorination of oxybenzone: Kinetics, transformation, disinfection byproducts formation, and genotoxicity changes.

PubMed

Zhang, Shujuan; Wang, Xiaomao; Yang, Hongwei; Xie, Yuefeng F

2016-07-01

UV filters are a kind of emerging contaminant, and their transformation behavior in water treatment processes has aroused great concern. In particular, toxic products might be produced during reaction with disinfectants during the disinfection process. As one of the most widely used UV filters, oxybenzone has received significant attention, because its transformation and toxicity changes during chlorine oxidation are a concern. In our study, the reaction between oxybenzone and chlorine followed pseudo-first-order and second-order kinetics. Three transformation products were detected by LC-MS/MS, and the stability of products followed the order of tri-chloro-methoxyphenoyl > di-chlorinated oxybenzone > mono-chlorinated oxybenzone. Disinfection byproducts (DBPs) including chloroform, trichloroacetic acid, dichloroacetic acid and chloral hydrate were quickly formed, and increased at a slower rate until their concentrations remained constant. The maximum DBP/oxybenzone molar yields for the four compounds were 12.02%, 6.28%, 0.90% and 0.23%, respectively. SOS/umu genotoxicity test indicated that genotoxicity was highly elevated after chlorination, and genotoxicity showed a significantly positive correlation with the response of tri-chloro-methoxyphenoyl. Our results indicated that more genotoxic transformation products were produced in spite of the elimination of oxybenzone, posing potential threats to drinking water safety. This study shed light on the formation of DBPs and toxicity changes during the chlorination process of oxybenzone. Copyright © 2016 Elsevier Ltd. All rights reserved.

Is the fish embryo toxicity test (FET) with the zebrafish (Danio rerio) a potential alternative for the fish acute toxicity test?

PubMed

Lammer, E; Carr, G J; Wendler, K; Rawlings, J M; Belanger, S E; Braunbeck, Th

2009-03-01

The fish acute toxicity test is a mandatory component in the base set of data requirements for ecotoxicity testing. The fish acute toxicity test is not compatible with most current animal welfare legislation because mortality is the primary endpoint and it is often hypothesized that fish suffer distress and perhaps pain. Animal alternative considerations have also been incorporated into new European REACH regulations through strong advocacy for the reduction of testing with live animals. One of the most promising alternative approaches to classical acute fish toxicity testing with live fish is the fish embryo toxicity (FET) test. The FET has been a mandatory component in routine whole effluent testing in Germany since 2005 and has already been standardized at the international level. In order to analyze the applicability of the FET also in chemical testing, a comparative re-evaluation of both fish and fish embryo toxicity data was carried out for a total of 143 substances, and statistical approaches were developed to evaluate the correlation between fish and fish embryo toxicity data. Results confirm that fish embryo tests are neither better nor worse than acute fish toxicity tests and provide strong scientific support for the FET as a surrogate for the acute fish toxicity test.

Health care industries: potential generators of genotoxic waste.

PubMed

Sharma, Pratibha; Kumar, Manish; Mathur, N; Singh, A; Bhatnagar, P; Sogani, M

2013-08-01

Health care waste includes all the waste generated by health care establishments, research facilities, and laboratories. This constitutes a variety of chemical substances, such as pharmaceuticals, radionuclides, solvents, and disinfectants. Recently, scientists and environmentalists have discovered that wastewater produced by hospitals possesses toxic properties due to various toxic chemicals and pharmaceuticals capable of causing environmental impacts and even lethal effects to organisms in aquatic ecosystems. Many of these compounds resist normal wastewater treatment and end up in surface waters. Besides aquatic organisms, humans can be exposed through drinking water produced from contaminated surface water. Indeed, some of the substances found in wastewaters are genotoxic and are suspected to be potential contributors to certain cancers. The aim of this study was to evaluate the genotoxic and cytotoxic potential of wastewaters from two hospitals and three clinical diagnostic centers located in Jaipur (Rajasthan State), India using the prokaryotic Salmonella mutagenicity assay (Ames assay) and the eukaryotic Saccharomyces cerevisiae respiration inhibition assay. In the Ames assay, untreated wastewaters from both of the health care sectors resulted in significantly increased numbers of revertant colonies up to 1,000-4,050 as measured by the Salmonella typhimurium TA98 and TA100 strains (with and without metabolic activation) after exposure to undiluted samples, which indicated the highly genotoxic nature of these wastewaters. Furthermore, both hospital and diagnostic samples were found to be highly cytotoxic. Effective concentrations at which 20 % (EC20) and 50 % (EC50) inhibition of the respiration rate of the cells occurred ranged between ~0.00 and 0.52 % and between 0.005 and 41.30 % (calculated with the help of the MS excel software XLSTAT 2012.1.01; Addinsoft), respectively, as determined by the S. cerevisiae assay. The results indicated that hospital

Detection of genotoxic and non-genotoxic carcinogens in Xpc{sup −/−}p53{sup +/−} mice

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

Melis, Joost P.M.; Leiden University Medical Center, Department of Toxicogenetics, Leiden; Speksnijder, Ewoud N.

2013-01-15

An accurate assessment of the carcinogenic potential of chemicals and pharmaceutical drugs is essential to protect humans and the environment. Therefore, substances are extensively tested before they are marketed to the public. Currently, the rodent two-year bioassay is still routinely used to assess the carcinogenic potential of substances. However, over time it has become clear that this assay yields false positive results and also has several economic and ethical drawbacks including the use of large numbers of animals, the long duration, and the high cost. The need for a suitable alternative assay is therefore high. Previously, we have proposed themore » Xpa*p53 mouse model as a very suitable alternative to the two-year bioassay. We now show that the Xpc*p53 mouse model preserves all the beneficial traits of the Xpa*p53 model for sub-chronic carcinogen identification and can identify both genotoxic and non-genotoxic carcinogens. Moreover, Xpc*p53 mice appear to be more responsive than Xpa*p53 mice towards several genotoxic and non-genotoxic carcinogens. Furthermore, Xpc*p53 mice are far less sensitive than Xpa*p53 mice for the toxic activity of DNA damaging agents and as such clearly respond in a similar way as wild type mice do. These advantageous traits of the Xpc*p53 model make it a better alternative for in vivo carcinogen testing than Xpa*p53. This pilot study suggests that Xpc*p53 mice are suited for routine sub-chronic testing of both genotoxic and non-genotoxic carcinogens and as such represent a suitable alternative to possibly replace the murine life time cancer bioassay. Highlights: ► The Xpc*p53 mouse model is able to identify genotoxic and non-genotoxic carcinogens. ► Time, animals and cost can be significantly reduced compared to the 2-year bioassay. ► Xpc*p53 mice are more advantageous for carcinogen identification than Xpa*p53 mice. ► Xpc*p53 mice exhibit a wild type response upon exposure to genotoxicants.« less

OECD validation study to assess intra- and inter-laboratory reproducibility of the zebrafish embryo toxicity test for acute aquatic toxicity testing.

PubMed

Busquet, François; Strecker, Ruben; Rawlings, Jane M; Belanger, Scott E; Braunbeck, Thomas; Carr, Gregory J; Cenijn, Peter; Fochtman, Przemyslaw; Gourmelon, Anne; Hübler, Nicole; Kleensang, André; Knöbel, Melanie; Kussatz, Carola; Legler, Juliette; Lillicrap, Adam; Martínez-Jerónimo, Fernando; Polleichtner, Christian; Rzodeczko, Helena; Salinas, Edward; Schneider, Katharina E; Scholz, Stefan; van den Brandhof, Evert-Jan; van der Ven, Leo T M; Walter-Rohde, Susanne; Weigt, Stefan; Witters, Hilda; Halder, Marlies

2014-08-01

The OECD validation study of the zebrafish embryo acute toxicity test (ZFET) for acute aquatic toxicity testing evaluated the ZFET reproducibility by testing 20 chemicals at 5 different concentrations in 3 independent runs in at least 3 laboratories. Stock solutions and test concentrations were analytically confirmed for 11 chemicals. Newly fertilised zebrafish eggs (20/concentration and control) were exposed for 96h to chemicals. Four apical endpoints were recorded daily as indicators of acute lethality: coagulation of the embryo, lack of somite formation, non-detachment of the tail bud from the yolk sac and lack of heartbeat. Results (LC50 values for 48/96h exposure) show that the ZFET is a robust method with a good intra- and inter-laboratory reproducibility (CV<30%) for most chemicals and laboratories. The reproducibility was lower (CV>30%) for some very toxic or volatile chemicals, and chemicals tested close to their limit of solubility. The ZFET is now available as OECD Test Guideline 236. Considering the high predictive capacity of the ZFET demonstrated by Belanger et al. (2013) in their retrospective analysis of acute fish toxicity and fish embryo acute toxicity data, the ZFET is ready to be considered for acute fish toxicity for regulatory purposes. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Early genotoxic response and accumulation induced by waterborne copper, lead, and arsenic in European seabass, Dicentrarchus labrax.

PubMed

Canalejo, Antonio; Diaz-de-Alba, Margarita; Granado-Castro, M Dolores; Cordoba, Francisco; Espada-Bellido, Estrella; Galindo-Riaño, M Dolores; Torronteras, Rafael

2016-02-01

Cu, Pb, and As, which are among the most abundant metals in the aquatic environment, are also among the most health-threatened by causing diverse cellular injuries. The aim of this study was to assess and compare the potential early induction of genotoxic effects after waterborne Cu, Pb, and As exposure in European seabass, Dicentrarchus labrax, a commercial widely cultured fish, using the micronucleus (MN) assay in peripheral blood erythrocytes. Fish were exposed under laboratory conditions to nominal solutions ranging 0-10 mg/L for 24 and 96 h. Furthermore, actual metal ion concentrations were measured by inductively coupled plasma atomic emission spectroscopy (ICP-AES) or differential pulse anodic stripping voltammetry (DPASV) in water and four fish tissues differentially related to environmental exposition and metal accumulation, i.e. the gills, liver, muscle, and brain. Dose-dependent increases of micronuclei (MNi) frequency were observed after these very short exposures; based on measured metal concentrations in water, the genotoxic effect ordered as Cu > As > Pb. Significant genotoxic effect at 0.009 mg/L Cu, 0.57 mg/L Pb, and 0.01 mg/L As was seen. For Cu and Pb these are only slightly higher, but for As it is notably lower than the USEPA criteria of maximum concentration to prevent acute toxicity in aquatic organisms. Furthermore, genotoxicity was differentially related to metal accumulation. MNi frequency correlated positively with the content of Pb in all the organs, with the content of As in liver and gills and only with the content of Cu in the brain. In conclusion, our findings raised environmental concerns because these depicted a genotoxic potential of Cu, Pb, and As after a very short exposure to low but environmentally relevant concentrations, too close to regulatory thresholds. In addition, the MN test in D. labrax could be considered an early biomarker of genotoxicity induced by these metals in fish.

Genotoxic effects of boric acid and borax in zebrafish, Danio rerio using alkaline comet assay

PubMed Central

Gülsoy, Nagihan; Yavas, Cüneyd; Mutlu, Özal

2015-01-01

The present study is conducted to determine the potential mechanisms of Boron compounds, boric acid (BA) and borax (BX), on genotoxicity of zebrafish Danio rerio for 24, 48, 72 and 96-hours acute exposure (level:1, 4, 16, 64 mg/l BA and BX) in semi-static bioassay experiment. For that purpose, peripheral erythrocytes were drawn from caudal vein and Comet assay was applied to assess genotoxicity. Acute (96 hours) exposure and high concentrations of boric acid and borax increases % tail DNA and Olive tail moment. Genotoxicity was found for BA as concentration-dependent and BX as concentration and time dependent manner. In general, significant effects (P < 0,05) on both concentrations and exposure times were observed in experimental groups. DNA damage was highest at 96 h and 24 h for all BX and BA concentrations, respectively in peripheral blood of D. rerio. For the first time, our study demonstrates the effect of waterborne BA and BX exposure on genotoxicity at the molecular level, which may contribute to understanding the mechanism of boric acid and borax-induced genotoxicity in fish. PMID:26862320

Genotoxic effects of boric acid and borax in zebrafish, Danio rerio using alkaline comet assay.

PubMed

Gülsoy, Nagihan; Yavas, Cüneyd; Mutlu, Özal

2015-01-01

The present study is conducted to determine the potential mechanisms of Boron compounds, boric acid (BA) and borax (BX), on genotoxicity of zebrafish Danio rerio for 24, 48, 72 and 96-hours acute exposure (level:1, 4, 16, 64 mg/l BA and BX) in semi-static bioassay experiment. For that purpose, peripheral erythrocytes were drawn from caudal vein and Comet assay was applied to assess genotoxicity. Acute (96 hours) exposure and high concentrations of boric acid and borax increases % tail DNA and Olive tail moment. Genotoxicity was found for BA as concentration-dependent and BX as concentration and time dependent manner. In general, significant effects (P < 0,05) on both concentrations and exposure times were observed in experimental groups. DNA damage was highest at 96 h and 24 h for all BX and BA concentrations, respectively in peripheral blood of D. rerio. For the first time, our study demonstrates the effect of waterborne BA and BX exposure on genotoxicity at the molecular level, which may contribute to understanding the mechanism of boric acid and borax-induced genotoxicity in fish.

The genotoxic effects of the imidacloprid-based insecticide formulation Glacoxan Imida on Montevideo tree frog Hypsiboas pulchellus tadpoles (Anura, Hylidae).

PubMed

Pérez-Iglesias, J M; Ruiz de Arcaute, C; Nikoloff, N; Dury, L; Soloneski, S; Natale, G S; Larramendy, M L

2014-06-01

The neonicotinoid insecticide imidacloprid (IMI) affects the insect central nervous system and is successfully applied to control pests for a variety of agricultural crops. In the current study, acute toxicity and genotoxicity of the IMI-containing commercial formulation insecticide Glacoxan Imida (35 percent IMI) was evaluated on Hypsiboas pulchellus (Anura: Hylidae) tadpoles exposed under laboratory conditions. A lethal effect was evaluated as the end point for lethality, whereas micronucleus (MN) frequency and DNA single-strand breaks evaluated by the single cell gel electrophoresis (SCGE) assay were employed as end points for genotoxicity. Sublethal end points were assayed within the 12.5-37.5mg/L IMI concentration range. Experiments were performed on tadpoles at stage 36 (range, 35-37) according to the classification proposed by Gosner. Lethality studies revealed an LC50 96h value of 52.622mg/L IMI. Increased frequency of MNs was only observed when 25.0mg/L was assayed for 96h, whereas no other nuclear abnormalities were induced. Increase of the genetic damage index was observed at 48h of treatment within the 12.5-37.5mg/L concentration range, whereas an increased frequency of DNA damage was observed only in tadpoles treated with 37.5mg/L IMI for 96h. This study represents the first evidence of the acute lethal and genotoxic effects exerted by IMI on tadpoles of an amphibian species native to Argentina under laboratory conditions. Copyright © 2014 Elsevier Inc. All rights reserved.

Application of fish cell lines for evaluating the chromium induced cytotoxicity, genotoxicity and oxidative stress.

PubMed

Taju, G; Abdul Majeed, S; Nambi, K S N; Sahul Hameed, A S

2017-10-01

In the present study, we hypothesize that cytotoxicity, genotoxicity and oxidative stress play a key role in chromium induced toxicity in SISS, SISK, IEE, IEK, IEG, SICH and ICG cell lines after 24 h exposure. Three fish species namely Lates calcarifer, Etroplus suratensis and Catla catla were exposed to the concentrations of 0, 10, 20, 30, 40 and 50 mg/L of chromium for 96 h under static conditions for conducting acute toxicity tests. LC 50 was then calculated. The percentage cell survival was assessed by multiple endpoints such as MTT, NR, AB and CB assays in the seven fish cell lines exposed to different concentrations of chromium and EC 50 values of all the four endpoints were calculated. High significances were noted in the correlations between each in vitro cytotoxicity assays and in vivo mortality data. Cell shrinkage, cell detachment, vacuolations and cell swelling at the highest concentration of chromium (50 mg/L) were seen on microscopic examination of cell morphology. Comet assay and Hoechst staining were carried out to assess DNA damage and nuclear fragmentation in the seven fish lines exposed to chromium. The results of antioxidant parameters obtained indicate a significant reduction in the level of catalase, superoxide dismutase, glutathione S-transferase and Glutathione peroxidase, and increased level of lipid peroxidation in all the cell lines exposed to chromium. These results confirm that fish cell lines could be used as an alternative to whole fish for cytotoxicity, genotoxicity and oxidative stress assessment in chromium toxicity studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nrf2-dependent protection against acute sodium arsenite toxicity in zebrafish

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

Fuse, Yuji; Nguyen, Vu Thanh; Kobayashi, Makoto, E

Transcription factor Nrf2 induces a number of detoxifying enzymes and antioxidant proteins to confer protection against the toxic effects of a diverse range of chemicals including inorganic arsenicals. Although a number of studies using cultured cells have demonstrated that Nrf2 has a cell-protective function against acute and high-dose arsenic toxicity, there is no clear in vivo evidence of this effect. In the present study, we genetically investigated the protective role of Nrf2 against acute sodium arsenite toxicity using the zebrafish Nrf2 mutant, nrf2a{sup fh318}. After treatment with 1 mM sodium arsenite, the survival of nrf2a{sup fh318} larvae was significantly shortermore » than that of wild-type siblings, suggesting that Nrf2 protected the zebrafish larvae against high-dose arsenite exposure. To understand the molecular basis of the Nrf2-dependent protection, we analyzed the gene expression profiles after arsenite exposure, and found that the genes involved in the antioxidative function (prdx1 and gclc), arsenic metabolism (gstp1) and xenobiotic elimination (abcc2) were induced in an Nrf2-dependent manner. Furthermore, pre-treatment with sulforaphane, a well-known Nrf2 activator improved the survival of zebrafish larvae after arsenic exposure. Based on these results, we concluded that Nrf2 plays a fundamental and conserved role in protection against acute sodium arsenite toxicity. - Highlights: • The role of Nrf2 under arsenite exposure was valuated using zebrafish. • Nrf2 mutant zebrafish was highly sensitive to acute arsenic toxicity. • Nrf2 induced anti-arsenic genes in response to arsenite. • Sulforaphane attenuated arsenic toxicity through Nrf2 activation. • Nrf2 system plays an important role in the defense against acute arsenic toxicity.« less

Genotoxic alkenylbenzene flavourings, a contribution to risk assessment.

PubMed

Martins, Célia; Rueff, José; Rodrigues, António S

2018-06-15

Alkenylbenzenes, such as estragole, myristicin and eugenol, are present is several flavourings, functional foods, plant food supplements (PFS) and in complementary and alternative medicines (CAM) including herbal medicines. The increase in consumption in functional foods observed worldwide requires a strict analysis of the scientific validity of their benefits and risk-benefit ratio associated with their intake. Some instances of acute toxicity have been reported associated with the use of herbal medicines and PFS, in particular because quality control is poor, and this poses a risk especially in internet marketed products. In particular, chronic exposure to low levels of these constituents may pose a hazard. However, given the variability in dietary habits, plant properties, plant misidentification or interaction with pharmaceutical drugs or nutrients, the assessment of risk due to the intake of alkenylbenzenes is difficult. We herein review the regulatory status of the most common alkenylbenzenes and their genotoxic activity and potential carcinogenic activity. Copyright © 2018. Published by Elsevier Ltd.

[Acute toxicity analysis performance of CellSense biosensor with E. coli].

PubMed

Wang, Xue-Jiang; Wang, Hong; Zhao, Jian-Fu; Xia, Si-Qing; Zhao, Hong-Ning

2009-04-15

E. coli microbial electrodes for CellSense biosensor were prepared by polycarbonate membrane immobilization process, and their performance for heavy metals and toxic organic compounds acute toxicity determination were studied. The results showed that when E. coli was in logarithmic and stationary phase, the CellSense biosensor with E. coli showed good performance in heavy metal ions and organic pollutants acute toxicity analysis, when E. coli was in its decline phase, the stability and sensitivity of the CellSense biosensor was poor. The EC50 values of Hg2+, Cu2+, Zn2+, o-chlorophenol (2-CP) and p-nitrophenol (4-NP) detected by CellSense biosensor with E. coli were 0.6, 3.1, 5.8, 180 and 94 microg/mL, respectively. The immobilized E. coli electrodes could still suit for acute toxicity assessment after 2 months storage at 4 degrees C.

Comet Assay on Daphnia magna in eco-genotoxicity testing.

PubMed

Pellegri, Valerio; Gorbi, Gessica; Buschini, Annamaria

2014-10-01

Detection of potentially hazardous compounds in water bodies is a priority in environmental risk assessment. For the evaluation and monitoring of water quality, a series of methodologies may be applied. Among them, the worldwide used toxicity tests with organisms of the genus Daphnia is one of the most powerful. In recent years, some attempts were made to utilize Daphnia magna in genotoxicity testing as many of the new environmental contaminants are described as DNA-damaging agents in aquatic organisms. The aim of this research was to develop a highly standardized protocol of the Comet Assay adapted for D. magna, especially regarding the isolation of cells derived from the same tissue (haemolymph) from newborn organisms exposed in vivo. Several methods for haemolymph extraction and different Comet Assay parameters were compared. Electrophoretic conditions were adapted in order to obtain minimum DNA migration in cells derived from untreated organisms and, at the same time, maximum sensitivity in specimens treated with known genotoxicants (CdCl2 and H2O2). Additional tests were performed to investigate if life-history traits of the cladoceran (such as the age of adult organisms that provide newborns, the clutch size of origin, the number of generations reared in standard conditions) and the water composition as well, might influence the response of the assay. This study confirms the potential application of the Comet Assay in D. magna for assessing genotoxic loads in aqueous solution. The newly developed protocol could integrate the acute toxicity bioassay, thus expanding the possibility of using this model species in freshwater monitoring (waters, sediment and soil elutriates) and is in line with the spirit of the EU Water Framework Directive in reducing the number of bioassays that involve medium-sized species. Copyright © 2014 Elsevier B.V. All rights reserved.

Safety assessment of hydroethanolic rambutan rind extract: acute and sub-chronic toxicity studies.

PubMed

Thinkratok, Aree; Suwannaprapha, Parin; Srisawat, Rungrudee

2014-10-01

This study evaluated the safety of rambutan rind extract (RRE) in male Wistar rats. While acute toxicity was evaluated by feeding the rats with single doses of RRE (1000, 2000, 3000, 4000, and 5000 mg/kg) and its sub-chronic toxicity was observed in rats orally administered with RRE (500, 1000, and 2000 mg/kg) daily for 30 days. In acute toxicity study, the LD50 was found to be greater than 5000 mg/kg of RRE. In sub-chronic toxicity study, no mortality and sign of toxicity was found up to 1000 mg/kg/day of RRE. At 2000 mg/kg/day dose, the mortality rate was 12.5%. Significant decreases in body weight gain and food consumption were found in both acute and sub-chronic toxicity studies. In acute toxicity study, all the studied doses of RRE did not alter serum levels of triglyceride (TG), aspartate aminotransferase (AST) andalanine aminotransferase (ALT). In sub-chronic toxicity study, all studied doses of RRE significantly decreased plasma levels of TG and blood urea nitrogen, but did not alter plasma levels of AST and ALT. TC levels did not show any significant change in both the studies. The obtained results provide basic information for in vivo experimental studies of the pharmacological potentiality of RRE.

Aspect ratio has no effect on genotoxicity of multi-wall carbon nanotubes.

PubMed

Kim, Jin Sik; Lee, Kyu; Lee, Young Hee; Cho, Hyun Sun; Kim, Ki Heon; Choi, Kyung Hee; Lee, Sang Hee; Song, Kyung Seuk; Kang, Chang Soo; Yu, Il Je

2011-07-01

Carbon nanotubes (CNTs) have specific physico-chemical and electrical properties that are useful for telecommunications, medicine, materials, manufacturing processes and the environmental and energy sectors. Yet, despite their many advantages, it is also important to determine whether CNTs may represent a hazard to the environment and human health. Like asbestos, the aspect ratio (length:diameter) and metal components of CNTs are known to have an effect on the toxicity of carbon nanotubes. Thus, to evaluate the toxic potential of CNTs in relation to their aspect ratio and metal contamination, in vivo and in vitro genotoxicity tests were conducted using high-aspect-ratio (diameter: 10-15 nm, length: ~10 μm) and low-aspect-ratio multi-wall carbon nanotubes (MWCNTs, diameter: 10-15 nm, length: ~150 nm) according to OECD test guidelines 471 (bacterial reverse mutation test), 473 (in vitro chromosome aberration test), and 474 (in vivo micronuclei test) with a good laboratory practice system. To determine the treatment concentration for all the tests, a solubility and dispersive test was performed, and a 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) solution found to be more suitable than distilled water. Neither the high- nor the low-aspect-ratio MWCNTs induced any genotoxicity in a bacterial reverse mutation test (~1,000 μg/plate), in vitro chromosome aberration test (without S9: ~6.25 μg/ml, with S9: ~50 μg/ml), or in vivo micronuclei test (~50 mg/kg). However, the high-aspect-ratio MWCNTs were found to be more toxic than the low-aspect-ratio MWCNTs. Thus, while high-aspect-ratio MWCNTs do not induce direct genotoxicity or metabolic activation-mediated genotoxicity, genotoxicity could still be induced indirectly through oxidative stress or inflammation.

Towards an alternative for the acute fish LC(50) test in chemical assessment: the fish embryo toxicity test goes multi-species -- an update.

PubMed

Braunbeck, Thomas; Boettcher, Melanie; Hollert, Henner; Kosmehl, Thomas; Lammer, Eva; Leist, Erik; Rudolf, Mark; Seitz, Nadja

2005-01-01

After its standardisation at the national level in Germany (DIN 38415-6, 2001, 2001), the 48 h sewage testing assay with zebrafish (Danio rerio) embryos has been submitted for standardisation to ISO. As an alternative to the conventional acute (96 h) fish test, a modified fish embryo test will be submitted to the OECD for chemical testing in late 2005. For this, a protocol originally designed for zebrafish was adapted to fit also the requirements of other OECD species, namely medaka (Oryzias latipes) and fathead minnow (Pimephales promelas). Results document that the transfer of the protocol is possible with only minor modifications. Data obtained from embryo tests with the three species are comparable. Statistical analysis of existing zebrafish embryo toxicity data resulted in the conclusions (1) that there is a reliable correlation between the fish embryo test and the acute fish test, (2) that the confidence belt of the regression line was relatively small, but that the prediction range was relatively wide. The regression thus seems appropriate to describe the relationship between acute fish and embryo LC(50) with good confidence, but is less appropriate as a prediction model. Investigations into oxygen requirements of zebrafish embryos reveal that they adapt to a broad range of oxygen levels and survive at concentrations of 2 mg/l without malformations. Zebrafish embryos can thus be exposed in very small toxicant volumes (100 microl), which is of particular interest for the testing of metabolites. Dechorionation studies with 48 h old zebrafish embryos indicate that the barrier function of the chorion increases with the lipophilicity of the test compound. Finally, examples are given as to how additional endpoints can be incorporated into the fish embryo test protocol to extend its scope, e.g. to sediment toxicity assessment or genotoxicity and mutagenicity testing.

Acute toxicity value extrapolation with fish and aquatic invertebrates

USGS Publications Warehouse

Buckler, Denny R.; Mayer, Foster L.; Ellersieck, Mark R.; Asfaw, Amha

2005-01-01

Assessment of risk posed by an environmental contaminant to an aquatic community requires estimation of both its magnitude of occurrence (exposure) and its ability to cause harm (effects). Our ability to estimate effects is often hindered by limited toxicological information. As a result, resource managers and environmental regulators are often faced with the need to extrapolate across taxonomic groups in order to protect the more sensitive members of the aquatic community. The goals of this effort were to 1) compile and organize an extensive body of acute toxicity data, 2) characterize the distribution of toxicant sensitivity across taxa and species, and 3) evaluate the utility of toxicity extrapolation methods based upon sensitivity relations among species and chemicals. Although the analysis encompassed a wide range of toxicants and species, pesticides and freshwater fish and invertebrates were emphasized as a reflection of available data. Although it is obviously desirable to have high-quality acute toxicity values for as many species as possible, the results of this effort allow for better use of available information for predicting the sensitivity of untested species to environmental contaminants. A software program entitled “Ecological Risk Analysis” (ERA) was developed that predicts toxicity values for sensitive members of the aquatic community using species sensitivity distributions. Of several methods evaluated, the ERA program used with minimum data sets comprising acute toxicity values for rainbow trout, bluegill, daphnia, and mysids provided the most satisfactory predictions with the least amount of data. However, if predictions must be made using data for a single species, the most satisfactory results were obtained with extrapolation factors developed for rainbow trout (0.412), bluegill (0.331), or scud (0.041). Although many specific exceptions occur, our results also support the conventional wisdom that invertebrates are generally more

DETERMINANTS OF VARIABILITY IN ACUTE TO CHRONIC TOXICITY RATIOS IN AQUATIC INVERTEBRATES AND FISH

EPA Science Inventory

Variability in acute to chronic ratios (ACRs; LC50/chronic value) has been a continuing interest in aquatic toxicology because of the reliance on ACRs to estimate chronic toxicity for chemicals and species with known acute toxicity but limited or no information on sublethal toxic...

The acute toxicity of local anesthetics.

PubMed

Mather, Laurence E

2010-11-01

Systemic toxicity, usually from overdose or intravascular dose, is feared because it mainly affects the heart and brain, and may be acutely life-threatening. Pharmacological studies of local anesthetic toxicity have largely been reviewed primarily relating to the evaluation of ropivacaine and levobupivacaine during the past decade. This review/opinion focuses more on the principles and concepts underlying the main models used, from chemical pharmacological and pharmacokinetic perspectives. Research models required to produce pivotal toxicity data are discussed. The potencies for neural blockade and systemic toxicity are associated across virtually all models, with some deviations through molecular stereochemistry. These models show that all local anesthetics can produce direct cardiovascular system toxicity and CNS excitotoxicity that may further affect the cardiovascular system response. Whereas the longer-acting local anesthetics are more likely to cause cardiac death by malignant arrhythmias, the shorter-acting agents are more likely to cause cardiac contraction failure. In most models, equi-anesthetic doses of ropivacaine and levobupivacaine are less likely to produce serious toxicity than bupivacaine. Of the various models, this reviewer favors a whole-body large animal preparation because of the comprehensive data collection possible. The conscious sheep preparation has contributed more than any other, and may be regarded as the de facto 'standard' experimental model for concurrent study of local anesthetic toxicity ± pharmacokinetics, using experimental designs that can reproduce the toxicity seen in clinical accidents.

PREDICTING CHRONIC TOXICITY OF CHEMICALS TO FISHES FROM ACUTE TOXICITY TEST DATA: CONCEPT AND LINEAR REGRESSION

EPA Science Inventory

A comprehensive approach to predicting chronic toxicity from acute.toxicity data was developed in which simultaneous consideration is given to concentration, degree of response, and time course of effect. onsistent endpoint (lethality) and degree of response (O%) were used to com...

Quantification of umu genotoxicity level of urban river water.

PubMed

Kameya, T; Nagato, T; Nakagawa, K; Yamashita, D; Kobayashi, T; Fujie, K

2011-01-01

In recent years, the request of environmental safety management for carcinogenic substances, mutagenic substances and/or reproductive toxicity substances (CMR) has increased. This study focused on clarifying the genotoxicity level of environmental water and its release source by using the umu test provided in ISO13829. Although a genotoxicity index "induction ratio (IR)" is used in ISO13829, we normalised it to make it possible to compare various environmental water quantitatively to each other as a new index "genotoxic activity (GA=(IR-1)/Dose)". Sample water was collected and concentrated to 100 times or 1,000 times by a solid phase extraction method. As the test results, it was found that GA level in actual river water varied widely from less than the determination limit of 23 [1/L] to 1,100 [1/L] by quantitative comparison, and the value was also equivalent to more than 50 times the level of tap water. The GA level of household wastewater was not so high, but the levels of treated water from wastewater treatment plant (WTP) were from 220 [1/L] to 3,200 [1/L]. Raw sewage of some WTP shows high level genotoxicity. A part of genotoxicity substances, for example 50%, could be removed by conventional wastewater treatment, but it was not enough to reduce the water environmental load of genotoxicity.

Acute Toxicity Grade 3 and 4 After Irradiation in Children and Adolescents: Results From the IPPARCA Collaboration

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

Pixberg, Caroline; Koch, Raphael; Eich, Hans Theodor, E-mail: Hans.Eich@ukmuenster.de

Purpose: In the context of oncologic therapy for children, radiation therapy is frequently indicated. This study identified the frequency of and reasons for the development of high-grade acute toxicity and possible sequelae. Materials and Methods: Irradiated children have been prospectively documented since 2001 in the Registry for the Evaluation of Side Effects After Radiation in Childhood and Adolescence (RiSK) database in Germany and since 2008 in the registry for radiation therapy toxicity (RADTOX) in Sweden. Data were collected using standardized, published forms. Toxicity classification was based on Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. Results: Asmore » of June 2013, 1500 children have been recruited into the RiSK database and 485 into the RADTOX registry leading to an analysis population of 1359 patients (age range 0-18). A total of 18.9% (n=257) of all investigated patients developed high-grade acute toxicity (grades 3/4). High-grade toxicity of the bone marrow was documented for 63.8% (n=201) of those patients, oral mucositis for 7.6% (n=24), and dermatitis for 7.6% (n=24). Patients with high-grade acute toxicity received concomitant chemotherapy more frequently (56%) than patients with no or lower acute toxicity (31.5%). In multivariate analyses, concomitant chemotherapy, diagnosis of Ewing sarcoma, and total radiation dose showed a statistically noticeable effect (P≤.05) on acute toxicity, whereas age, concomitant chemotherapy, Hodgkin lymphoma, Ewing sarcoma, total radiation dose, and acute toxicity influenced the time until maximal late toxicity. Conclusions: Generally, high-grade acute toxicity after irradiation in children and adolescence occurs in a moderate proportion of patients (18.9%). As anticipated, the probability of acute toxicity appeared to depend on the prescribed dose as well as concomitant chemotherapy. The occurrence of chronic toxicity correlates with the prior

Use of the microscreen phage-induction assay to assess the genotoxicity of 14 hazardous industrial wastes

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

Houk, V.S.; DeMarini, D.M.

1988-01-01

The Microscreen phage-induction assay, which quantitatively measures the induction of prophage lambda in Escherichia coli WP2s(lambda), was used to test 14 crude (unfractionated) hazardous industrial waste samples for genotoxic activity in the presence and absence of metabolic activation. Eleven of the 14 wastes induced prophage, and induction was observed at concentrations as low as 0.4 pg per ml. Comparisons between the ability of these waste samples to induce prophage and their mutagenicity in the Salmonella reverse mutation assay indicate that the phage-induction assay detected genotoxic activity in all but one of the wastes that were mutagenic in Salmonella. Moreover, themore » Microscreen assay detected as genotoxic five additional wastes that were not detected in the Salmonella assay. The applicability of the Microscreen phage-induction assay for screening hazardous wastes for genotoxic activity is discussed, as are some of the problems associated with screening highly toxic wastes containing toxic volatile compounds.« less

Use of the Microscreen phage-induction assay to assess the genotoxicity of 14 hazardous industrial wastes

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

Houk, V.S.; DeMarini, D.M.

1988-01-01

The Microscreen phage-induction assay, which quantitatively measures the induction of prophage lambda in Escherichia coli WP2s lambda, was used to test 14 crude (unfractionated) hazardous industrial-waste samples for genotoxic activity in the presence and absence of metabolic activation. Eleven of the 14 wastes induced prophage, and induction was observed at concentrations as low as 0.4 picograms per ml. Comparisons between the mutagenicity of these waste samples in Salmonella and their ability to induce prophage lambda indicate that the Microscreen phage-induction assay detected genotoxic activity in all but one of the wastes that were mutagenic in Salmonella. Moreover, the Microscreen assaymore » detected as genotoxic 5 additional wastes that were not detected in the Salmonella assay. The applicability of the Microscreen phage-induction assay for screening hazardous wastes for genotoxic activity is discussed along with some of the problems associated with screening highly toxic wastes containing toxic volatile compounds.« less

Toxic and genotoxic effects of the imazethapyr-based herbicide formulation Pivot H® on montevideo tree frog Hypsiboas pulchellus tadpoles (Anura, Hylidae).

PubMed

Pérez-Iglesias, J M; Soloneski, S; Nikoloff, N; Natale, G S; Larramendy, M L

2015-09-01

Acute lethal and sublethal toxicity of the imidazolinone imazethapyr (IMZT)-based commercial formulation herbicide Pivot H® (10.59% IMZT) was evaluated on Hypsiboas pulchellus tadpoles. Whereas mortality was used as the end point for lethality, frequency of micronuclei (MNs) and other nuclear abnormalities as well as DNA single-strand breaks evaluated by the single cell gel electrophoresis assay were employed to test genotoxicity. Behavioral, growth, developmental, and morphological abnormalities were also employed as sublethal end points. Mortality studies revealed equivalent LC50 (96h) values of 1.49mg/L (confidence limit, 1.09-1.63) and 1.55mg/L (confidence limit, 1.51-1.60) IMZT for Gosner stage (GS) 25 and GS36, respectively. Behavioral changes, i.e., irregular swimming and immobility, as well as a decreased frequency of keratodonts were observed. The herbicide increased the frequency of MNs in circulating erythrocytes of tadpoles exposed for 48h to the highest concentration assayed (1.17mg/L). However, regardless of the concentration of the herbicide assayed, an enhanced frequency of MNs was observed in tadpoles exposed for 96h. The herbicide was able to induce other nuclear abnormalities, i.e., blebbed and notched nuclei, only when tadpoles were exposed for 96h. In addition, we observed that exposure to IMZT within the 0.39-1.17mg/L range increased the genetic damage index in treatments lasting for both 48 and 96h. This study represents the first evidence of acute lethal and sublethal effects exerted by IMZT on amphibians. Finally, our findings highlight the properties of this herbicide that jeopardize nontarget living species exposed to IMZT. Copyright © 2015 Elsevier Inc. All rights reserved.

Evaluation of genotoxic and antigenotoxic effects of hydroalcoholic extracts of Zuccagnia punctata Cav.

PubMed

Zampini, Iris Catiana; Villarini, Milena; Moretti, Massimo; Dominici, Luca; Isla, María Inés

2008-01-17

Zuccagnia punctata Cav. (Fabaceae), a widely used plant species in Argentine folk medicine, has been shown to have a broad spectrum of antibacterial, antifungal, antioxidant and cytoprotective activities. In this study, the hydroalcoholic extract of Zuccagnia punctata and 2',4'-dihydroxychalcone isolated from it were investigated for genotoxicity/antigenotoxicity in the in vitro comet assay test on human hepatoma HepG2 cells. No acute toxicity of the extract could be determined. HepG2 cells were treated with three different concentrations (2.5, 5.0 and 10.0 microg/mL) or 2',4'-dihydroxychalcone (0.01, 0.10 and 1.00 microg/mL). To explore the potential mechanisms of action, two approaches were followed: co-treatment with 4-nitroquinoline-N-oxyde (4-NQO), a direct genotoxic compound, and a pre-treatment protocol with benzo[a]pyrene (B[a]P), an indirect genotoxic compound. The natural products neither affected cell viability nor induced DNA damage in the concentration range tested. Zuccagnia punctata tinctures were able to diminish the DNA damage induced in HepG2 cells by 4-NQO and B[a]P in 31% and 10%, respectively at 10 microg/mL. Pre-treatment of HepG2 cells with 2',4'-dihydroxychalcone was highly effective in decreasing B[a]P-induced DNA damage at a statistically significant level, with an almost clear dose-response relationship. The inhibition values were 28.2-43.9% for the tested concentrations of 0.01-1 microg/mL, respectively. The results clearly indicate that the phytoextract from Zuccagnia punctata, under the experimental conditions tested, is not genotoxic and that 2',4'-dihydroxychalcone contributes to a high degree to the antigenotoxic effects of Zuccagnia punctata tincture.

Acute Vilazodone Toxicity in a Pediatric Patient.

PubMed

Acker, Emily C; Sinclair, Elizabeth A; Beardsley, Andrew L; Ahmed, Sheikh S; Froberg, Blake A

2015-09-01

Vilazodone is a selective serotonin reuptake inhibitor and 5HT1A agonist recently approved to treat depression in adults. To date, there are minimal data available regarding the expected course and treatment of acute vilazodone ingestions. We report a case of a previously healthy 19-month-old girl who presented after an acute ingestion of an estimated 37 mg/kg vilazodone. She was taken to an outside emergency department approximately 1 h after an unwitnessed ingestion. Initially, the patient was noted to have decreased responsiveness, sluggish but reactive pupils, altered mental status, and reported seizure activity. She was given intravenous lorazepam for seizure control, intubated, and transferred to a pediatric tertiary care facility, where she continued to show signs of serotonin toxicity and received treatment with benzodiazepines and cyproheptadine. Despite vilazodone's long half-life and the large amount ingested, the patient was extubated within 10 h of presentation, had returned to baseline mental status by 22 h, and was discharged home approximately 57 h after ingestion. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Accidental ingestions are common in the pediatric population. Emergency physicians need to be aware of the signs and symptoms of acute medication toxicities, the expected clinical course, and the necessary supportive measures used to treat these patients. Because vilazodone is a recently approved medication, there is little experience with acute vilazodone ingestions. This report considerably increases the understanding of vilazodone's effects in the setting of an acute ingestion. Copyright © 2015 Elsevier Inc. All rights reserved.

Acute and chronic toxicity of boron to a variety of freshwater organisms.

PubMed

Soucek, David J; Dickinson, Amy; Koch, Brian T

2011-08-01

Boron enters the aquatic environment from various sources, including weathering of borates, sewage effluents, coal combustion, use of cleaning compounds, and agrochemicals. The present study was designed to generate data on acute and chronic boron toxicity in support of an update of water quality standards in Illinois, USA. We examined the acute toxicity of boron to eight different freshwater organisms including a fish, an insect, two crustaceans, and four bivalve mollusks. To our knowledge, this is the first study to present data on the toxicity of boron to freshwater mollusks. We also sought to clarify whether hardness or pH affect boron toxicity to aquatic life, and to quantify chronic effect levels in two freshwater species. Sensitivity among the various species ranged widely, with the fathead minnow (Pimephales promelas) being the most sensitive. Neither pH nor hardness had a consistent effect on acute boron toxicity to two crustaceans (Ceriodaphnia dubia and Hyalella azteca), but we observed evidence that chloride reduces boron toxicity to H. azteca. The fathead minnow, while more acutely sensitive than the other species, had a lower acute to chronic ratio than did H. azteca, which had reduced reproduction at 13 mg/L. While we do not know the extent to which the eight tested species represent the range of sensitivities of native but untested species in Illinois, the current water quality standard for Illinois (1 mg/L) is conservative with regard to the native species tested thus far. Copyright © 2011 SETAC.

Development of an acute toxicity test with the tropical marine amphipod Parhyale hawaiensis.

PubMed

Artal, Mariana Coletty; Dos Santos, Amanda; Henry, Theodore Burdick; Umbuzeiro, Gisela de Aragão

2018-03-01

There is a lack of suitable tropical marine species for ecotoxicity tests. An attractive model organism for ecotoxicology is the marine amphipod Parhyale hawaiensis, which is already a model for genetic and developmental studies. This species is widespread, can tolerate changes in salinity, is easy to handle and is representative of circumtropical regions. The aim of this work was to describe standardized procedures for laboratory husbandry, define conditions for acute toxicity tests, and to provide acute toxicity test results for some reference toxicants. Culturing conditions for the organism in the laboratory were established in reconstituted seawater (30 ± 2 salinity), 24 ± 2 °C, photoperiod 12/12 h light/dark. Acute toxicity test procedures were developed for 96 h-exposure time, and organisms at ages <7 days. The miniaturized version of the test, based on 96-well microplates and 200 µL of exposure media provided consistent results compared to larger exposure volumes (80-mL vials protocol). Acute toxicity of Ag, Cd, Cu, Zn and ammonia determined for P. hawaiensis were consistent to previous results for other marine amphipods. We conclude that P. hawaiensis can be successfully cultured in standardized conditions and be effectively used in acute toxicity testing. Further development and use of this model will enable standardized and reproducible ecotoxicology investigations in understudied and vulnerable tropical marine ecosystems.

An evaluation of acute toxicity of colloidal silver nanoparticles.

PubMed

Maneewattanapinyo, Pattwat; Banlunara, Wijit; Thammacharoen, Chuchaat; Ekgasit, Sanong; Kaewamatawong, Theerayuth

2011-11-01

Tests for acute oral toxicity, eye irritation, corrosion and dermal toxicity of colloidal silver nanoparticles (AgNPs) were conducted in laboratory animals following OECD guidelines. Oral administration of AgNPs at a limited dose of 5,000 mg/kg produced neither mortality nor acute toxic signs throughout the observation period. Percentage of body weight gain of the mice showed no significant difference between control and treatment groups. In the hematological analysis, there was no significant difference between mice treated with AgNPs and controls. Blood chemistry analysis also showed no differences in any of the parameter examined. There was neither any gross lesion nor histopathological change observed in various organs. The results indicated that the LD(50) of colloidal AgNPs is greater than 5,000 mg/kg body weight. In acute eye irritation and corrosion study, no mortality and toxic signs were observed when various doses of colloidal AgNPs were instilled in guinea pig eyes during 72 hr observation period. However, the instillation of AgNPs at 5,000 ppm produced transient eye irritation during early 24 hr observation time. No any gross abnormality was noted in the skins of the guinea pigs exposed to various doses of colloidal AgNPs. In addition, no significant AgNPs exposure relating to dermal tissue changes was observed microscopically. In summary, these findings of all toxicity tests in this study suggest that colloidal AgNPs could be relatively safe when administered to oral, eye and skin of the animal models for short periods of time.

Effects of light on the cytotoxicity and genotoxicity of benzo(a)pyrene and an oil refinery effluent in the newt

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

Fernandez, M.; l`Haridon, J.

1994-12-31

The genotoxicity and/or toxicity of benzo(a)pyrene (BaP) were evaluated under different lighting conditions in larvae and embryos of the newt Pleurodeles waltl. Visible light alone, UVA alone, or BaP alone had no toxic effects on the larvae. Conversely, toxic effects were observed in animals exposed to BaP + daylight, or BaP + UVA. The genotoxicity of BaP (50 ppb) was halved by its previous exposure to UVA, and was abolished at the lowest concentration (12.5 ppb). In other experiments, the larvae were exposed alternatively to BaP or Irr BaP (18 hours in dark) and UVA (6 hr in water), everymore » day for 8 days. All animals that had accumulated non-irradiated BaP (50 ppb) showed signs of severe toxicity, and 90% died before the end of the test. On the other hand, irradiated BaP (50 ppb) was a 4-fold less toxic and half as genotoxic as non-irradiated BaP. In addition, exposure of the animals to UVA alone for 4 days prior to treatment with BaP did not affect the genotoxicity or toxicity of this hydrocarbon. In the dark, the embryotoxicity of BaP was markedly attenuated by the presence of the jelly coats. Although UVA alone did not affect growth of the embryos, the toxicity of BaP was enhanced by the combined action of the two agents together or in succession (BaP + UVA or BaP then UVA). Larvae were treated with an oil refinery effluent (EF). At 125 ml/l, EF was not found to be genotoxic in the dark. However, in animals exposed to both EF and UVA, there was a progressive increase in level of micronucleated erythrocytes with increasing duration of daily exposure to UVA. Moreover, the genotoxic potential of irradiated EF + UVA was systematically below that of non-irradiated EF + UVA for all durations of exposure to ultraviolet light. Irradiation of this type of effluent might help reduce its harmful effects on aquatic species. Our results also suggest that metabolic activation is not necessary for hydrocarbons to induce toxic effects. 51 refs., 5 tabs., 3 figs.« less

Modulation of genotoxicity and endocrine disruptive effects of malathion by dietary honeybee pollen and propolis in Nile tilapia (Oreochromis niloticus)

PubMed Central

Kandiel, Mohamed M.M.; El-Asely, Amel M.; Radwan, Hasnaa A.; Abbass, Amany A.

2013-01-01

The present study aimed at verifying the usefulness of dietary 2.5% bee-pollen (BP) or propolis (PROP) to overcome the genotoxic and endocrine disruptive effects of malathion polluted water in Oreochromis niloticus (O. niloticus). The acute toxicity test was conducted in O. niloticus in various concentrations (0–8 ppm); mortality rate was assessed daily for 96 h. The 96 h-LC50 was 5 ppm and therefore 1/5 of the median lethal concentration (1 ppm) was used for chronic toxicity assessment. In experiment (1), fish (n = 8/group) were kept on a diet (BP/PROP or without additive (control)) and exposed daily to malathion in water at concentration of 5 ppm for 96 h “acute toxicity experiment”. Protective efficiency against the malathion was verified through chromosomal aberrations (CA), micronucleus (MN) and DNA-fragmentation assessment. Survival rate in control, BP and PROP groups was 37.5%, 50.0% and 100.0%, respectively. Fish in BP and PROP groups showed a significant (P < 0.05) reduction in the frequency of CA (57.14% and 40.66%), MN (53.13% and 40.63%) and DNA-fragmentation (53.08% and 30.00%). In experiment (2), fish (10 males and 5 females/group) were kept on a diet with/without BP for 21 days before malathion-exposure in water at concentration of 0 ppm (control) or 1 ppm (Exposed) for further 10 days “chronic toxicity experiment”. BP significantly (P < 0.05) reduced CA (86.33%), MN (82.22%) and DNA-fragmentation (93.11%), prolonged the sperm motility when exposed to 0.01 ppm of pollutant in vitro and increased the estradiol level in females comparing to control. In conclusion, BP can be used as a feed additive for fish prone to be raised in integrated fish farms or cage culture due to its potency to chemo-protect against genotoxicity and sperm-teratogenicity persuaded by malathion-exposure. PMID:25685536

Genotoxic potential of montmorillonite clay mineral and alteration in the expression of genes involved in toxicity mechanisms in the human hepatoma cell line HepG2.

PubMed

Maisanaba, Sara; Hercog, Klara; Filipic, Metka; Jos, Ángeles; Zegura, Bojana

2016-03-05

Montmorillonite, also known as Cloisite(®)Na(+) (CNa(+)), is a natural clay with a wide range of well-documented and novel applications, such as pharmaceutical products or food packaging. Although considered a low toxic product, the expected increased exposure to CNa(+) arises concern on the potential consequences on human and environmental health especially as its genotoxicity has scarcely been investigated so far. Thus, we investigated, for the first time, the influence of non-cytotoxic concentrations of CNa(+) (15.65, 31.25 and 62.5 μg/mL) on genomic instability of human hepatoma cell line (HepG2) by determining the formation of micronuclei (MNi), nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) with the Cytokinesis block micronucleus cytome assay. Further on we studied the influence of CNa(+) on the expression of several genes involved in toxicity mechanisms using the real-time quantitative PCR. The results showed that CNa(+) increased the number of MNi, while the numbers of NBUDs and NPBs were not affected. In addition it deregulated genes in all the groups studied, mainly after longer time of exposure. These findings provide the evidence that CNa(+) is potentially genotoxic. Therefore further studies that will elucidate the molecular mechanisms involved in toxic activity of CNa(+) are needed for hazard identification and human safety assessment. Copyright © 2015 Elsevier B.V. All rights reserved.

Alternative approaches for identifying acute systemic toxicity: Moving from research to regulatory testing.

PubMed

Hamm, Jon; Sullivan, Kristie; Clippinger, Amy J; Strickland, Judy; Bell, Shannon; Bhhatarai, Barun; Blaauboer, Bas; Casey, Warren; Dorman, David; Forsby, Anna; Garcia-Reyero, Natàlia; Gehen, Sean; Graepel, Rabea; Hotchkiss, Jon; Lowit, Anna; Matheson, Joanna; Reaves, Elissa; Scarano, Louis; Sprankle, Catherine; Tunkel, Jay; Wilson, Dan; Xia, Menghang; Zhu, Hao; Allen, David

2017-06-01

Acute systemic toxicity testing provides the basis for hazard labeling and risk management of chemicals. A number of international efforts have been directed at identifying non-animal alternatives for in vivo acute systemic toxicity tests. A September 2015 workshop, Alternative Approaches for Identifying Acute Systemic Toxicity: Moving from Research to Regulatory Testing, reviewed the state-of-the-science of non-animal alternatives for this testing and explored ways to facilitate implementation of alternatives. Workshop attendees included representatives from international regulatory agencies, academia, nongovernmental organizations, and industry. Resources identified as necessary for meaningful progress in implementing alternatives included compiling and making available high-quality reference data, training on use and interpretation of in vitro and in silico approaches, and global harmonization of testing requirements. Attendees particularly noted the need to characterize variability in reference data to evaluate new approaches. They also noted the importance of understanding the mechanisms of acute toxicity, which could be facilitated by the development of adverse outcome pathways. Workshop breakout groups explored different approaches to reducing or replacing animal use for acute toxicity testing, with each group crafting a roadmap and strategy to accomplish near-term progress. The workshop steering committee has organized efforts to implement the recommendations of the workshop participants. Copyright © 2017 Elsevier Ltd. All rights reserved.

Alternative Approaches for Identifying Acute Systemic Toxicity: Moving from Research to Regulatory Testing

PubMed Central

Hamm, Jon; Sullivan, Kristie; Clippinger, Amy J.; Strickland, Judy; Bell, Shannon; Bhhatarai, Barun; Blaauboer, Bas; Casey, Warren; Dorman, David; Forsby, Anna; Garcia-Reyero, Natàlia; Gehen, Sean; Graepel, Rabea; Hotchkiss, Jon; Lowit, Anna; Matheson, Joanna; Reaves, Elissa; Scarano, Louis; Sprankle, Catherine; Tunkel, Jay; Wilson, Dan; Xia, Menghang; Zhu, Hao; Allen, David

2017-01-01

Acute systemic toxicity testing provides the basis for hazard labeling and risk management of chemicals. A number of international efforts have been directed at identifying non-animal alternatives for in vivo acute systemic toxicity tests. A September 2015 workshop, Alternative Approaches for Identifying Acute Systemic Toxicity: Moving from Research to Regulatory Testing, reviewed the state-of-the-science of non-animal alternatives for this testing and explored ways to facilitate implementation of alternatives. Workshop attendees included representatives from international regulatory agencies, academia, nongovernmental organizations, and industry. Resources identified as necessary for meaningful progress in implementing alternatives included compiling and making available high-quality reference data, training on use and interpretation of in vitro and in silico approaches, and global harmonization of testing requirements. Attendees particularly noted the need to characterize variability in reference data to evaluate new approaches. They also noted the importance of understanding the mechanisms of acute toxicity, which could be facilitated by the development of adverse outcome pathways. Workshop breakout groups explored different approaches to reducing or replacing animal use for acute toxicity testing, with each group crafting a roadmap and strategy to accomplish near-term progress. The workshop steering committee has organized efforts to implement the recommendations of the workshop participants. PMID:28069485

METABOLISM, GENOTOXICITY, AND CARCINOGENICITY OF COMFREY

PubMed Central

Mei, Nan; Guo, Lei; Fu, Peter P.; Fuscoe, James C.; Luan, Yang; Chen, Tao

2018-01-01

Comfrey has been consumed by humans as a vegetable and a tea and used as an herbal medicine for more than 2000 years. Comfrey, however, produces hepatotoxicity in livestock and humans and carcinogenicity in experimental animals. Comfrey contains as many as 14 pyrrolizidine alkaloids (PA), including 7-acetylintermedine, 7-acetyllycopsamine, echimidine, intermedine, lasiocarpine, lycopsamine, myoscorpine, symlandine, symphytine, and symviridine. The mechanisms underlying comfrey-induced genotoxicity and carcinogenicity are still not fully understood. The available evidence suggests that the active metabolites of PA in comfrey interact with DNA in liver endothelial cells and hepatocytes, resulting in DNA damage, mutation induction, and cancer development. Genotoxicities attributed to comfrey and riddelliine (a representative genotoxic PA and a proven rodent mutagen and carcinogen) are discussed in this review. Both of these compounds induced similar profiles of 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-derived DNA adducts and similar mutation spectra. Further, the two agents share common mechanisms of drug metabolism and carcinogenesis. Overall, comfrey is mutagenic in liver, and PA contained in comfrey appear to be responsible for comfrey-induced toxicity and tumor induction. PMID:21170807

A Challenging Case of Acute Mercury Toxicity

PubMed Central

Alghoula, Faysal; Holewinski, Christopher

2018-01-01

Background Mercury exists in multiple forms: elemental, organic, and inorganic. Its toxic manifestations depend on the type and magnitude of exposure. The role of colonoscopic decompression in acute mercury toxicity is still unclear. We present a case of acute elemental mercury toxicity secondary to mercury ingestion, which markedly improved with colonoscopic decompression. Clinical Case A 54-year-old male presented to the ED five days after ingesting five ounces (148 cubic centimeters) of elemental mercury. Examination was only significant for a distended abdomen. Labs showed elevated serum and urine mercury levels. An abdominal radiograph showed radiopaque material throughout the colon. Succimer and laxatives were initiated. The patient had recurrent bowel movements, and serial radiographs showed interval decrease of mercury in the descending colon with interval increase in the cecum and ascending colon. Colonoscopic decompression was done successfully. The colon was evacuated, and a repeat radiograph showed decreased hyperdense material in the colon. Three months later, a repeat radiograph showed no hyperdense material in the colon. Conclusion Ingested elemental mercury can be retained in the colon. Although there are no established guidelines for colonoscopic decompression, our patient showed significant improvement. We believe further studies on this subject are needed to guide management practices. PMID:29559996

Zebrafish (Danio rerio) Models To Assess Acute, Developmental, And Neurodevelopmental Toxicity

EPA Science Inventory

Zebrafish (Danio rerio) acute, developmental, and neurodevelopmental model systems have been developed to assess both known and unknown environmental contaminants. Developmental toxicity is assessed using death and dysmorphology as endpoints, whereas neurodevelopmental toxicity ...

Prevalidation of an Acute Inhalation Toxicity Test Using the EpiAirway In Vitro Human Airway Model.

PubMed

Jackson, George R; Maione, Anna G; Klausner, Mitchell; Hayden, Patrick J

2018-06-01

Introduction: Knowledge of acute inhalation toxicity potential is important for establishing safe use of chemicals and consumer products. Inhalation toxicity testing and classification procedures currently accepted within worldwide government regulatory systems rely primarily on tests conducted in animals. The goal of the current work was to develop and prevalidate a nonanimal ( in vitro ) test for determining acute inhalation toxicity using the EpiAirway™ in vitro human airway model as a potential alternative for currently accepted animal tests. Materials and Methods: The in vitro test method exposes EpiAirway tissues to test chemicals for 3 hours, followed by measurement of tissue viability as the test endpoint. Fifty-nine chemicals covering a broad range of toxicity classes, chemical structures, and physical properties were evaluated. The in vitro toxicity data were utilized to establish a prediction model to classify the chemicals into categories corresponding to the currently accepted Globally Harmonized System (GHS) and the Environmental Protection Agency (EPA) system. Results: The EpiAirway prediction model identified in vivo rat-based GHS Acute Inhalation Toxicity Category 1-2 and EPA Acute Inhalation Toxicity Category I-II chemicals with 100% sensitivity and specificity of 43.1% and 50.0%, for GHS and EPA acute inhalation toxicity systems, respectively. The sensitivity and specificity of the EpiAirway prediction model for identifying GHS specific target organ toxicity-single exposure (STOT-SE) Category 1 human toxicants were 75.0% and 56.5%, respectively. Corrosivity and electrophilic and oxidative reactivity appear to be the predominant mechanisms of toxicity for the most highly toxic chemicals. Conclusions: These results indicate that the EpiAirway test is a promising alternative to the currently accepted animal tests for acute inhalation toxicity.

Consensus Modeling of Oral Rat Acute Toxicity

EPA Science Inventory

An acute toxicity dataset (oral rat LD50) with about 7400 compounds was compiled from the ChemIDplus database. This dataset was divided into a modeling set and a prediction set. The compounds in the prediction set were selected so that they were present in the modeling set used...

An interspecies correlation model to predict acute dermal toxicity of plant protection products to terrestrial life stages of amphibians using fish acute toxicity and bioconcentration data.

PubMed

Weltje, Lennart; Janz, Philipp; Sowig, Peter

2017-12-01

This paper presents a model to predict acute dermal toxicity of plant protection products (PPPs) to terrestrial amphibian life stages from (regulatory) fish data. By combining existing concepts, including interspecies correlation estimation (ICE), allometric relations, lethal body burden (LBB) and bioconcentration modelling, an equation was derived that predicts the amphibian median lethal dermal dose (LD 50 ) from standard acute toxicity values (96-h LC 50 ) for fish and bioconcentration factors (BCF) in fish. Where possible, fish BCF values were corrected to 5% lipid, and to parent compound. Then, BCF values were adjusted to an exposure duration of 96 h, in case steady state took longer to be achieved. The derived correlation equation is based on 32 LD 50 values from acute dermal toxicity experiments with 15 different species of anuran amphibians, comprising 15 different PPPs. The developed ICE model can be used in a screening approach to estimate the acute risk to amphibian terrestrial life stages from dermal exposures to PPPs with organic active substances. This has the potential to reduce unnecessary testing of vertebrates. Copyright © 2017 Elsevier Ltd. All rights reserved.

Antigenotoxic effect of acute, subacute and chronic treatments with Amazonian camu-camu (Myrciaria dubia) juice on mice blood cells.

PubMed

da Silva, Francisco Carlos; Arruda, Andrelisse; Ledel, Alexandre; Dauth, Cíntia; Romão, Nathalia Faria; Viana, Rafaele Nazário; de Barros Falcão Ferraz, Alexandre; Picada, Jaqueline Nascimento; Pereira, Patrícia

2012-07-01

Myrciaria dubia, a plant native to the Amazon region, stands out as a fruit rich in vitamin C and other metabolites with nutritional potential. We evaluated the antioxidant, genotoxic and antigenotoxic potential of M. dubia juice on blood cells of mice after acute, subacute and chronic treatments. Flavonoids and vitamin C present in the fruit of M. dubia were quantified. In vitro antioxidant activity was evaluated by DPPH assay. Blood samples were collected for analysis after treatment, and the alkaline comet assay was used to analyze the genotoxic and antigenotoxic activity (ex vivo analysis using H(2)O(2)). The amount of vitamin C per 100mL of M. dubia was 52.5mg. DPPH assay showed an antioxidant potential of the fruit. No M. dubia concentration tested exerted any genotoxic effect on mice blood cells. In the ex vivo test, the juice demonstrated antigenotoxic effect, and acute treatment produced the most significant results. After the treatments, there was no evidence of toxicity or death. In conclusion, our data show that M. dubia juice has antigenotoxic and antioxidant activities, though with no genotoxicity for blood cells. Nevertheless, more in-depth studies should be conducted to assess the safety of this fruit for human consumption. Copyright © 2012 Elsevier Ltd. All rights reserved.

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.

Setting Occupational Exposure Limits for Genotoxic Substances in the Pharmaceutical Industry.

PubMed

Lovsin Barle, Ester; Winkler, Gian Christian; Glowienke, Susanne; Elhajouji, Azeddine; Nunic, Jana; Martus, Hans-Joerg

2016-05-01

In the pharmaceutical industry, genotoxic drug substances are developed for life-threatening indications such as cancer. Healthy employees handle these substances during research, development, and manufacturing; therefore, safe handling of genotoxic substances is essential. When an adequate preclinical dataset is available, a risk-based decision related to exposure controls for manufacturing is made following a determination of safe health-based limits, such as an occupational exposure limit (OEL). OELs are calculated for substances based on a threshold dose-response once a threshold is identified. In this review, we present examples of genotoxic mechanisms where thresholds can be demonstrated and OELs can be calculated, including a holistic toxicity assessment. We also propose a novel approach for inhalation Threshold of Toxicological Concern (TTC) limit for genotoxic substances in cases where the database is not adequate to determine a threshold. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Acute toxicity of diphacinone in Northern bobwhite: Effects on survival and blood clotting

USGS Publications Warehouse

Rattner, Barnett A.; Horak, Katherine E.; Warner, Sarah E.; Johnston, John J.

2010-01-01

The anticoagulant rodenticide diphacinone was slightly toxic (acute oral LD50 2014 mg/kg) to Northern bobwhite (Colinus virginianus) in a 14-day acute toxicity trial. Precise and sensitive assays of blood clotting (prothrombin time, Russell?s Viper venom time, and thrombin clotting time) were adapted for use in quail, and this combination of assays is recommended to measure the effects of anticoagulant rodenticides. A single oral sublethal dose of diphacinone (434 mg/kg body weight) prolonged clotting time at 48 h post-dose compared to controls. At 783 mg/kg (approximate LD02), clotting time was prolonged at both 24 and 48 h post-dose. Prolongation of in vitro clotting time reflects impaired coagulation complex activity, and was detected before overt signs of toxicity were apparent at the greatest dosages (2868 and 3666 mg/kg) in the acute toxicity trial. These clotting time assays and toxicity data will assist in the development of a pharmacodynamic model to predict toxicity, and also facilitate rodenticide hazard and risk assessments in avian species.

Acute toxicity and chemical evaluation of coking wastewater under biological and advanced physicochemical treatment processes.

PubMed

Dehua, Ma; Cong, Liu; Xiaobiao, Zhu; Rui, Liu; Lujun, Chen

2016-09-01

This study investigated the changes of toxic compounds in coking wastewater with biological treatment (anaerobic reactor, anoxic reactor and aerobic-membrane bioreactor, A1/A2/O-MBR) and advanced physicochemical treatment (Fenton oxidation and activated carbon adsorption) stages. As the biological treatment stages preceding, the inhibition effect of coking wastewater on the luminescence of Vibrio qinghaiensis sp. Nov. Q67 decreased. Toxic units (TU) of coking wastewater were removed by A1/A2/O-MBR treatment process, however approximately 30 % TU remained in the biologically treated effluent. There is a tendency that fewer and fewer residual organic compounds could exert equal acute toxicity during the biological treatment stages. Activated carbon adsorption further removed toxic pollutants of biologically treated effluent but the Fenton effluent increased acute toxicity. The composition of coking wastewater during the treatment was evaluated using the three-dimensional fluorescence spectra, gas chromatography-mass spectrometry (GC-MS). The organic compounds with high polarity were the main cause of acute toxicity in the coking wastewater. Aromatic protein-like matters in the coking wastewater with low biodegradability and high toxicity contributed mostly to the remaining acute toxicity of the biologically treated effluents. Chlorine generated from the oxidation process was responsible for the acute toxicity increase after Fenton oxidation. Therefore, the incorporation of appropriate advanced physicochemical treatment process, e.g., activated carbon adsorption, should be implemented following biological treatment processes to meet the stricter discharge standards and be safer to the environment.

The acute toxicity of major ion salts to Ceriodaphnia dubia: III. Mathematical models for mixture toxicity

EPA Science Inventory

Based on previous research on the acute toxicity of major ions (Na+, K+, Ca2+, Mg2+, Cl, SO42, and HCO3/CO32) to C. dubia, two mathematical models were developed for predicting the LC50 for any ion mixture, excluding those dominated by K toxicity. One model addresses a mechanism...

Acute and Subacute Toxicity of Safranal, a Constituent of Saffron, in Mice and Rats

PubMed Central

Hosseinzadeh, Hossein; Sadeghi Shakib, Saied; Khadem Sameni, Abbas; Taghiabadi, Elahe

2013-01-01

The acute and sub-acute toxicity of safranal were studied in rat and mice within 2 and 21 days after exposure, respectively. For subacute toxicity, changes in weight as well as biochemical, hematological and pathological parameters were studied. The intraperitoneal LD50 values of safranal were 1.48 mL/kg in male mice, 1.88 mL/kg in female mice and 1.50 mL/kg in male rats. Oral LD50 values were 21.42 mL/kg in male mice, 11.42 mL/kg in female mice and 5.53 mL/kg in male rats. For subacute toxicity, safranal was administered orally to male rats once daily for 21 days. In hematological tests, a significant decrease in RBC counts, hematocrit, hemoglobin and platelets were observed. Safranal decreased cholesterol, triglyceride and alkalin phosphatase. Lactate dehydrogenase and serum urea nitrogen were increased by safranal. Histological studies indicated that safranal did not have any toxic effect on the heart, liver and spleen. However, pathological changes were seen in the kidney and lung. According to LD50 values, safranal was low-toxic in acute intraperitoneal route and practically non-toxic in acute oral administration in both mice and rats. In subacute toxicity, safranal changed some hematological and biochemical parameters. PMID:24250576

A comparative assessment of the acute inhalation toxicity of vanadium compounds.

PubMed

Rajendran, N; Seagrave, J C; Plunkett, L M; MacGregor, J A

2016-11-01

Vanadium compounds have become important in industrial processes, resulting in workplace exposure potential and are present in ambient air as a result of fossil fuel combustion. A series of acute nose-only inhalation toxicity studies was conducted in both rats and mice in order to obtain comparative data on the acute toxicity potential of compounds used commercially. V 2 O 3 , V 2 O 4 , and V 2 O 5 , which have different oxidation states (+3, +4, +5, respectively), were delivered as micronized powders; the highly water-soluble and hygroscopic VOSO 4 (+4) could not be micronized and was instead delivered as a liquid aerosol from an aqueous solution. V 2 O 5 was the most acutely toxic micronized powder in both species. Despite its lower overall percentage vanadium content, a liquid aerosol of VOSO 4 was more toxic than the V 2 O 5 particles in mice, but not in rats. These data suggest that an interaction of characteristics, i.e., bioavailability, solubility and oxidation state, as well as species sensitivity, likely affect the toxicity potential of vanadium compounds. Based on clinical observations and gross necropsy findings, the lung appeared to be the target organ for all compounds. The level of hazard posed will depend on the specific chemical form of the vanadium. Future work to define the inhalation toxicity potential of vanadium compounds of various oxidation states after repeated exposures will be important in understanding how the physico-chemical and biological characteristics of specific vanadium compounds interact to affect toxicity potential and the potential risks posed to human health.

Prevalidation of an Acute Inhalation Toxicity Test Using the EpiAirway In Vitro Human Airway Model

PubMed Central

Jackson, George R.; Maione, Anna G.; Klausner, Mitchell

2018-01-01

Abstract Introduction: Knowledge of acute inhalation toxicity potential is important for establishing safe use of chemicals and consumer products. Inhalation toxicity testing and classification procedures currently accepted within worldwide government regulatory systems rely primarily on tests conducted in animals. The goal of the current work was to develop and prevalidate a nonanimal (in vitro) test for determining acute inhalation toxicity using the EpiAirway™ in vitro human airway model as a potential alternative for currently accepted animal tests. Materials and Methods: The in vitro test method exposes EpiAirway tissues to test chemicals for 3 hours, followed by measurement of tissue viability as the test endpoint. Fifty-nine chemicals covering a broad range of toxicity classes, chemical structures, and physical properties were evaluated. The in vitro toxicity data were utilized to establish a prediction model to classify the chemicals into categories corresponding to the currently accepted Globally Harmonized System (GHS) and the Environmental Protection Agency (EPA) system. Results: The EpiAirway prediction model identified in vivo rat-based GHS Acute Inhalation Toxicity Category 1–2 and EPA Acute Inhalation Toxicity Category I–II chemicals with 100% sensitivity and specificity of 43.1% and 50.0%, for GHS and EPA acute inhalation toxicity systems, respectively. The sensitivity and specificity of the EpiAirway prediction model for identifying GHS specific target organ toxicity-single exposure (STOT-SE) Category 1 human toxicants were 75.0% and 56.5%, respectively. Corrosivity and electrophilic and oxidative reactivity appear to be the predominant mechanisms of toxicity for the most highly toxic chemicals. Conclusions: These results indicate that the EpiAirway test is a promising alternative to the currently accepted animal tests for acute inhalation toxicity. PMID:29904643

Acute oral toxicity and biodistribution study of zinc-aluminium-levodopa nanocomposite

NASA Astrophysics Data System (ADS)

Kura, Aminu Umar; Saifullah, Bullo; Cheah, Pike-See; Hussein, Mohd Zobir; Azmi, Norazrina; Fakurazi, Sharida

2015-03-01

Layered double hydroxide (LDH) is an inorganic-organic nano-layered material that harbours drug between its two-layered sheets, forming a sandwich-like structure. It is attracting a great deal of attention as an alternative drug delivery (nanodelivery) system in the field of pharmacology due to their relative low toxic potential. The production of these nanodelivery systems, aimed at improving human health through decrease toxicity, targeted delivery of the active compound to areas of interest with sustained release ability. In this study, we administered zinc-aluminium-LDH-levodopa nanocomposite (ZAL) and zinc-aluminium nanocomposite (ZA) to Sprague Dawley rats to evaluate for acute oral toxicity following OECD guidelines. The oral administration of ZAL and ZA at a limit dose of 2,000 mg/kg produced neither mortality nor acute toxic signs throughout 14 days of the observation. The percentage of body weight gain of the animals showed no significant difference between control and treatment groups. Animal from the two treated groups gained weight continuously over the study period, which was shown to be significantly higher than the weight at the beginning of the study ( P < 0.05). Biochemical analysis of animal serum showed no significant difference between rats treated with ZAL, ZA and controls. There was no gross lesion or histopathological changes observed in vital organs of the rats. The results suggested that ZAL and ZA at 2,000 mg/kg body weight in rats do not induce acute toxicity in the animals. Elemental analysis of tissues of treated animals demonstrated the wider distribution of the nanocomposite including the brain. In summary, findings of acute toxicity tests in this study suggest that zinc-aluminium nanocomposite intercalated with and the un-intercalated were safe when administered orally in animal models for short periods of time. It also highlighted the potential distribution ability of Tween-80 coated nanocomposite after oral administration.

Cytotoxicity and genotoxicity property of hydroxyapatite-mullite eluates.

PubMed

Kalmodia, Sushma; Sharma, Vyom; Pandey, Alok K; Dhawan, Alok; Basu, Bikramjit

2011-02-01

Long-term biomedical applications of implant materials may cause osteolysis, aseptic losing and toxicity. Therefore, we investigated the cytotoxic and genotoxic potential of hydroxyapatite (HA) mullite eluates in L929 mouse fibroblast cells. The spark plasma sintered HA-20% mullite biocomposite (HA20M) were ground using mortar and pestle as well as ball milling. The cells were exposed for 6 h to varying concentrations (10, 25, 50, 75 and 100%) of the eluates of HA-20% mullite (87 nm), HA (171 nm) and mullite (154 nm). The scanning electron microscopy and MTT assay revealed the concentration dependent toxicity of H20M eluate at and above 50%. The analysis of the DNA damaging potential of HA, mullite and HA20M eluates using Comet assay demonstrated a significant DNA damage by HA20M which was largely related to the presence of mullite. The results collectively demonstrate the cytotoxic and genotoxic potential of HA20M eluate in L929 cells is dependent on particle size, concentration and composition.

ACUTE BEHAVIORAL TOXICITY OF SULFOLANE: INFLUENCE OF HYPOTHERMIA

EPA Science Inventory

Sulfolane is a solvent which produces hypothermia and decreased oxygen consumption following acute exposure. In the present experiment, the author investigated effects of sulfolane on a behavioral measure of toxicity at ambient temperatures which would either prevent or facilitat...

Potential genotoxic and cytotoxicity of emamectin benzoate in human normal liver cells

PubMed Central

Zhang, Zhijie; Zhao, Xinyu; Qin, Xiaosong

2017-01-01

Pesticide residue inducing cancer-related health problems draw people more attention recently. Emamectin benzoate (EMB) has been widely used in agriculture around the world based on its specificity targets. Although potential risk and the molecular mechanism of EMB toxicity to human liver has not been well-characterized. Unlike well-reported toxicity upon central nervous system, potential genotoxic and cytotoxicity of EMB in human liver cell was ignored and very limited. In this study, we identify genotoxicity and cytotoxicity of EMB to human normal liver cells (QSG7701 cell line) in vitro. We demonstrate that EMB inhibited the viability of QSG7701 cells and induced the DNA damage. Established assays of cytotoxicity were performed to characterize the mechanism of EMB toxicity on QSG7701 cells. Typical chromatin condensation and DNA fragmentation indicated the apoptosis of QSG7701 cells induced by EMB. And the intracellular biochemical results demonstrated that EMB-enhanced apoptosis of QSG7701 cells concurrent with generated ROS, a loss of mitochondrial membrane potential, the cytochrome-c release, up regulate the Bax/Bcl-2 and the activation of caspase-9/-3. Our results of EMB induces the death of QSG7701 cells maybe via mitochondrial-mediated intrinsic apoptotic pathways would contribute to promote the awareness of EMB as an extensive used pesticide to human being effects and reveal the underlying mechanisms of potential genotoxic. PMID:29137255

Potential genotoxic and cytotoxicity of emamectin benzoate in human normal liver cells.

PubMed

Zhang, Zhijie; Zhao, Xinyu; Qin, Xiaosong

2017-10-10

Pesticide residue inducing cancer-related health problems draw people more attention recently. Emamectin benzoate (EMB) has been widely used in agriculture around the world based on its specificity targets. Although potential risk and the molecular mechanism of EMB toxicity to human liver has not been well-characterized. Unlike well-reported toxicity upon central nervous system, potential genotoxic and cytotoxicity of EMB in human liver cell was ignored and very limited. In this study, we identify genotoxicity and cytotoxicity of EMB to human normal liver cells (QSG7701 cell line) in vitro . We demonstrate that EMB inhibited the viability of QSG7701 cells and induced the DNA damage. Established assays of cytotoxicity were performed to characterize the mechanism of EMB toxicity on QSG7701 cells. Typical chromatin condensation and DNA fragmentation indicated the apoptosis of QSG7701 cells induced by EMB. And the intracellular biochemical results demonstrated that EMB-enhanced apoptosis of QSG7701 cells concurrent with generated ROS, a loss of mitochondrial membrane potential, the cytochrome-c release, up regulate the Bax/Bcl-2 and the activation of caspase-9/-3. Our results of EMB induces the death of QSG7701 cells maybe via mitochondrial-mediated intrinsic apoptotic pathways would contribute to promote the awareness of EMB as an extensive used pesticide to human being effects and reveal the underlying mechanisms of potential genotoxic.

Study on acute toxicity of amoxicillin wastewater to Zebrafish

NASA Astrophysics Data System (ADS)

Xie, Weifang; Shen, Hongyan

2017-12-01

The main research in this paper is to obtain the effect of pharmaceutical wastewater on the acute toxicity of Zebrafish. The experimental method of exposure is used in this research. Experiments were carried out with different groups of pharmaceutical wastewater. Zebrafish was cultivated in a five liter fish tank. In the experiment, according to mortality, initially a 96h preliminary test was carried out at exposure concentrations to determine if the amoxicillin wastewater was toxic and to define the concentration range (24h LC100, 96h LC0) to be employed in the definitive tests. Based on the half lethal concentration of Zebrafish, the acute toxicity of amoxicillin wastewater to Zebrafish was calculated and the toxicity grade of wastewater was determined. In the experiment, the Zebrafish was exposed with amoxicillin wastewater during 96h. The 24h, 48h, 72h and 96h LC50 of amoxicillin wastewater on the Zebrafish were 63.10%, 53.70%, 41.69% and 40.74%, respectively. At 96h, the test time is the longest, and the value of LC50 is the smallest. In the observation period of 96 hours, the LC50 of amoxicillin wastewater were in the range of 40% ~ 60% and the value of Tua is 1 ~ 2. It indicates amoxicillin wastewater is low toxic wastewater when the experimental time is shorter than 48h, amoxicillin wastewater is moderate toxicity wastewater when the experimental time is higher than 48h. According to the experimental data, with the exposure time and the volume percentage of amoxicillin wastewater increases, the mortality rate of Zebrafish is gradually increased and the toxicity of amoxicillin wastewater increases. It indicates that the toxicity of amoxicillin wastewater is the biggest and the effect of wastewater on Zebrafish is greatest. In some ways, the toxicity of amoxicillin wastewater can be affected by the test time.

Acute and sub acute toxicity and efficacy studies of Hippophae rhamnoides based herbal antioxidant supplement.

PubMed

Ali, Rashid; Ali, Raisuddin; Jaimini, Abhinav; Nishad, Dhruv Kumar; Mittal, Gaurav; Chaurasia, Om Prakash; Kumar, Raj; Bhatnagar, Aseem; Singh, Shashi Bala

2012-01-01

Present study was carried out to evaluate acute and subacute toxicity and efficacy of Seabuckthorn (Hippophae rhamnoides) based herbal antioxidant supplement (HAOS). In vivo toxicity studies were performed in male balb 'C' mice by oral administration. Acute toxicity study was done at doses ranging from 2000 to 10 000 mg/ kg while in subacute studies, HAOS was given at doses of 2000, 4000, and 8000 mg/kg body weight. Animals were observed for any toxic sign and symptoms periodically. At completion of study animals were sacrificed; their hematological, biochemical parameters were analyzed and histopathology of vital organs was done. In vivo efficacy studies in human volunteers were done and the levels of vitamin A and Vitamin C in blood samples were analyzed in comparison to a similar commercially available formulation. No mortality and any clinical signs of toxicity were found in HAOS administered group of animals. There were no significant alterations in hematological and biochemical parameters. Histopathological analysis of vital organs showed normal architecture in all the HAOS administered groups. Human studies showed an increase of 32% and 172% in Vitamin A and Vitamin C levels respectively in term of bioavailability. The data obtained indicate no toxicity of this antioxidant supplement up to the highest dose studied. Efficacy in terms of increased bioavailability of vitamin A and C in human volunteers indicates the clinical usefulness of the supplement.

Non-animal Replacements for Acute Toxicity Testing.

PubMed

Barker-Treasure, Carol; Coll, Kevin; Belot, Nathalie; Longmore, Chris; Bygrave, Karl; Avey, Suzanne; Clothier, Richard

2015-07-01

Current approaches to predicting adverse effects in humans from acute toxic exposure to cosmetic ingredients still heavily necessitate the use of animals under EU legislation, particularly in the context of the REACH system, when cosmetic ingredients are also destined for use in other industries. These include the LD50 test, the Up-and-Down Procedure and the Fixed Dose Procedure, which are regarded as having notable scientific deficiencies and low transferability to humans. By expanding on previous in vitro tests, such as the animal cell-based 3T3 Neutral Red Uptake (NRU) assay, this project aims to develop a truly animal-free predictive test for the acute toxicity of cosmetic ingredients in humans, by using human-derived cells and a prediction model that does not rely on animal data. The project, funded by Innovate UK, will incorporate the NRU assay with human dermal fibroblasts in animal product-free culture, to generate an in vitro protocol that can be validated as an accepted replacement for the currently available in vivo tests. To date, the project has successfully completed an assessment of the robustness and reproducibility of the method, by using sodium lauryl sulphate (SLS) as a positive control, and displaying analogous results to those of the original studies with mouse 3T3 cells. Currently, the testing of five known ingredients from key groups (a surfactant, a preservative, a fragrance, a colour and an emulsifier) is under way. The testing consists of initial range-finding runs followed by three valid runs of a main experiment with the appropriate concentration ranges, to generate IC50 values. Expanded blind trials of 20 ingredients will follow. Early results indicate that this human cell-based test holds the potential to replace aspects of in vivo animal acute toxicity testing, particularly with reference to cosmetic ingredients. 2015 FRAME.

Saving two birds with one stone: using active substance avian acute toxicity data to predict formulated plant protection product toxicity.

PubMed

Maynard, Samuel K; Edwards, Peter; Wheeler, James R

2014-07-01

Environmental safety assessments for exposure of birds require the provision of acute avian toxicity data for both the pesticidal active substance and formulated products. As an example, testing on the formulated product is waived in Europe using an assessment of data for the constituent active substance(s). This is often not the case globally, because some countries require acute toxicity tests with every formulated product, thereby triggering animal welfare concerns through unnecessary testing. A database of 383 formulated products was compiled from acute toxicity studies conducted with northern bobwhite (Colinus virginianus) or Japanese quail (Coturnix japonica) (unpublished regulatory literature). Of the 383 formulated products studied, 159 contained only active substances considered functionally nontoxic (median lethal dose [LD50] > highest dose tested). Of these, 97% had formulated product LD50 values of >2000 mg formulated product/kg (limit dose), indicating that no new information was obtained in the formulated product study. Furthermore, defined (point estimated) LD50 values for formulated products were compared with LD50 values predicted from toxicity of the active substance(s). This demonstrated that predicted LD50 values were within 2-fold and 5-fold of the measured formulated product LD50 values in 90% and 98% of cases, respectively. This analysis demonstrates that avian acute toxicity testing of formulated products is largely unnecessary and should not be routinely required to assess avian acute toxicity. In particular, when active substances are known to be functionally nontoxic, further formulated product testing adds no further information and unnecessarily increases bird usage in testing. A further analysis highlights the fact that significant reductions (61% in this dataset) could be achieved by using a sequential testing design (Organisation for Economic Co-operation and Development test guideline 223), as opposed to established single

Comparative In Vitro Toxicity Evaluation of Heavy Metals (Lead, Cadmium, Arsenic, and Methylmercury) on HT-22 Hippocampal Cell Line.

PubMed

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

2018-07-01

Heavy metals are considered some of the most toxic environmental pollutants. Exposure to heavy metals including lead (Pb), cadmium (Cd), arsenic (As), and methyl mercury (MeHg) has long been known to cause damage to human health. Many recent studies have supported the hippocampus as the major target for these four metals for inflicting cognitive dysfunction. In the present study, we proposed hippocampal relevant in vitro toxicity of Pb, Cd, As, and MeHg in HT-22 cell line. This study reports, initially, cytotoxic effects in acute, subchronic, chronic exposures. We further investigated the mechanistic potency of DNA damage and apoptosis damage with the observed cytotoxicity. The genotoxicity and apoptosis were measured by using the comet assay, annexin-V FTIC / propidium iodide (PI) assay, respectively. The results of cytotoxicity assay clearly demonstrated significant concentration and time-dependent effects on HT-22 cell line. The genotoxic and apoptosis effects also concentration-dependent fashion with respect to their potency in the range of IC 10 -IC 30, maximal level of damage observed in MeHg. In conclusion, the obtained result suggests concentration and potency-dependent response; the maximal level of toxicity was observed in MeHg. These novel findings support that Pb, Cd, As, and MeHg induce cytotoxic, genotoxic, and apoptotic effects on HT-22 cells in potency-dependent manner; MeHg> As> Cd> Pb. Therefore, the toxicity of Pb, Cd, As, and MeHg could be useful for knowing the common underlying molecular mechanism, and also for estimating the mixture impacts on HT-22 cell line.

ACUTE TOXICITY OF PARA-NONYLPHENOL TO SALTWATER ANIMALS

EPA Science Inventory

?para-Nonylphenol (PNP), a mixture of alkylphenols used in producing nonionic surfactants, is distributed widely in surface waters and aquatic sediments, where it can affect saltwater species. This article describes a database for acute toxicity of PNP derived for calculating a n...

Acute Toxicity and Cytotoxicity of Pereskia aculeata, a Highly Nutritious Cactaceae Plant.

PubMed

Silva, Debora O; Seifert, Mauricio; Nora, Fabiana R; Bobrowski, Vera L; Freitag, Rogerio A; Kucera, Heidi R; Nora, Leonardo; Gaikwad, Nilesh W

2017-04-01

Pereskia aculeata is a Cactaceae plant with valuable nutritional properties, including terrific amounts of protein, minerals, vitamins, and fiber. However, P. aculeata is reported to contain antinutrients and alkaloids in its leaves. In addition, in a study on growth and development, Wistar rats fed with P. aculeata and casein as protein source grew less than the control group (fed with casein only). Therefore, in this study, we evaluated, for the first time, the oral acute toxicity of P. aculeata in rats and also the cytotoxicity behavior of the plant on lettuce seeds. The acute toxicity research was carried out using dried P. aculeata ethanolic extract, in three different doses, administered by gavage to 24 female Wistar rats. The rats were then examined for signs of toxicity, food intake, body weight, and fecal excretion fluctuations, as well as histopathological alterations, using eight different body tissues. The acute toxicity study did not show any difference among the groups in either clinical evaluation or histopathological analyses. For the cytotoxicity study, dried P. aculeata ethanolic extract was applied on lettuce seeds in five different concentrations. These seeds were evaluated for germination, root and shoot length, and mitotic index. The results show that P. aculeata extract affects lettuce root and shoot growth, but not germination or mitotic index. In conclusion, the acute toxicity on rats and the cytogenotoxicity on lettuce of P. aculeata are neglectable, validating the potential of this plant to be used as a functional food.

Three dimensional quantitative structure-toxicity relationship modeling and prediction of acute toxicity for organic contaminants to algae.

PubMed

Jin, Xiangqin; Jin, Minghao; Sheng, Lianxi

2014-08-01

Although numerous chemicals have been identified to have significant toxicological effect on aquatic organisms, there is still lack of a reliable, high-throughput approach to evaluate, screen and monitor the presence of organic contaminants in aquatic system. In the current study, we proposed a synthetic pipeline to automatically model and predict the acute toxicity of chemicals to algae. In the procedure, a new alignment-free three dimensional (3D) structure characterization method was described and, with this method, several 3D-quantitative structure-toxicity relationship (3D-QSTR) models were developed, from which two were found to exhibit strong internal fitting ability and high external predictive power. The best model was established by Gaussian process (GP), which was further employed to perform extrapolation on a random compound library consisting of 1014 virtually generated substituted benzenes. It was found that (i) substitution number can only exert slight influence on chemical׳s toxicity, but low-substituted benzenes seem to have higher toxicity than those of high-substituted entities, and (ii) benzenes substituted by nitro group and halogens exhibit high acute toxicity as compared to other substituents such as methyl and carboxyl groups. Subsequently, several promising candidates suggested by computational prediction were assayed by using a standard algal growth inhibition test. Consequently, four substituted benzenes, namely 2,3-dinitrophenol, 2-chloro-4-nitroaniline, 1,2,3-trinitrobenzene and 3-bromophenol, were determined to have high acute toxicity to Scenedesmus obliquus, with their EC50 values of 2.5±0.8, 10.5±2.1, 1.4±0.2 and 42.7±5.4μmol/L, respectively. Copyright © 2014 Elsevier Ltd. All rights reserved.

Genotoxic effects of environmental endocrine disruptors on the aquatic insect Chironomus riparius evaluated using the comet assay.

PubMed

Martínez-Paz, Pedro; Morales, Mónica; Martínez-Guitarte, José Luis; Morcillo, Gloria

2013-12-12

Genotoxicity is one of the most important toxic endpoints in chemical toxicity testing and environmental risk assessment. The aim of this study was to evaluate the genotoxic potential of various environmental pollutants frequently found in aquatic environments and characterized by their endocrine disrupting activity. Monitoring of DNA damage was undertaken after in vivo exposures of the aquatic larvae of the midge Chironomus riparius, a model organism that represents an abundant and ecologically relevant macroinvertebrate, widely used in freshwater toxicology. DNA-induced damage, resulting in DNA fragmentation, was quantified by the comet assay after short (24 h) and long (96 h) exposures to different concentrations of the selected toxicants: bisphenol A (BPA), nonylphenol (NP), pentachlorophenol (PCP), tributyltin (TBT) and triclosan (TCS). All five compounds were found to have genotoxic activity as demonstrated by significant increases in all the comet parameters (%DNA in tail, tail length, tail moment and Olive tail moment) at all tested concentrations. Persistent exposure did not increase the extent of DNA damage, except for TCS at the highest concentration, but generally there was a reduction in DNA damage thought to be associated with the induction of the detoxification processes and repairing mechanisms. Comparative analysis showed differences in the genotoxic potential between the chemicals, as well as significant time and concentration-dependent variations, which most likely reflect differences in the ability to repair DNA damage under the different treatments. The present report demonstrates the sensitivity of the benthic larvae of C. riparius to these environmental genotoxins suggesting its potential as biomonitor organism in freshwater ecosystems. The results obtained about the DNA-damaging potential of these environmental pollutants reinforce the need for additional studies on the genotoxicity of endocrine active substances that, by linking genotoxic

Critique on the use of the standardized avian acute oral toxicity test for first generation anticoagulant rodenticides

USGS Publications Warehouse

Vyas, Nimish B.; Rattner, Barnett A.

2012-01-01

Avian risk assessments for rodenticides are often driven by the results of standardized acute oral toxicity tests without regards to a toxicant's mode of action and time course of adverse effects. First generation anticoagulant rodenticides (FGARs) generally require multiple feedings over several days to achieve a threshold concentration in tissue and cause adverse effects. This exposure regimen is much different than that used in the standardized acute oral toxicity test methodology. Median lethal dose values derived from standardized acute oral toxicity tests underestimate the environmental hazard and risk of FGARs. Caution is warranted when FGAR toxicity, physiological effects, and pharmacokinetics derived from standardized acute oral toxicity testing are used for forensic confirmation of the cause of death in avian mortality incidents and when characterizing FGARs' risks to free-ranging birds.

Protective effect of thymoquinone against diazinon-induced hematotoxicity, genotoxicity and immunotoxicity in rats.

PubMed

Danaei, Gholam Hassan; Karami, Mohammad

2017-10-01

Several studies have shown that oxidative stress and cell damage can occur in the very early stages of diazinon (DZN) exposure. The present study was designed to determine the beneficial effect of thymoquinone (Thy), the main component of Nigella sativa (black seed or black cumin) against DZN immunotoxicity, hematotoxicity and genotoxicity in rats. In the present experimental study, 48 male Wistar rats were randomly divided into six groups, (eight per group) as follows: control (receiving corn oil as the DZN solvent), DZN (20mg/kg), Thy (10mg/kg), Thy (2.5mg/kg)+DZN, Thy (5mg/kg)+DZN and Thy (10mg/kg)+DZN. After four weeks of treatment, the hematological parameters of red blood cells (RBCs), white blood cells (WBCs), hemoglobin (Hb), hematocrit (Hct) and platelets (PLTs) were evaluated. The evaluation of genotoxicity was carried out using the micronucleus assay. For measurement of cytokine production, interferon gamma (IFN-γ), interleukin 10 (IL10) and interleukin 4 (IL4) were chosen as immunotoxicity indicators of DZN toxicity. DZN was found to decrease RBCs, WBCs, Hb, Hct, PLTs, butyrl- and acetyl-cholinesterase activity and I FN-γ and increased the micronucleus indices of IL10 and IL4 as compared with the control group. Treatment with Thy reduced DZN hematotoxicity and immunotoxicity, but, significantly, did not prevent genotoxicity. This study showed that Thy (without the significant effect on genotoxicity) decreased the hematological toxicity, immunotoxicity and butyrl and acetyl cholinesterase activity induced by DZN. The success of Thy supplementation against DZN toxicity can be attributed to the antioxidant effects of its constituents. Copyright © 2017. Published by Elsevier B.V.

Mutagenicity and Acute Oral Toxicity Test for Herbal Poultry Feed Supplements.

PubMed

Srinivasa Rao, Boddapati; Chandrasekaran, C V; Srikanth, H S; Sasikumar, Murugan; Edwin Jothie, R; Haseena, Begum; Bharathi, Bethapudi; Selvam, Ramasamy; Prashanth, D'Souza

2018-01-01

Herbal products are being used and trusted globally for thousands of years for their health benefits and limited side effects. Globally, a general belief amongst the consumers is that herbal supplements are always safe because they are "natural." But later, research reveals that they may not be safe. This raises concern on their safety and implications for their use as feed supplement or medicine. Toxicity testing can reveal some of the risks that may be associated with use of herbs, therefore avoiding potential harmful effects. The present study was designed to investigate five poultry feed supplements (PFS), EGMAX® (to revitalize ovarian activity), FEED-X ™ (feed efficiency enhancer), KOLIN PLUS ™ (natural replacer of synthetic choline chloride), PHYTOCEE® (natural defence enhancer), and STODI® (to prevent and control loose droppings), for their possible mutagenicity and toxicity. Bacterial reverse mutation (BRMT) and acute oral toxicity tests were employed to assess the PFS for their possible mutagenicity and toxicity. Results indicated that the PFS were devoid of mutagenic effects in BRMT and showed higher safety profile in rodent acute oral toxicity test.

Assessment of toxicity and genotoxicity of low doses of 5-fluorouracil in zebrafish (Danio rerio) two-generation study.

PubMed

Kovács, Róbert; Csenki, Zsolt; Bakos, Katalin; Urbányi, Béla; Horváth, Ákos; Garaj-Vrhovac, Vera; Gajski, Goran; Gerić, Marko; Negreira, Noelia; López de Alda, Miren; Barceló, Damià; Heath, Ester; Kosjek, Tina; Žegura, Bojana; Novak, Matjaž; Zajc, Irena; Baebler, Špela; Rotter, Ana; Ramšak, Živa; Filipič, Metka

2015-06-15

Residues of anti-neoplastic drugs represent new and emerging pollutants in aquatic environments. Many of these drugs are genotoxic, and it has been postulated that they can cause adverse effects in aquatic ecosystems. 5-Fluorouracil (5-FU) is one of the most extensively used anti-neoplastic drugs in cancer therapy, and this article describes the results of the first investigation using a two-generation toxicity study design with zebrafish (Danio rerio). Exposure of zebrafish to 5-FU (0.01, 1.0 and 100 μg/L) was initiated with adult zebrafish (F0 generation) and continued through the hatchings and adults of the F1 generation, and the hatchings of the F2 generation, to day 33 post-fertilisation. The exposure did not affect survival, growth and reproduction of the zebrafish; however, histopathological changes were observed in the liver and kidney, along with genotoxic effects, at all 5-FU concentrations. Increases in DNA damage determined using the comet assay were significant in the liver and blood cells, but not in the gills and gonads. In erythrocytes, a significant, dose-dependent increase in frequency of micronuclei was observed at all 5-FU concentrations. Whole genome transcriptomic analysis of liver samples of F1 generation zebrafish exposed to 0.01 μg/L and 1 μg/L 5-FU revealed dose-dependent increases in the number of differentially expressed genes, including up-regulation of several DNA-damage-responsive genes and oncogenes (i.e., jun, myca). Although this chronic exposure to environmentally relevant concentrations of 5-FU did not affect the reproduction of the exposed zebrafish, it cannot be excluded that 5-FU can lead to degenerative changes, including cancers, which over long-term exposure of several generations might affect fish populations. The data from this study contribute to a better understanding of the potential consequences of chronic exposure of fish to low concentrations of anti-neoplastic drugs, and they demonstrate that further studies

Safety assessment of the Cistanche tubulosa health food product Memoregain®: Genotoxicity and 28-day repeated dose toxicity test.

PubMed

Liao, Po-Lin; Li, Ching-Hao; Tse, Ling-Shan; Kang, Jaw-Jou; Cheng, Yu-Wen

2018-06-07

The pharmacological effects of Cistanches Herba, known as "Ginseng of the desert", have been extensively studied. In this study, we aimed to assess the genotoxic and oral toxic effects of the Cistanche tubulosa health food product Memoregain ® using in vitro and in vivo tests. Ames tests using five strains of Salmonella typhimurium showed no signs of increased reverse mutation upon exposure to Memoregain ® up to a concentration of 5 mg/plate. Exposure of Chinese hamster ovary (CHO-K1) cells to Memoregain ® did not increase the frequency of chromosomal aberrations in vitro. Moreover, Memoregain ® treatment did not affect the proportions of immature to total erythrocytes or the number of micronuclei in the immature erythrocytes of ICR mice. Additionally, after 28-day repeated oral dose toxicity tests (0, 0.15, 0.3, and 0.5g/kg body weight) in rats, no observable adverse effects were found. These toxicological assessments supported the safety of Memoregain ® for human consumption. Copyright © 2018 Elsevier Ltd. All rights reserved.

Acute and sub acute toxicity and efficacy studies of Hippophae rhamnoides based herbal antioxidant supplement

PubMed Central

Ali, Rashid; Ali, Raisuddin; Jaimini, Abhinav; Nishad, Dhruv Kumar; Mittal, Gaurav; Chaurasia, Om Prakash; Kumar, Raj; Bhatnagar, Aseem; Singh, Shashi Bala

2012-01-01

Objectives: Present study was carried out to evaluate acute and subacute toxicity and efficacy of Seabuckthorn (Hippophae rhamnoides) based herbal antioxidant supplement (HAOS). Materials and Methods: In vivo toxicity studies were performed in male balb ‘C’ mice by oral administration. Acute toxicity study was done at doses ranging from 2000 to 10 000 mg/ kg while in subacute studies, HAOS was given at doses of 2000, 4000, and 8000 mg/kg body weight. Animals were observed for any toxic sign and symptoms periodically. At completion of study animals were sacrificed; their hematological, biochemical parameters were analyzed and histopathology of vital organs was done. In vivo efficacy studies in human volunteers were done and the levels of vitamin A and Vitamin C in blood samples were analyzed in comparison to a similar commercially available formulation. Results: No mortality and any clinical signs of toxicity were found in HAOS administered group of animals. There were no significant alterations in hematological and biochemical parameters. Histopathological analysis of vital organs showed normal architecture in all the HAOS administered groups. Human studies showed an increase of 32% and 172% in Vitamin A and Vitamin C levels respectively in term of bioavailability. Conclusion: The data obtained indicate no toxicity of this antioxidant supplement up to the highest dose studied. Efficacy in terms of increased bioavailability of vitamin A and C in human volunteers indicates the clinical usefulness of the supplement. PMID:23087514

Acute toxicity and its dosimetric correlates for high-risk prostate cancer treated with moderately hypofractionated radiotherapy

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

Arunsingh, Moses; Mallick, Indranil, E-mail: imallick@gmail.com; Prasath, Sriram

Aims: To report the acute toxicity and the dosimetric correlates after moderately hypofractionated radiotherapy for localized prostate cancer. Methods: A total of 101 patients with localized prostate cancer were treated with image-guided intensity-modulated radiation therapy. Patients were treated to 65 Gy/25 Fr/5 weeks (n = 18), or 60 Gy/20 Fr/4 weeks (n = 83). Most (82.2%) had high-risk or pelvic node-positive disease. Acute toxicity was assessed using Radiation Therapy Oncology Group (RTOG) acute morbidity scoring criteria. Dose thresholds for acute rectal and bladder toxicity were identified. Results: The incidence of acute grade 2 GI toxicity was 20.8%, and grade 2more » genitourinary (GU) toxicity was 6.9%. No Grade 3 to 4 toxicity occurred. Small bowel toxicity was uncommon (Gr 2 = 4%). The 2 Gy equivalent doses (EQD2) to the rectum and bladder (α/β = 3) calculated showed that the absolute doses were more consistent predictors of acute toxicities than the relative volumes. Those with grade 2 or more GI symptoms had significantly higher V{sub EQD2-60} {sub Gy} (13.2 vs 9.9 cc, p = 0.007) and V{sub EQD2-50} {sub Gy} (20.6 vs 15.4 cc, p = 0.005). Those with grade 2 or more GU symptoms had significantly higher V{sub EQD2-70} {sub Gy} (30.4 vs 18.4 cc, p = 0.001) and V{sub EQD2-65} {sub Gy} (44.0 vs 28.8 cc, p = 0.001). The optimal cutoff value for predicting grade 2 acute proctitis, for V{sub EQD2-60} {sub Gy} was 9.7 cc and for V{sub EQD2-50} {sub Gy} was 15.9 cc. For grade 2 GU symptoms, the threshold values were 23.6 cc for V{sub EQD2-70} {sub Gy} and 38.1 cc for V{sub EQD2-65} {sub Gy}. Conclusions: Hypofractionated radiotherapy for prostate cancer is well tolerated and associated with manageable acute side effects. The absolute dose-volume parameters of rectum and bladder predict for acute toxicities.« less

Acute lethal toxicity of environmental pollutants to aquatic organisms.

PubMed

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

2002-06-01

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

Study of serum interaction with a cationic nanoparticle: Implications for in vitro endocytosis, cytotoxicity and genotoxicity.

PubMed

Merhi, Maysaloun; Dombu, Christophe Youta; Brient, Alizée; Chang, Jiang; Platel, Anne; Le Curieux, Frank; Marzin, Daniel; Nesslany, Fabrice; Betbeder, Didier

2012-02-14

We used well-characterized and positively charged nanoparticles (NP(+)) to investigate the importance of cell culture conditions, specifically the presence of serum and proteins, on NP(+) physicochemical characteristics, and the consequences for their endocytosis and genotoxicity in bronchial epithelial cells (16HBE14o-). NP(+) surface charge was significantly reduced, proportionally to NP(+)/serum and NP(+)/BSA ratios, while NP(+) size was not modified. Microscopy studies showed high endocytosis of NP(+) in 16HBE14o-, and serum/proteins impaired this internalization in a dose-dependent manner. Toxicity studies showed no cytotoxicity, even for very high doses of NP(+). No genotoxicity was observed with classic comet assay while primary oxidative DNA damage was observed when using the lesion-specific repair enzyme, formamidopyrimidine DNA-glycosylase (FPG). The micronucleus test showed NP(+) genotoxicity only for very high doses that cannot be attained in vivo. The low toxicity of these NP(+) might be explained by their high exocytosis from 16HBE14o- cells. Our results confirm the importance of serum and proteins on nanoparticles endocytosis and genotoxicity. Copyright © 2011 Elsevier B.V. All rights reserved.

INTER-SPECIES MODELS FOR ACUTE AQUATIC TOXICITY BASED ON MECHANISM OF ACTION

EPA Science Inventory

This presentation will provide interspecies QSARs for acute toxicity to 17 aquatic species, such as fish, snail, tadpole, hydrozoan, crustacean, insect larvae, and bacteria developed using 5,000 toxic effect results for approximately 2400 chemicals.

A subchronic toxicity study in rats and genotoxicity tests with an aqueous ethylcellulose dispersion.

PubMed

DeMerlis, C C; Schoneker, D R; Borzelleca, J F

2005-09-01

Surelease Aqueous Ethylcellulose Dispersion is an excipient used as a modified release coating for beads, granules, non-pariels, drug crystals and tablets and for taste masking applications for drug products and dietary supplement products. A study was conducted to assess the toxicity of spray-dried Surelease when administered orally, via dietary admixture, to Sprague-Dawley CD rats (20/sex/group) at dose levels of 0, 2000, 3500, and 5000 mg/kg/day for a period of at least 3 months. After 3 months of treatment, all rats scheduled for terminal sacrifice were killed and selected organs were weighed. Complete macroscopic examinations and histopathological evaluation of selected tissues were conducted on all animals. Neuropathological evaluations were performed on 5 animals/sex/group. No mortality occurred during the study. Clinical observations, ophthalmology, body weight and food consumption, hematology, coagulation, clinical chemistry, urinalysis, functional observational assessments, motor activity, organ weights and ratios and macroscopic and microscopic observations did not reveal any significant, consistent, dose-dependent test article-related adverse effects. The NOAEL (no-observed-adverse-effect-level) is 5000 mg/kg/day, the highest dose tested. A series of genotoxicity tests were conducted with Surelease. Surelease showed no evidence of mutagenic activity in the bacterial reverse mutation test with and without metabolic activation and in the in vitro cell mutation assay under the experimental conditions employed. Surelease did not show any evidence of causing chromosome damage or bone marrow cell toxicity when administered by gavage in the mouse micronucleus in vivo test procedure. These findings support the safety of Surelease for use as an excipient.

Feasibility and Acute Toxicity of Hypofractionated Radiation in Large-breasted Patients

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

Dorn, Paige L., E-mail: pdorn@radonc.uchicago.edu; Corbin, Kimberly S.; Al-Hallaq, Hania

Purpose: To determine the feasibility of and acute toxicity associated with hypofractionated whole breast radiation (HypoRT) after breast-conserving surgery in patients excluded from or underrepresented in randomized trials comparing HypoRT with conventional fractionation schedules. Methods and Materials: A review was conducted of all patients consecutively treated with HypoRT at University of Chicago. All patients were treated to 42.56 Gy in 2.66 Gy daily fractions in either the prone or supine position. Planning was performed in most cases using wedges and large segments or a 'field-in-field' technique. Breast volume was estimated using volumetric measurements of the planning target volume (PTV). Dosimetricmore » parameters of heterogeneity (V105, V107, V110, and maximum dose) were recorded for each treatment plan. Acute toxicity was scored for each treated breast. Results: Between 2006 and 2010, 78 patients were treated to 80 breasts using HypoRT. Most women were overweight or obese (78.7%), with a median body mass index of 29.2 kg/m{sup 2}. Median breast volume was 1,351 mL. Of the 80 treated breasts, the maximum acute skin toxicity was mild erythema or hyperpigmentation in 70.0% (56/80), dry desquamation in 21.25% (17/80), and focal moist desquamation in 8.75% (7/80). Maximum acute toxicity occurred after the completion of radiation in 31.9% of patients. Separation >25 cm was not associated with increased toxicity. Breast volume was the only patient factor significantly associated with moist desquamation on multivariable analysis (p = 0.01). Patients with breast volume >2,500 mL experienced focal moist desquamation in 27.2% of cases compared with 6.34% in patients with breast volume <2,500 mL (p = 0.03). Conclusions: HypoRT is feasible and safe in patients with separation >25 cm and in patients with large breast volume when employing modern planning and positioning techniques. We recommend counseling regarding expected increases in skin toxicity in women

Ecotoxicity assessment of artificial groundwater recharge with reclaimed water: a pilot-scale study.

PubMed

Zhang, Xue; Zhao, Xuan

2013-11-01

A demonstration of artificial groundwater recharge with tertiary effluent was evaluated using a set of bioassays (acute toxicity to Daphnia, genotoxicity, estrogenic and antiestrogenic toxicity). Around 95 % genotoxicity and 53 % antiestrogenicity were removed from the feed water by ozonation, whereas significant reduction of acute toxicity to Daphnia magna was achieved during a 3 days vadose soil treatment. The toxicity was further removed to the same level as the local groundwater during a 20 days aquifer soil treatment. The pilot study has shown that ozonation and soil treatments can improve the quality of municipal wastewater treatment plant effluents for possible groundwater recharge purposes.

In silico assessment of the acute toxicity of chemicals: recent advances and new model for multitasking prediction of toxic effect.

PubMed

Kleandrova, Valeria V; Luan, Feng; Speck-Planche, Alejandro; Cordeiro, M Natália D S

2015-01-01

The assessment of acute toxicity is one of the most important stages to ensure the safety of chemicals with potential applications in pharmaceutical sciences, biomedical research, or any other industrial branch. A huge and indiscriminate number of toxicity assays have been carried out on laboratory animals. In this sense, computational approaches involving models based on quantitative-structure activity/toxicity relationships (QSAR/QSTR) can help to rationalize time and financial costs. Here, we discuss the most significant advances in the last 6 years focused on the use of QSAR/QSTR models to predict acute toxicity of drugs/chemicals in laboratory animals, employing large and heterogeneous datasets. The advantages and drawbacks of the different QSAR/QSTR models are analyzed. As a contribution to the field, we introduce the first multitasking (mtk) QSTR model for simultaneous prediction of acute toxicity of compounds by considering different routes of administration, diverse breeds of laboratory animals, and the reliability of the experimental conditions. The mtk-QSTR model was based on artificial neural networks (ANN), allowing the classification of compounds as toxic or non-toxic. This model correctly classified more than 94% of the 1646 cases present in the whole dataset, and its applicability was demonstrated by performing predictions of different chemicals such as drugs, dietary supplements, and molecules which could serve as nanocarriers for drug delivery. The predictions given by the mtk-QSTR model are in very good agreement with the experimental results.

A combined evaluation of the characteristics and acute toxicity of antibiotic wastewater.

PubMed

Yu, Xin; Zuo, Jiane; Li, Ruixia; Gan, Lili; Li, Zaixing; Zhang, Fei

2014-08-01

The conventional parameters and acute toxicities of antibiotic wastewater collected from each treatment unit of an antibiotic wastewater treatment plant have been investigated. The investigation of the conventional parameters indicated that the antibiotic wastewater treatment plant performed well under the significant fluctuation in influent water quality. The results of acute toxicity indicated that the toxicity of antibiotic wastewater could be reduced by 94.3 percent on average after treatment. However, treated antibiotic effluents were still toxic to Vibrio fischeri. The toxicity of antibiotic production wastewater could be attributed to the joint effects of toxic compound mixtures in wastewater. Moreover, aerobic biological treatment processes, including sequencing batch reactor (SBR) and aerobic biofilm reactor, played the most important role in reducing toxicity by 92.4 percent. Pearson׳s correlation coefficients revealed that toxicity had a strong and positive linear correlation with organic substances, nitrogenous compounds, S(2-), volatile phenol, cyanide, As, Zn, Cd, Ni and Fe. Ammonia nitrogen (NH4(+)) was the greatest contributor to toxicity according to the stepwise regression method. The multiple regression model was a good fit for [TU50-15 min] as a function of [NH₄(+)] with the determination coefficient of 0.981. Copyright © 2014 Elsevier Inc. All rights reserved.

Review of genotoxicity biomonitoring studies of glyphosate-based formulations

PubMed Central

Kier, Larry D.

2015-01-01

Abstract Human and environmental genotoxicity biomonitoring studies involving exposure to glyphosate-based formulations (GBFs) were reviewed to complement an earlier review of experimental genotoxicity studies of glyphosate and GBFs. The environmental and most of the human biomonitoring studies were not informative because there was either a very low frequency of GBF exposure or exposure to a large number of pesticides without analysis of specific pesticide effects. One pesticide sprayer biomonitoring study indicated there was not a statistically significant relationship between frequency of GBF exposure reported for the last spraying season and oxidative DNA damage. There were three studies of human populations in regions of GBF aerial spraying. One study found increases for the cytokinesis-block micronucleus endpoint but these increases did not show statistically significant associations with self-reported spray exposure and were not consistent with application rates. A second study found increases for the blood cell comet endpoint at high exposures causing toxicity. However, a follow-up to this study 2 years after spraying did not indicate chromosomal effects. The results of the biomonitoring studies do not contradict an earlier conclusion derived from experimental genotoxicity studies that typical GBFs do not appear to present significant genotoxic risk under normal conditions of human or environmental exposures. PMID:25687244

Acute oral toxicity of Pereskia bleo and Pereskia grandifolia in mice

PubMed Central

Sim, K. S.; Sri Nurestri, A. M.; Sinniah, S. K.; Kim, K. H.; Norhanom, A. W.

2010-01-01

Pereskia bleo and Pereskia grandifolia, belonging to the botanical family Cactaceae, have been traditionally used by the locals in Malaysia for treatment of various ailments. The current study reports the outcome of acute oral toxicity investigation of Pereskia bleo and Pereskia grandifolia, on ICR mice. No mortalities or evidence of adverse effects have been observed in ICR mice following acute oral administration at the highest dose of 2500 mg/ kg crude extracts of Pereskia bleo and Pereskia grandifolia. This is the first report on the acute oral toxicity of Pereskia bleo and Pereskia grandifolia and the findings of this study are in agreement with those of in vitro experiments and thus provide scientific validation on the use of the leaves of Pereskia bleo and Pereskia grandifolia. PMID:20548939

Genotoxicity and subchronic toxicity evaluation of dried Euglena gracilis ATCC PTA-123017.

PubMed

Simon, Ryan R; Vo, Trung D; Levine, Robert

2016-10-01

Euglena gracilis is a microalga capable of synthesizing various nutrients of interest in human and animal nutrition. When cultivated aerobically in the dark, Euglena synthesize paramylon, a storage polysaccharide comprised of high molecular weight beta-1,3-D-glucose polymers organized in cytoplasmic granules. Beta-glucans have been shown to have immune modulation effects, including anti-microbial, anti-tumor, and anti-oxidant properties, and metabolic effects, such as regulation of cholesterol and blood sugar levels. Preparations of E. gracilis and paramylon may therefore have potential utility as functional food ingredients for human and animal nutrition. A battery of toxicological studies was conducted on a dried preparation of E. gracilis and paramylon to support their safe food use. The dried alga was not genotoxic in a bacterial reverse mutation test and mammalian micronucleus test. In the subchronic toxicity study, rats were provided E. gracilis in the diet at levels of 0, 12,500, 25,000 or 50,000 ppm. Paramylon was provided at a concentration of 50,000 ppm. No effects that could be attributable to treatment were observed in clinical observations, body weight, food consumption, ophthalmology, hematology and clinical chemistry, urinalysis, and macroscopic and microscopic findings. A NOAEL of 50,000 ppm in the diet was determined for both ingredients. Copyright © 2016 Elsevier Inc. All rights reserved.

Acute radiotherapy toxicity in 57 dogs with gross and microscopic mast cell tumours.

PubMed

Blackwood, L; Tanis, J B; Harper, A; Amores-Fuster, I; Killick, D R; Finotello, R

2018-05-15

Mast cell tumours (MCTs) are commonly treated with radiation therapy, most often in a microscopic disease setting. Poorer outcomes are expected in patients with gross disease, and irradiation of gross disease may be associated with greater toxicity. The aim of this study was to compare acute radiation adverse events (AE) in dogs with gross and microscopic MCTs receiving radiotherapy. Fifty-seven dogs were included, 28 with gross disease and 29 with microscopic. In order to assess mucosal and skin toxicity, patients were assigned to 2 groups: head (29 patients, 14 patients with gross and 15 microscopic) and other sites (28 patients, 14 each). All were treated with external beam radiotherapy, and toxicity assessed at the end of treatment and 10 to 14 days later (first recheck). All patients developed some acute radiation toxicity by the end of the course. However, there was no difference in the severity of toxicity between gross and microscopic disease in either site group at either time point. The only variable associated with an increased frequency of grade 2 or 3 toxicity at the first recheck was the use of prednisolone prior to radiotherapy (P = .05). No other factors were identified which were associated with increased toxicity. For the head group, the site of highest grade toxicity was mucosa or, if included in the field, nasal planum, which was often more severely affected than the mucosa. No significant late toxicity was identified. Two dogs developed acute haematemesis during the radiotherapy course, but both completed the course without further events. © 2018 John Wiley & Sons Ltd.

Acute toxicity of chlorantraniliprole to non-target crayfish (Procambarus clarkii) associated with rice-crayfish cropping systems.

PubMed

Barbee, Gary C; McClain, W Ray; Lanka, Srinivas K; Stout, Michael J

2010-09-01

Chlorantraniliprole, a novel anthranilic diamide insecticide, was recently introduced into the United States where rice-crayfish crop rotations are practiced to control rice water weevil (Lissorhoptrus oryzophilus Kuschel) infestations. Chlorantraniliprole has high margins of mammalian safety and excellent insecticidal efficacy, but its toxicity to non-target crayfish is uncertain. In this study, the acute toxicity of chlorantraniliprole to the red swamp crayfish Procambarus clarkii Girard was determined using aquatic and feeding assays. The aquatic 96 h median lethal toxicity (LC(50)) data indicate that technical-grade chlorantraniliprole is highly toxic (US EPA category) to crayfish with an LC(50) of 951 microg L(-1) (95% CL = 741-1118 microg L(-1)). A no observed effect concentration (NOEC) of 480 microg L(-1) was recorded. Neither the 36 day chronic feeding study, where crayfish fed on chlorantraniliprole-treated rice seed in aquaria, nor the 144 h acute feeding test, where crayfish fed on rice seeds treated with chlorantraniliprole, produced mortality or abnormal behavior. Chlorantraniliprole is three orders of magnitude less acutely toxic to P. clarkii than lambda-cyhalothrin and etofenprox, two pyrethroid insecticides also used in rice, and is less likely to cause acute crayfish toxicity in rice pond ecosystems. Based on acute toxicity data, the use of chlorantraniliprole should be more compatible with rice-crayfish crop rotations than pyrethroids. (c) 2010 Society of Chemical Industry.

Acute oral and percutaneous toxicity of pesticides to mallards: Correlations with mammalian toxicity data

USGS Publications Warehouse

Hudson, R.H.; Haegele, M.A.; Tucker, R.K.

1979-01-01

Acute oral (po) and 24-hr percutaneous (perc) LD50 values for 21 common pesticides (19 anticholinesterases, of which 18 were organophosphates, and one was a carbamate; one was an organochlorine central nervous system stimulant; and one was an organonitrogen pneumotoxicant) were determined in mallards (Anas platyrhynchos). Three of the pesticides tested were more toxic percutaneously than orally. An index to the percutaneous hazard of a pesticide, the dermal toxicity index (DTI = po LD50/perc LD50 ? 100), was also calculated for each pesticide. These toxicity values in mallards were compared with toxicity data for rats from the literature. Significant positive correlations were found between log po and log percutaneous LD50 values in mallards (r = 0.65, p 0.10). Variations in percutaneous methodologies are discussed with reference to interspecies variation in toxicity values. It is recommended that a mammalian DTI value approaching 30 be used as a guideline for the initiation of percutaneous toxicity studies in birds, when the po LD50 and/or projected percutaneous LD50 are less than expected field exposure levels.

Systemic Lupus Erythematosus, Radiotherapy, and the Risk of Acute and Chronic Toxicity: The Mayo Clinic Experience

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

Pinn, Melva E.; Gold, Douglas G. M.; Petersen, Ivy A.

2008-06-01

Purpose: To determine the acute and chronic toxic effects of radiotherapy in patients with systemic lupus erythematosus (SLE). Methods and Materials: Medical records of 21 consecutive patients with SLE, who had received 34 courses of external beam radiotherapy and one low-dose-rate prostate implant, were retrospectively reviewed. Patients with discoid lupus erythematosus were excluded. Results: Median survival was 2.3 years and median follow-up 5.6 years. Eight (42%) of 19 patients evaluable for acute toxicity during radiotherapy experienced acute toxicity of Grade 1 or greater, and 4 (21%) had acute toxicity of Grade 3 or greater. The 5- and 10-year incidence ofmore » chronic toxicity of Grade 1 or greater was 45% (95% confidence interval [CI], 22-72%) and 56% (95% CI, 28-81%), respectively. The 5- and 10-year incidence of chronic toxicity of Grade 3 or greater was 28% (95% CI, 18-60%) and 40% (95% CI, 16-72%), respectively. Univariate analysis showed that chronic toxicity of Grade 1 or greater correlated with SLE renal involvement (p < 0.006) and possibly with the presence of five or more American Rheumatism Association criteria (p < 0.053). Chronic toxicity of Grade 3 or greater correlated with an absence of photosensitivity (p < 0.02), absence of arthritis (p < 0.03), and presence of a malar rash (p < 0.04). Conclusions: The risk of acute and chronic toxicity in patients with SLE who received radiotherapy was moderate but was not prohibitive of the use of radiotherapy. Patients with more advanced SLE may be at increased risk for chronic toxicity.« less

Physico-chemical and genotoxicity analysis of Guaribas river water in the Northeast Brazil.

PubMed

de Castro E Sousa, João Marcelo; Peron, Ana Paula; da Silva, Felipe Cavalcanti Carneiro; de Siqueira Dantas, Ellifran Bezerra; de Macedo Vieira Lima, Ataíde; de Oliveira, Victor Alves; Matos, Leomá Albuquerque; Paz, Márcia Fernanda Correia Jardim; de Alencar, Marcus Vinicius Oliveira Barros; Islam, Muhammad Torequl; de Carvalho Melo-Cavalcante, Ana Amélia; Bonecker, Cláudia Costa; Júlio, Horácio Ferreira

2017-06-01

River pollution in Brazil is significant. This study aimed to evaluate the physico-chemical and genotoxic profiles of the Guaribas river water, located in Northeast Brazil (State of Piauí, Brazil). The study conducted during the dry and wet seasons to understand the frequency of pollution throughout the year. Genotoxicity analysis was done with the blood of Oreochromis niloticus by using the comet assay. Water samples were collected from upstream, within and downstream the city Picos. The results suggest a significant (p < 0.05) genotoxic effect of the Guaribas river water when compared to the control group. In comparison to the control group, in the river water we found a significant increase in metals such as - Fe, Zn, Cr, Cu and Al. In conclusion, Guaribas river carries polluted water, especially a large quantity of toxic metals, which may impart the genotoxic effect. Copyright © 2017 Elsevier Ltd. All rights reserved.

Testing the genotoxicity of coking wastewater using Vicia faba and Hordeum vulgare bioassays.

PubMed

Dong, Yiru; Zhang, Jintun

2010-07-01

The coking wastewater induces severe environmental problems in China, however, its toxicity has not been well known. In the present study, the genotoxicity of coking wastewater was studied using Vicia faba and Hordeum vulgare root tip cytogenetic bioassays. Results show that the tested coking wastewater decreased the mitotic index, and significantly enhanced the frequencies of micronucleus, sister chromatid exchange and pycnotic cell in concentration-dependent manners. Exposure to the same concentration wastewater, the increasing ratios of above genetic injuries were higher in V. faba than that in H. vulgare. The results imply that coking wastewater is a genotoxic agent in plant cells and exposure to the wastewater in environment may pose a potential genotoxic risk to organisms. It also suggests that both bioassays can be used for testing the genotoxicity of coking wastewater, but the V. faba assay is more sensitive than H. vulgare assay during the process. Copyright (c) 2010. Published by Elsevier Inc.

Intensity-modulated radiotherapy as primary treatment for prostate cancer: acute toxicity in 114 patients.

PubMed

De Meerleer, Gert; Vakaet, Luc; Meersschout, Sabine; Villeirs, Geert; Verbaeys, Antony; Oosterlinck, Wim; De Neve, Wilfried

2004-11-01

Dose escalation improves local control in prostate cancer. At Ghent University Hospital, intensity-modulated radiotherapy (IMRT) is used to increase the dose to the prostate and/or seminal vesicles. We report on acute toxicity in 114 patients who received IMRT for prostate cancer. Intensity-modulated radiotherapy was initiated after approval of our ethics committee. A class solution was used to plan all cases. Three beams (gantry 0 degrees , 116 degrees , and 244 degrees ) and anatomy-based segmentation were used to create an intensity-modulated dose distribution. Maximal rectal dose was set at 2 Gy per fraction. Detailed dose-volume histograms for all relevant structures were present. For all patients, we determined the pretreatment morbidity by a detailed preradiotherapy, in-house developed symptom scale. All patients were treated with 18 MV photons of an Elekta linear accelerator. Patients were seen on a weekly basis during treatment, and 1 month (M1) and 3 months (M3) thereafter. The registration of acute toxicity was standardized by a fixed questionnaire. The Radiation Therapy Oncology Group (RTOG) toxicity scale served as a basis, but additional symptoms, such as rectal blood loss, urgency, and incontinence, were scored as well. All 114 IMRT plans were delivered successfully without any interruption or technical problem. Daily treatment time was always less than 8 min and less than 6 min in 90% of the cases. Grade 1 and Grade 2 gastrointestinal (GI) toxicities were observed in 44% and 29% of the patients, respectively, during the whole period. If only the RTOG scale was used, Grade 1 and Grade 2 GI toxicities were noted in 39% and 27% of the patients, respectively, leaving 34% free of acute RTOG-scaled toxicity. Grade 3 genitourinary (GU) toxicity was seen in 8 patients (7%), all but 1 during treatment. Grade 2 and Grade 1 GU toxicities were seen in 36% and 47% of the patients, respectively, leaving only 10% free of acute GU toxicity. Anatomy-based IMRT to

Use of fish embryo toxicity tests for the prediction of acute fish toxicity to chemicals.

PubMed

Belanger, Scott E; Rawlings, Jane M; Carr, Gregory J

2013-08-01

The fish embryo test (FET) is a potential animal alternative for the acute fish toxicity (AFT) test. A comprehensive validation program assessed 20 different chemicals to understand intra- and interlaboratory variability for the FET. The FET had sufficient reproducibility across a range of potencies and modes of action. In the present study, the suitability of the FET as an alternative model is reviewed by relating FET and AFT. In total, 985 FET studies and 1531 AFT studies were summarized. The authors performed FET-AFT regressions to understand potential relationships based on physical-chemical properties, species choices, duration of exposure, chemical classes, chemical functional uses, and modes of action. The FET-AFT relationships are very robust (slopes near 1.0, intercepts near 0) across 9 orders of magnitude in potency. A recommendation for the predictive regression relationship is based on 96-h FET and AFT data: log FET median lethal concentration (LC50) = (0.989 × log fish LC50) - 0.195; n = 72 chemicals, r = 0.95, p < 0.001, LC50 in mg/L. A similar, not statistically different regression was developed for the entire data set (n = 144 chemicals, unreliable studies deleted). The FET-AFT regressions were robust for major chemical classes with suitably large data sets. Furthermore, regressions were similar to those for large groups of functional chemical categories such as pesticides, surfactants, and industrial organics. Pharmaceutical regressions (n = 8 studies only) were directionally correct. The FET-AFT relationships were not quantitatively different from acute fish-acute fish toxicity relationships with the following species: fathead minnow, rainbow trout, bluegill sunfish, Japanese medaka, and zebrafish. The FET is scientifically supportable as a rational animal alternative model for ecotoxicological testing of acute toxicity of chemicals to fish. Copyright © 2013 SETAC.

The BIOSAFEPAPER project for in vitro toxicity assessments: preparation, detailed chemical characterisation and testing of extracts from paper and board samples.

PubMed

Bradley, E L; Honkalampi-Hämäläinen, U; Weber, A; Andersson, M A; Bertaud, F; Castle, L; Dahlman, O; Hakulinen, P; Hoornstra, D; Lhuguenot, J-C; Mäki-Paakkanen, J; Salkinoja-Salonen, M; Speck, D R; Severin, I; Stammati, A; Turco, L; Zucco, F; von Wright, A

2008-07-01

Nineteen food contact papers and boards and one non-food contact board were extracted following test protocols developed within European Union funded project BIOSAFEPAPER. The extraction media were either hot or cold water, 95% ethanol or Tenax, according to the end use of the sample. The extractable dry matter content of the samples varied from 1200 to 11,800 mg/kg (0.8-35.5 mg/dm2). According to GC-MS the main substances extracted into water were pulp-derived natural products such as fatty acids, resin acids, natural wood sterols and alkanols. Substances extracted into ethanol particularly, were diisopropylnaphthalenes, alkanes and phthalic acid esters. The non-food contact board showed the greatest number and highest concentrations of GC-MS detectable compounds. The extracts were subjected to a battery of in vitro toxicity tests measuring both acute and sublethal cytotoxicity and genotoxic effects. None of the water or Tenax extracts was positive in cytotoxicity or genotoxicity assays. The ethanol extract of the non-food contact board gave a positive response in the genotoxicity assays, and all four ethanol extracts gave positive response(s) in the cytotoxicity assays to some extent. These responses could not be pinpointed to any specific compound, although there appeared a correlation between the total amount of extractables and toxicity.

Acute methaemoglobinaemia initially treated as organophosphate poisoning leading to atropine toxicity.

PubMed

Kakhandki, Srinivas; Yahya, Mohammed; Praveen, Mudalgi

2012-07-01

A case of unknown compound poisoning is presented. It was initially treated as organophosphate poisoning with lack of response. A timely diagnosis of acute methaemoglobinaemia and iatrogenic atropine toxicity was made based on clinical evaluation. Treatment of methaemoglobinaemia using oral methylene blue and of atropine toxicity with supportive measures could save the patient.

Evaluation of acute and sub-acute toxicity of Pinus eldarica bark extract in Wistar rats

PubMed Central

Ghadirkhomi, Akram; Safaeian, Leila; Zolfaghari, Behzad; Agha Ghazvini, Mohammad Reza; Rezaei, Parisa

2016-01-01

Objective: Pinus eldarica (P. eldarica) is one of the most common pines in Iran which has various bioactive constituents and different uses in traditional medicine. Since there is no documented evidence for P. eldarica safety, the acute and sub-acute oral toxicities of hydroalcoholic extract of P. eldarica bark were investigated in male and female Wistar rats in this study. Materials and Methods: In the acute study, a single dose of extract (2000 mg/kg) was orally administered and animals were monitored for 7 days. In the sub-acute study, repeated doses (125, 250 and 500 mg/kg/day) of the extract were administered for 28 days and biochemical, hematological and histopathological parameters were evaluated. Results: Our results showed no sign of toxicity and no mortality after single or repeated administration of P. eldarica. The median lethal dose (LD50) of P. eldarica was determined to be higher than 2000 mg/kg. The mean body weight and most of the biochemical and hematological parameters showed normal levels. There were only significant decreases in serum triglyceride levels at the doses of 250 and 500 mg/kg of the extract in male rats (p<0.05 and p<0.01, respectively) and in monocyte counts at the highest dose of the extract in both male and female rats (p<0.05). Mild inflammation was also found in histological examination of kidney and liver tissues at the highest dose of extract. Conclusion: Oral administration of the hydroalcoholic extract of P. eldarica bark may be considered as relatively non-toxic particularly at the doses of 125 and 250 mg/kg. PMID:27761426

Status of acute systemic toxicity testing requirements and data uses by U.S. regulatory agencies.

PubMed

Strickland, Judy; Clippinger, Amy J; Brown, Jeffrey; Allen, David; Jacobs, Abigail; Matheson, Joanna; Lowit, Anna; Reinke, Emily N; Johnson, Mark S; Quinn, Michael J; Mattie, David; Fitzpatrick, Suzanne C; Ahir, Surender; Kleinstreuer, Nicole; Casey, Warren

2018-04-01

Acute systemic toxicity data are used by a number of U.S. federal agencies, most commonly for hazard classification and labeling and/or risk assessment for acute chemical exposures. To identify opportunities for the implementation of non-animal approaches to produce these data, the regulatory needs and uses for acute systemic toxicity information must first be clarified. Thus, we reviewed acute systemic toxicity testing requirements for six U.S. agencies (Consumer Product Safety Commission, Department of Defense, Department of Transportation, Environmental Protection Agency, Food and Drug Administration, Occupational Safety and Health Administration) and noted whether there is flexibility in satisfying data needs with methods that replace or reduce animal use. Understanding the current regulatory use and acceptance of non-animal data is a necessary starting point for future method development, optimization, and validation efforts. The current review will inform the development of a national strategy and roadmap for implementing non-animal approaches to assess potential hazards associated with acute exposures to industrial chemicals and medical products. The Acute Toxicity Workgroup of the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), U.S. agencies, non-governmental organizations, and other stakeholders will work to execute this strategy. Copyright © 2018 Elsevier Inc. All rights reserved.

The acute toxicity of major ion salts to Ceriodaphnia dubia: I. ...

EPA Pesticide Factsheets

The ions Na+, K+, Ca2+, Mg2+, Cl-, SO42-, and HCO3-/CO32- (referred to as “major ions”) are present in all fresh waters and are physiologically required by aquatic organisms, but can be increased to harmful levels by a variety of anthropogenic activities that speed geochemical weathering or otherwise introduce or concentrate ions. While toxicity of these ions to aquatic organisms has been previously shown, it is also known that their toxicity can vary depending on the concentrations of other co-occurring anions, and understanding these relationships is key to predicting toxicity and establishing appropriate environmental limits. In this paper we conduct a series of experiments with Ceriodaphnia dubia to evaluate the acute toxicity of all twelve major ionsalts (pairing one of the cations with one of the anions) and to determine how toxicity of these salts varies as a function of background water chemistry. All salts except CaSO4 and CaCO3 were acutely toxic to C. dubia below saturation, with the lowest LC50s found for K salts. Of the remaining salts, all but CaCl2 showed some degree of decreased toxicity as the ionic content of the background water increased. Experiments that independently varied Ca:Mg ratio, Na:K ratio, Cl:SO4 ratio, and alkalinity/pH were used to show that Ca concentration was the primary factor influencing the toxicities of Na and Mg salts. In contrast, the toxicities of K salts were primarily influenced by the concentration of Na. Th

Cytotoxicity and genotoxicity of biogenic silver nanoparticles

NASA Astrophysics Data System (ADS)

Lima, R.; Feitosa, L. O.; Ballottin, D.; Marcato, P. D.; Tasic, L.; Durán, N.

2013-04-01

Biogenic silver nanoparticles with 40.3 ± 3.5 nm size and negative surface charge (- 40 mV) were prepared with Fusarium oxysporum. The cytotoxicity of 3T3 cell and human lymphocyte were studied by a TaliTM image-based cytometer and the genotoxicity through Allium cepa and comet assay. The results of BioAg-w (washed) and BioAg-nw (unwashed) biogenic silver nanoparticles showed cytotoxicity exceeding 50 μg/mL with no significant differences of response in 5 and 10 μg/mL regarding viability. Results of genotoxicity at concentrations 5.0 and 10.0 ug/mL show some response, but at concentrations 0.5 and 1.0 μg/mL the washed and unwashed silver nanoparticles did not present any effect. This in an important result since in tests with different bacteria species and strains, including resistant, MIC (minimal inhibitory concentration) had good answers at concentrations less than 1.9 μg/mL. This work concludes that biogenic silver nanoparticles may be a promising option for antimicrobial use in the range where no cyto or genotoxic effect were observed. Furthermore, human cells were found to have a greater resistance to the toxic effects of silver nanoparticles in comparison with other cells.

Acute Toxicity and Environmental Risks of Five Veterinary Pharmaceuticals for Aquatic Macroinvertebrates.

PubMed

Bundschuh, Mirco; Hahn, Torsten; Ehrlich, Bert; Höltge, Sibylla; Kreuzig, Robert; Schulz, Ralf

2016-02-01

Due to the high use of antibiotics and antiparasitics for the treatment of livestock, there is concern about the potential impacts of the release of these compounds into freshwater ecosystems. In this context, the present study quantified the acute toxicity of two antibiotics (sulfadiazine and sulfadimidine), and three antiparasitic agents (flubendazole, fenbendazole, ivermectin) for nine freshwater invertebrate species. These experiments revealed a low degree of toxicity for the sulfonamide antibiotics, with limited implications in the survival of all test species at the highest test concentrations (50 and 100 mg/L). In contrast, all three antiparasitic agents indicated on the basis of their acute toxicity risks for the aquatic environment. Moreover, chronic toxicity data from the literature for antiparasitics, including effects on reproduction in daphnids, support the concern about the integrity of aquatic ecosystems posed by releases of these compounds. Thus, these pharmaceuticals warrant further careful consideration by environmental risk managers.

Prostate Hypofractionated Radiation Therapy With Injection of Hyaluronic Acid: Acute Toxicities in a Phase 2 Study

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

Chapet, Olivier, E-mail: olivier.chapet@chu-lyon.fr; EMR3738, Université Lyon 1, Lyon; Decullier, Evelyne

Purpose: Hypofractionated radiation therapy (RT) in prostate cancer can be developed only if the risk of rectal toxicity is controlled. In a multicenter phase 2 trial, hypofractionated irradiation was combined with an injection of hyaluronic acid (HA) to preserve the rectal wall. Tolerance of the injection and acute toxicity rates are reported. Methods and Materials: The study was designed to assess late grade 2 toxicity rates. The results described here correspond to the secondary objectives. Acute toxicity was defined as occurring during RT or within 3 months after RT and graded according to the Common Terminology Criteria for Adverse Eventsmore » version 4.0. HA tolerance was evaluated with a visual analog scale during the injection and 30 minutes after injection and then by use of the Common Terminology Criteria at each visit. Results: From 2010 to 2012, 36 patients with low-risk to intermediate-risk prostate cancer were included. The HA injection induced a mean pain score of 4.6/10 ± 2.3. Thirty minutes after the injection, 2 patients still reported pain (2/10 and 3/10), which persisted after the intervention. Thirty-three patients experienced at least 1 acute genitourinary toxicity and 20 patients at least 1 acute gastrointestinal toxicity. Grade 2 toxicities were reported for 19 patients with urinary obstruction, frequency, or both and for 1 patient with proctitis. No grade 3 or 4 toxicities were reported. At the 3-month visit, 4 patients described grade 2 obstruction or frequency, and no patients had any grade 2 gastrointestinal toxicities. Conclusions: The injection of HA makes it possible to deliver hypofractionated irradiation over 4 weeks with a dose per fraction of > 3 Gy, with limited acute rectal toxicity.« less

High Throughput Genotoxicity Profiling of the US EPA ToxCast Chemical Library

EPA Science Inventory

A key aim of the ToxCast project is to investigate modern molecular and genetic high content and high throughput screening (HTS) assays, along with various computational tools to supplement and perhaps replace traditional assays for evaluating chemical toxicity. Genotoxicity is a...

Variability of LD50 Values from Rat Oral Acute Toxicity Studies: Implications for Alternative Model Development

EPA Science Inventory

Alternative models developed for estimating acute systemic toxicity are generally evaluated using in vivo LD50 values. However, in vivo acute systemic toxicity studies can produce variable results, even when conducted according to accepted test guidelines. This variability can ma...

What's your poison? Impact of individual repair capacity on the outcomes of genotoxic therapies in cancer. Part II - information content and validity of biomarkers for individual repair capacity in the assessment of outcomes of anticancer therapy.

PubMed

Petkova, Rumena; Chelenkova, Pavlina; Georgieva, Elena; Chakarov, Stoian

2014-01-02

The individual variance in the efficiency of repair of damage induced by genotoxic therapies may be an important factor in the assessment of eligibility for different anticancer treatments, the outcomes of various treatments and the therapy-associated complications, including acute and delayed toxicity and acquired drug resistance. The second part of this paper analyses the currently available information about the possibilities of using experimentally obtained knowledge about individual repair capacity for the purposes of personalised medicine and healthcare.

Toxicological analysis and anti-inflammatory effects of essential oil from Piper vicosanum leaves.

PubMed

Hoff Brait, Débora Regina; Mattos Vaz, Márcia Soares; da Silva Arrigo, Jucicléia; Borges de Carvalho, Luciana Noia; Souza de Araújo, Flávio Henrique; Vani, Juliana Miron; da Silva Mota, Jonas; Cardoso, Claudia Andrea Lima; Oliveira, Rodrigo Juliano; Negrão, Fábio Juliano; Kassuya, Cândida Aparecida Leite; Arena, Arielle Cristina

2015-12-01

This study assessed the anti-inflammatory effects of the essential oil from Piper vicosanum leaves (OPV) and evaluated the toxicological potential of this oil through acute toxicity, genotoxicity and mutagenicity tests. The acute toxicity of OPV was evaluated following oral administration to female rats at a single dose of 2 g/kg b.w. To evaluate the genotoxic and mutagenic potential, male mice were divided into five groups: I: negative control; II: positive control; III: 500 mg/kg of OPV; IV: 1000 mg/kg of OPV; V: 2000 mg/kg of OPV. The anti-inflammatory activity of OPV was evaluated in carrageenan-induced pleurisy and paw edema models in rats. No signs of acute toxicity were observed, indicating that the LD50 of this oil is greater than 2000 mg/kg. In the comet assay, OPV did not increase the frequency or rate of DNA damage in groups treated with any of the doses assessed compared to that in the negative control group. In the micronucleus test, the animals treated did not exhibit any cytotoxic or genotoxic changes in peripheral blood erythrocytes. OPV (100 and 300 mg/kg) significantly reduced edema formation and inhibited leukocyte migration analyzed in the carrageenan-induced edema and pleurisy models. These results show that OPV has anti-inflammatory potential without causing acute toxicity or genotoxicity. Copyright © 2015 Elsevier Inc. 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.

Effects of soil pH on the Vicia-micronucleus genotoxicity assay.

PubMed

Dhyèvre, Adrien; Foltête, Anne Sophie; Aran, Delphine; Muller, Serge; Cotelle, Sylvie

2014-11-01

In the field of contaminated sites and soil management, chemical analyses only bring typological data about pollution. As far as bioavailability and effects on organisms are concerned, we need ecotoxicology tools. In this domain, among many existing tests, we chose to study genotoxicity because it is a short-term endpoint with long-term consequences. The aim of this study is to assess the effects of soil pH on the results of the Vicia faba root tip micronucleus test for the two following reasons: (i) to define the pH range within which the test can be performed without modifying the soil to be tested, within the framework of the ISO standard of the test and (ii) to provides information about the effects of the pH on the genotoxic potential of soils. In this context, we modified the pH of a standard soil with HCl or NaOH and we spiked the matrix with copper (2, 4 and 8 mmol kg(-1) dry soil) or with maleic hydrazide, an antigerminative chemical (5, 10 and 20 μmol kg(-1) dry soil). We concluded that the pH had no effect on the mitotic index or micronucleus frequency in the root cells of the negative controls: extreme pH values did not induce micronucleus formation in root cells. Moreover, according to our results, the Vicia-micronucleus test can be performed with pH values ranging between 3.2 and 9.0, but in the ISO 29200 "Soil quality--assessment of genotoxic effects on higher plants--V. faba micronucleus test" we recommended to use a control soil with a pH value ranging between 5 and 8 for a more accurate assessment of chemical genotoxicity. We also found that acid pH could increase the genotoxic potential of pollutants, especially heavy metals. With hydrazide maleic spiked soil, plants were placed in a situation of double stress, i.e. toxicity caused by extreme pH values and toxicity induced by the pollutant. Copyright © 2014 Elsevier B.V. All rights reserved.

Haloactamides versus halomethanes formation and toxicity in chloraminated drinking water.

PubMed

Yang, Fan; Zhang, Jing; Chu, Wenhai; Yin, Daqiang; Templeton, Michael R

2014-06-15

In this study we quantified the concentrations of nine haloacetamides (HAcAms) and nine halomethanes (HMs) in the final waters of five drinking water treatment plants (DWTPs) that use either chlorination or chloramination for disinfection and evaluated the toxicity of dichloroacetamide (DCAcAm) and dichloromethane (DCM) in normal rat kidney (NRK) cells using four in vitro toxicity assays. All the DWTPs final waters contained primarily di-HAcAms, followed by tri- and mono-HAcAms, and DCAcAm was the most abundant species of the 9 HAcAms, regardless of chlorination or chloramination being applied. In the final waters of DWTPs using chlorination, tri-HMs (trihalomethanes, THMs) accounted for the majority of HMs, whereas chloramination resulted in more di-HMs (especially DCM) than THMs. All four in vitro toxicity assays indicated that the NRK cell chronic cytotoxicity and acute genotoxicity of DCAcAm were substantially higher than that of DCM. In view of observed occurrence concentrations and quantified toxicity levels, the findings of this study suggest that DCAcAm represents a higher toxicity risk than DCM in chloraminated drinking waters. Copyright © 2014 Elsevier B.V. All rights reserved.

Vectorization by nanoparticles decreases the overall toxicity of airborne pollutants

PubMed Central

Maiz-Gregores, Helena; Nesslany, Fabrice; Betbeder, Didier

2017-01-01

Atmospheric pollution is mainly composed of volatile pollutants and particulate matter that strongly interact. However, their specific roles in the induction of cellular toxicity, in particular the impact of the vectorization of atmospheric pollutants by ultrafine particles, remains to be fully elucidated. For this purpose, non-toxic poly-lactic co-glycolic acid (PLGA) nanoparticles were synthesized and three pollutants (benzo(a)pyrene, naphthalene and di-ethyl-hexyl-phthalate) were adsorbed on the surface of the nanoparticles in order to evaluate the toxicity (cytotoxicity, genotoxicity and ROS induction) of these complexes to a human airway epithelial cell line. The adsorption of the pollutants onto the nanoparticles was confirmed by HPLC analysis. Interestingly, the cytotoxicity assays (MTT, LDH and CellTox Green) clearly demonstrated that the vectorization by nanoparticles decreases the toxicity of the adsorbed pollutants. Genotoxicity was assessed by the micronucleus test and the comet assay and showed no increase in primary DNA damage or in chromosomal aberrations of nanoparticle vectorized pollutants. Neither cytotoxicity nor genotoxicity was correlated with ROS induction. To conclude, our results indicate that the vectorization of pollutants by nanoparticles does not potentiate the toxicity of the pollutants studied and that, on the contrary, adsorption onto nanoparticles could protect cells against pollutants’ toxicity. PMID:28813539

Vectorization by nanoparticles decreases the overall toxicity of airborne pollutants.

PubMed

Carpentier, Rodolphe; Platel, Anne; Maiz-Gregores, Helena; Nesslany, Fabrice; Betbeder, Didier

2017-01-01

Atmospheric pollution is mainly composed of volatile pollutants and particulate matter that strongly interact. However, their specific roles in the induction of cellular toxicity, in particular the impact of the vectorization of atmospheric pollutants by ultrafine particles, remains to be fully elucidated. For this purpose, non-toxic poly-lactic co-glycolic acid (PLGA) nanoparticles were synthesized and three pollutants (benzo(a)pyrene, naphthalene and di-ethyl-hexyl-phthalate) were adsorbed on the surface of the nanoparticles in order to evaluate the toxicity (cytotoxicity, genotoxicity and ROS induction) of these complexes to a human airway epithelial cell line. The adsorption of the pollutants onto the nanoparticles was confirmed by HPLC analysis. Interestingly, the cytotoxicity assays (MTT, LDH and CellTox Green) clearly demonstrated that the vectorization by nanoparticles decreases the toxicity of the adsorbed pollutants. Genotoxicity was assessed by the micronucleus test and the comet assay and showed no increase in primary DNA damage or in chromosomal aberrations of nanoparticle vectorized pollutants. Neither cytotoxicity nor genotoxicity was correlated with ROS induction. To conclude, our results indicate that the vectorization of pollutants by nanoparticles does not potentiate the toxicity of the pollutants studied and that, on the contrary, adsorption onto nanoparticles could protect cells against pollutants' toxicity.

Acute and chronic toxicity of six anticancer drugs on rotifers and crustaceans.

PubMed

Parrella, Alfredo; Lavorgna, Margherita; Criscuolo, Emma; Russo, Chiara; Fiumano, Vittorio; Isidori, Marina

2014-11-01

The growing use of cytostatic drugs is gaining relevance as an environmental concern. Environmental and distribution studies are increasing due to the development of accurate analytical methods, whereas ecotoxicological studies are still lacking. The aim of the present study was to investigate the acute and chronic toxicity of six cytostatics (5-fluorouracil, capecitabine, cisplatin, doxorubicin, etoposide, and imatinib) belonging to five classes of Anatomical Therapeutic Classification (ATC) on primary consumers of the aquatic chain (Daphnia magna, Ceriodaphnia dubia, Brachionus calyciflorus, and Thamnocephalus platyurus). Acute ecotoxicological effects occurred at concentrations in the order of mgL(-)(1), higher than those predicted in the environment, and the most acutely toxic drugs among those tested were cisplatin and doxorubicin for most aquatic organisms. For chronic toxicity, cisplatin and 5-fluorouracil showed the highest toxic potential in all test organisms, inducing 50% reproduction inhibition in crustaceans at concentrations on the order of μgL(-)(1). Rotifers were less susceptible to these pharmaceuticals. On the basis of chronic results, the low effective concentrations suggest a potential environmental risk of cytostatics. Thus, this study could be an important starting point for establishing the real environmental impact of these substances. Copyright © 2014 Elsevier Ltd. All rights reserved.

Mycotoxins' activity at toxic and sub-toxic concentrations: differential cytotoxic and genotoxic effects of single and combined administration of sterigmatocystin, ochratoxin A and citrinin on the hepatocellular cancer cell line Hep3B.

PubMed

Anninou, Nikolia; Chatzaki, Ekaterini; Papachristou, Fotini; Pitiakoudis, Muichail; Simopoulos, Constantinos

2014-02-07

Food safety organizations indicate the likelihood of constant human and animal exposure to mycotoxin mixtures as a possible negative public health impact. Risk assessment demonstrates that certain mycotoxins of Aspergillus and Penicillium spp. are toxic and hold a significant genotoxic efficacy at nanomolar concentrations. The aim of the current study was to investigate the potential cytogenetic effects of sterigmatocystin (STER), ochratoxin A (OTA) and citrinin (CTN) alone or in combination, at pM to μΜ concentrations, on the human hepatocellular cancer cell line Hep3B. MTT reduction, mitotic divisions, cell cycle delays and sister chromatid exchange rates (SCE) were determined as endpoints of metabolic activity, cytotoxicity, cytostaticity, and genotoxicity, respectively. All mycotoxin treatments induce SCE rates from 10-12 M, while their cytotoxic and cytostatic potential varies. In PRI and MI assays, but not at MTT, STER alone or in combination with OTA + CTN appeared cytostatic and cytotoxic, even at 10-12 M, while CTN alone and all other combinations displayed substantial cellular survival inhibition in doses ≥ 10-8 M. Co-administration of STER + OTA or STER + CTN in concentrations ≤ 10-1 M, increased the MI and MTT activity, while it did not affect the PRI. Mycotoxin co-treatments revealed in general similar-to-additive or antagonistic genotoxic and cytotoxic effects. Our results for the first time describe that STER alone or in combination with OTA and/or CTN share a cytotoxic and cytogenetic potential even at picoMolar concentrations on human hepatoma cells in vitro.

Dredged Material Analysis Tools; Performance of Acute and Chronic Sediment Toxicity Methods

DTIC Science & Technology

2008-04-01

Chronic Sediment Toxicity Methods Jeffery Steevens, Alan Kennedy, Daniel Farrar, Cory McNemar, Mark R. Reiss, Roy K. Kropp, Jon Doi, and Todd Bridges...Research Program ERDC/EL TR-08-16 April 2008 Dredged Material Analysis Tools Performance of Acute and Chronic Sediment Toxicity Methods Jeffery...potential advan- tages and disadvantages of using chronic sediment toxicity tests with relevant benthic macroinvertebrates as part of dredged material

Dredged Material Analysis Tools; Performance of Acute and Chronic Sediment Toxicity Methods

DTIC Science & Technology

2008-07-01

Chronic Sediment Toxicity Methods Jeffery Steevens, Alan Kennedy, Daniel Farrar, Cory McNemar, Mark R. Reiss, Roy K. Kropp, Jon Doi, and Todd Bridges...Environmental Research Program ERDC/EL TR-08-16 July 2008 Revised Dredged Material Analysis Tools Performance of Acute and Chronic Sediment Toxicity ...insight into the potential advan- tages and disadvantages of using chronic sediment toxicity tests with relevant benthic macroinvertebrates as part of

40 CFR 797.1400 - Fish acute toxicity test.

Code of Federal Regulations, 2010 CFR

2010-07-01

... prescribes tests to be used to develop data on the acute toxicity of chemicals to fish. The United States...) Death means the lack of opercular movement by a test fish. (6) Flow-through means a continuous or an... dilution water. If a flow-through test is performed, the flow of dilution water through each chamber is...

Effect of malachite green toxicity on non target soil organisms.

PubMed

Gopinathan, R; Kanhere, J; Banerjee, J

2015-02-01

Although malachite green (MG), is banned in Europe and US for its carcinogenic and teratogenic effect, the dye being cheap, is persistently used in various countries for fish farming, silk, dye, leather and textile industries. Current research, however, fails to elucidate adequate knowledge concerning the effects of MG in our ecosystem. In the present investigation, for the first time, an attempt has been made to study the effects of MG on soil biota by testing Bacillus subtilis, Azotobacter chroococcum, Saccharomyces cerevisiae, Penicillium roqueforti, Eisenia fetida and seeds of three crop plants of different families. Various tests were conducted for determining cytotoxicity, genotoxicity, acute toxicity, morphological and germination effect. Our data confirmed MG toxicity on fungi and bacteria (gram positive and gram negative organisms) showing elevated level of ROS. Genotoxicity caused in the microorganisms was detected by DNA polymorphism and fragmentation. Also, scanning electron microscopy data suggests that the inhibitory effect of MG to these beneficial microbes in the ecosystem might be due to pore formation in the cell and its eventual disruption. Filter paper and artificial soil test conducted on earthworms demonstrated a LC 50 of 2.6 mg cm(-2) and 1.45 mg kg(-1) respectively with severe morphological damage. However, seed germination of Mung bean, Wheat and Mustard was found to be unaffected in presence of MG up to 100 mL(-1) concentration. Thus, understanding MG toxicity in non target soil organisms and emphasis on its toxicological effects would potentially explicate its role as an environmental contaminant. Copyright © 2014 Elsevier Ltd. All rights reserved.

EFFECTS OF HEAT SHOCK PROTEIN 70 (HSP70) ON ARSENITE INDUCED GENOTOXICITY

EPA Science Inventory

Arsenic (As), a human carcinogen, is known to be genotoxic although its mechanism(s) of action for tumorigenesis is not well understood. Among the toxicity-related properties of this chemical are its clastogenic and aneugenic activities, as well as its capacity for inducing stres...

Investigating the different mechanisms of genotoxic and non-genotoxic carcinogens by a gene set analysis.

PubMed

Lee, Won Jun; Kim, Sang Cheol; Lee, Seul Ji; Lee, Jeongmi; Park, Jeong Hill; Yu, Kyung-Sang; Lim, Johan; Kwon, Sung Won

2014-01-01

Based on the process of carcinogenesis, carcinogens are classified as either genotoxic or non-genotoxic. In contrast to non-genotoxic carcinogens, many genotoxic carcinogens have been reported to cause tumor in carcinogenic bioassays in animals. Thus evaluating the genotoxicity potential of chemicals is important to discriminate genotoxic from non-genotoxic carcinogens for health care and pharmaceutical industry safety. Additionally, investigating the difference between the mechanisms of genotoxic and non-genotoxic carcinogens could provide the foundation for a mechanism-based classification for unknown compounds. In this study, we investigated the gene expression of HepG2 cells treated with genotoxic or non-genotoxic carcinogens and compared their mechanisms of action. To enhance our understanding of the differences in the mechanisms of genotoxic and non-genotoxic carcinogens, we implemented a gene set analysis using 12 compounds for the training set (12, 24, 48 h) and validated significant gene sets using 22 compounds for the test set (24, 48 h). For a direct biological translation, we conducted a gene set analysis using Globaltest and selected significant gene sets. To validate the results, training and test compounds were predicted by the significant gene sets using a prediction analysis for microarrays (PAM). Finally, we obtained 6 gene sets, including sets enriched for genes involved in the adherens junction, bladder cancer, p53 signaling pathway, pathways in cancer, peroxisome and RNA degradation. Among the 6 gene sets, the bladder cancer and p53 signaling pathway sets were significant at 12, 24 and 48 h. We also found that the DDB2, RRM2B and GADD45A, genes related to the repair and damage prevention of DNA, were consistently up-regulated for genotoxic carcinogens. Our results suggest that a gene set analysis could provide a robust tool in the investigation of the different mechanisms of genotoxic and non-genotoxic carcinogens and construct a more detailed

Investigating the Different Mechanisms of Genotoxic and Non-Genotoxic Carcinogens by a Gene Set Analysis

PubMed Central

Lee, Won Jun; Kim, Sang Cheol; Lee, Seul Ji; Lee, Jeongmi; Park, Jeong Hill; Yu, Kyung-Sang; Lim, Johan; Kwon, Sung Won

2014-01-01

Based on the process of carcinogenesis, carcinogens are classified as either genotoxic or non-genotoxic. In contrast to non-genotoxic carcinogens, many genotoxic carcinogens have been reported to cause tumor in carcinogenic bioassays in animals. Thus evaluating the genotoxicity potential of chemicals is important to discriminate genotoxic from non-genotoxic carcinogens for health care and pharmaceutical industry safety. Additionally, investigating the difference between the mechanisms of genotoxic and non-genotoxic carcinogens could provide the foundation for a mechanism-based classification for unknown compounds. In this study, we investigated the gene expression of HepG2 cells treated with genotoxic or non-genotoxic carcinogens and compared their mechanisms of action. To enhance our understanding of the differences in the mechanisms of genotoxic and non-genotoxic carcinogens, we implemented a gene set analysis using 12 compounds for the training set (12, 24, 48 h) and validated significant gene sets using 22 compounds for the test set (24, 48 h). For a direct biological translation, we conducted a gene set analysis using Globaltest and selected significant gene sets. To validate the results, training and test compounds were predicted by the significant gene sets using a prediction analysis for microarrays (PAM). Finally, we obtained 6 gene sets, including sets enriched for genes involved in the adherens junction, bladder cancer, p53 signaling pathway, pathways in cancer, peroxisome and RNA degradation. Among the 6 gene sets, the bladder cancer and p53 signaling pathway sets were significant at 12, 24 and 48 h. We also found that the DDB2, RRM2B and GADD45A, genes related to the repair and damage prevention of DNA, were consistently up-regulated for genotoxic carcinogens. Our results suggest that a gene set analysis could provide a robust tool in the investigation of the different mechanisms of genotoxic and non-genotoxic carcinogens and construct a more detailed

Sirc-cvs cytotoxicity test: an alternative for predicting rodent acute systemic toxicity.

PubMed

Kitagaki, Masato; Wakuri, Shinobu; Hirota, Morihiko; Tanaka, Noriho; Itagaki, Hiroshi

2006-10-01

An in vitro crystal violet staining method using the rabbit cornea-derived cell line (SIRC-CVS) has been developed as an alternative to predict acute systemic toxicity in rodents. Seventy-nine chemicals, the in vitro cytotoxicity of which was already reported by the Multicenter Evaluation of In vitro Toxicity (MEIC) and ICCVAM/ECVAM, were selected as test compounds. The cells were incubated with the chemicals for 72 hrs and the IC(50) and IC(35) values (microg/mL) were obtained. The results were compared to the in vivo (rat or mouse) "most toxic" oral, intraperitoneal, subcutaneous and intravenous LD(50) values (mg/kg) taken from the RTECS database for each of the chemicals by using Pearson's correlation statistics. The following parameters were calculated: accuracy, sensitivity, specificity, prevalence, positive predictability, and negative predictability. Good linear correlations (Pearson's coefficient; r>0.6) were observed between either the IC(50) or the IC(35) values and all the LD(50) values. Among them, a statistically significant high correlation (r=0.8102, p<0.001) required for acute systemic toxicity prediction was obtained between the IC(50) values and the oral LD(50) values. By using the cut-off concentrations of 2,000 mg/kg (LD(50)) and 4,225 microg/mL (IC(50)), no false negatives were observed, and the accuracy was 84.8%. From this, it is concluded that this method could be used to predict the acute systemic toxicity potential of chemicals in rodents.

Acute oral toxicities of wildland fire control chemicals to birds

USGS Publications Warehouse

Vyas, N.B.; Spann, J.W.; Hill, E.F.

2009-01-01

Wildland fire control chemicals are released into the environment by aerial and ground applications to manage rangeland, grassland, and forest fires. Acute oral 24 h median lethal dosages (LD50) for three fire retardants (Fire-Trol GTS-R?, Phos-Chek D-75F?, and Fire-Trol LCG-R?) and two Class A fire suppressant foams (Silv-Ex? and Phos-Chek WD881?) were estimated for northern bobwhites, Colinus virginianus, American kestrels, Falco sparverius, and red-winged blackbirds, Agelaius phoeniceus. The LD50s of all chemicals for the bobwhites and red-winged blackbirds and for kestrels dosed with Phos-Chek WD881? and Silv-Ex? were above the predetermined 2000 mg chemical/kg body mass regulatory limit criteria for acute oral toxicity. The LD50s were not quantifiable for kestrels dosed with Fire-Trol GTS-R?, Phos-Chek D-75F?, and Fire-Trol LCG-R? because of the number of birds which regurgitated the dosage. These chemicals appear to be of comparatively low order of acute oral toxicity to the avian species tested.

MAMMALIAN CELL CYTOTOXICITY AND GENOTOXICITY OF NEW DRINKING WATER DISINFECTION BY-PRODUCTS

EPA Science Inventory

The disinfection of drinking water continues to protect the public health against acute disease. Drinking water disinfection by-products (DBPs) are formed by the reaction of a disinfectant with naturally occurring organic matter. Many DBPs are genotoxic and are implicated as huma...

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.

Cyanotoxins: producing organisms, occurrence, toxicity, mechanism of action and human health toxicological risk evaluation.

PubMed

Buratti, Franca M; Manganelli, Maura; Vichi, Susanna; Stefanelli, Mara; Scardala, Simona; Testai, Emanuela; Funari, Enzo

2017-03-01

Cyanobacteria were present on the earth 3.5 billion years ago; since then they have colonized almost all terrestrial and aquatic ecosystems. They produce a high number of bioactive molecules, among which some are cyanotoxins. Cyanobacterial growth at high densities, forming blooms, is increasing in extension and frequency, following anthropogenic activities and climate changes, giving rise to some concern for human health and animal life exposed to cyanotoxins. Numerous cases of lethal poisonings have been associated with cyanotoxins ingestion in wild animal and livestock. In humans few episodes of lethal or severe human poisonings have been recorded after acute or short-term exposure, but the repeated/chronic exposure to low cyanotoxin levels remains a critical issue. The properties of the most frequently detected cyanotoxins (namely, microcystins, nodularins, cylindrospermopsin and neurotoxins) are here critically reviewed, describing for each toxin the available information on producing organisms, biosynthesis/genetic and occurrence, with a focus on the toxicological profile (including kinetics, acute systemic toxicity, mechanism and mode of action, local effects, repeated toxicity, genotoxicity, carcinogenicity, reproductive toxicity; human health effects and epidemiological studies; animal poisoning) with the derivation of health-based values and considerations on the risks for human health.

Genotoxic effects of high dose rate X‐ray and low dose rate gamma radiation in ApcMin/+ mice

PubMed Central

Eide, Dag M.; Brede, Dag A.; Ellender, Michele; Lindbo Hansen, Elisabeth; Oughton, Deborah H.; Bouffler, Simon D.; Brunborg, Gunnar; Olsen, Ann Karin

2017-01-01

Risk estimates for radiation‐induced cancer in humans are based on epidemiological data largely drawn from the Japanese atomic bomb survivor studies, which received an acute high dose rate (HDR) ionising radiation. Limited knowledge exists about the effects of chronic low dose rate (LDR) exposure, particularly with respect to the application of the dose and dose rate effectiveness factor. As part of a study to investigate the development of colon cancer following chronic LDR vs. acute HDR radiation, this study presents the results of genotoxic effects in blood of exposed mice. CBAB6 F1 Apc+/+ (wild type) and ApcMin/+ mice were chronically exposed to estimated whole body absorbed doses of 1.7 or 3.2 Gy 60Co‐γ‐rays at a LDR (2.2 mGy h−1) or acutely exposed to 2.6 Gy HDR X‐rays (1.3 Gy min−1). Genotoxic endpoints assessed in blood included chromosomal damage (flow cytometry based micronuclei (MN) assay), mutation analyses (Pig‐a gene mutation assay), and levels of DNA lesions (Comet assay, single‐strand breaks (ssb), alkali labile sites (als), oxidized DNA bases). Ionising radiation (ca. 3 Gy) induced genotoxic effects dependent on the dose rate. Chromosomal aberrations (MN assay) increased 3‐ and 10‐fold after chronic LDR and acute HDR, respectively. Phenotypic mutation frequencies as well as DNA lesions (ssb/als) were modulated after acute HDR but not after chronic LDR. The ApcMin/+ genotype did not influence the outcome in any of the investigated endpoints. The results herein will add to the scant data available on genotoxic effects following chronic LDR of ionising radiation. Environ. Mol. Mutagen. 58:560–569, 2017. © 2017 The Authors Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society PMID:28856770

Cytotoxic and genotoxic potential of food-borne nitriles in a liver in vitro model

PubMed Central

Kupke, Franziska; Herz, Corinna; Hanschen, Franziska S.; Platz, Stefanie; Odongo, Grace A.; Helmig, Simone; Bartolomé Rodríguez, María M.; Schreiner, Monika; Rohn, Sascha; Lamy, Evelyn

2016-01-01

Isothiocyanates are the most intensively studied breakdown products of glucosinolates from Brassica plants and well recognized for their pleiotropic effects against cancer but also for their genotoxic potential. However, knowledge about the bioactivity of glucosinolate-borne nitriles in foods is very poor. As determined by GC-MS, broccoli glucosinolates mainly degrade to nitriles as breakdown products. The cytotoxicity of nitriles in human HepG2 cells and primary murine hepatocytes was marginal as compared to isothiocyanates. Toxicity of nitriles was not enhanced in CYP2E1-overexpressing HepG2 cells. In contrast, the genotoxic potential of nitriles was found to be comparable to isothiocyanates. DNA damage was persistent over a certain time period and CYP2E1-overexpression further increased the genotoxic potential of the nitriles. Based on actual in vitro data, no indications are given that food-borne nitriles could be relevant for cancer prevention, but could pose a certain genotoxic risk under conditions relevant for food consumption. PMID:27883018

Acute Oral Toxicity of Trimethylolethane Trinitrate (TMETN) in Sprague- Dawley Rats

DTIC Science & Technology

1989-07-01

classification scheme of Hodge and Steiner, these results indicate that TMETN is a slightly toxic compound.1 20. ON-RIBUTION /AVAILABILITY OF ABSTRACT 21. ABSTRACT...the classification scheme of Hodge and Sterner, these results indcate that TMETN is a slightly toxic compound. KEY WORDS: Acute Oral Toxicit-y...Dawley rats and 1027.4 63.7 mg/kg in female Sprague-Dawley rats. These MLD values place TMETN in the "slightly toxic" range by the system of Hodge and

Baclofen Toxicity Causing Acute, Reversible Dyskinesia.

PubMed

Niehaus, Matthew T; Elliott, Nicole C; Katz, Kenneth D

2016-12-01

The following unique case demonstrates an episode of acute dyskinesia secondary to oral baclofen toxicity. We discuss an 80-year-old man with a history of Stage III chronic kidney disease, coronary artery disease, diabetes and stroke who presented to the Emergency Department with new onset of behavioral changes and irregular jerking movements. The patient had been recently prescribed baclofen 10mg twice daily for a back strain he suffered; he subsequently was admitted to the hospital, and his symptoms resolved within 48 hours of admission and discontinuance of baclofen.

QSAR Modeling of Rat Acute Toxicity by Oral Exposure

PubMed Central

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

2009-01-01

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

The combination of two novel tobacco blends and filter technologies to reduce the in vitro genotoxicity and cytotoxicity of prototype cigarettes.

PubMed

Crooks, Ian; Scott, Ken; Dalrymple, Annette; Dillon, Debbie; Meredith, Clive

2015-04-01

Tobacco smoke from a combustible cigarette contains more than 6000 constituents; approximately 150 of these are identified as toxicants. Technologies that modify the tobacco blend to reduce toxicant emissions have been developed. These include tobacco sheet substitute to dilute toxicants in smoke and blend treated tobacco to reduce the levels of nitrogenous precursors and some polyphenols. Filter additives to reduce gas (vapour) phase constituents have also been developed. In this study, both tobacco blend and filter technologies were combined into an experimental cigarette and smoked to International Organisation on Standardisation and Health Canada puffing parameters. The resulting particulate matter was subjected to a battery of in vitro genotoxicity and cytotoxicity assays - the Ames test, mouse lymphoma assay, the in vitro micronucleus test and the Neutral Red Uptake assay. The results indicate that cigarettes containing toxicant reducing technologies may be developed without observing new additional genotoxic hazards as assessed by the assays specified. In addition, reductions in bacterial mutagenicity and mammalian genotoxicity of the experimental cigarette were observed relative to the control cigarettes. There were no significant differences in cytotoxicity relative to the control cigarettes. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Investigation of acute toxicity of fenitrothion on peppered corydoras (Corydoras paleatus) (Jenyns, 1842).

PubMed

Sarikaya, Rabia; Selvi, Mahmut; Erkoç, Figen

2004-08-01

Fenitrothion, as an organophosphothionate insecticide, is a contact insecticide and selective acaricide, also used as a vector control agent for malaria in public health programs. A 96 h LC50 value of fenitrothion, a potential toxic pollutant contaminating aquatic ecosystems, was determined on the adult peppered corydoras (Corydoras paleatus). The experiments were repeated three times. The static test method of acute toxicity test was used. Water temperature was regulated at 23 +/- 1 degrees C. In addition, behavioral changes at each fenitrothion concentration were observed for the individual fish. Data obtained from acute toxicity tests were evaluated using the Probit Analysis Statistical Method. The 96 h LC50 value for peppered corydoras was estimated as 3.51 mg/l.

Lack of genotoxic effect of food dyes amaranth, sunset yellow and tartrazine and their metabolites in the gut micronucleus assay in mice.

PubMed

Poul, Martine; Jarry, Gérard; Elhkim, Mostafa Ould; Poul, Jean-Michel

2009-02-01

The food dyes amaranth, sunset yellow and tartrazine were administered twice, at 24h intervals, by oral gavage to mice and assessed in the in vivo gut micronucleus test for genotoxic effects (frequency of micronucleated cells) and toxicity (apoptotic and mitotic cells). The concentrations of each compound and their main metabolites (sulfanilic acid and naphthionic acid) were measured in faeces during a 24-h period after single oral administrations of the food dyes to mice. Parent dye compounds and their main aromatic amine metabolites were detected in significant amounts in the environment of colonic cells. Acute oral exposure to food dye additives amaranth, sunset yellow and tartrazine did not induce genotoxic effect in the micronucleus gut assay in mice at doses up to 2000 mg/kg b.w. Food dyes administration increased the mitotic cells at all dose levels when compared to controls. These results suggest that the transient DNA damages previously observed in the colon of mice treated by amaranth and tartrazine by the in vivo comet assay [Sasaki, Y.F., Kawaguchi, S., Kamaya, A., Ohshita, M., Kabasawa, K., Iwama, K., Taniguchi, K., Tsuda, S., 2002. The comet assay with 8 mouse organs: results with 39 currently used food additives. Mutat. Res. 519, 103-119] are unable to be fixed in stable genotoxic lesions and might be partly explained by local cytotoxicity of the dyes.

Application of the TGx‐28.65 transcriptomic biomarker to classify genotoxic and non‐genotoxic chemicals in human TK6 cells in the presence of rat liver S9

PubMed Central

Buick, Julie K.; Williams, Andrew; Swartz, Carol D.; Recio, Leslie; Li, Heng‐Hong; Fornace, Albert J.; Thomson, Errol M.; Aubrecht, Jiri

2016-01-01

In vitro transcriptional signatures that predict toxicities can facilitate chemical screening. We previously developed a transcriptomic biomarker (known as TGx‐28.65) for classifying agents as genotoxic (DNA damaging) and non‐genotoxic in human lymphoblastoid TK6 cells. Because TK6 cells do not express cytochrome P450s, we confirmed accurate classification by the biomarker in cells co‐exposed to 1% 5,6 benzoflavone/phenobarbital‐induced rat liver S9 for metabolic activation. However, chemicals may require different types of S9 for activation. Here we investigated the response of TK6 cells to higher percentages of Aroclor‐, benzoflavone/phenobarbital‐, or ethanol‐induced rat liver S9 to expand TGx‐28.65 biomarker applicability. Transcriptional profiles were derived 3 to 4 hr following a 4 hr co‐exposure of TK6 cells to test chemicals and S9. Preliminary studies established that 10% Aroclor‐ and 5% ethanol‐induced S9 alone did not induce the TGx‐28.65 biomarker genes. Seven genotoxic and two non‐genotoxic chemicals (and concurrent solvent and positive controls) were then tested with one of the S9s (selected based on cell survival and micronucleus induction). Relative survival and micronucleus frequency was assessed by flow cytometry in cells 20 hr post‐exposure. Genotoxic/non‐genotoxic chemicals were accurately classified using the different S9s. One technical replicate of cells co‐treated with dexamethasone and 10% Aroclor‐induced S9 was falsely classified as genotoxic, suggesting caution in using high S9 concentrations. Even low concentrations of genotoxic chemicals (those not causing cytotoxicity) were correctly classified, demonstrating that TGx‐28.65 is a sensitive biomarker of genotoxicity. A meta‐analysis of datasets from 13 chemicals supports that different S9s can be used in TK6 cells, without impairing classification using the TGx‐28.65 biomarker. Environ. Mol. Mutagen. 57:243–260, 2016. © 2016 Her Majesty the

Assessment of Genotoxic Potential of Hridayarnava Rasa (A Herbo-Mineralo-Metallic Ayurvedic Formulation) Using Chromosomal Aberration and Sperm Abnormality Assays

PubMed Central

Jagtap, Chandrashekhar Y.; Chaudhari, Swapnil Y.; Thakkar, Jalaram H.; Galib, R.; Prajapati, P. K.

2014-01-01

Objectives: Herbo-mineral formulations are being successfully used in therapeutics since centuries. But recently, they came under the scanner for their metallic contents especially the presence of heavy metals. Hence it is the need of the hour to assess and establish the safety of these formulations through toxicity studies. In line with the various toxicity studies that are being carried out, Government of India expressed the need for conducting genotoxicity studies of different metal- or mineral-based drugs. Till date very few Ayurvedic herbo-mineral formulations have been studied for their genotoxic potential. The present study is aimed to evaluate the genotoxic potential of Hridayarnava Rasa. Materials and Methods: It was prepared as per classical guidelines and administered to Swiss albino mice for 14 consecutive days. Chromosomal aberration and sperm abnormality assay were done to evaluate the genotoxic potential of the test drugs. Cyclophosphamide (CP) was taken as positive group and results were compared. Results: All treated groups exhibited significant body weight gain in comparison to CP group. Results revealed no structural deformity in the above parameters in comparison to the CP-treated group. Conclusion: Reported data showed that both tested samples of Hridayarnava Rasa does not possess genotoxic potential under the experimental conditions and can be safely used. PMID:25948961

Developmental toxicity, acute toxicity and mutagenicity testing in freshwater snails Biomphalaria glabrata (Mollusca: Gastropoda) exposed to chromium and water samples.

PubMed

Tallarico, Lenita de Freitas; Borrely, Sueli Ivone; Hamada, Natália; Grazeffe, Vanessa Siqueira; Ohlweiler, Fernanda Pires; Okazaki, Kayo; Granatelli, Amanda Tosatte; Pereira, Ivana Wuo; Pereira, Carlos Alberto de Bragança; Nakano, Eliana

2014-12-01

A protocol combining acute toxicity, developmental toxicity and mutagenicity analysis in freshwater snail Biomphalaria glabrata for application in ecotoxicological studies is described. For acute toxicity testing, LC50 and EC50 values were determined; dominant lethal mutations induction was the endpoint for mutagenicity analysis. Reference toxicant potassium dichromate (K2Cr2O7) was used to characterize B. glabrata sensitivity for toxicity and cyclophosphamide to mutagenicity testing purposes. Compared to other relevant freshwater species, B. glabrata showed high sensitivity: the lowest EC50 value was obtained with embryos at veliger stage (5.76mg/L). To assess the model applicability for environmental studies, influent and effluent water samples from a wastewater treatment plant were evaluated. Gastropod sensitivity was assessed in comparison to the standardized bioassay with Daphnia similis exposed to the same water samples. Sampling sites identified as toxic to daphnids were also detected by snails, showing a qualitatively similar sensitivity suggesting that B. glabrata is a suitable test species for freshwater monitoring. Holding procedures and protocols implemented for toxicity and developmental bioassays showed to be in compliance with international standards for intra-laboratory precision. Thereby, we are proposing this system for application in ecotoxicological studies. Copyright © 2014 Elsevier Inc. All rights reserved.

Comparing anti-hyperglycemic activity and acute oral toxicity of three different trivalent chromium complexes in mice.

PubMed

Li, Fang; Wu, Xiangyang; Zou, Yanmin; Zhao, Ting; Zhang, Min; Feng, Weiwei; Yang, Liuqing

2012-05-01

Three different ligands (rutin, folate and stachyose) of chromium(III) complexes were compared to examine whether they have similar effect on anti-hyperglycemic activity as well as the acute toxicity status. Anti-hyperglycemic activities of chromium rutin complex (CrRC), chromium folate complex (CrFC) and chromium stachyose complex (CrSC) were examined in alloxan-induced diabetic mice with daily oral gavage for a period of 2 weeks at the dose of 0.5-3.0 mg Cr/kg. Acute toxicities of CrRC and CrFC were tested using ICR mice at the dose of 1.0-5.0 g/kg with a single oral gavage and observed for a period of 2 weeks. Biological activities results indicated that only CrRC and CrFC could decrease blood glucose level, reduce the activities of aspartate transaminase, alanine transaminase, alkaline phosphatase, and increase liver glycogen level. In acute toxicity study, LD(50) values for both CrRC and CrFC were above 5.0 g/kg. The minimum lethal dose for CrFC was above 5.0 g/kg, while that for CrRC was 1.0 g/kg. Anti-diabetic activity of those chromium complexes was not similar and their acute toxicities were also different. CrFC represent an optimal chromium supplement among those chromium complexes with potential therapeutic value to control blood glucose in diabetes and non-toxicity in acute toxicity. Copyright © 2012 Elsevier Ltd. All rights reserved.

Evaluation of the cytotoxicity, genotoxicity, mutagenicity, and antimutagenicity of propolis from Tucuman, Argentina.

PubMed

Nieva Moreno, María I; Zampini, Iris C; Ordóñez, Roxana M; Jaime, Gloria S; Vattuone, Marta A; Isla, María I

2005-11-16

This study evaluates the toxic, genotoxic/mutagenic, and antimutagenic effects of propolis extract from Amaicha del Valle, Tucumán, Argentina. The cytotoxicity assays carried out with the lethality test of Artemia salina revealed that the LD50 was around 100 microg/mL. Propolis extracts showed no toxicity to Salmonella typhimurium TA98 and TA100 strains and Allium cepa at concentrations that have antibiotic and antioxidant activities. Otherwise, for the testing doses, neither genotoxicity nor mutagenicity was found in any sample. The propolis extracts were able to inhibit the mutagenesis of isoquinoline (IQ) and 4-nitro o-phenylenediamine (NPD) with ID50 values of 40 and 20 microg/plate, respectively. From this result, the studied propolis may be inferred to contain some chemical compounds capable of inhibiting the mutagenicity of direct-acting and indirect-acting mutagens. A compound isolated from Amaicha del Valle propolis, 2',4'-dihydroxychalcone, showed cytotoxic activity (LC50 values of 0.5 microg/mL) but was not genotoxic or mutagenic. Furthermore, this compound was able to inhibit the mutagenicity of IQ (ID50 values of 1 microg/plate) but was unable to inhibit the mutagenicity of NPD. Our results suggest a potential anticarcinogenic activity of Amaicha del Valle propolis and the chalcone isolated from it.

Evaluation of Genotoxic and Mutagenic Activity of Organic Extracts from Drinking Water Sources

PubMed Central

Guan, Ying; Wang, Xiaodong; Wong, Minghung; Sun, Guoping; An, Taicheng; Guo, Jun

2017-01-01

An increasing number of industrial, agricultural and commercial chemicals in the aquatic environment lead to various deleterious effects on organisms, which is becoming a serious global health concern. In this study, the Ames test and SOS/umu test were conducted to investigate the potential genotoxicity and mutagenicity caused by organic extracts from drinking water sources. Organic content of source water was extracted with XAD-2 resin column and organic solvents. Four doses of the extract equivalent to 0.25, 0.5, 1 and 2L of source water were tested for toxicity. All the water samples were collected from six different locations in Guangdong province. The results of the Ames test and SOS/umu test showed that all the organic extracts from the water samples could induce different levels of DNA damage and mutagenic potentials at the dose of 2 L in the absence of S9 mix, which demonstrated the existence of genotoxicity and mutagenicity. Additionally, we found that Salmonella typhimurium strain TA98 was more sensitive for the mutagen. Correlation analysis between genotoxicity, Organochlorine Pesticides (OCPs) and Polycyclic Aromatic Hydrocarbons (PAHs) showed that most individual OCPs were frame shift toxicants in drinking water sources, and there was no correlation with total OCPs and PAHs. PMID:28125725

Toxic impact of bromide and iodide on drinking water disinfected with chlorine or chloramines.

PubMed

Yang, Yang; Komaki, Yukako; Kimura, Susana Y; Hu, Hong-Ying; Wagner, Elizabeth D; Mariñas, Benito J; Plewa, Michael J

2014-10-21

Disinfectants inactivate pathogens in source water; however, they also react with organic matter and bromide/iodide to form disinfection byproducts (DBPs). Although only a few DBP classes have been systematically analyzed for toxicity, iodinated and brominated DBPs tend to be the most toxic. The objectives of this research were (1) to determine if monochloramine (NH2Cl) disinfection generated drinking water with less toxicity than water disinfected with free chlorine (HOCl) and (2) to determine the impact of added bromide and iodide in conjunction with HOCl or NH2Cl disinfection on mammalian cell cytotoxicity and genomic DNA damage induction. Water disinfected with chlorine was less cytotoxic but more genotoxic than water disinfected with chloramine. For both disinfectants, the addition of Br(-) and I(-) increased cytotoxicity and genotoxicity with a greater response observed with NH2Cl disinfection. Both cytotoxicity and genotoxicity were highly correlated with TOBr and TOI. However, toxicity was weakly and inversely correlated with TOCl. Thus, the forcing agents for cytotoxicity and genotoxicity were the generation of brominated and iodinated DBPs rather than the formation of chlorinated DBPs. Disinfection practices need careful consideration especially when using source waters containing elevated bromide and iodide.

Genotoxic effects of nickel, trivalent and hexavalent chromium on the Eisenia fetida earthworm.

PubMed

Bigorgne, Emilie; Cossu-Leguille, Carole; Bonnard, Marc; Nahmani, Johanne

2010-08-01

The aim of this study was to examine genotoxic effects of nickel (Ni=105 mg kg(-1)), trivalent and hexavalent chromium (Cr=491 mg kg(-1)) on the Eisenia fetida earthworm after 2 and 4d of exposure to two different spiked soils (an artificial (OECD) and a natural one). DNA damages were evaluated on the earthworm's coelomocytes using the comet assay. After an exposure into OECD spiked soils, Ni did not induce genotoxic effect whereas Cr(III) and Cr(VI) revealed to be genotoxic after 2d of exposure. After 4d of exposure, only Cr(VI) still induced significant damages. In natural spiked soils, nickel and Cr(III) revealed to be genotoxic after 2 and 4d of exposure. Concerning Cr(VI) toxicity, all the earthworms died after 1d of exposure. These results underline the importance to take into account the nature and the speciation of metallic pollutants, although the experiment has been performed on spiked soil with higher bioavailibity than in contaminated natural soil. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Acute and subacute toxicity of the Carapa guianensis Aublet (Meliaceae) seed oil.

PubMed

Costa-Silva, J H; Lima, C R; Silva, E J R; Araújo, A V; Fraga, M C C A; Ribeiro E Ribeiro, A; Arruda, A C; Lafayette, S S L; Wanderley, A G

2008-03-28

Carapa guianensis (Meliaceae), known as Andiroba in Brazil, has been used by Amazon Rainforest indigenous communities for treatment of coughs, convulsions, skin diseases, arthritis, rheumatism, ear infections, to heal wounds and bruises and as an insect repellent. Carapa guianensis seed oil (SO) was evaluated for its acute and subacute toxicity (30 days) by the oral route in Wistar rats. In the acute toxicity test, SO (0.625-5.0g/kg, n=5/sex) did not produce any hazardous symptoms or deaths. The subacute treatment with SO (0.375, 0.75 and 1.5g/kg, n=10/group) failed to change body weight gain, food and water consumption. Hematological analysis showed no significant differences in any of the parameters examined. However, in the biochemical parameters, there was an increase in the alanine aminotransferase (ALT) serum level (29%) in the group SO 1.5g/kg. In addition, absolute and relative liver weights were increased at the doses of 0.75g/kg (23.4 and 19.1%) and 1.5g/kg (18.7 and 33.1%). In conclusion, acute and subacute administration of Carapa guianensis seed oil did not produce toxic effects in male Wistar rats. However, the increase in the ALT serum level and in both absolute and relative liver weights may indicate a possible hepatic toxicity.

Chemoradiation related acute morbidity in carcinoma cervix and correlation with hematologic toxicity: a South Indian prospective study.

PubMed

Kumaran, Aswathy; Guruvare, Shyamala; Sharan, Krishna; Rai, Lavanya; Hebbar, Shripad

2014-01-01

To assess chemoradiation related acute morbidity in women with carcinoma cervix and to find and correlation between hematologic toxicity and organ system specific damage. A prospective study was carried out between August 2012 and July 2013 enrolling 79 women with cancer cervix receiving chemo-radiotherapy. Weekly assessment of acute morbidity was done using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4 and the toxicities were graded. Anemia [77 (97.5%)], vomiting [75 (94.8%)] and diarrhea [72 (91.1%)], leukopenia [11 (13.9%)], cystitis [28 (35.4%], dermatitis [19 (24.1%)] and fatigue [29 (36.71%)] were the acute toxicities noted. The toxicities were most severe in 3rd and 5th week. All women could complete radiotherapy except two due to causes unrelated to radiation morbidity; seven (8.86%) had to discontinue chemotherapy due to leukopenia and intractable diarrhea. Though there was no correlation between anemia and other toxicities, it was found that all with leukopenia had diarrhea. Chemoradiation for cancer cervix is on the whole well tolerated. Leukopenia and severe diarrhea were the acute toxicities that compelled discontinuation of chemotherapy in two women. Though anemia had no correlation with gastrointestinal toxicity, all of those with leukopenia had diarrhea.

Identification of acute toxicants in New Bedford Harbor sediments

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

Ho, K.T.; McKinney, R.A.; Kuhn, A.

1997-03-01

New Bedford Harbor (NBH) is a marine Superfund site contaminated with high concentrations of polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs) and metals. Experiments were conducted to determine the causal toxic agent(s) in pore waters from New Bedford Harbor sediments to amphipods and mysid shrimp. Chemical manipulations to characterize toxicity revealed that pore-water toxicity was organic in nature. Fractionation and subsequent mass spectral identification of peaks in the toxic fraction indicated that PCBs. PAHs, and unknown compounds were present. Comparisons of PAH LC50s and PAH concentrations in this fraction indicated that the toxicity was not due to PAHs because themore » PAH concentrations were much lower than the reported PAH LC50s. One unknown peak was positively identified as bis(2-ethylhexyl) phthalate, and the other tentatively identified as pyrazole. Toxicity tests and comparison of toxicity in the blank and toxic fractions eliminated the two unknowns as toxic causal agents. The authors determined the range of PCB LC50s to fall between 10 and 110 ppb for Mysidopsis bahia and Ampelisca abdita. Concentrations of PCBs for the toxic fractions ranged from 12 to 27 ppb. This range falls within the observed PCB LC50s for M. bahia and A. abdita. Based upon these PCB concentrations, they concluded that PCBs were the acute toxic agents in NBH pore waters. Other compounds in the toxic fractions, or compounds that coeluted and were undistinguished from PCBs had minor contributions to the measured toxicity.« less

Acute and subacute toxicity of 10B-paraboronophenylalanine

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

Taniyama, K.; Fujiwara, H.; Kuno, T.

1989-07-01

The acute and subacute toxicities of 10B-paraboronophenylalanine (10B-BPA) were investigated in the rat, according to the Good Laboratory Practice Standard for safety studies on drugs in Japan. In the acute toxicity test of 10B-BPA, LD50 values of acidic 10B-BPA for intraperitoneal and subcutaneous injections were 640 mg/kg for male and 710 mg/kg for female rats, and more than 1,000 mg/kg for male and female rats, respectively. The LD50 values of neutral 10B-BPA for intraperitoneal and subcutaneous injections were more than 3,000 mg/kg for male and female rats. The difference in LD50 values between acidic and neutral 10B-BPA may be attributedmore » to the acidity of material. From the subacute toxicity test, in which the rats were injected daily subcutaneously for 28 days, the following toxic effects of 10B-BPA were observed. Increase in ketone level in the urine was induced in all rats treated with 10B-BPA. High dose of 10B-BPA (1,500 mg/kg) induced increase in spleen weight and reticulocyte count, and decrease in hemoglobin count, thereby suggesting that 10B-BPA causes hemolysis. Increases in the leukocyte count and the ratio of neutrophils and lymphocytes were also observed in rats treated with a high dose of 10B-BPA. This may be attributed to local reactions at the injection site. There were no significant differences in the findings between control rats and rats treated with a low dose of 10B-BPA (300 mg/kg). Thus, low doses of neutral 10B-BPA may be available for use as a drug.« less

Evaluation of cytotoxicity, genotoxicity and teratogenicity of marine sediments from Qingdao coastal areas using in vitro fish cell assay, comet assay and zebrafish embryo test.

PubMed

Yang, Fan; Zhang, Qianqian; Guo, Huarong; Zhang, Shicui

2010-10-01

Marine sediments are often a final sink for numerous anthropogenic contaminants and may impose serious effects on benthic organisms and ecosystem. An in vitro cell assay using a cell line derived from flounder gill (FG) cells, an in vitro comet assay in FG cells, and an in vitro zebrafish embryo assay were used to evaluate the in vitro cytotoxicity (measured by MTT reduction), genotoxicity and teratogenicity of crude sediment extracts of Li Cang (LC), Zhan Qiao (ZQ) and Olympic Sailing Center (OSC) from Qingdao coastal area. Sediments from the three sites displayed different cytotoxicity, genotoxicity and teratogenicity potencies; however, all three assays yielded similar LOECs (lowest observed effect concentration) for each site, suggesting that the assays were equally sensitive to and suitable for initial screening of the LOECs of marine sediments. The cytotoxicity, genotoxicity and teratogenicity for these three sampling sites were in the same order of LC>ZQ>OSC, indicating different degrees of contamination. Interestingly, trials with the three sediment extracts at the doses inducing a similar cytotoxicity as evaluated with MTT reduction did not produce similar genotoxicity and teratogenicity, with the genotoxic and teratogenic activities of LC and ZQ extracts being markedly higher than those of OSC sediments. These findings indicate that cytotoxicity does not form a fully equivalent toxicity index with that of genotoxicity and teratogenicity. Therefore, in order to assess the true toxic potential of marine sediments, all three assays should be performed. Analysis of 16 EPA (US Environmental Protection Agency) priority PAHs in these three sediment samples showed a clear correlation between PAH concentrations and sediment toxicities, with a higher PAH content corresponding to higher toxicity although PAHs are surely not the only cause. Copyright © 2010 Elsevier Ltd. All rights reserved.

Protective effect of boric acid on lead- and cadmium-induced genotoxicity in V79 cells.

PubMed

Ustündağ, Aylin; Behm, Claudia; Föllmann, Wolfram; Duydu, Yalçin; Degen, Gisela H

2014-06-01

The toxic heavy metals cadmium (Cd) and lead (Pb) are important environmental pollutants which can cause serious damage to human health. As the metal ions (Cd(2+) and Pb(2+)) accumulate in the organism, there is special concern regarding chronic toxicity and damage to the genetic material. Metal-induced genotoxicity has been attributed to indirect mechanisms, such as induction of oxidative stress and interference with DNA repair. Boron is a naturally occurring element and considered to be an essential micronutrient, although the cellular activities of boron compounds remain largely unexplored. The present study has been conducted to evaluate potential protective effects of boric acid (BA) against genotoxicity induced by cadmium chloride (CdCl2) and lead chloride (PbCl2) in V79 cell cultures. Cytotoxicity assays (neutral red uptake and cell titer blue assay) served to determine suitable concentrations for subsequent genotoxicity assays. Chromosomal damage and DNA strand breaks were assessed by micronucleus tests and comet assays. Both PbCl2 and CdCl2 (at 3, 5 and 10 µM) were shown to induce concentration-dependent increases in micronucleus frequencies and DNA strand breaks in V79 cells. BA itself was not cytotoxic (up to 300 µM) and showed no genotoxic effects. Pretreatment of cells with low levels of BA (2.5 and 10 µM) was found to strongly reduce the genotoxic effects of the tested metals. Based on the findings of this in vitro study, it can be suggested that boron provides an efficient protection against the induction of DNA strand breaks and micronuclei by lead and cadmium. Further studies on the underlying mechanisms for the protective effect of boron are needed.

Genotoxicity of the Musi River (Hyderabad, India) investigated with the VITOTOX test.

PubMed

Vijayashree, B; Ahuja, Y R; Regniers, L; Rao, V; Verschaeve, L

2005-01-01

The bacterial VITOTOX genotoxicity test was used to screen water samples collected from three different stations along the banks of the river Musi, in Hyderabad, India. Water was collected at three stations that differed from each other in the nature of the surrounding industrial and other activities. A number of different pollutants were also measured in water, soil and air samples. The three stations were found highly polluted and different with regard to the genotoxicity and toxicity of their samples. These results demonstrate the need for further biological studies in this area to generate valuable data on genomic instability, risk assessment of cancer, and to provide avenues for risk management.

40 CFR 797.1930 - Mysid shrimp acute toxicity test.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 31 2010-07-01 2010-07-01 true Mysid shrimp acute toxicity test. 797... acclimated in accordance with the test design into the test chambers. Mysids in the test chambers are... individuals are of similar age and experimental history. Mysids used for establishing laboratory cultures may...

What's your poison? Impact of individual repair capacity on the outcomes of genotoxic therapies in cancer. Part II – information content and validity of biomarkers for individual repair capacity in the assessment of outcomes of anticancer therapy

PubMed Central

Petkova, Rumena; Chelenkova, Pavlina; Georgieva, Elena; Chakarov, Stoian

2014-01-01

ABSTRACT The individual variance in the efficiency of repair of damage induced by genotoxic therapies may be an important factor in the assessment of eligibility for different anticancer treatments, the outcomes of various treatments and the therapy-associated complications, including acute and delayed toxicity and acquired drug resistance. The second part of this paper analyses the currently available information about the possibilities of using experimentally obtained knowledge about individual repair capacity for the purposes of personalised medicine and healthcare. PMID:26019482

Acute dyskerin depletion triggers cellular senescence and renders osteosarcoma cells resistant to genotoxic stress-induced apoptosis

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

Lin, Ping; Mobasher, Maral E.; Alawi, Faizan, E-mail: falawi@upenn.edu

Highlights: • Dyskerin depletion triggers cellular senescence in U2OS osteosarcoma cells. • Dyskerin-depleted cells are resistant to apoptosis induced by genotoxic stress. • Chromatin relaxation sensitizes dyskerin-depleted cells to apoptosis. - Abstract: Dyskerin is a conserved, nucleolar RNA-binding protein implicated in an increasing array of fundamental cellular processes. Germline mutation in the dyskerin gene (DKC1) is the cause of X-linked dyskeratosis congenita (DC). Conversely, wild-type dyskerin is overexpressed in sporadic cancers, and high-levels may be associated with poor prognosis. It was previously reported that acute loss of dyskerin function via siRNA-mediated depletion slowed the proliferation of transformed cell lines. However,more » the mechanisms remained unclear. Using human U2OS osteosarcoma cells, we show that siRNA-mediated dyskerin depletion induced cellular senescence as evidenced by proliferative arrest, senescence-associated heterochromatinization and a senescence-associated molecular profile. Senescence can render cells resistant to apoptosis. Conversely, chromatin relaxation can reverse the repressive effects of senescence-associated heterochromatinization on apoptosis. To this end, genotoxic stress-induced apoptosis was suppressed in dyskerin-depleted cells. In contrast, agents that induce chromatin relaxation, including histone deacetylase inhibitors and the DNA intercalator chloroquine, sensitized dyskerin-depleted cells to apoptosis. Dyskerin is a core component of the telomerase complex and plays an important role in telomere homeostasis. Defective telomere maintenance resulting in premature senescence is thought to primarily underlie the pathogenesis of X-linked DC. Since U2OS cells are telomerase-negative, this leads us to conclude that loss of dyskerin function can also induce cellular senescence via mechanisms independent of telomere shortening.« less

Risk assessment of petroleum-contaminated soil using soil enzyme activities and genotoxicity to Vicia faba.

PubMed

Ma, Jun; Shen, Jinglong; Liu, Qingxing; Fang, Fang; Cai, Hongsheng; Guo, Changhong

2014-05-01

Pollution caused by petroleum is one of the most serious problems worldwide. To better understand the toxic effects of petroleum-contaminated soil on the microflora and phytocommunity, we conducted a comprehensive field study on toxic effects of petroleum contaminated soil collected from the city of Daqing, an oil producing region of China. Urease, protease, invertase, and dehydrogenase activity were significantly reduced in microflora exposed to contaminated soils compared to the controls, whereas polyphenol oxidase activity was significantly increased (P < 0.05). Soil pH, electrical conductivity, and organic matter content were correlated with total petroleum hydrocarbons (TPHs) and a correlation (P < 0.01) existed between the C/N ratio and TPHs. Protease, invertase and catalase were correlated with TPHs. The Vicia faba micronucleus (MN) test, chromosome aberrant (CA) analyses, and the mitotic index (MI) were used to detect genotoxicity of water extracts of the soil. Petroleum-contaminated samples indicated serious genotoxicity to plants, including decreased index level of MI, increased frequency of MN and CA. The combination of enzyme activities and genotoxicity test via Vicia faba can be used as an important indicator for assessing the impact of TPH on soil ecosystem.

The Cytotoxicity and Genotoxicity of Hexavalent Chromium in Steller Sea Lion Lung Fibroblasts Compared to Human Lung Fibroblasts

PubMed Central

Wise, John Pierce; Wise, Sandra S.; Holmes, Amie L.; LaCerte, Carolyne; Shaffiey, Fariba; Aboueissa, AbouEl-Makarim

2010-01-01

In this study we directly compared soluble and particulate chromate cytotoxicity and genotoxicity in human (Homo sapiens) and sea lion (Eumetopias jubatus) lung fibroblasts. Our results show that hexavalent chromium induces increased cell death and chromosome damage in both human and sea lion cells with increasing intracellular chromium ion levels. The data further indicate that both sodium chromate and lead chromate are less cytotoxic and genotoxic to sea lion cells than human cells, based on administered dose. Differences in chromium ion uptake explained some but not all of the reduced amounts of sodium chromate-induced cell death. By contrast, uptake differences could explain the differences in sodium chromate-induced chromosome damage and particulate chromate-induced toxicity. Altogether they indicate that while hexavalent chromium induces similar toxic effects in sea lion and human cells, there are different mechanisms underlying the toxic outcomes. PMID:20211760

Genistein genotoxicity: Critical considerations of in vitro exposure dose

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

Klein, Catherine B.; King, Audrey A.

The potential health benefits of soy-derived phytoestrogens include their reported utility as anticarcinogens, cardioprotectants and as hormone replacement alternatives in menopause. Although there is increasing popularity of dietary phytoestrogen supplementation and of vegetarian and vegan diets among adolescents and adults, concerns about potential detrimental or other genotoxic effects persist. While a variety of genotoxic effects of phytoestrogens have been reported in vitro, the concentrations at which such effects occurred were often much higher than the physiologically relevant doses achievable by dietary or pharmacologic intake of soy foods or supplements. This review focuses on in vitro studies of the most abundantmore » soy phytoestrogen, genistein, critically examining dose as a crucial determinant of cellular effects. In consideration of levels of dietary genistein uptake and bioavailability we have defined in vitro concentrations of genistein > 5 {mu}M as non-physiological, and thus 'high' doses, in contrast to much of the previous literature. In doing so, many of the often-cited genotoxic effects of genistein, including apoptosis, cell growth inhibition, topoisomerase inhibition and others become less obvious. Recent cellular, epigenetic and microarray studies are beginning to decipher genistein effects that occur at dietarily relevant low concentrations. In toxicology, the well accepted principle of 'the dose defines the poison' applies to many toxicants and can be invoked, as herein, to distinguish genotoxic versus potentially beneficial in vitro effects of natural dietary products such as genistein.« less

Investigation of Acute and Chronic Toxicity Trends of Pesticides Using High-Throughput Bioluminescence Assay Based on the Test Organism Vibrio fischeri.

PubMed

Westlund, Paul; Nasuhoglu, Deniz; Isazadeh, Siavash; Yargeau, Viviane

2018-05-01

High-throughput acute and chronic toxicity tests using Vibrio fischeri were used to assess the toxicity of a variety of fungicides, herbicides, and neonicotinoids. The use of time points beyond the traditional 30 min of an acute test highlighted the sensitivity and applicability of the chronic toxicity test and indicated that for some compounds toxicity is underestimated using only the acute test. The comparison of EC 50 values obtained from acute and chronic tests provided insight regarding the toxicity mode of action, either being direct or indirect. Using a structure-activity relationship approach similar to the one used in hazard assessments, the relationship between toxicity and key physicochemical properties of pesticides was investigated and trends were identified. This study not only provides new information regarding acute toxicity of some pesticides but also is one of the first studies to investigate the chronic toxicity of pesticides using the test organism V. fischeri. The findings demonstrated that the initial bioluminescence has a large effect on the calculated effective concentrations for target compounds in both acute and chronic tests, providing a way to improve and standardize the test protocol. In addition, the findings emphasize the need for additional investigation regarding the relationship between a toxicant's physicochemical properties and mode of action in nontarget organisms.

Acute and subchronic oral toxicity of Coriolus versicolor standardized water extract in Sprague-Dawley rats.

PubMed

Hor, Sook Yee; Ahmad, Mariam; Farsi, Elham; Lim, Chung Pin; Asmawi, Mohd Zaini; Yam, Mun Fei

2011-10-11

Coriolus versicolor, which is known as Yun Zhi, is one of the commonly used Chinese medicinal herbs. Recent studies have demonstrated its antitumor activities on cancer cells which led to its widespread use in cancer patient. However, little toxicological information is available regarding its safety. The present study evaluated the potential toxicity of Coriolus versicolor standardized water extract after acute and subchronic administration in rats. In acute toxicity study, Coriolus versicolor water extract was administered by oral gavage to Sprague-Dawley (SD) rats (6 males, 6 females) at single doses of varying concentrations 1250, 2500 and 5000 mg/kg. In subchronic toxicity study, the extract was administered orally at doses of 1250, 2500 and 5000 mg/kg/day for 28 days to male and female SD rats respectively. General behavior, adverse effects and mortality were determined throughout the experimental period. Haematological and biochemical parameters, relative organ weights and histopathological were evaluated at the end of the experiment. There were no mortality and signs of toxicity in acute and subchronic toxicity studies. In the single dose acute toxicity and repeated dose 28-day subchronic toxicity studies, there were no significant difference in body weight, relative organ weight, haematological parameters, clinical chemistry, gross pathology and histopathology between treatment and control groups. Coriolus versicolor water extract did not cause remarkable adverse effect in SD rats. The oral lethal dose of Coriolus versicolor water extract is more than 5000 mg/kg and no-observed-adverse-effect level (NOAEL) of the extract for both male and female rats is 5000 mg/kg per day for 28 days. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Safety evaluation of tangeretin and the effect of using emulsion-based delivery system: Oral acute and 28-day sub-acute toxicity study using mice.

PubMed

Ting, Yuwen; Chiou, Yi-Shiou; Jiang, Yike; Pan, Min-Hsiung; Lin, Zhengyu; Huang, Qingrong

2015-08-01

Polymethoxyflavones, found widely in the peel of citrus fruits, is an emerging group of bioactive compounds with wide arrays of disease prevention functionalities. To understand the potential oral toxicity, tangeretin, being one of the most abundant polymethoxyflavones from natural sources, was used as model compound for the safety evaluation. Acute oral toxicity study was conducted using both male and female mice giving 1000, 2000, or 3000mg/kgbody weight (bw) of tangeretin in oil suspension from single gavage administration. No evidence of death was observed during 14-day post-administration period. Alterations of the hepatic cell and clinical chemistry profile increased dose dependently and exhibited distinct injury recovery pattern among different sexes. To determine the potential safety concern related to emulsification, the sub-acute toxicity of tangeretin in emulsion was evaluated and compared with un-processed oil suspension when conducting the sub-acute toxicity study over 28days. In the sub-acute study, emulsion system did not induce a significant increase of toxicity response. However, the daily low-dose application of tangeretin showed U-shaped dose-response pattern in regard to hepatic alteration. The result from this study can serve as a good safety reference for future application of polymethoxyflavone as a functional ingredient in food. Copyright © 2015 Elsevier Ltd. All rights reserved.

A re-evaluation of PETROTOX for predicting acute and chronic toxicity of petroleum substances.

PubMed

Redman, Aaron D; Parkerton, Thomas F; Leon Paumen, Miriam; Butler, Josh D; Letinski, Daniel J; den Haan, Klass

2017-08-01

The PETROTOX model was developed to perform aquatic hazard assessment of petroleum substances based on substance composition. The model relies on the hydrocarbon block method, which is widely used for conducting petroleum substance risk assessments providing further justification for evaluating model performance. Previous work described this model and provided a preliminary calibration and validation using acute toxicity data for limited petroleum substance. The objective of the present study was to re-evaluate PETROTOX using expanded data covering both acute and chronic toxicity endpoints on invertebrates, algae, and fish for a wider range of petroleum substances. The results indicated that recalibration of 2 model parameters was required, namely, the algal critical target lipid body burden and the log octanol-water partition coefficient (K OW ) limit, used to account for reduced bioavailability of hydrophobic constituents. Acute predictions from the updated model were compared with observed toxicity data and found to generally be within a factor of 3 for algae and invertebrates but overestimated fish toxicity. Chronic predictions were generally within a factor of 5 of empirical data. Furthermore, PETROTOX predicted acute and chronic hazard classifications that were consistent or conservative in 93 and 84% of comparisons, respectively. The PETROTOX model is considered suitable for the purpose of characterizing petroleum substance hazard in substance classification and risk assessments. Environ Toxicol Chem 2017;36:2245-2252. © 2017 SETAC. © 2017 SETAC.

Fluorescence-based recombination assay for sensitive and specific detection of genotoxic carcinogens in human cells.

PubMed

Ireno, Ivanildce C; Baumann, Cindy; Stöber, Regina; Hengstler, Jan G; Wiesmüller, Lisa

2014-05-01

In vitro genotoxicity tests are known to suffer from several shortcomings, mammalian cell-based assays, in particular, from low specificities. Following a novel concept of genotoxicity detection, we developed a fluorescence-based method in living human cells. The assay quantifies DNA recombination events triggered by DNA double-strand breaks and damage-induced replication fork stalling predicted to detect a broad spectrum of genotoxic modes of action. To maximize sensitivities, we engineered a DNA substrate encompassing a chemoresponsive element from the human genome. Using this substrate, we screened various human tumor and non-transformed cell types differing in the DNA damage response, which revealed that detection of genotoxic carcinogens was independent of the p53 status but abrogated by apoptosis. Cell types enabling robust and sensitive genotoxicity detection were selected for the generation of reporter clones with chromosomally integrated DNA recombination substrate. Reporter cell lines were scrutinized with 21 compounds, stratified into five sets according to the established categories for identification of carcinogenic compounds: genotoxic carcinogens ("true positives"), non-genotoxic carcinogens, compounds without genotoxic or carcinogenic effect ("true negatives") and non-carcinogenic compounds, which have been reported to induce chromosomal aberrations or mutations in mammalian cell-based assays ("false positives"). Our results document detection of genotoxic carcinogens in independent cell clones and at levels of cellular toxicities <60 % with a sensitivity of >85 %, specificity of ≥90 % and detection of false-positive compounds <17 %. Importantly, through testing cyclophosphamide in combination with primary hepatocyte cultures, we additionally provide proof-of-concept for the identification of carcinogens requiring metabolic activation using this novel assay system.

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.

Identifying and designing chemicals with minimal acute aquatic toxicity

PubMed Central

Kostal, Jakub; Voutchkova-Kostal, Adelina; Anastas, Paul T.; Zimmerman, Julie Beth

2015-01-01

Industrial ecology has revolutionized our understanding of material stocks and flows in our economy and society. For this important discipline to have even deeper impact, we must understand the inherent nature of these materials in terms of human health and the environment. This paper focuses on methods to design synthetic chemicals to reduce their intrinsic ability to cause adverse consequence to the biosphere. Advances in the fields of computational chemistry and molecular toxicology in recent decades allow the development of predictive models that inform the design of molecules with reduced potential to be toxic to humans or the environment. The approach presented herein builds on the important work in quantitative structure–activity relationships by linking toxicological and chemical mechanistic insights to the identification of critical physical–chemical properties needed to be modified. This in silico approach yields design guidelines using boundary values for physiochemical properties. Acute aquatic toxicity serves as a model endpoint in this study. Defining value ranges for properties related to bioavailability and reactivity eliminates 99% of the chemicals in the highest concern for acute aquatic toxicity category. This approach and its future implementations are expected to yield very powerful tools for life cycle assessment practitioners and molecular designers that allow rapid assessment of multiple environmental and human health endpoints and inform modifications to minimize hazard. PMID:24639521

Identifying and designing chemicals with minimal acute aquatic toxicity.

PubMed

Kostal, Jakub; Voutchkova-Kostal, Adelina; Anastas, Paul T; Zimmerman, Julie Beth

2015-05-19

Industrial ecology has revolutionized our understanding of material stocks and flows in our economy and society. For this important discipline to have even deeper impact, we must understand the inherent nature of these materials in terms of human health and the environment. This paper focuses on methods to design synthetic chemicals to reduce their intrinsic ability to cause adverse consequence to the biosphere. Advances in the fields of computational chemistry and molecular toxicology in recent decades allow the development of predictive models that inform the design of molecules with reduced potential to be toxic to humans or the environment. The approach presented herein builds on the important work in quantitative structure-activity relationships by linking toxicological and chemical mechanistic insights to the identification of critical physical-chemical properties needed to be modified. This in silico approach yields design guidelines using boundary values for physiochemical properties. Acute aquatic toxicity serves as a model endpoint in this study. Defining value ranges for properties related to bioavailability and reactivity eliminates 99% of the chemicals in the highest concern for acute aquatic toxicity category. This approach and its future implementations are expected to yield very powerful tools for life cycle assessment practitioners and molecular designers that allow rapid assessment of multiple environmental and human health endpoints and inform modifications to minimize hazard.

Absence of in vivo genotoxicity of 3-monochloropropane-1,2-diol and associated fatty acid esters in a 4-week comprehensive toxicity study using F344 gpt delta rats.

PubMed

Onami, Saeko; Cho, Young-Man; Toyoda, Takeshi; Horibata, Katsuyoshi; Ishii, Yuji; Umemura, Takashi; Honma, Masamitsu; Nohmi, Takehiko; Nishikawa, Akiyoshi; Ogawa, Kumiko

2014-07-01

3-Monochloropropane-1,2-diol (3-MCPD) is regarded as a rat renal and testicular carcinogen and has been classified as a possible human carcinogen (group 2B) by International Agency for Research on Cancer. This is potentially of great importance given that esters of this compound have recently found to be generated in many foods and food ingredients as a result of food processing. There have been a few reports about their toxicity, although we have recently found that the toxicity profile of 3-MCPD esters was similar to that of 3-MCPD in a rat 13-week repeated dose study, except for the acute renal toxicity seen in 3-MCPD-treated females. In the present study, to examine in vivo genotoxicity we administered equimolar doses of 3-MCPD or 3-MCPD fatty acid esters (palmitate diester, palmitate monoester and oleate diester) to 6-week-old male F344 gpt delta rats carrying a reporter transgene for 4 weeks by intragastric administration. In vivo micronucleus, Pig-a mutation and gpt assays were performed, as well as investigations of major toxicological parameters including histopathological features. As one result, the relative kidney weights of the 3-MCPD and all three ester groups were significantly increased compared with the vehicle control group. However, the frequency of micronucleated reticulocytes and Pig-a mutant red blood cells did not differ among groups. Moreover, no changes were observed in mutant frequencies of gpt and red/gam (Spi(-)) genes in the kidney and the testis of 3-MCPD and 3-MCPD-fatty-acid-esters-treated rats. In histopathological analyses, no treatment related changes were observed, except for decrease of eosinophilic bodies in the kidneys of all treated groups. These results suggest that 3-MCPD and its fatty acid esters are not in vivo genotoxins, although they may exert renal toxicity. © The Author 2014. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e

Intestinal inflammation induces genotoxicity to extraintestinal tissues and cell types in mice

PubMed Central

Westbrook, Aya M.; Wei, Bo; Braun, Jonathan; Schiestl, Robert H.

2011-01-01

Chronic intestinal inflammation leads to increased risk of colorectal and small intestinal cancers, and is also associated with extraintestinal manifestations such as lymphomas, other solid cancers, and autoimmune disorders. We have previously found that acute and chronic intestinal inflammation causes DNA damage to circulating peripheral leukocytes, manifesting a systemic effect in genetic and chemically-induced models of intestinal inflammation. This study addresses the scope of tissue targets and genotoxic damage induced by inflammation-associated genotoxicity. Using several experimental models of intestinal inflammation, we analyzed various types of DNA damage in leukocyte subpopulations of the blood, spleen, mesenteric and peripheral lymph nodes; and, in intestinal epithelial cells, hepatocytes, and the brain. Genotoxicity in the form of DNA single and double stranded breaks accompanied by oxidative base damage was found in leukocyte subpopulations of the blood, diverse lymphoid organs, intestinal epithelial cells, and hepatocytes. The brain did not demonstrate significant levels of DNA double strand breaks as measured by γ-H2AX immunostaining. CD4+ and CD8+ T-cells were most sensitive to DNA damage versus other cell types in the peripheral blood. In vivo measurements and in vitro modeling suggested that genotoxicity was induced by increased levels of systemically circulating proinflammatory cytokines. Moreover, genotoxicity involved increased damage rather than reduced repair, since it not associated with decreased expression of the DNA double-strand break recognition and repair protein, ataxia telangiectasia mutated (ATM). These findings suggest that levels of intestinal inflammation contribute to the remote tissue burden of genotoxicity, with potential effects on non-intestinal diseases and cancer. PMID:21520038

Psychosis associated with acute recreational drug toxicity: a European case series.

PubMed

Vallersnes, Odd Martin; Dines, Alison M; Wood, David M; Yates, Christopher; Heyerdahl, Fridtjof; Hovda, Knut Erik; Giraudon, Isabelle; Dargan, Paul I

2016-08-18

Psychosis can be associated with acute recreational drug and novel psychoactive substance (NPS) toxicity. However, there is limited data available on how common this is and which drugs are most frequently implicated. We describe a European case series of psychosis associated with acute recreational drug toxicity, and estimate the frequency of psychosis for different recreational drugs. The European Drug Emergencies Network (Euro-DEN) collects data on presentations to Emergency Departments (EDs) with acute recreational drug and NPS toxicity at 16 centres in ten countries. Euro-DEN data from October 2013 through September 2014 was retrospectively searched, and cases with psychosis were included. The proportion of cases with psychosis per drug was calculated in the searched Euro-DEN dataset. Psychosis was present in 348 (6.3 %) of 5529 cases. The median (interquartile range) age was 29 (24-38) years, 276 (79.3 %) were male and 114 (32.8 %) were admitted to psychiatric ward. The drugs most commonly reported were cannabis in 90 (25.9 %) cases, amphetamine in 87 (25.0 %) and cocaine in 56 (16.1 %). More than one drug was taken in 189 (54.3 %) cases. Psychosis was frequent in those ED presentations involving tryptamines (4/7; 57.1 %), methylenedioxypyrovalerone (MDPV) (6/22; 27.3 %), methylphenidate (6/26; 23.1 %), lysergic acid diethylamide (LSD) (18/86; 20.9 %), psilocybe mushrooms (3/16; 18.8 %), synthetic cannabinoid receptor agonists (4/26; 15.4 %) and amphetamine (87/593; 14.7 %), but less common in those involving mephedrone (14/245; 5.7 %), methylenedioxymethamphetamine (MDMA) (20/461; 4.3 %) and methedrone (3/92; 3.3 %). Amphetamine was the most frequent drug associated with psychosis when only one agent was reported, with psychosis occurring in 32.4 % of these presentations. The frequency of psychosis in acute recreational drug toxicity varies considerably between drugs, but is a major problem in amphetamine poisoning. In rapidly changing drug markets and

Acute toxicity of nickel nanoparticles in rats after intravenous injection

PubMed Central

Magaye, Ruth R; Yue, Xia; Zou, Baobo; Shi, Hongbo; Yu, Hongsheng; Liu, Kui; Lin, Xialu; Xu, Jin; Yang, Cui; Wu, Aiguo; Zhao, Jinshun

2014-01-01

This study was carried out to add scientific data in regard to the use of metallic nanoparticles in nanomedicine. The acute toxicity of nickel (Ni) nanoparticles (50 nm), intravenously injected through the dorsal penile vein of Sprague Dawley rats was evaluated in this study. Fourteen days after injection, Ni nanoparticles induced liver and spleen injury, lung inflammation, and caused cardiac toxicity. These results indicate that precautionary measures should be taken with regard to the use of Ni nanoparticles or Ni compounds in nanomedicine. PMID:24648736

Acute toxicity of peracetic acid (PAA) formulations to Ichthyophthirius multifiliis theronts.

PubMed

Straus, David L; Meinelt, Thomas

2009-04-01

Peracetic acid (PAA) is an antimicrobial disinfectant used in agriculture, food processing, and medical facilities. It has recently been suggested as a means to control infestations of Ichthyophthirius multifiliis. The purpose of this study was to determine the acute toxicity of two products containing 4.5% and 40% PAA to I. multifiliis theronts from two geographically separate isolates. Theronts were exposed to concentrations of PAA in 96-well plates containing groundwater at 23 degrees C. Acute toxicity was observed over a 4-h period. No significant difference in the median lethal concentration (LC(50)) estimates was evident between the two isolates at 4 h with the 4.5% PAA product (0.146 versus 0.108 mg/l PAA), while there was a statistical difference between the 4 h LC(50) with the 40% PAA product (0.274 versus 0.158 mg/l PAA). These results suggest that PAA is toxic to I. multifiliis theronts at low concentrations and that one of the isolates was more resistant to this compound.

Predictors of Severe Acute and Late Toxicities in Patients With Localized Head-and-Neck Cancer Treated With Radiation Therapy

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

Meyer, Francois, E-mail: francois.meyer@chuq.qc.ca; Fortin, Andre; Wang, Chang Shu

2012-03-15

Purpose: Radiation therapy (RT) causes acute and late toxicities that affect various organs and functions. In a large cohort of patients treated with RT for localized head and neck cancer (HNC), we prospectively assessed the occurrence of RT-induced acute and late toxicities and identified characteristics that predicted these toxicities. Methods and Materials: We conducted a randomized trial among 540 patients treated with RT for localized HNC to assess whether vitamin E supplementation could improve disease outcomes. Adverse effects of RT were assessed using the Radiation Therapy Oncology Group Acute Radiation Morbidity Criteria during RT and one month after RT, andmore » the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring Scheme at six and 12 months after RT. The most severe adverse effect among the organs/tissues was selected as an overall measure of either acute or late toxicity. Grade 3 and 4 toxicities were considered as severe. Stepwise multivariate logistic regression models were used to identify all independent predictors (p < 0.05) of acute or late toxicity and to estimate odds ratios (OR) for severe toxicity with their 95% confidence intervals (CI). Results: Grade 3 or 4 toxicity was observed in 23% and 4% of patients, respectively, for acute and late toxicity. Four independent predictors of severe acute toxicity were identified: sex (female vs. male: OR = 1.72, 95% confidence interval [CI]: 1.06-2.80), Karnofsky Performance Status (OR = 0.67 for a 10-point increment, 95% CI: 0.52-0.88), body mass index (above 25 vs. below: OR = 1.88, 95% CI: 1.22-2.90), TNM stage (Stage II vs. I: OR = 1.91, 95% CI: 1.25-2.92). Two independent predictors were found for severe late toxicity: female sex (OR = 3.96, 95% CI: 1.41-11.08) and weight loss during RT (OR = 1.26 for a 1 kg increment, 95% CI: 1.12-1.41). Conclusions: Knowledge of these predictors easily collected in a clinical setting

Lack of in vivo embryotoxic and genotoxic activities of orally administered stem bark aqueous extract of Mangifera indica L. (Vimang).

PubMed

González, J E; Rodríguez, M D; Rodeiro, I; Morffi, J; Guerra, E; Leal, F; García, H; Goicochea, E; Guerrero, S; Garrido, G; Delgado, R; Nuñez-Selles, A J

2007-12-01

Mango (Mangifera indica L.) stem bark aqueous extract (MSBE) is a new natural product with antioxidant, anti-inflammatory and immunomodulatory effects known by the brand name of its formulations as Vimang. Previously, the oral toxicity studies of the extract showed a low toxicity potential up to 2000 mg/kg. This work reports the results about teratogenic and genotoxicologic studies of MSBE. For embryotoxicity study, MSBE (20, 200, or 2000 mg/kg/day) was given to Sprague-Dawley rats by gavage on days 6-15 of gestation. For genotoxicity, MSBE was administered three times during 48 h to NMRI mice. Cyclophosphamide (50 mg/kg) was used as a positive control. No maternal or developmental toxicities were observed when the rats were killed on day 20th. The maternal body-weight gain was not affected. No dose-related effects were observed in implantations, fetal viability or external fetal development. Skeletal and visceral development was similar among fetuses from all groups. No genotoxicity was observed in bone marrow erythrocytes and liver cells after administration. MSBE appears to be neither embryotoxic nor genotoxic as measured by bone marrow cytogenetics in rodents.

Development of an acceptable factor to estimate chronic end points from acute toxicity data

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

Venman, B.C.; Flaga, C.

1985-12-01

Acceptable daily intake (ADI) values are routinely developed for threshold toxicants from NOAELs determined from human or animal chronic or subchronic data. These NOAELs are then divided by appropriate uncertainty factors ranging from 10 to 1000 depending on the quality of the data. However, for the vast majority of chemicals used industrially, adequate toxicity data needed to use this process are not available. Thus, a procedure to estimate a chronic toxicity endpoint from acute toxicity data, such as an oral rat LD50, becomes necessary. An acute-to-chronic application factor of 0.0001 was developed, which when multiplied by an oral LD50 formore » an individual chemical, yields a surrogate chronic NOAEL. This figure can then be used to estimate an acceptable daily exposure for humans. The process used to estimate this application factor is detailed.« less

Comparison of Reversibility of Rat Forestomach Lesions Induced by Genotoxic and Non‐genotoxic Carcinogens

PubMed Central

Kagawa, Masataka; Hakoi, Kazuo; Yamamoto, Atsushi; Futakuchi, Mitsuru

1993-01-01

Reversibility of forestomach lesions induced by genotoxic and non‐genotoxic carcinogens was compared histopathologically. Groups of 30 to 33 male F344 rats were given dietary 0.1% 8‐nitroquinoline, dietary 0.4–0.2% 2‐(2‐furyl)‐3‐(5‐nitro‐2‐furyl)acrylamide, an intragastric dose of 20 mg/kg body weight N‐methyl‐N′‐nitro‐N‐nitrosoguanidine once a week, or 20 ppm N‐methylnitrosourethane in the drinking water as a genotoxic carcinogen, or 2% butylated hydroxyanisole, 2% caffeic acid, 2% sesamol or 2% 4‐methoxyphenol in the diet as a non‐genotoxic carcinogen for 24 weeks. Ten or 11 rats in each group were killed at week 24. Half of the remainder were maintained on basal diet alone for an additional 24 weeks and the other half were given the same chemical for 48 weeks, and then killed. Forestomach lesions induced by genotoxic carcinogens did not regress after removal of carcinogens. In contrast, simple or papillary hyperplasia (SPH), but not basal cell hyperplasia (BCH), induced by non‐genotoxic carcinogens clearly regressed after cessation of insult. SFH labeling indices in the non‐genotoxic carcinogen‐treated cases decreased after removal of the carcinogenic stimulus whereas BCH values were low irrespective of treatment. Atypical hyperplasia (AH), observed at high incidences in rats treated with genotoxic carcinogens, was also evident in animals receiving non‐genotoxic agents, even after their withdrawal, albeit at low incidences. AH labeling indices remained high even without continued insult. These results indicate that even with non‐genotoxic carcinogens, heritable alterations at the DNA level could occur during strong cell proliferation and result in AH development. This putative preneoplastic lesion might then progress to produce carcinomas. PMID:8276717

Development of a general baseline toxicity QSAR model for the fish embryo acute toxicity test.

PubMed

Klüver, Nils; Vogs, Carolina; Altenburger, Rolf; Escher, Beate I; Scholz, Stefan

2016-12-01

Fish embryos have become a popular model in ecotoxicology and toxicology. The fish embryo acute toxicity test (FET) with the zebrafish embryo was recently adopted by the OECD as technical guideline TG 236 and a large database of concentrations causing 50% lethality (LC 50 ) is available in the literature. Quantitative Structure-Activity Relationships (QSARs) of baseline toxicity (also called narcosis) are helpful to estimate the minimum toxicity of chemicals to be tested and to identify excess toxicity in existing data sets. Here, we analyzed an existing fish embryo toxicity database and established a QSAR for fish embryo LC 50 using chemicals that were independently classified to act according to the non-specific mode of action of baseline toxicity. The octanol-water partition coefficient K ow is commonly applied to discriminate between non-polar and polar narcotics. Replacing the K ow by the liposome-water partition coefficient K lipw yielded a common QSAR for polar and non-polar baseline toxicants. This developed baseline toxicity QSAR was applied to compare the final mode of action (MOA) assignment of 132 chemicals. Further, we included the analysis of internal lethal concentration (ILC 50 ) and chemical activity (La 50 ) as complementary approaches to evaluate the robustness of the FET baseline toxicity. The analysis of the FET dataset revealed that specifically acting and reactive chemicals converged towards the baseline toxicity QSAR with increasing hydrophobicity. The developed FET baseline toxicity QSAR can be used to identify specifically acting or reactive compounds by determination of the toxic ratio and in combination with appropriate endpoints to infer the MOA for chemicals. Copyright © 2016 Elsevier Ltd. All rights reserved.

20180311 - Variability of LD50 Values from Rat Oral Acute Toxicity Studies: Implications for Alternative Model Development (SOT)

EPA Science Inventory

Alternative models developed for estimating acute systemic toxicity are generally evaluated using in vivo LD50 values. However, in vivo acute systemic toxicity studies can produce variable results, even when conducted according to accepted test guidelines. This variability can ma...

The role of natural indigo dye in alleviation of genotoxicity of sodium dithionite as a reducing agent.

PubMed

Bektaş, İdris; Karaman, Şengül; Dıraz, Emel; Çelik, Mustafa

2016-12-01

Indigo blue is a natural dye used for thousands of years by civilizations to dye fabric blue and it is naturally obtained from Isatis tinctoria. I. tinctoria is not only used for extraction of indigo blue color but also used medicinally in Traditional Chinese Medicine because of its active compounds. Sodium dithionite (Na 2 S 2 O 4 ) is used in dye bath for indigo blue extraction, but this reducing agent and its derivatives are major pollutants of textile industry and subsequently have hazardous influences on public health. Herein, the present study was designed to obtain the high yield of natural indigo dye but with low possible toxic effect. In this context, genotoxic effects of particular combinations of natural dye solutions obtained from Isatis tinctoria subsp. tomentolla with Na 2 S 2 O 4 as reducing agent were investigated. Dye solutions were obtained using two different pH levels (pH 9 and 11) and three different concentrations of Na 2 S 2 O 4 (2.5, 5 and 10 mg/ml). In addition to the dye solutions and reducing agent, aqueous extracts of I. tinctoria were assessed for their genotoxicity on human lymphocytes. For in vitro testing of genotoxicity, chromosomal aberrations (CAs), sister chromatid exchanges (SCEs) and mitotic indexes (MI) assays were used. Accordingly, Na 2 S 2 O 4 caused significant increases in CA and SCE as well decrease in MI but the genotoxic effects of sodium dithionite were reduced with natural indigo dye. As a result, aqueous extracts of Isatis leaves removed the toxic effects of sodium dithionite and showed anti-genotoxic effect. For the optimal and desired quality but with less toxic effects of natural dye, 2.5 mg/ml (for wool yarn) and 5 mg/ml (for cotton yarn) of Na 2 S 2 O 4 doses were found to be the best doses for reduction in the dye bath at Ph 9.

Acute oral toxicity: variability, reliability, relevance and interspecies comparison of rodent LD50 data from literature surveyed for the ACuteTox project.

PubMed

Hoffmann, Sebastian; Kinsner-Ovaskainen, Agnieszka; Prieto, Pilar; Mangelsdorf, Inge; Bieler, Christian; Cole, Thomas

2010-12-01

The ACuteTox project has aimed to optimise and prevalidate an in vitro testing strategy for predicting human acute toxicity. Ninety-seven reference substances were selected and an in vivo acute toxicity database was compiled. Comprehensive statistical analyses of the in vivo LD50 data to evaluate variability and reliability, interspecies correlation, predictive capacities with regard to EU and GHS toxicity categories, and deduction of performance criteria for in vitro methods is presented. For the majority of substances variability among rodent data followed a log normal distribution where good reproducibility was found. Rat and mouse interspecies comparison of LD50 studies by ordinary regression showed high correlation, with coefficients of determination, ranging between 0.8 and 0.9. Substance specific differences were only significant for warfarin and cycloheximide. No correlation of compound LD50 range with presumed study quality rank (by assigning Klimisch reliability scores) was found. Modelling based on LD50 variability showed that with at least 90% probability ∼54% of the substances would fall into only one GHS category and ∼44% would fall within two adjacent categories. These results could form the basis for deriving a predictive capacity that should be expected from alternative approaches to the conventional in vivo acute oral toxicity test. Copyright © 2010 Elsevier Inc. All rights reserved.

Genotoxic effects of high dose rate X-ray and low dose rate gamma radiation in ApcMin/+ mice.

PubMed

Graupner, Anne; Eide, Dag M; Brede, Dag A; Ellender, Michele; Lindbo Hansen, Elisabeth; Oughton, Deborah H; Bouffler, Simon D; Brunborg, Gunnar; Olsen, Ann Karin

2017-10-01

Risk estimates for radiation-induced cancer in humans are based on epidemiological data largely drawn from the Japanese atomic bomb survivor studies, which received an acute high dose rate (HDR) ionising radiation. Limited knowledge exists about the effects of chronic low dose rate (LDR) exposure, particularly with respect to the application of the dose and dose rate effectiveness factor. As part of a study to investigate the development of colon cancer following chronic LDR vs. acute HDR radiation, this study presents the results of genotoxic effects in blood of exposed mice. CBAB6 F1 Apc +/+ (wild type) and Apc Min/+ mice were chronically exposed to estimated whole body absorbed doses of 1.7 or 3.2 Gy 60 Co-γ-rays at a LDR (2.2 mGy h -1 ) or acutely exposed to 2.6 Gy HDR X-rays (1.3 Gy min -1 ). Genotoxic endpoints assessed in blood included chromosomal damage (flow cytometry based micronuclei (MN) assay), mutation analyses (Pig-a gene mutation assay), and levels of DNA lesions (Comet assay, single-strand breaks (ssb), alkali labile sites (als), oxidized DNA bases). Ionising radiation (ca. 3 Gy) induced genotoxic effects dependent on the dose rate. Chromosomal aberrations (MN assay) increased 3- and 10-fold after chronic LDR and acute HDR, respectively. Phenotypic mutation frequencies as well as DNA lesions (ssb/als) were modulated after acute HDR but not after chronic LDR. The Apc Min/+ genotype did not influence the outcome in any of the investigated endpoints. The results herein will add to the scant data available on genotoxic effects following chronic LDR of ionising radiation. Environ. Mol. Mutagen. 58:560-569, 2017. © 2017 The Authors Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society. © 2017 The Authors Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society.

Soil ingestion: a concern for acute toxicity in children.

PubMed Central

Calabrese, E J; Stanek, E J; James, R C; Roberts, S M

1997-01-01

Several soil ingestion studies have indicated that some children ingest substantial amounts of soil on given days. Although the EPA has assumed that 95% of children ingest 200 mg soil/day or less for exposure assessment purposes, some children have been observed to ingest up to 25-60 g soil during a single day. In light of the potential for children to ingest such large amounts of soil, an assessment was made of the possibility for soil pica episodes to result in acute intoxication from contaminant concentrations the EPA regards as representing conservative screening values (i.e., EPA soil screening levels and EPA Region III risk-based concentrations for residential soils). For a set of 13 chemicals included in the analysis, contaminant doses resulting from a one-time soil pica episode (5-50 g of soil ingested) were compared with acute dosages shown to produce toxicity in humans in clinical studies or case reports. For four of these chemicals, a soil pica episode was found to result in a contaminant dose approximating or exceeding the acute human lethal dose. For five of the remaining chemicals, the contaminant dose from a soil pica episode was well within the reported dose range in humans for toxicity other than lethality. Because both the exposure episodes and the toxicological response information are derived from observations in humans, these findings are regarded as particularly relevant for human health risk assessment. They suggest that, for some chemicals, ostensibly conservative soil criteria based on chronic exposure using current EPA methodology may not be protective of children during acute soil pica episodes. PMID:9405323

Genotoxicity Studies Performed in the Ecuadorian Population

PubMed Central

Paz-y-Miño, César; Cumbal, Nadia; Sánchez, María Eugenia

2012-01-01

Genotoxicity studies in Ecuador have been carried out during the past two decades. The focuses of the research were mainly the area of environmental issues, where the populations have been accidentally exposed to contaminants and the area of occupational exposure of individuals at the workplace. This paper includes studies carried out in the population of the Amazon region, a zone known for its rich biodiversity as well as for the ecological damage caused by oil spills and chemical sprayings whose consequences continue to be controversial. Additionally, we show the results of studies comprised of individuals occupationally exposed to toxic agents in two very different settings: flower plantation workers exposed to pesticide mixtures and X-ray exposure of hospital workers. The results from these studies confirm that genotoxicity studies can help evaluate current conditions and prevent further damage in the populations exposed to contaminants. As such, they are evidence of the need for biomonitoring employers at risk, stricter law enforcement regarding the use of pesticides, and increasingly conscientious oil extraction activities. PMID:22496977

Acute and chronic toxicity of sodium sulfate to four freshwater organisms in water-only exposures

USGS Publications Warehouse

Wang, Ning; Consbrock, Rebecca A.; Ingersoll, Christopher G.; Hardesty, Douglas K.; Brumbaugh, William G.; Hammer, Edward J.; Bauer, Candice R.; Mount, David R.

2016-01-01

The acute and chronic toxicity of sulfate (tested as sodium sulfate) was determined in diluted well water (hardness of 100 mg/L and pH 8.2) with a cladoceran (Ceriodaphnia dubia; 2-d and 7-d exposures), a midge (Chironomus dilutus; 4-d and 41-d exposures), a unionid mussel (pink mucket, Lampsilis abrupta; 4-d and 28-d exposures), and a fish (fathead minnow, Pimephales promelas; 4-d and 34-d exposures). Among the 4 species, the cladoceran and mussel were acutely more sensitive to sulfate than the midge and fathead minnow, whereas the fathead minnow was chronically more sensitive than the other 3 species. Acute-to-chronic ratios ranged from 2.34 to 5.68 for the 3 invertebrates but were as high as 12.69 for the fish. The fathead minnow was highly sensitive to sulfate during the transitional period from embryo development to hatching in the diluted well water, and thus, additional short-term (7- to 14-d) sulfate toxicity tests were conducted starting with embryonic fathead minnow in test waters with different ionic compositions at a water hardness of 100 mg/L. Increasing chloride in test water from 10 mg Cl/L to 25 mg Cl/L did not influence sulfate toxicity to the fish, whereas increasing potassium in test water from 1mg K/L to 3mg K/L substantially reduced the toxicity of sulfate. The results indicate that both acute and chronic sulfate toxicity data, and the influence of potassium on sulfate toxicity to fish embryos, need to be considered when environmental guidance values for sulfate are developed or refined.

Penicillium sp. as an organism that degrades endosulfan and reduces its genotoxic effects.

PubMed

Romero-Aguilar, Mariana; Tovar-Sánchez, Efrain; Sánchez-Salinas, Enrique; Mussali-Galante, Patricia; Sánchez-Meza, Juan Carlos; Castrejón-Godínez, María Luisa; Dantán-González, Edgar; Trujillo-Vera, Miguel Ángel; Ortiz-Hernández, Ma Laura

2014-01-01

Endosulfan is an organochloride and persistent pesticide that has caused concern because of its impact in the environment and its toxicity to and bioaccumulation in living organisms. In this study, we isolated an endosulfan-degrading fungus from the activated sludge from an industrial wastewater treatment plant. Through repetitive enrichment and successive subculture in media containing endosulfan as the sole carbon source, a fungus designated CHE 23 was isolated. Based on a phylogenetic analysis, strain CHE 23 was assigned to the genus Penicillium sp. In a mineral salt medium with 50 mg/l endosulfan as the sole source carbon, CHE 23 removed the added endosulfan in a period of six days. To verify the decrease in endosulfan toxicity due to the activity of the fungus, we performed genotoxicity tests trough the single cell gel electrophoresis assay or comet assay, with Eisenia fetida as the bioindicator species. This organism was exposed to the supernatants of the culture of the fungus and endosulfan. Our results indicated that the genotoxicity of endosulfan was completely reduced due the activity of this fungus. These results suggest that the Penicillium sp. CHE 23 strain can be used to degrade endosulfan residues and/or for water and soil bioremediation processes without causing toxicity problems, which are probably due to the generation of no-toxic metabolites during biodegradation.

Genotoxicity testing of a fenugreek extract.

PubMed

Flammang, A M; Cifone, M A; Erexson, G L; Stankowski, L F

2004-11-01

Fenugreek seeds have been used in traditional medicines as a remedy for diabetes. Rich in protein, fenugreek seeds contain the unique major free amino acid 4-hydroxyisoleucine (4-OH-Ile), which has been characterized as one of the active ingredients for blood glucose control. Current use of fenugreek in foodstuff has been limited to its role as a flavoring agent, and not as an ingredient to help mitigate the blood glucose response for people with diabetes. As part of a safety evaluation of novel ingredients for use in blood glucose control, the potential genotoxicity of a fenugreek seed extract (THL), containing a minimum of 40% 4-OH-ILE, was evaluated using the standard battery of tests (reverse mutation assay; mouse lymphoma forward mutation assay; mouse micronucleus assay) recommended by US Food and Drug Administration (FDA) for food ingredients. THL was determined not to be genotoxic under the conditions of the tested genetic toxicity battery. The negative assay results provide support that addition of THL to foodstuffs formulated for people with diabetes is expected to be safe. A wide safety margin is established, as anticipated doses are small compared to the doses administered in the assays.

Histopathological and genotoxic effects of chlorpyrifos in rats.

PubMed

Ezzi, Lobna; Belhadj Salah, Imen; Haouas, Zohra; Sakly, Amina; Grissa, Intissar; Chakroun, Sana; Kerkeni, Emna; Hassine, Mohsen; Mehdi, Meriem; Ben Cheikh, Hassen

2016-03-01

This study aims to investigate the effects of chlorpyrifos's sub-acute exposure on male rats. Two groups with six animals each were orally treated, respectively, with 3.1 mg/kg b w and 6.2 mg/kg b w of chlorpyrifos during 4 weeks. The genotoxic effect of chlopyrifos was investigated using the comet assay and the micronucleus test. Some hematological and liver's histopathological changes were also evaluated. Results revealed that chlorpyrifos induced histopathological alterations in liver parenchyma. The lymphoid infiltration observed in liver sections and the increase in white blood cells parameter are signs of inflammation. A significant increase in the platelet' count and in polychromatic erythrocytes/normochromatic erythrocytes (PCE/NCE) ratio was observed in chlorpyrifos-treated groups which could be due to the stimulatory effect of chlorpyrifos on cell formation in the bone marrow at lower doses. In addition, the increase of bone marrow micronucleus percentage and the comet tail length revealed a genotoxic potential of chlorpyrifos in vivo.

Acute Toxic Neuropathy Mimicking Guillain Barre Syndrome

PubMed Central

Jalal, Muhammed Jasim Abdul; Fernandez, Shirley Joan; Menon, Murali Krishna

2015-01-01

Case: A 30 year old male presented with numbness of palms and soles followed by weakness of upper limbs and lower limbs of 5 days duration, which was ascending and progressive. Three months back he was treated for oral and genital ulcers with oral steroids. His ulcers improved and shifted to indigenous medication. His clinical examination showed polyneuropathy. CSF study did not show albuminocytological dissociation. Nerve conduction study showed demyelinating polyneuropathy. His blood samples and the ayurvedic drug samples were sent for toxicological analysis. Inference: Acute toxic neuropathy - Arsenic PMID:25811007

Clinical and neuropathological findings of acute carbon monoxide toxicity in chihuahuas following smoke inhalation.

PubMed

Kent, Marc; Creevy, Kate E; Delahunta, Alexander

2010-01-01

Three adult Chihuahuas were presented for evaluation after smoke inhalation during a house fire. All three dogs received supportive care and supplemental oxygen. After initial improvement, the dogs developed seizures. Despite anticonvulsant therapy and supportive care, the dogs died. The brains of two dogs were examined. Lesions were identified that were compatible with acute carbon monoxide (CO) toxicity. Lesions were confined to the caudate nucleus, the globus pallidus, and the substantia nigra bilaterally, as well as the cerebellum, cerebral cortex, and dorsal thalamus. This case report describes the clinicopathological sequelae in acute CO toxicity.

Acute photo-induced toxicity and toxicokinetics of single compounds and mixtures of polycyclic aromatic hydrocarbons in zebrafish.

PubMed

Willis, Alison M; Oris, James T

2014-09-01

The present study examined photo-induced toxicity and toxicokinetics for acute exposure to selected polycyclic aromatic hydrocarbons (PAHs) in zebrafish. Photo-enhanced toxicity from co-exposure to ultraviolet (UV) radiation and PAHs enhanced the toxicity and exhibited toxic effects at PAH concentrations orders of magnitude below effects observed in the absence of UV. Because environmental exposure to PAHs is usually in the form of complex mixtures, the present study examined the photo-induced toxicity of both single compounds and mixtures of PAHs. In a sensitive larval life stage of zebrafish, acute photo-induced median lethal concentrations (LC50s) were derived for 4 PAHs (anthracene, pyrene, carbazole, and phenanthrene) to examine the hypothesis that phototoxic (anthracene and pyrene) and nonphototoxic (carbazole and phenanthrene) pathways of mixtures could be predicted from single exposures. Anthracene and pyrene were phototoxic as predicted; however, carbazole exhibited moderate photo-induced toxicity and phenanthrene exhibited weak photo-induced toxicity. The toxicity of each chemical alone was used to compare the toxicity of mixtures in binary, tertiary, and quaternary combinations of these PAHs, and a predictive model for environmental mixtures was generated. The results indicated that the acute toxicity of PAH mixtures was additive in phototoxic scenarios, regardless of the magnitude of photo-enhancement. Based on PAH concentrations found in water and circumstances of high UV dose to aquatic systems, there exists potential risk of photo-induced toxicity to aquatic organisms. © 2014 SETAC.

Genotoxicity and carcinogenicity of acrylamide: a critical review.

PubMed

Carere, Angelo

2006-01-01

In 2002, public health concerns were raised by Swedish studies showing that relatively high levels of acrylamide were formed during the frying, roasting, or baking of a variety of foods, including potatoes, cereal products and coffee at temperatures above 120 degrees C. Acrylamide possesses a range of hazardous properties, the key effects being carcinogenicity, genotoxicity, neurotoxicity and reproductive toxicity. Acrylamide is clearly carcinogenic in studies in animals, in which it causes increased tumour incidence at a variety of sites. Although the mechanisms for tumour induction in experimental animals have not yet fully elucidated, the in vivo genotoxicity at gene and chromosome level in somatic and germ cells in rodents cannot be discounted from contributing to it. At this time, there is no information to indicate any significant difference between rodents and humans in sensitivity to cancer formation from acrylamide. The present available epidemiological studies of human industrial and accidental exposures have to be considered not suitable for use in the cancer risk assessment of acrylamide in food, due to several limitations. In reviewing the genotoxicity and carcinogenicity of acrylamide, the author has taken into account also the evaluations made by the IARC in 1994, the FAO/WHO in 2002 by the European Commission Scientific Committee on Food (SCF) in 2002 and by the Joint FAO/WHO Expert Committee on Food Additive (JECFA) in 2005.

Toxicity of two effluents from agricultural activity: Comparing the genotoxicity of sugar cane and orange vinasse.

PubMed

Garcia, Camila Fernandes H; Souza, Raphael B de; de Souza, Cleiton Pereira; Christofoletti, Cintya Ap; Fontanetti, Carmem S

2017-08-01

Vinasse, produced by several countries as a by-product of agricultural activity, has different alternatives for its reuse, mainly fertirrigation. Several monocultures, such as sugar cane and orange crops, produce this effluent. Sugar cane vinasse is already widely used in fertirrigation and orange vinasse has potential for this intention. However, its use as a fertilizer has caused great concern. Thus, ecotoxicological evaluation is extremely important in order to assess the possible effects on the environment. Therefore, the aim of this study was to evaluate the potential toxicity of vinasse of two different crops: sugar cane and orange. For this purpose, bioassays with Allium cepa as a test organism were performed with two vinasse dilutions (2.5% and 5%) to detect chromosomal aberrations and micronucleus induction. The results showed that both types of vinasse are able to induce chromosomal aberrations in meristematic cells, mainly nuclear and anaphasic bridges, suggesting genotoxic potential. The induction of micronuclei in cells of the F 1 region suggests that the two residues have mutagenic potential. Thus, caution is advised when applying these effluents in the environment. Copyright © 2017. Published by Elsevier Inc.

Acute toxicity of 6 neonicotinoid insecticides to freshwater invertebrates.

PubMed

Raby, Melanie; Nowierski, Monica; Perlov, Dmitri; Zhao, Xiaoming; Hao, Chunyan; Poirier, David G; Sibley, Paul K

2018-05-01

Neonicotinoids are a group of insecticides commonly used in agriculture. Due to their high water solubility, neonicotinoids can be transported to surface waters and have the potential to be toxic to aquatic life. The present study assessed and compared the acute (48- or 96-h) toxicity of 6 neonicotinoids (acetamiprid, clothianidin, dinotefuran, imidacloprid, thiacloprid, and thiamethoxam) to 21 laboratory-cultured and field-collected aquatic invertebrates spanning 10 aquatic arthropod orders. Test conditions mimicked species' habitat, with lentic taxa exposed under static conditions, and lotic taxa exposed under recirculating systems. Median lethal concentrations (LC50s) and median effect concentrations (EC50s; immobility) were calculated and used to construct separate lethal- and immobilization-derived species sensitivity distributions for each neonicotinoid, from which 5th percentile hazard concentrations (HC5s) were calculated. The results showed that the most sensitive invertebrates were insects from the orders Ephemeroptera (Neocloeon triangulifer) and Diptera (Chironomus dilutus), whereas cladocerans (Daphnia magna, Ceriodaphnia dubia) were the least sensitive. The HC5s were compared with neonicotinoid environmental concentrations from Ontario (Canada) monitoring studies. For all neonicotinoids except imidacloprid, the resulting hazard quotients indicated little to no hazard in terms of acute toxicity to aquatic communities in Ontario freshwater streams. For the neonicotinoid imidacloprid, a moderate hazard was found when only invertebrate immobilization, and not lethality, data were considered. Environ Toxicol Chem 2018;37:1430-1445. © 2018 SETAC. © 2018 SETAC.

MONITORING THE AIR FOR TOXIC AND GENOTOXIC COMPOUNDS

EPA Science Inventory

A time-integrated sampling system interfaced with a toxicity-based assay is reported for monitoring volatile toxic industrial chemicals (TICs). Semipermeable membrane devices (SPMDs) using dimethyl sulfoxide (DMSO) as the fill solvent accumulated each of 17 TICs from the vapor p...

Use of butterflies as nontarget insect test species and the acute toxicity and hazard of mosquito control insecticides.

PubMed

Hoang, Tham C; Pryor, Rachel L; Rand, Gary M; Frakes, Robert A

2011-04-01

Honeybees are the standard insect test species used for toxicity testing of pesticides on nontarget insects for the U.S. Environmental Protection Agency (U.S. EPA) under the Federal Insecticide Fungicide and Rodenticide Act (FIFRA). Butterflies are another important insect order and a valued ecological resource in pollination. The current study conducted acute toxicity tests with naled, permethrin, and dichlorvos on fifth larval instar (caterpillars) and adults of different native Florida, USA, butterfly species to determine median lethal doses (24-h LD50), because limited acute toxicity data are available with this major insect group. Thorax- and wing-only applications of each insecticide were conducted. Based on LD50s, thorax and wing application exposures were acutely toxic to both caterpillars and adults. Permethrin was the most acutely toxic insecticide after thorax exposure to fifth instars and adult butterflies. However, no generalization on acute toxicity (sensitivity) of the insecticides could be concluded based on exposures to fifth instars versus adult butterflies or on thorax versus wing exposures of adult butterflies. A comparison of LD50s of the butterflies from this study (caterpillars and adults) with honeybee LD50s for the adult mosquito insecticides on a µg/organism or µg/g basis indicates that several butterfly species are more sensitive to these insecticides than are honeybees. A comparison of species sensitivity distributions for all three insecticides shows that permethrin had the lowest 10th percentile. Using a hazard quotient approach indicates that both permethrin and naled applications in the field may present potential acute hazards to butterflies, whereas no acute hazard of dichlorvos is apparent in butterflies. Butterflies should be considered as potential test organisms when nontarget insect testing of pesticides is suggested under FIFRA. Copyright © 2011 SETAC.

Acute toxicity of selected herbicides and surfactants to larvae of the midge Chironomus riparius

USGS Publications Warehouse

Buhl, Kevin J.; Faerber, Neil L.

1989-01-01

The acute toxicities of eight commercial herbicides and two surfactants to early fourth instar larvae of the midgeChironomus riparius were determined under static conditions. The formulated herbicides tested were Eradicane® (EPTC), Fargo® (triallate), Lasso® (alachlor), ME4 Brominal® (bromoxynil), Ramrod® (propachlor), Rodeo® (glyphosate), Sencor®(metribuzin), and Sutan (+)® (butylate); the two surfactants were Activator N.F.® and Ortho X-77®. In addition, technical grade alachlor, metribuzin, propachlor, and triallate were tested for comparison with the formulated herbicides. The relative toxicity of the commercial formulations, based on percent active ingredient, varied considerably. The EC50 values ranged from 1.23 mg/L for Fargo® to 5,600 mg/L for Rodeo®. Fargo®, ME4 Brominal®, and Ramrod®were moderately toxic to midge larvae; Lasso®, Sutan (+)®, and Eradicane® were slightly toxic; and Sencor® and Rodeo® were practically non-toxic. The 48-hr EC50 values of the two surfactants were nearly identical and were considered moderately toxic to midges. For two of the herbicides in which the technical grade material was tested, the inert ingredients in the formulations had a significant effect on the toxicity of the active ingredients. Fargo® was twice as toxic as technical grade triallate, whereas Sencor® was considerably less toxic than technical grade metribuzin. A comparison of the slope function values indicated that the toxic action of all the compounds occurred within a relatively narrow range. Published acute toxicity data on these compounds for other freshwater biota were tabulated and compared with our results. In general, the relative order of toxicity toC. riparius was similar to those for other freshwater invertebrates and fish. Maximum concentrations of each herbicide in bulk runoff during a projected “critical” runoff event were calculated as a percentage of the application rate lost in a given volume of runoff. A comparison

Combined cyto/genotoxic activity of a selected antineoplastic drug mixture in human circulating blood cells.

PubMed

Gajski, Goran; Gerić, Marko; Domijan, Ana-Marija; Garaj-Vrhovac, Vera

2016-12-01

Antineoplastic drugs are highly cytotoxic chemotherapeutic agents that can often interfere directly or indirectly with the cell's genome. In an environmental or medical setting simultaneous exposure may occur. Such multiple exposures may pose a higher risk than it could be assumed from the studies evaluating the effect of a single substance. Therefore, in the present study we tested the combined cyto/genotoxicity of a mixture of selected antineoplastic drugs with different mechanisms of action (5-fluorouracil, etoposide, and imatinib mesylate) towards human lymphocytes in vitro. The results suggest that the selected antineoplastic drug mixture is potentially cyto/genotoxic and that it can induce cell and genome damage even at low concentrations. Moreover, the changes in the measured oxidative stress parameters suggest the participation of reactive oxygen species in the cyto/genotoxicity of the selected mixture. The obtained results indicate not only that such mixtures may pose a risk to cell and genome integrity, but also that single compound toxicity data are not sufficient for the predicting toxicity in a complex environment. Altogether, the results emphasise the need for further toxicological screening of antineoplastic drug mixtures, especially at low environmentally relevant concentrations, as to avoid any possible adverse effects on the environment and human health. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evaluation of multiwalled carbon nanotubes toxicity in two fish species.

PubMed

Cimbaluk, Giovani Valentin; Ramsdorf, Wanessa Algarte; Perussolo, Maiara Carolina; Santos, Hayanna Karla Felipe; Da Silva De Assis, Helena Cristina; Schnitzler, Mariane Cristina; Schnitzler, Danielle Caroline; Carneiro, Pedro Gontijo; Cestari, Marta Margarete

2018-04-15

Carbon Nanotubes are among the most promising materials for the technology industry. Their unique physical and chemical proprieties may reduce the production costs and improve the efficiency of a large range of products. However, the same characteristics that have made nanomaterials interesting for industry may be responsible for inducing toxic effects on the aquatic organisms. Since the carbon nanotubes toxicity is still a controversial issue, we performed tests of acute and subchronic exposure to a commercial sample of multiwalled carbon nanotubes in two fish species, an exotic model (Danio rerio) and a native one (Astyanax altiparanae). Using the alkaline version of the comet assay on erythrocytes and the piscine micronucleous, also performed on erythrocytes, it was verified that the tested carbon nanotubes sample did not generate apparent genotoxicity by means of single/double DNA strand break or clastogenic/aneugenic effects over any of the species, independently of the exposure period. Although, our findings indicate the possibility of the occurrence of CNTs-DNA crosslinks. Apparently, the sample tested induces oxidative stress after subchronic exposure as shown by activity of superoxide dismutase and catalase. The data obtained by the activity levels of acetylcholinesterase suggests acute neurotoxicity in Astyanax altiparanae and subchronic neurotoxicity in Danio rerio. Copyright © 2017 Elsevier Inc. All rights reserved.

Assessment of antimutagenic and genotoxic potential of senna (Cassia angustifolia Vahl.) aqueous extract using in vitro assays.

PubMed

Silva, C R; Monteiro, M R; Rocha, H M; Ribeiro, A F; Caldeira-de-Araujo, A; Leitão, A C; Bezerra, R J A C; Pádula, M

2008-02-01

Senna (Cassia angustifolia Vahl.) is widely used as a laxative, although potential side effects, such as toxicity and genotoxicity, have been reported. This study evaluated genotoxic and mutagenic effects of senna aqueous extract (SAE) by means of four experimental assays: inactivation of Escherichia coli cultures; bacterial growth inhibition; reverse mutation test (Mutoxitest) and DNA strand break analysis in plasmid DNA. Our results demonstrated that SAE produces single and double strand breaks in plasmid DNA in a cell free system. On the other hand, SAE was not cytotoxic or mutagenic to Escherichia coli strains tested. In effect, SAE was able to avoid H(2)O(2)-induced mutagenesis and toxicity in Escherichia coli IC203 (uvrA oxyR) and IC205 (uvrA mutM) strains, pointing to a new antioxidant/antimutagenic action of SAE.

Acute toxicity assessment of explosive-contaminated soil extracting solution by luminescent bacteria assays.

PubMed

Xu, Wenjie; Jiang, Zhenming; Zhao, Quanlin; Zhang, Zhenzhong; Su, Hongping; Gao, Xuewen; Ye, Zhengfang

2016-11-01

Explosive-contaminated soil is harmful to people's health and the local ecosystem. The acute toxicity of its extracting solution was tested by bacterial luminescence assay using three kinds of luminescent bacteria to characterize the toxicity of the soil. An orthogonal test L 16 (4 5 ) was designed to optimize the soil extracting conditions. The optimum extracting conditions were obtained when the ultrasonic extraction time, ultrasonic extraction temperature, and the extraction repeat times were 6 h, 40 °C, and three, respectively. Fourier transform infrared spectroscopy (FTIR) results showed that the main components of the contaminated soil's extracting solution were 2,4-dinitrotoluene-3-sulfonate (2,4-DNT-3-SO 3 - ); 2,4-dinitrotoluene-5-sulfonate (2,4-DNT-5-SO 3 - ); and 2,6-dinitrotoluene (2,6-DNT). Compared with Photobacterium phosphoreum and Vibrio fischeri, Vibrio qinghaiensis sp. Nov. is more suitable for assessing the soil extracting solution's acute toxicity. Soil washing can remove most of the contaminants toxic to luminescent bacterium Vibrio qinghaiensis sp. Nov., suggesting that it may be a potential effective remediation method for explosive-contaminated soil.

High-Grade Acute Organ Toxicity as a Positive Prognostic Factor in Primary Radiochemotherapy for Anal Carcinoma

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

Wolff, Hendrik Andreas; Raus, Ismene; Jung, Klaus

Purpose: To test for a possible correlation between high-grade acute organ toxicity during primary radiochemotherapy and treatment outcome for patients with anal carcinoma. Methods and Materials: From 1991 to 2009, 72 patients with anal carcinoma were treated at our department (10 patients had stage I, 28 patients had stage II, 11 patients had stage IIIA, and 13 patients had stage IIIB cancer [Union Internationale Contre le Cancer criteria]). All patients received normofractionated (1.8 Gy/day, five times/week) whole-pelvis irradiation including iliac and inguinal lymph nodes with a cumulative dose of 50.4 Gy. Concomitant chemotherapy regimen consisted of two cycles of 5-fluorouracilmore » (1,000 mg/m{sup 2}total body surface area (TBSA)/day as continuous intravenous infusion on days 1-4 and 29-32) and mitomycin C (10 mg/m{sup 2}/TBSA, intravenously on days 1 and 29). Toxicity during treatment was monitored weekly, and any incidence of Common Toxicity Criteria (CTC) grade of {>=}3 for skin reaction, cystitis, proctitis, or enteritis was assessed as high-grade acute organ toxicity for later analysis. Results: We found significant correlation between high-grade acute organ toxicity and overall survival, locoregional control, and stoma-free survival, which was independent in multivariate analysis from other possible prognostic factors: patients with a CTC acute organ toxicity grade of {>=}3 had a 5-year overall survival rate of 97% compared to 30% in patients without (p < 0.01, multivariate analysis; 97% vs. 48%, p = 0.03 for locoregional control, and 95% vs. 59%, p = 0.05 for stoma-free survival). Conclusions: Our data indicate that normal tissue and tumor tissue may behave similarly with respect to treatment response, since high-grade acute organ toxicity during radiochemotherapy showed itself to be an independent prognostic marker in our patient population. This hypothesis should be further analyzed by using biomolecular and clinical levels in future clinical

In vivo dosimetry and acute toxicity in breast cancer patients undergoing intraoperative radiotherapy as boost

PubMed Central

Lee, Jason Joon Bock; Choi, Jinhyun; Ahn, Sung Gwe; Jeong, Joon; Lee, Ik Jae; Park, Kwangwoo; Kim, Kangpyo; Kim, Jun Won

2017-01-01

Purpose To report the results of a correlation analysis of skin dose assessed by in vivo dosimetry and the incidence of acute toxicity. This is a phase 2 trial evaluating the feasibility of intraoperative radiotherapy (IORT) as a boost for breast cancer patients. Materials and Methods Eligible patients were treated with IORT of 20 Gy followed by whole breast irradiation (WBI) of 46 Gy. A total of 55 patients with a minimum follow-up of 1 month after WBI were evaluated. Optically stimulated luminescence dosimeter (OSLD) detected radiation dose delivered to the skin during IORT. Acute toxicity was recorded according to the Common Terminology Criteria for Adverse Events v4.0. Clinical parameters were correlated with seroma formation and maximum skin dose. Results Median follow-up after IORT was 25.9 weeks (range, 12.7 to 50.3 weeks). Prior to WBI, only one patient developed acute toxicity. Following WBI, 30 patients experienced grade 1 skin toxicity and three patients had grade 2 skin toxicity. Skin dose during IORT exceeded 5 Gy in two patients: with grade 2 complications around the surgical scar in one patient who received 8.42 Gy. Breast volume on preoperative images (p = 0.001), ratio of applicator diameter and breast volume (p = 0.002), and distance between skin and tumor (p = 0.003) showed significant correlations with maximum skin dose. conclusions IORT as a boost was well-tolerated among Korean women without severe acute complication. In vivo dosimetry with OSLD can help ensure safe delivery of IORT as a boost. PMID:28712278

In vivo dosimetry and acute toxicity in breast cancer patients undergoing intraoperative radiotherapy as boost.

PubMed

Lee, Jason Joon Bock; Choi, Jinhyun; Ahn, Sung Gwe; Jeong, Joon; Lee, Ik Jae; Park, Kwangwoo; Kim, Kangpyo; Kim, Jun Won

2017-06-01

To report the results of a correlation analysis of skin dose assessed by in vivo dosimetry and the incidence of acute toxicity. This is a phase 2 trial evaluating the feasibility of intraoperative radiotherapy (IORT) as a boost for breast cancer patients. Eligible patients were treated with IORT of 20 Gy followed by whole breast irradiation (WBI) of 46 Gy. A total of 55 patients with a minimum follow-up of 1 month after WBI were evaluated. Optically stimulated luminescence dosimeter (OSLD) detected radiation dose delivered to the skin during IORT. Acute toxicity was recorded according to the Common Terminology Criteria for Adverse Events v4.0. Clinical parameters were correlated with seroma formation and maximum skin dose. Median follow-up after IORT was 25.9 weeks (range, 12.7 to 50.3 weeks). Prior to WBI, only one patient developed acute toxicity. Following WBI, 30 patients experienced grade 1 skin toxicity and three patients had grade 2 skin toxicity. Skin dose during IORT exceeded 5 Gy in two patients: with grade 2 complications around the surgical scar in one patient who received 8.42 Gy. Breast volume on preoperative images (p = 0.001), ratio of applicator diameter and breast volume (p = 0.002), and distance between skin and tumor (p = 0.003) showed significant correlations with maximum skin dose. IORT as a boost was well-tolerated among Korean women without severe acute complication. In vivo dosimetry with OSLD can help ensure safe delivery of IORT as a boost.

Mechanisms related to the genotoxicity of particles in the subway and from other sources.

PubMed

Karlsson, Hanna L; Holgersson, Asa; Möller, Lennart

2008-03-01

Negative health effects of airborne particles have clearly been shown in epidemiological studies. People get exposed to particles from various sources such as the combustion of, for example, diesel and wood and also from particles arising from tire-road wear. Another source of importance for certain populations is exposure to particles in subway systems. We recently reported that these particles were more genotoxic when compared to that of several other particle types. The aim of this study was to further investigate and compare the toxicity of subway particles and particles from other sources as well as investigate some mechanisms behind the genotoxicity of subway particles. This was done by comparing the ability of subway particles and particles from a street, pure tire-road wear particles, and particles from wood and diesel combustion to cause mitochondrial depolarization and to form intracellular reactive oxygen species (ROS). Furthermore, the genotoxicity and ability to cause oxidative stress was compared to magnetite particles since this is a main component in subway particles. It was concluded that the subway particles and also street particles and particles from wood and diesel combustion caused mitochondrial depolarization. The ability to damage the mitochondria is thus not the only explanation for the high genotoxicity of subway particles. Subway particles also formed intracellular ROS. This effect may be part of the explanation as to why subway particles show such high genotoxicity when compared to that of other particles. Genotoxicity can, however, not be explained by the main component, magnetite, by water-soluble metals, or by intracellular mobilized iron. The genotoxicity is most likely caused by highly reactive surfaces giving rise to oxidative stress.

Acute toxicity study of tilmicosin-loaded hydrogenated castor oil-solid lipid nanoparticles.

PubMed

Xie, Shuyu; Wang, Fenghua; Wang, Yan; Zhu, Luyan; Dong, Zhao; Wang, Xiaofang; Li, Xihe; Zhou, Wenzhong

2011-11-20

Our previous studies demonstrated that tilmicosin-loaded hydrogenated castor oil solid lipid nanoparticles (Til-HCO-SLN) are a promising formulation for enhanced pharmacological activity and therapeutic efficacy in veterinary use. The purpose of this work was to evaluate the acute toxicity of Til-HCO-SLN. Two nanoparticle doses were used for the study in ICR mice. The low dose (766 mg/kg.bw) with tilmicosin 7.5 times of the clinic dosage and below the median lethal dose (LD(50)) was subcutaneously administered twice on the first and 7th day. The single high dose (5 g/kg.bw) was the practical upper limit in an acute toxicity study and was administered subcutaneously on the first day. Blank HCO-SLN, native tilmicosin, and saline solution were included as controls. After medication, animals were monitored over 14 days, and then necropsied. Signs of toxicity were evaluated via mortality, symptoms of treatment effect, gross and microscopic pathology, and hematologic and biochemical parameters. After administration of native tilmicosin, all mice died within 2 h in the high dose group, in the low dose group 3 died after the first and 2 died after the second injections. The surviving mice in the tilmicosin low dose group showed hypoactivity, accelerated breath, gloomy spirit and lethargy. In contrast, all mice in Til-HCO-SLN and blank HCO-SLN groups survived at both low and high doses. The high nanoparticle dose induced transient clinical symptoms of treatment effect such as transient reversible action retardation, anorexy and gloomy spirit, increased spleen and liver coefficients and decreased heart coefficients, microscopic pathological changes of liver, spleen and heart, and minor changes in hematologic and biochemical parameters, but no adverse effects were observed in the nanoparticle low dose group. The results revealed that the LD50 of Til-HCO-SLN and blank HCO-SLN exceeded 5 g/kg.bw and thus the nanoparticles are considered low toxic according to the toxicity

Acute toxicity study of tilmicosin-loaded hydrogenated castor oil-solid lipid nanoparticles

PubMed Central

2011-01-01

Background Our previous studies demonstrated that tilmicosin-loaded hydrogenated castor oil solid lipid nanoparticles (Til-HCO-SLN) are a promising formulation for enhanced pharmacological activity and therapeutic efficacy in veterinary use. The purpose of this work was to evaluate the acute toxicity of Til-HCO-SLN. Methods Two nanoparticle doses were used for the study in ICR mice. The low dose (766 mg/kg.bw) with tilmicosin 7.5 times of the clinic dosage and below the median lethal dose (LD50) was subcutaneously administered twice on the first and 7th day. The single high dose (5 g/kg.bw) was the practical upper limit in an acute toxicity study and was administered subcutaneously on the first day. Blank HCO-SLN, native tilmicosin, and saline solution were included as controls. After medication, animals were monitored over 14 days, and then necropsied. Signs of toxicity were evaluated via mortality, symptoms of treatment effect, gross and microscopic pathology, and hematologic and biochemical parameters. Results After administration of native tilmicosin, all mice died within 2 h in the high dose group, in the low dose group 3 died after the first and 2 died after the second injections. The surviving mice in the tilmicosin low dose group showed hypoactivity, accelerated breath, gloomy spirit and lethargy. In contrast, all mice in Til-HCO-SLN and blank HCO-SLN groups survived at both low and high doses. The high nanoparticle dose induced transient clinical symptoms of treatment effect such as transient reversible action retardation, anorexy and gloomy spirit, increased spleen and liver coefficients and decreased heart coefficients, microscopic pathological changes of liver, spleen and heart, and minor changes in hematologic and biochemical parameters, but no adverse effects were observed in the nanoparticle low dose group. Conclusions The results revealed that the LD50 of Til-HCO-SLN and blank HCO-SLN exceeded 5 g/kg.bw and thus the nanoparticles are considered low

The use of the zebrafish (Danio rerio) embryo for the acute toxicity testing of surfactants, as a possible alternative to the acute fish test.

PubMed

Vaughan, Martin; van Egmond, Roger

2010-06-01

At present, the acute toxicity of chemicals to fish is most commonly estimated by means of a short-term test on juvenile or adult animals (OECD TG 203). Although, over the last few years, the numbers used have been reduced due to the implementation of the Three Rs (Reduction, Refinement and Replacement), significant numbers of fish are still used in acute toxicity tests. With the introduction of the new European Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) system, this number is likely to increase dramatically. The aim of this work was to test the acute toxicity of a number of anionic, cationic and non-ionic surfactants to embryos of the zebrafish (Danio rerio), over 48 hours, as a possible alternative to the standard 96-hour fish acute test. We measured the toxicities of 15 surfactants, and compared the results to previously generated adult D. rerio LC50 data (or other fish species, if these data were not available). Comparison of the LC50 data showed that embryos appear to be as sensitive to cationic and non-ionic surfactants as the adult fish, but possibly are more sensitive to anionic surfactants. Toxicity testing with the embryo test can be carried out more quickly than with the adult test, uses much less space and media, requires less effort, and therefore can be performed at a reduced cost. The embryo test may also uncover additional sub-lethal effects, although these were not observed for surfactants. The data presented here show that the 48-hour embryo test can be considered as a suitable alternative to the adult acute fish test for surfactants.

Acute and subacute oral toxicity of periodate salts in rats.

PubMed

Lent, Emily May; Crouse, Lee C B; Eck, William S

2017-02-01

Periodate salts are being developed as potential replacements for perchlorate due to potential health hazards associated with exposure to perchlorate. The aim of this study was to investigate acute and subacute effects of periodate salts in rats. Acute oral toxicity of potassium and sodium periodate was determined using the Sequential Stage-Wise Probit method. The LD 50 for potassium periodate was 732 (95% CI = 539-838, slope = 13.4) and 685 mg/kg (95% CI = 580-809, slope = 10.6) for females and males, respectively. The LD 50 for sodium periodate was 318 (95% CI = 292-347, slope = 24.3) and 741 mg/kg (95% CI = 704-779, slope = 31.2) for females and males, respectively. In the subacute study, rats were administered sodium periodate at five doses (1/16 LD 50 up to LD 50 ) or distilled water for 14-days via oral gavage. Female rats in the 318 mg/kg-day group and male rats in the 185, 370, and 741 mg/kg-day groups exhibited moribundity, kidney toxicity, uremia, and a stress response. BMDL 10 s of 17.2 and 33.7 mg/kg-day were derived for females and males, respectively. Comparison with the NOAEL for perchlorate-induced thyroid toxicity in rats (0.009 mg/kg-day) suggests sodium periodate is less toxic than perchlorate on a subacute basis. Copyright © 2016. Published by Elsevier Inc.

Cytotoxic, mutagenicity, and genotoxicity effects of guanylhydrazone derivatives.

PubMed

Pinhatti, Valéria Rodrigues; da Silva, Juliana; Martins, Tales Leandro Costa; Moura, Dinara Jaqueline; Rosa, Renato Moreira; Villela, Izabel; Stopiglia, Cheila Denise Ottonelli; da Silva Santos, Selma; Scroferneker, Maria Lúcia; Machado, Carlos Renato; Saffi, Jenifer; Henriques, João Antonio Pêgas

2016-08-01

Several studies have reported that guanylhydrazones display a variety of desirable biological properties, such as antihypertensive, antibacterial, and antimalarial behaviour. They furthermore promote anti-pneumocystosis and anti-trypanosomiasis, exhibit antitumor activity, and show significant cytotoxicity against cancer cell lines. In this work, we have evaluated the cytotoxicity, mutagenicity, and genotoxicity of two guanylhydrazones derivatives, (E)-2-[(2,3-dimethoxyphenyl) methylene] hydrazine carboxymidamide hydrochloride (2,3-DMeB) and (E)-2-[(3,4-dimethoxyphenyl) methylene] hydrazine carboxymidamide hydrochloride (3,4-DMeB), in different biological models. Both 2,3-DMeB and 3,4-DMeB induce weak cytotoxic and mutagenic effects in bacteria and yeast. The genotoxicity of these compounds was determined in a fibroblast cell line (V79) using alkaline comet assay, as well as a modified comet assay with bacterial enzymes formamidopyrimidine DNA-glycosylase (FPG) and endonuclease III (EndoIII). Both guanylhydrazone derivatives induced DNA damage. Treatment of V79 cells with EndoIII and FPG proteins demonstrated a significant effect of 2,3-DMeB and 3,4-DMeB with respect to oxidized bases. In addition, the derivatives induced a significant increase in the frequency of micronucleated cells at high doses. The antifungal and anti-trypanosomal properties of these guanylhydrazone derivatives were also evaluated, and the obtained results suggest that 2,3-DMeB is more effective than 3,4-DMeB. The biological activity of 2,3-DMeB and 3,4-DMeB may thus be related, at least in part, to their oxidative potential, as well as to their ability to interact with DNA. Considering the previously reported in vitro antitumor activity of guanylhydrazone derivatives in combination with the lack of acute toxicity and the fact that DNA damage is only observed at high doses should render both compounds good candidates for in vivo studies on antitumor activity. Copyright © 2016 Elsevier B

Systemic stereoselectivity study of flufiprole: Stereoselective bioactivity, acute toxicity and environmental fate.

PubMed

Tian, Mingming; Zhang, Qing; Hua, Xiude; Tang, Bowen; Gao, Beibei; Wang, Minghua

2016-12-15

In this study, the stereoselectivity of flufiprole enantiomers in regards to their bioactivity, acute toxicity and environmental fate is reported for the first time. Four types of representative insects (Plutella xylostella, Nilaparvata lugens, Mythimna separata and Acyrthosiphon pisum) were used to investigate enantioselective bioactivity. Acute toxicities of flufiprole enantiomers toward two non-target organisms were also evaluated. Moreover, stereoselective degradation in four vegetables under field conditions was studied in response to food safety concerns. The bioactivity of (R)-flufiprole was 1.9-5.1 times higher than that of (S)-flufiprole. (R)-flufiprole also showed 3.7-5.7 times higher acute toxicity to Scenedesmus obliquus and Trichogramma japonicum Ashmead than (S)-flufiprole. Opposite stereoselective degradation of the two enantiomers was observed in pak choi, spinach cucumber, and tomato. (S)-flufiprole degraded faster in pak choi and spinach, resulting in an enrichment of (R)-isomer. By contrast, (R)-isomer was preferentially degraded in cucumber and tomato. Molecular simulation technology was used to illuminate the mechanism of enantioselective bioactivity. The Glide Score (-5.82kcal/mol) for (R)-isomer was better than that (-5.11kcal/mol) of (S)-isomer and this calculation showed (R)-flufiprole was more effective in pest control. Consequently, significant stereoselectivity of flufiprole enantiomers should be taken into account when assessing the environmental health risk of the pesticide. Copyright © 2016 Elsevier B.V. All rights reserved.

Acute and subchronic toxicity of naturally weathered Exxon Valdez crude oil in mallards and ferrets

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

Stubblefield, W.A.; Hancock, G.A.; Ford, W.H.

1995-11-01

The toxic properties of naturally weathered Exxon Valdez crude oil (WEVC) were assessed in a battery of acute and subchronic toxicity tests using mallards, Anas platyrhynchos, and European ferrets, Mustela putorius. Adult mallard acute oral toxicity study results indicated no mortalities or signs o toxicity, i.e., no-observed-adverse-effect level (NOAEL) and median lethal dose (LD50) > 5,000 mg/kg. Acute oral feeding and food avoidance tests with ducklings also indicated no toxicity (NOAEL and LC50 > 50,000 mg/kg diet) with no evidence of food avoidance (FAC50 > 20,000 mg/kg diet). No mortalities or toxic signs were noted in a 14-d feeding studymore » with adult birds at dietary concentrations up to 100,000 mg WEVC/kg diet. Among clinical and physiological end points evaluated, the only significant difference noted was an increase in liver: body weight ratios in the 100,000-mg WEVC/kg diet dose group. No differences in clinical chemistry or hematological parameters were noted, and there were no consistent differences in histological evaluations of organ tissues. Daily oral doses of up to 5,000 mg/kg of WEVC over 5 d resulted in minimal effects on ferrets. Increased serum albumin concentrations were observed in the 5,000-mg/kg dose group females and decreased spleen weights were noted in females of all WEVC treatment groups. No other significant observations were noted.« less

Assessment of acute toxicity of carbofuran in Macrobrachium olfersii (Wiegmann, 1836) at different temperature levels.

PubMed

Barbieri, Edison; Moreira, Priscila; Luchini, Luiz Alberto; Hidalgo, Karla Ruiz; Muñoz, Alejandro

2016-01-01

Carbofuran (2,3-dihydro-2,2-dimethyl-7-benzofuranyl methylcarbamate; C12H15NO3) is one of the most toxic carbamate pesticides. For acute toxicity of carbofuran, juveniles of Macrobrachium olfersii were exposed to different concentrations of carbofuran using the static renewal method at different temperature levels (15, 20 and 25°C) at pH 7.0. The main purpose of the present study was to detect the acute toxicity of carbofuran to M. olfersii and investigate its effects on oxygen consumption and ammonium excretion; these tests have not been carried out in this species before. First, the acute toxicity - median lethal concentration - of carbofuran to M. olfersii for 24, 48, 72 and 96 h was examined, which resulted in the following values: 1.64, 1.22, 0.86 and 0.42 mg L(-1), respectively. Furthermore, we also found that carbofuran caused an inhibition in oxygen consumption of 60.6, 65.3 and 66.2% with respect to the control. In addition, after separate exposures to carbofuran, elevations in ammonium excretion were more than 500% with respect to the control. © The Author(s) 2013.

ESTIMATION OF ACUTE TOXICITY BY FITTING A DOSE-TIME RESPONSE SURFACE

EPA Science Inventory

In acute toxicity testing, organisms are continuously exposed to progressively increasing concentrations of a chemical and deaths of test organisms are recorded at several selected times. he results of the test are traditionally summarized by a dose-response curve, and the time c...

Acute and chronic toxicities of Bacopa monnieri extract in Sprague-Dawley rats.

PubMed

Sireeratawong, Seewaboon; Jaijoy, Kanjana; Khonsung, Parirat; Lertprasertsuk, Nirush; Ingkaninan, Kornkanok

2016-07-27

Bacopa monnieri is a medicinal plant which has long been used in Ayurvedic medicines to augment brain function and to improve memory. The purpose of our study was to identify and evaluate possible toxic effects of B. monnieri extract in rats by assessing hematological, biochemical, and histopathological parameters. Acute oral toxicity of Bacopa monnieri extract was studied in female rats by giving a single orally administered dose at a level of 5,000 mg/kg. The rats were monitored for toxic signs for 14 days. In the chronic toxicity test, groups of both female and male rats were given daily oral doses of B. monnieri extract at dose levels of either 30, 60, 300 or 1,500 mg/kg for 270 days. The behavior and health of the animals was then monitored. At the end of the observation period, the body and organ weights of the rats in each group were measured. Blood was collected and necropsy was performed to evaluate their hematology, blood clinical chemistry, and microanatomy. The acute toxicity test found no significant differences between the experimental and the control group rats. In the chronic toxicity test, animal behavior and health of the experimental groups were normal, just as in the control rats. All values of other parameters assessed remained within the normal range. A single oral administration of B. monnieri extract at the dose of 5,000 mg/kg did not cause any serious undesirable effects. B. monnieri extract at doses of 30, 60, 300 and 1,500 mg/kg given for 270 days did not produce any toxicity in rats.

Pharmacogenetics predictive of response and toxicity in acute lymphoblastic leukemia therapy.

PubMed

Mei, Lin; Ontiveros, Evelena P; Griffiths, Elizabeth A; Thompson, James E; Wang, Eunice S; Wetzler, Meir

2015-07-01

Acute lymphoblastic leukemia (ALL) is a relatively rare disease in adults accounting for no more than 20% of all cases of acute leukemia. By contrast with the pediatric population, in whom significant improvements in long term survival and even cure have been achieved over the last 30years, adult ALL remains a significant challenge. Overall survival in this group remains a relatively poor 20-40%. Modern research has focused on improved pharmacokinetics, novel pharmacogenetics and personalized principles to optimize the efficacy of the treatment while reducing toxicity. Here we review the pharmacogenetics of medications used in the management of patients with ALL, including l-asparaginase, glucocorticoids, 6-mercaptopurine, methotrexate, vincristine and tyrosine kinase inhibitors. Incorporating recent pharmacogenetic data, mainly from pediatric ALL, will provide novel perspective of predicting response and toxicity in both pediatric and adult ALL therapies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Study on acute toxicity of anti-vertigo granule on mice

NASA Astrophysics Data System (ADS)

Wen, Zhonghua; Hao, Shaojun; Xie, Guoqi; Li, Jun; Su, Feng; Liu, Xiaobin; Wang, Xidong; Zhang, Zhengchen

2018-04-01

To observe the effect of anti - glare particles on acute toxicity of mice. Methods: 40 male and female mice weighing 18 - 21 g were randomly divided into anti - glare granule group and normal saline control group. The maximum volume of anti - glare particles (0.94 g/ml) was administered before the experiment. Results: the oral toxicity of the suspension was very small. The maximal concentration of mice was given at the maximum volume of gastric perfusion, and it was given three times in 1st. The cumulative maximum tolerance dose was 112.8g/kg per day. The dose was 226 times of clinical dosage and no death was found in mice. Conclusion: the toxicity of Kangxuan granules is very small and it can be considered safe in clinical use.

Hypofractionated IMRT of the Prostate Bed After Radical Prostatectomy: Acute Toxicity in the PRIAMOS-1 Trial

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

Katayama, Sonja, E-mail: sonja.katayama@med.uni-heidelberg.de; Striecker, Thorbjoern; Kessel, Kerstin

Purpose: Hypofractionated radiation therapy as primary treatment for prostate cancer is currently being investigated in large phase 3 trials. However, there are few data on postoperative hypofractionation. The Radiation therapy for the Prostate Bed With or Without the Pelvic Lymph Nodes (PRIAMOS 1) trial was initiated as a prospective phase 2 trial to assess treatment safety and toxicity of a hypofractionated intensity modulated radiation therapy (IMRT) of the prostate bed. Methods and Materials: From February to September 2012, 40 patients with indications for adjuvant or salvage radiation therapy were enrolled. One patient dropped out before treatment. Patients received 54 Gy inmore » 18 fractions to the prostate bed with IMRT and daily image guidance. Gastrointestinal (GI) and genitourinary (GU) toxicities (according to National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0) were recorded weekly during treatment and 10 weeks after radiation therapy. Results: Overall acute toxicity was favorable, with no recorded adverse events grade ≥3. Acute GI toxicity rates were 56.4% (grade 1) and 17.9% (grade 2). Acute GU toxicity was recorded in 35.9% of patients (maximum grade 1). Urinary stress incontinence was not influenced by radiation therapy. The incidence of grade 1 urinary urge incontinence increased from 2.6% before to 23.1% 10 weeks after therapy, but grade 2 urge incontinence remained unchanged. Conclusions: Postoperative hypofractionated IMRT of the prostate bed is tolerated well, with no severe acute side effects.« less

Essential oil from fruit of Xylopia langsdorffiana: antitumour activity and toxicity.

PubMed

Moura, Ana Paula Gomes; Beltrão, Daiene Martins; Pita, João Carlos Lima Rodrigues; Xavier, Aline Lira; Brito, Monalisa Taveira; Sousa, Tatyanna Kelvia Gomes de; Batista, Leônia Maria; Carvalho, João Ernesto de; Ruiz, Ana Lúcia Tasca Gois; Della Torre, Adriana; Duarte, Marcelo Cavalcante; Tavares, Josean Fechine; da Silva, Marcelo Sobral; Sobral, Marianna Vieira

2016-12-01

The genus Xylopia L. (Annonaceae) includes aromatic plants that have both nutritional and medicinal uses. Essential oils of Xylopia species have antitumour effects. However, the efficacy of the essential oil from the fruit of Xylopia langsdorffiana St. Hil & Tul. (EOX) has not been examined. EOX was evaluated to determine its chemical composition, antitumour activity and toxicity. EOX was obtained from fresh fruits of X. langsdorffiana subjected to hydrodistillation, and gas chromatography-mass spectrometry was used to characterize the chemical composition of EOX. The toxicity of EOX was evaluated using haemolysis, acute toxicity and micronucleus assays. The in vitro antitumour activity of EOX was investigated using the sulforhodamine B assay. The sarcoma 180 murine tumour model was used to evaluate the in vivo antitumour activity and toxicity of EOX (50 and 100 mg/kg) after 7 d of treatment. The major components of EOX were α-pinene (34.57%) and limonene (31.75%). The HC 50 (concentration producing 50% haemolysis) was 293.6 μg/ml. EOX showed greater selectivity for the leukaemia cell line K562, with total growth inhibition (TGI) (concentration producing TGI) of 1.8 μg/ml, and for multidrug-resistant ovarian tumour cell line NCI/ADR-RES (TGI of 45.4 μg/ml). The LD 50 was approximately 351.09 mg/kg. At doses of 50 and 100 mg/kg, EOX inhibited the in vivo growth of sarcoma 180 by 38.67 and 54.32%, respectively. EOX displayed minor hepatic alterations characteristic of acute hepatitis and induced no genotoxicity. EOX showed in vitro and in vivo antitumour activity and low toxicity, which warrants further pharmacological studies.

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

First reported case in the UK of acute prolonged neuropsychiatric toxicity associated with analytically confirmed recreational use of phenazepam.

PubMed

Dargan, Paul I; Davies, Susannah; Puchnarewicz, Malgorzata; Johnston, Atholl; Wood, David M

2013-03-01

There is increasing evidence from around Europe of the availability and misuse of long-acting benzodiazepines such as phenazepam. There is little information on the acute toxicity of these compounds; we describe here a case of analytically confirmed phenazepam-related acute toxicity. A 42-year-old man with no previous medical or psychiatric history was brought to the Emergency Department by his friends because he had developed prolonged ongoing confusion and disorientation following use of up to three different "legal high" powders. There was no obvious medical cause for this acute confusion and disorientation. His symptoms continued for approximately 60 h after suspected use. Subsequent toxicological analysis of a serum sample confirmed use of phenazepam (concentration 0.49 mg/L); no other drugs were detected during an extensive analytical screening. This is the second case of analytically confirmed acute toxicity related to phenazepam in Europe. This adds to the scant published information on the acute toxicity of this drug, and will provide healthcare and legislative authorities with further information on which to base advice and consideration of the need for its control.

Large Dataset of Acute Oral Toxicity Data Created for Testing ...

EPA Pesticide Factsheets

Acute toxicity data is a common requirement for substance registration in the US. Currently only data derived from animal tests are accepted by regulatory agencies, and the standard in vivo tests use lethality as the endpoint. Non-animal alternatives such as in silico models are being developed due to animal welfare and resource considerations. We compiled a large dataset of oral rat LD50 values to assess the predictive performance currently available in silico models. Our dataset combines LD50 values from five different sources: literature data provided by The Dow Chemical Company, REACH data from eChemportal, HSDB (Hazardous Substances Data Bank), RTECS data from Leadscope, and the training set underpinning TEST (Toxicity Estimation Software Tool). Combined these data sources yield 33848 chemical-LD50 pairs (data points), with 23475 unique data points covering 16439 compounds. The entire dataset was loaded into a chemical properties database. All of the compounds were registered in DSSTox and 59.5% have publically available structures. Compounds without a structure in DSSTox are currently having their structures registered. The structural data will be used to evaluate the predictive performance and applicable chemical domains of three QSAR models (TIMES, PROTOX, and TEST). Future work will combine the dataset with information from ToxCast assays, and using random forest modeling, assess whether ToxCast assays are useful in predicting acute oral toxicity. Pre

Systematic and comprehensive investigation of the toxicity of curcuminoid‑essential oil complex: A bioavailable turmeric formulation.

PubMed

Aggarwal, Madan L; Chacko, Karampendethu M; Kuruvilla, Binu T

2016-01-01

Curcumin, the active component present in Curcuma longa of the family Zingiberaceae, has a number of pharmacological effects, including potential anti‑inflammatory activity. One of the major limitations of curcumin/turmeric extract is its poor absorption through the gastrointestinal tract. Several approaches have been adopted to increase the bioavailability of curcumin, including loading curcumin into liposomes or nanoparticles, complexation with phospholipids, addition of essential oils and synthesizing structural analogues of curcumin. In the present study, the toxicity and safety of one such bioavailable turmeric formulation, curcuminoid‑essential oil complex (CEC), the toxicity profile of which has not been reported, were examined using in vivo and in vitro models, as per the guidelines of the Organisation for Economic Co-operation and Development. Investigations of acute toxicity study were performed in rats and mice, and the results revealed no signs and symptoms or toxicity or mortality in any of the animals at the maximum recommended dose level of 5,000 mg/kg body weight. The repeated administration of CEC for 90 days in Wistar rats at a dose of 1,000 mg/kg body weight did not induce any observable toxic effects, compared with corresponding control animals. Mutagenicity/genotoxicity investigations were also performed using a bacterial reverse mutation assay (Ames test), a mammalian bone marrow chromosome aberration test and a mammalian erythrocyte micronucleus test in mice. CEC was found to be non‑mutagenic in all three mutagenic investigations. Consequently, the present study indicated that CEC elicited no toxic effects in animals or in vitro. Therefore, following investigations of acute toxicity, repeated dose toxicity and mutagenicity, CEC was deemed a safe, non‑toxic pharmacological formulation.

Toxicological assessment of combined lead and cadmium: acute and sub-chronic toxicity study in rats.

PubMed

Yuan, Guiping; Dai, Shujun; Yin, Zhongqiong; Lu, Hongke; Jia, Renyong; Xu, Jiao; Song, Xu; Li, Li; Shu, Yang; Zhao, Xinghong

2014-03-01

The exposure to chemical mixtures is a common and important determinant of toxicity and receives concern for their introduction by inhalation and ingestion. However, few in vivo mixture studies have been conducted to understand the health effects of chemical mixtures compared with single chemicals. In this study, the acute and 90day sub-chronic toxicity tests of combined Pb and Cd were conducted. In the acute toxicity test, the LD50 value of Pb(NO3)2 and CdCl2 mixture by the oral route was 2696.54mg/kg by Bliss method. The sub-chronic treatment revealed that the low-dose combination of Pb and Cd exposures can significantly change the physiological and biochemical parameters of the blood of Sprague-Dawley (SD) rats with dose-response relationship and causes microcytic hypochromic anemia and the damages of liver and kidney of the SD rats to various degrees. Histopathological exams showed that the target organs of Pb and Cd were testicle, liver, and kidneys. These observations suggest that Pb and Cd are practically additive-toxic for the SD rats in oral acute toxicity studies. The lowest observed adverse-effect level in rats may be lower than a dose of 29.96mg/(kgbwday) when administered orally for 90 consecutive days. Copyright © 2014 Elsevier Ltd. All rights reserved.

GHS additivity formula: A true replacement method for acute systemic toxicity testing of agrochemical formulations.

PubMed

Corvaro, M; Gehen, S; Andrews, K; Chatfield, R; Arasti, C; Mehta, J

2016-12-01

Acute systemic (oral, dermal, inhalation) toxicity testing of agrochemical formulations (end-use products) is mainly needed for Classification and Labelling (C&L) and definition of personal protection equipment (PPE). A retrospective analysis of 225 formulations with available in vivo data showed that: A) LD 50 /LC 50 values were above limit doses in <20.2% via oral route but only in <1% and <2.4% of cases via dermal and inhalation route, respectively; B) for each formulation the acute oral toxicity is always equal or greater than the Acute Toxicity Estimate (ATE) via the other two routes; C) the GHS (Global Harmonised System) computational method based on ATE, currently of limited acceptance, has very high accuracy and specificity for prediction of agrochemical mixture toxicity according to the internationally established classification thresholds. By integrating this evidence, an exposure- and data-based waiving strategy is proposed to determine classification and adequate PPE and to ensure only triggered animal testing is used. Safety characterisation above 2000 mg/kg body weight or 1.0 mg/L air should not be recommended, based on the agrochemical exposure scenarios. The global implementation of these tools would allow a remarkable reduction (up to 95%) in in vivo testing, often inducing lethality and/or severe toxicity, for agrochemical formulations. Copyright © 2016. Published by Elsevier Inc.

Comparison of the in vivo and in vitro genotoxicity of glyphosate isopropylamine salt in three different organisms

PubMed Central

Alvarez-Moya, Carlos; Silva, Mónica Reynoso; Ramírez, Carlos Valdez; Gallardo, David Gómez; Sánchez, Rafael León; Aguirre, Alejandro Canales; Velasco, Alfredo Feria

2014-01-01

There is considerable controversy with regard to the genotoxicity of glyphosate, with some reports stating that this compound is non-toxic for fish, birds and mammals. In this work, we used the comet assay to examine the genotoxicity of glyphosate isopropylamine (0.7, 7, 70 and 700 μM) in human lymphocytes, erythrocytes of Oreochromis niloticus and staminal nuclei of Tradescantia (4430) in vitro and in vivo. Cells, nuclei and fish that had and had not been exposed to 5 mM N-nitrosodiethylamine (NDEA) were used as positive and negative controls, respectively. Significant (p < 0.01) genetic damage was observed in vivo and in vitro in all cell types and organisms tested. Human lymphocytes and Tradescantia hairs showed lower genetic damage in vivo compared to in vitro, possibly because of efficient metabolization of the herbicide. In O. niloticus erythrocytes, significant (p < 0.001) genotoxicity was observed at ≥ 7 μM, whereas in vitro, glyphosphate was genotoxic in human lymphocytes and Tradescantia hairs at ≥ 0.7 μM. These results indicate that glyphosate is genotoxic in the cells and organisms studied at concentrations of 0.7–7 μM. PMID:24688297

Comparison of the in vivo and in vitro genotoxicity of glyphosate isopropylamine salt in three different organisms.

PubMed

Alvarez-Moya, Carlos; Silva, Mónica Reynoso; Ramírez, Carlos Valdez; Gallardo, David Gómez; Sánchez, Rafael León; Aguirre, Alejandro Canales; Velasco, Alfredo Feria

2014-03-01

There is considerable controversy with regard to the genotoxicity of glyphosate, with some reports stating that this compound is non-toxic for fish, birds and mammals. In this work, we used the comet assay to examine the genotoxicity of glyphosate isopropylamine (0.7, 7, 70 and 700 μM) in human lymphocytes, erythrocytes of Oreochromis niloticus and staminal nuclei of Tradescantia (4430) in vitro and in vivo. Cells, nuclei and fish that had and had not been exposed to 5 mM N-nitrosodiethylamine (NDEA) were used as positive and negative controls, respectively. Significant (p < 0.01) genetic damage was observed in vivo and in vitro in all cell types and organisms tested. Human lymphocytes and Tradescantia hairs showed lower genetic damage in vivo compared to in vitro, possibly because of efficient metabolization of the herbicide. In O. niloticus erythrocytes, significant (p < 0.001) genotoxicity was observed at ≥ 7 μM, whereas in vitro, glyphosphate was genotoxic in human lymphocytes and Tradescantia hairs at ≥ 0.7 μM. These results indicate that glyphosate is genotoxic in the cells and organisms studied at concentrations of 0.7-7 μM.

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.

Chemically dispersed oil is cytotoxic and genotoxic to sperm whale skin cells.

PubMed

Wise, Catherine F; Wise, James T F; Wise, Sandra S; Wise, John Pierce

2018-06-01

Two major oil crises in United States history, the 1989 Exxon-Valdez oil spill in Alaska and the 2010 Deepwater Horizon Oil Rig explosion in the Gulf of Mexico, drew attention to the need for toxicological experiments on oil and chemically dispersed oil. We are still learning the effects these spills had on wildlife. However, little data is known about the toxicity of these substances in marine mammals. The objective of this study is to determine the toxicity of Alaskan oil, as well as chemically dispersed oil. Oil experiments were performed using the water accommodated fraction of Alaskan oil (WAF) and the chemically enhanced water accommodated fraction of Alaskan oil (CEWAF). The Alaskan WAF is not cytotoxic to sperm whale skin cells though it did induce chromosome damage; S9-mediated metabolism did not affect the cytotoxicity of WAF but did increase the levels of chromosome damage. Alaskan CEWAF is more cytotoxic and genotoxic than the WAF; S9 mediated metabolism increased both cytotoxicity and genotoxicity of CEWAF. Analysis of the PAH content of Alaskan WAF and CEWAF revealed a forty-fold increase in the total levels of PAHs in CEWAF compared to WAF. These findings show that chemically dispersed oil leads to higher levels of PAH exposure which are more toxic and likely to lead to longer and more persistent health effects. Copyright © 2017 Elsevier Inc. All rights reserved.

Genotoxicity investigations on nanomaterials.

PubMed

Oesch, Franz; Landsiedel, Robert

2012-07-01

This review is based on the lecture presented at the April 2010 nanomaterials safety assessment Postsatellite to the 2009 EUROTOX Meeting and summarizes genotoxicity investigations on nanomaterials published in the open scientific literature (up to 2008). Special attention is paid to the relationship between particle size and positive versus negative outcome, as well as the dependence of the outcome on the test used. Salient conclusions and outstanding recommendations emerging from the information summarized in this review are as follows: recognize that nanomaterials are not all the same; therefore know and document what nanomaterial has been tested and in what form; take nanomaterials specific properties into account; in order to make your results comparable with those of others and on other nanomaterials: use or at least include in your studies standardized methods; use in vivo studies to put in vitro results into perspective; take uptake and distribution of the nanomaterial into account; and in order to become able to make extrapolations to risk for human: learn about the mechanism of nanomaterials genotoxic effects. Past experience with standard non-nanosubstances already had shown that mechanisms of genotoxic effects can be complex and their elucidation can be demanding, while there often is an immediate need to assess the genotoxic hazard. Thus, a practical and pragmatic approach to genotoxicity investigations of novel nanomaterials is the use of a battery of standard genotoxicity testing methods covering a wide range of mechanisms. Application of these standard methods to nanomaterials demands, however, adaptations, and the interpretation of results from the genotoxicity testing of nanomaterials needs additional considerations exceeding those used for standard size materials.

The toxicity of textile reactive azo dyes after hydrolysis and decolourisation.

PubMed

Gottlieb, Anna; Shaw, Chris; Smith, Alan; Wheatley, Andrew; Forsythe, Stephen

2003-02-27

The toxicity of C.I. Reactive Black 5 and three Procion dyes, as found in textile effluents, was determined using the bioluminescent bacterium Vibrio fischeri. Hydrolysed Reactive Black had a slightly greater toxicity than the parent form (EC(50) 11.4+/-3.68 and 27.5+/-4.01 mg l(-1), respectively). A baffled bioreactor with anaerobic and aerobic compartments was used to decolourise hydrolysed Reactive Black 5 in a synthetic effluent. Decolourisation of hydrolysed Reactive Black resulted in an increased toxicity (EC(50) 0.2+/-0.03 mg l(-1)). Toxicity was not detectable when decolourised Reactive Black 5 was metabolised under aerobic conditions. No genotoxicity was detected after the decolourisation of either the parent or the hydrolysed reactive dyes, either in vitro or in the bioreactor. The toxicity and genotoxicity of decolourised C.I. Acid Orange 7 was due to the production of 1-amino-2-naphthol (EC(50) 0.1+/-0.03 mg l(-1)).

[Preclinical prognosis of pyracetam and picamilon safety based on acute toxicity data].

PubMed

Bugaeva, L I; Spasov, A A; Verovskiĭ, V E; Iezhitsa, I N

2003-01-01

A comparative acute toxicity test of the nootropic drugs piracetam and picamilon was performed on rats. The study was based on the principles of integral evaluation of the drug effect upon the functional and behavioral state of animals. It was found that the conventional therapeutic index does not coincide with the actual therapeutic activity range. Piracetam and picamilon, while exhibiting significantly different toxicity, are characterized by approximately equal ranges of the therapeutic activity.

Determination of spectral markers of cytotoxicity and genotoxicity using in vitro Raman microspectroscopy: cellular responses to polyamidoamine dendrimer exposure.

PubMed

Efeoglu, Esen; Casey, Alan; Byrne, Hugh J

2017-10-09

Although consumer exposure to nanomaterials is ever increasing, with potential increased applications in areas such as drug and/or gene delivery, contrast agents and diagnosis, the determination of the cyto- and geno-toxic effects of nanomaterials on human health and the environment still remains challenging. Although many techniques have been established and adapted to determine the cytotoxicity and genotoxicity of nano-sized materials, these techniques remain limited by the number of assays required, total cost, and use of labels and they struggle to explain the underlying interaction mechanisms. In this study, Raman microspectroscopy is employed as an in vitro label-free, high content screening technique to observe toxicological changes within the cell in a multi-parametric fashion. The evolution of spectral markers as a function of time and applied dose has been used to elucidate the mechanism of action of polyamidoamine (PAMAM) dendrimers associated with cytotoxicity and their impact on nuclear biochemistry. PAMAM dendrimers are chosen as a model nanomaterial due to their widely studied cytotoxic and genotoxic properties and commercial availability. Point spectra were acquired from the cytoplasm to monitor the cascade of toxic events occurring in the cytoplasm upon nanoparticle exposure, whereas the spectra acquired from the nucleus and the nucleolus were used to explore PAMAM-nuclear material interaction as well as genotoxic responses.

Evaluation of acute toxicity and intestinal transit time of Olax scandens Roxb. leaves.

PubMed

Naik, Raghavendra; Acharya, Rabinarayan; Nariya, Mukesh B; Borkar, Sneha D

2015-01-01

Olax scandens Roxb. is a shrub or small tree found throughout tropical India. Fruits and leaves of this plant are used for medicinal and food purpose. Traditionally, leaves of O. scandens are used as vegetable in constipation. To evaluate the acute toxicity and intestinal transit time of O. scandens leaves on experimental animals. Acute oral toxicity study for sample was carried out following OECD guidelines. Evaluation of intestinal transit time was carried out in the dose of 1300 mg/kg by adopting Kaolin expulsion test and latency of the onset of kaolin expulsion in fecal matter in mice. The results show that the test drug is not likely to produce any toxicity in higher dose. In kaolin expulsion test, the drug produced mild increase in intestinal motility in mice proved by fast clearance of kaolin pellet in comparison to control group. The leaves of O. scandens are safe at higher dose and showed mild laxative activity in the dose of 1300 mg/kg body weight of mice.

Phytochemical Screening and Acute Toxicity of Aqueous Extract of Leaves of Conocarpus erectus Linnaeus in Swiss Albino Mice.

PubMed

Nascimento, Dayane K D; Souza, Ivone A DE; Oliveira, Antônio F M DE; Barbosa, Mariana O; Santana, Marllon A N; Pereira, Daniel F; Lira, Eduardo C; Vieira, Jeymesson R C

2016-09-01

Mangroves represent areas of high biological productivity and it is a region rich in bioactive substances used in medicine production. Conocarpus erectus (Combretaceae) known as button mangrove is one of the species found in mangroves and it is used in folk medicine in the treatment of anemia, catarrh, conjunctivitis, diabetes, diarrhea, fever, gonorrhea, headache, hemorrhage, orchitis, rash, bumps and syphilis. The present study aimed to investigate the acute toxicity of aqueous extract of leaves of C. erectus in Swiss albino mice. The plant material was collected in Vila Velha mangroves, located in Itamaracá (PE). The material was subjected to a phytochemical screening where extractive protocols to identify majority molecules present in leaves were used. The evaluation of acute toxicity of aqueous extract of C. erectus followed the model of Acute Toxicity Class based on OECD 423 Guideline, 2001. The majority molecules were identified: flavonoids, tannins and saponins. The LD50 was estimated at 2,000 mg/kg bw. Therefore, the aqueous extract showed low acute toxicity classified in category 5.

Web-based Interspecies Correlation Estimation (Web-ICE) for Acute Toxicity: User Manual Version 3.3

EPA Science Inventory

Information on the acute toxicity to multiple species is needed for the assessment of the risks to, and the protection of, individuals, populations, and ecological communities. However, toxicity data are limited for the majority of species, while standard test species are general...

Genotoxicity assessment of membrane concentrates of landfill leachate treated with Fenton reagent and UV-Fenton reagent using human hepatoma cell line.

PubMed

Wang, Guifang; Lu, Gang; Yin, Pinghe; Zhao, Ling; Yu, Qiming Jimmy

2016-04-15

Membrane concentrates of landfill leachates contain organic and inorganic contaminants that could be highly toxic and carcinogenic. In this paper, the genotoxicity of membrane concentrates before and after Fenton and UV-Fenton reagent was assessed. The cytotoxicity and genotoxicity was determined by using the methods of methyltetrazolium (MTT), cytokinesis-block micronucleus (CBMN) and comet assay in human hepatoma cells. MTT assay showed a cytotoxicity of 75% after 24h of exposure to the highest tested concentration of untreated concentrates, and no cytotoxocity for UV-Fenton and Fenton treated concentrates. Both CBMN and comet assays showed increased levels of genotoxicity in cells exposed to untreated concentrates, compared to those occurred in cells exposed to UV-Fenton and Fenton reagent treated concentrates. There was no significant difference between negative control and UV-Fenton treated concentrates for micronucleus and comet assay parameters. UV-Fenton and Fenton treatment, especially the former, were effective methods for degradation of bisphenol A and nonylphenol in concentrates. These findings showed UV-Fenton and Fenton reaction were effective methods for treatment of such complex concentrates, UV-Fenton reagent provided toxicological safety of the treated effluent, and the genotoxicity assays were found to be feasible tools for assessment of toxicity risks of complex concentrates. Copyright © 2016 Elsevier B.V. All rights reserved.

Acute and sub-chronic toxicity of Cajanus cajan leaf extracts.

PubMed

Tang, Rong; Tian, Ru-Hua; Cai, Jia-Zhong; Wu, Jun-Hui; Shen, Xiao-Ling; Hu, Ying-Jie

2017-12-01

The leaves of Cajanus cajan (L.) Millsp. (Fabaceae) have diverse bioactivities, but little safety data are reported. This study examines the toxicological profiles of C. cajan leaf extracts. The leaves were extracted by water or 90% ethanol to obtain water or ethanol extract (WEC or EEC). EEC was suspended in water and successively fractionated into dichloroform and n-butanol extracts (DEC and BEC). Marker compounds of the extracts were monitored by high-performance liquid chromatography (HPLC). Kunming mice were administered with a single maximum acceptable oral dose (15.0 g/kg for WEC, EEC and BEC and 11.3 g/kg for DEC) to determine death rate or maximal tolerated doses (MTDs). In sub-chronic toxicity investigation, Sprague-Dawley rats were orally given WEC or EEC at 1.5, 3.0 or 6.0 g/kg doses for four weeks and observed for two weeks after dosing to determine toxicological symptoms, histopathology, biochemistry and haematology. Flavonoids and stilbenes in the extracts were assayed. In acute toxicity test, no mortality and noted alterations in weight and behavioural abnormality were observed, and the maximum oral doses were estimated as MTDs. In sub-chronic toxicity study, no mortality and significant variances in haematological and biochemical parameters or organ histopathology were observed, but increased kidney weight in 3.0 g/kg WEC- or 3.0 and 6.0 g/kg EEC-treated female rats, and reduced testes and epididymis weight in EEC-treated male rats were recorded. These changes returned to the level of control after recovery period. Acute and sub-chronic toxicity of Cajanus cajan leaf extracts was not observed.

Genotoxicity Assessment of Volatile Organic Compounds in Landfill Gas Emission Using Comet Assay in Higher Terrestrial Plant.

PubMed

Na Roi-Et, Veerapas; Chiemchaisri, Wilai; Chiemchaisri, Chart

2017-02-01

Genotoxicity model is developed to assess the individual subacute toxicity of benzene, toluene, ethylbenzene, and xylene (BTEX) at very low levels as in a landfill gas. Golden Pothos (Epipremnum aureum), a higher plant, was tested under variation of benzene 54-5656 ng/L, toluene 10-4362 ng/L, ethylbenzene 28-4997 ng/L, xylene 53-4845 ng/L, for 96 h. DNA fragmentation in plant leaves were investigated via comet assay. The results show that DNA migration ratio increased with the BTEX concentrations, but at different rates. The 50% effective concentration (EC 50 ) of DNA fragmentation from the dose-response relationships indicated toluene has the highest EC 50 value and followed by benzene, xylene and ethylbenzene. Alternatively, ethylbenzene has the highest toxicity unit and followed by xylene, benzene and toluene as described by toxicity unit (TU). In conclusion, comet assay of Pothos can be used in differentiating DNA fragmentation against very low levels of BTEX in the atmosphere. Pothos is recommended for genotoxicity assessment of a low BTEX contaminated atmosphere.

ACUTE AND CHRONIC TOXICITY OF BREVETOXIN TO OYSTERS AND GRASS SHRIMP

EPA Science Inventory

Walker, Calvin C., James T. Winstead, Steven S. Foss, Janis C. Kurtz, James Watts, Jeanne E. Scott and William S. Fisher. In press. Acute and Chronic Toxicity of Brevetoxin to Oysters and Grass Shrimp (Abstract). To be presented at the SETAC Fourth World Congress, 14-18 November ...

Toxicological evaluation of neem (Azadirachta indica) oil: acute and subacute toxicity.

PubMed

Deng, Yun-xia; Cao, Mei; Shi, Dong-xia; Yin, Zhong-qiong; Jia, Ren-yong; Xu, Jiao; Wang, Chuan; Lv, Cheng; Liang, Xiao-xia; He, Chang-liang; Yang, Zhi-rong; Zhao, Jian

2013-03-01

Neem (Azadirachta indica), popularly known as traditional medicine is a native plant in India. Neem oil is a vegetable oil derived from seeds or fruits of the neem tree through pressing or solvent extraction, and largely used in popular medicine to have antifungal, antibacterial, antimalarial, antiparasitic, anti-inflammatory, as well as immunemodulatory properties in different animal species. In the present study, acute and 28-day subacute toxicity tests were carried out. In the acute toxicity test, the LD50 values of neem oil were found to be 31.95g/kg. The subacute treatment with neem oil failed to change body weight gain, food and water consumption. Serum biochemistry analysis showed no significant differences in any of the parameters examined under the dose of 1600mg/kg/day. Histopathological exams showed that the target organs of neem oil were testicle, liver and kidneys up to the dose of 1600mg/kg/day. Copyright © 2013 Elsevier B.V. All rights reserved.

Acute aquatic toxicity of tire and road wear particles to alga, daphnid, and fish.

PubMed

Marwood, Christopher; McAtee, Britt; Kreider, Marisa; Ogle, R Scott; Finley, Brent; Sweet, Len; Panko, Julie

2011-11-01

Previous studies have indicated that tire tread particles are toxic to aquatic species, but few studies have evaluated the toxicity of such particles using sediment, the likely reservoir of tire wear particles in the environment. In this study, the acute toxicity of tire and road wear particles (TRWP) was assessed in Pseudokirchneriella subcapita, Daphnia magna, and Pimephales promelas using a sediment elutriate (100, 500, 1000 or 10000 mg/l TRWP). Under standard test temperature conditions, no concentration response was observed and EC/LC(50) values were greater than 10,000 mg/l. Additional tests using D. magna were performed both with and without sediment in elutriates collected under heated conditions designed to promote the release of chemicals from the rubber matrix to understand what environmental factors may influence the toxicity of TRWP. Toxicity was only observed for elutriates generated from TRWP leached under high-temperature conditions and the lowest EC/LC(50) value was 5,000 mg/l. In an effort to identify potential toxic chemical constituent(s) in the heated leachates, toxicity identification evaluation (TIE) studies and chemical analysis of the leachate were conducted. The TIE coupled with chemical analysis (liquid chromatography/mass spectrometry/mass spectrometry [LC/MS/MS] and inductively coupled plasma/mass spectrometry [ICP/MS]) of the leachate identified zinc and aniline as candidate toxicants. However, based on the high EC/LC(50) values and the limited conditions under which toxicity was observed, TRWP should be considered a low risk to aquatic ecosystems under acute exposure scenarios.

Acute and chronic systemic chromium toxicity.

PubMed

Gad, S C

1989-10-01

Although chromium and compounds containing it have been recognized as having potential severe adverse effects on health for more than 160 years, understanding of the systemic toxicology and true hazard of these compounds is still not complete. A review of the current state of knowledge is attempted in this paper, with appropriate attention given to the complications of multiple valence states and solubility. Selected chromium compounds, particularly hexavalent ones, are carcinogens, corrosives, delayed contact sensitizers, and have the kidney as their primary target organ. But chromium is also an essential element for humans. The body clearly possesses some effective detoxification mechanisms for some degree of exposure to hexavalent chrome compounds. The significant features of acute and chronic chromium toxicity are presented in view of these considerations.

Silymarin and dimercaptosuccinic acid ameliorate lead-induced nephrotoxicity and genotoxicity in rats.

PubMed

Alcaraz-Contreras, Y; Mendoza-Lozano, R P; Martínez-Alcaraz, E R; Martínez-Alfaro, M; Gallegos-Corona, M A; Ramírez-Morales, M A; Vázquez-Guevara, M A

2016-04-01

We studied the effect of silymarin and dimercaptosuccinic acid (DMSA), a chelating agent that was administered individually or in combination against lead (Pb) toxicity in rats. Wistar rats (200 ± 20) were randomly divided into five groups. Group A served as a control. Groups B-E were exposed to 2000 ppm of lead acetate in drinking water for 8 weeks. Group B served as a positive control. Group C received silymarin (100 mg kg(-1) orally) for 8 weeks. Group D received DMSA (75 mg kg(-1) orally) once daily for the last 5 days of treatment. Group E received DMSA and silymarin as groups C and D, respectively. The effect of Pb was evaluated and accordingly the treatments on blood lead levels (BLLs), renal system, and genotoxic effects were calculated using comet assay. The BLLs were significantly increased following the exposition of lead acetate. The administration of silymarin and DMSA provided reduction in BLLs. Silymarin and DMSA provided significant protection on the genotoxic effect of Pb. The toxic effect of Pb on kidneys was also studied. Our data suggest that silymarin and DMSA improve the renal histopathological lesions. © The Author(s) 2015.

Quantitative Structure--Activity Relationship Modeling of Rat Acute Toxicity by Oral Exposure

EPA Science Inventory

Background: Few Quantitative Structure-Activity Relationship (QSAR) studies have successfully modeled large, diverse rodent toxicity endpoints. Objective: In this study, a combinatorial QSAR approach has been employed for the creation of robust and predictive models of acute toxi...

Acute and subacute toxicity evaluation of ethanolic extract from fruits of Schinus molle in rats.

PubMed

Ferrero, Adriana; Minetti, Alejandra; Bras, Cristina; Zanetti, Noelia

2007-09-25

Ethanolic and hexanic extracts from fruits and leaves of Schinus molle showed ability to control several insect pests. Potential vertebrate toxicity associated with insecticidal plants requires investigation before institutional promotion. The aim of the present study was to evaluate the acute and subacute toxicity of ethanolic extracts from fruits of Schinus molle in rats. The plant extract was added to the diet at 2g/kg body weight/day during 1 day to evaluate acute toxicity and at 1g/kg body weight/day during 14 days to evaluate subacute toxicity. At the end of the exposure and after 7 days, behavioral and functional parameters in a functional observational battery and motor activity in an open field were assessed. Finally, histopathological examinations were conducted on several organs. In both exposures, an increase in the arousal level was observed in experimental groups. Also, the landing foot splay parameter increased in the experimental group after acute exposure. Only the subacute exposure produced a significant increase in the motor activity in the open field. All these changes disappeared after 7 days. None of the exposures affected the different organs evaluated. Our results suggest that ethanolic extracts from fruits and leaves of Schinus molle should be relatively safe to use as insecticide.

New investigations into the genotoxicity of cobalt compounds and their impact on overall assessment of genotoxic risk.

PubMed

Kirkland, David; Brock, Tom; Haddouk, Hasnaà; Hargeaves, Victoria; Lloyd, Melvyn; Mc Garry, Sarah; Proudlock, Raymond; Sarlang, Séverine; Sewald, Katherina; Sire, Guillaume; Sokolowski, Andrea; Ziemann, Christina

2015-10-01

The genotoxicity of cobalt metal and cobalt compounds has been widely studied. Several publications show induction of chromosomal aberrations, micronuclei or DNA damage in mammalian cells in vitro in the absence of S9. Mixed results were seen in gene mutation studies in bacteria and mammalian cells in vitro, and in chromosomal aberration or micronucleus assays in vivo. To resolve these inconsistencies, new studies were performed with soluble and poorly soluble cobalt compounds according to OECD-recommended protocols. Induction of chromosomal damage was confirmed in vitro, but data suggest this may be due to oxidative stress. No biologically significant mutagenic responses were obtained in bacteria, Tk(+/-) or Hprt mutation tests. Negative results were also obtained for chromosomal aberrations (in bone marrow and spermatogonia) and micronuclei at maximum tolerated doses in vivo. Poorly soluble cobalt compounds do not appear to be genotoxic. Soluble compounds do induce some DNA and chromosomal damage in vitro, probably due to reactive oxygen. The absence of chromosome damage in robust GLP studies in vivo suggests that effective protective processes are sufficient to prevent oxidative DNA damage in whole mammals. Overall, there is no evidence of genetic toxicity with relevance for humans of cobalt substances and cobalt metal. Copyright © 2015 The Authors. Published by Elsevier Inc. 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.

Predicting acute contact toxicity of pesticides in honeybees (Apis mellifera) through a k-nearest neighbor model.

PubMed

Como, F; Carnesecchi, E; Volani, S; Dorne, J L; Richardson, J; Bassan, A; Pavan, M; Benfenati, E

2017-01-01

Ecological risk assessment of plant protection products (PPPs) requires an understanding of both the toxicity and the extent of exposure to assess risks for a range of taxa of ecological importance including target and non-target species. Non-target species such as honey bees (Apis mellifera), solitary bees and bumble bees are of utmost importance because of their vital ecological services as pollinators of wild plants and crops. To improve risk assessment of PPPs in bee species, computational models predicting the acute and chronic toxicity of a range of PPPs and contaminants can play a major role in providing structural and physico-chemical properties for the prioritisation of compounds of concern and future risk assessments. Over the last three decades, scientific advisory bodies and the research community have developed toxicological databases and quantitative structure-activity relationship (QSAR) models that are proving invaluable to predict toxicity using historical data and reduce animal testing. This paper describes the development and validation of a k-Nearest Neighbor (k-NN) model using in-house software for the prediction of acute contact toxicity of pesticides on honey bees. Acute contact toxicity data were collected from different sources for 256 pesticides, which were divided into training and test sets. The k-NN models were validated with good prediction, with an accuracy of 70% for all compounds and of 65% for highly toxic compounds, suggesting that they might reliably predict the toxicity of structurally diverse pesticides and could be used to screen and prioritise new pesticides. Copyright © 2016 Elsevier Ltd. All rights reserved.

Biotoxicity assessment and toxicity mechanism on coal gasification wastewater (CGW): A comparative analysis of effluent from different treatment processes.

PubMed

Ma, Weiwei; Han, Yuxing; Xu, Chunyan; Han, Hongjun; Zhu, Hao; Li, Kun; Zheng, Mengqi

2018-05-04

Even though coal gasification wastewater (CGW) treated by various biochemical treatment processes generally met the national discharge standard, its potential biotoxicity was still unknown. Therefore, in this study, bioassay with Tetrahymena thermophila (T. thermophila) was conducted to comprehensively evaluate the variation of biotoxicity in raw CGW and the treated effluent from lab-scale micro-electrolysis integrated with biological reactor (MEBR), single iron-carbon micro-electrolysis (ICME) and conventional activated sludge (CAS) processes. The results illustrated that raw CGW presented intensive acute toxicity with 24 h EC 50 value of 8.401% and toxic unit (TU) value of 11.90. Moreover, it performed significant cell membrane destruction and DNA damage even at 10% dilution concentration. The toxicant identification results revealed that multiple toxic polar compounds such as phenolic, heterocyclic and polycyclic aromatic compounds were the main contributors for biotoxicity. Furthermore, these compounds could accelerate oxidative stress, thereby inducing oxidative damage of cell membrane and DNA. As for treated effluent, TU value was decreased by 90.58% in MEBR process. An effective biotoxicity reduction was achieved in MEBR process owing to high removal efficiency in polar organic toxicants. In contrast, effluent from ICME and CAS processes presented relatively high acute toxicity and genotoxicity, because various heterocyclic and polycyclic aromatic compounds were difficult to be degraded in these processes. Therefore, it was suggested that MEBR was a potential and feasible process for improving CGW treatment and minimizing ecological risk. Copyright © 2018. Published by Elsevier B.V.

Acute and chronic toxicity of nickel to rainbow trout (Oncorhynchus mykiss).

PubMed

Brix, Kevin V; Keithly, James; DeForest, David K; Laughlin, Jim

2004-09-01

Of the fish species tested in chronic Ni exposures, rainbow trout (Oncorhynchus mykiss) is the most sensitive. To develop additional Ni toxicity data and to investigate the toxic mode of action for Ni, we conducted acute (96-h) and chronic (85-d early life-stage) flow-through studies using rainbow trout. In addition to standard toxicological endpoints, we investigated the effects of Ni on ionoregulatory physiology (Na, Ca, and Mg). The acute median lethal concentration for Ni was 20.8 mg/L, and the 24-h gill median lethal accumulation was 666 nmol/g wet weight. No effects on plasma Ca, Mg, or Na were observed during acute exposure. In the chronic study, no significant effects on embryo survival, swim-up, hatching, or fingerling survival or growth were observed at dissolved Ni concentrations up to 466 microg/L, the highest concentration tested. This concentration is considerably higher than the only other reported chronic no-observed-effect concentration (<33 microg/L) for rainbow trout. Accumulation of Ni in trout eggs indicates the chorion is only a partial barrier with 36%, 63%, and 1% of total accumulated Ni associated with the chorion, yolk, and embryo, respectively. Whole-egg ion concentrations were reduced by Ni exposure. However, most of this reduction occurred in the chorion rather than in the embryos, and no effects on hatching success or larval survival were observed as a result. Plasma ion concentrations measured in swim-up fingerlings at the end of the chronic-exposure period were not significantly reduced by exposure to Ni. Nickel accumulated on the gill in an exponential manner but plateaued in trout plasma at waterborne Ni concentrations of 118 microg/L or greater. Consistent with previous studies, Ni did not appear to disrupt ionoregulation in acute exposures of rainbow trout. Our results also suggest that Ni is not an ionoregulatory toxicant in long-term exposures, but the lack of effects in the highest Ni treatment precludes a definitive

Development of an acute oral toxicity dataset to facilitate assessment of existing QSARs and development of new models (WC10)

EPA Science Inventory

Acute oral toxicity data are used to meet both regulatory and non-regulatory needs. Recently, there have been efforts to explore alternative approaches for predicting acute oral toxicity such as QSARs. Evaluating the performance and scope of existing models and investigating the ...

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.

Acute Toxicity of Ammonia, Nitrite and Nitrate to Shrimp Litopenaeus vannamei Postlarvae in Low-Salinity Water.

PubMed

Valencia-Castañeda, Gladys; Frías-Espericueta, Martin G; Vanegas-Pérez, Ruth C; Pérez-Ramírez, Jesús A; Chávez-Sánchez, María C; Páez-Osuna, Federico

2018-05-12

Shrimp farming in low salinities waters is an alternative to increasing production, and counteracting disease problems in brackish and marine waters. However, in low-salinity waters, toxicity of nitrogen compounds increases, and there is no available data of its acute toxicity in shrimp postlarvae. This study determined the acute toxicity of ammonia, nitrite and nitrate in Litopenaeus vannamei postlarvae in 1 and 3 g/L salinity, as well as the safety levels. The LC 50 confirms that nitrite is more toxic than ammonia and nitrate in low salinity waters, and that its toxicity increases with a decrease in salinity. The safe levels estimated for salinities of 1 and 3 g/L were 0.54 and 0.81 mg/L for total ammonia-N, 0.17 and 0.25 mg/L for NO 2 -N, and 5.6 and 21.5 mg/L for NO 3 -N, respectively.

Acute toxicity of multi-walled carbon nanotubes, sodium pentachlorophenate, and their complex on earthworm Eisenia fetida.

PubMed

Zhang, Liujun; Hu, Changwei; Wang, Weili; Ji, Funian; Cui, Yibin; Li, Mei

2014-05-01

Laboratory experiments were undertaken to relate biomarker responses to the toxicities of multi-walled carbon nanotubes (MWCNTs) and sodium pentachlorophenate (PCP-Na), both individually and combined. The acute toxicities of MWCNTs and PCP-Na on earthworm Eisenia fetida were studied through different exposure methods (filter paper contact test, immersion contact test, and artificial soil contact test). Enzyme activity and malondialdehyde (MDA) content in the earthworm E. fetida exposed to MWCNTs and PCP-Na in filter paper contact test, both individually and under combined exposure, were determined. After exposure, PCP-Na induced observable acute toxicity while the MWCNTs induced slight toxicity. Interestingly the earthworms exposed to the mixture of MWCNTs and PCP-Na demonstrated different expression of enzymatic biomarkers from those exposed to MWCNTs or PCP-Na alone. Our results indicated that the toxicity of PCP-Na on E. fetida may be alleviated by the appearance of MWCNTs for all exposure methods except for immersion contact test. Copyright © 2014 Elsevier Inc. 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.

Genotoxicity and apoptosis in Drosophila melanogaster exposed to benzene, toluene and xylene: Attenuation by quercetin and curcumin

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

Singh, Mahendra P.; Mishra, M.; Sharma, A.

2011-05-15

Monocyclic aromatic hydrocarbons (MAHs) such as benzene, toluene and xylene are being extensively used for various industrial and household purposes. Exposure to these hydrocarbons, occupationally or non-occupationally, is harmful to organisms including human. Several studies tested for toxicity of benzene, toluene and xylene, and interestingly, only a few studies looked into the attenuation. We used Drosophila model to test the genotoxic and apoptotic potential of these compounds and subsequently evaluated the efficiency of two phytochemicals, namely, quercetin and curcumin in attenuating test chemical induced toxicity. We exposed third instar larvae of wild type Drosophila melanogaster (Oregon R{sup +}) to 1.0-100.0more » mM benzene, toluene or xylene, individually, for 12, 24 and 48 h and examined their apoptotic and genotoxic potential. We observed significantly (P < 0.001) increased apoptotic markers and genotoxicity in a concentration- and time-dependent manner in organisms exposed to benzene, toluene or xylene. We also observed significantly (P < 0.001) increased cytochrome P450 activity in larvae exposed to test chemicals and this was significantly reduced in the presence of 3',4'-dimethoxyflavone, a known Aryl hydrocarbon receptor (AhR) blocker. Interestingly, we observed a significant reduction in cytochrome P450 activity, GST levels, oxidative stress parameters, genotoxic and apoptotic endpoints when organisms were exposed simultaneously to test chemical along with quercetin or curcumin. The study further suggests the suitability of D. melanogaster as an alternate animal model for toxicological studies involving benzene, toluene and xylene and its potential in studying the protective role(s) of phytochemicals.« less

Toxicity Studies on Antiradiation Agents.

DTIC Science & Technology

1979-03-01

Mice 193-403 WI 2823 Acute Oral and IP Toxicity in Guinea Pigs 193-404 WR 2823 14-Day IV Toxicity in Rats 193-405 WI 2823 Acute IV Toxicity in Dogs ...193-406 W 2823 14-Day Subacute IV Toxicity in Dogs 193-407 WI 2721 28-Day Oral Toxicity in Monkeys 193-408 WI 2529 Acute Oral Toxicity in Mice 193-409... Dogs 193-415 WI 149, 024 Acute IV Toxicity in Monkeys 193-416 WI 149, 024 2-Week IV Toxicity in Dogs 193-417 WI 149, 024 2-Week Toxicity in Monkeys 193

Monohalogenated acetamide-induced cellular stress and genotoxicity are related to electrophilic softness and thiol/thiolate reactivity.

PubMed

Pals, Justin A; Wagner, Elizabeth D; Plewa, Michael J; Xia, Menghang; Attene-Ramos, Matias S

2017-08-01

Haloacetamides (HAMs) are cytotoxic, genotoxic, and mutagenic byproducts of drinking water disinfection. They are soft electrophilic compounds that form covalent bonds with the free thiol/thiolate in cysteine residues through an S N 2 reaction mechanism. Toxicity of the monohalogenated HAMs (iodoacetamide, IAM; bromoacetamide, BAM; or chloroacetamide, CAM) varied depending on the halogen substituent. The aim of this research was to investigate how the halogen atom affects the reactivity and toxicological properties of HAMs, measured as induction of oxidative/electrophilic stress response and genotoxicity. Additionally, we wanted to determine how well in silico estimates of electrophilic softness matched thiol/thiolate reactivity and in vitro toxicological endpoints. Each of the HAMs significantly induced nuclear Rad51 accumulation and ARE signaling activity compared to a negative control. The rank order of effect was IAM>BAM>CAM for Rad51, and BAM≈IAM>CAM for ARE. In general, electrophilic softness and in chemico thiol/thiolate reactivity provided a qualitative indicator of toxicity, as the softer electrophiles IAM and BAM were more thiol/thiolate reactive and were more toxic than CAM. Copyright © 2017. Published by Elsevier B.V.

Toxicity assessment of zinc oxide nanoparticles using sub-acute and sub-chronic murine inhalation models.

PubMed

Adamcakova-Dodd, Andrea; Stebounova, Larissa V; Kim, Jong Sung; Vorrink, Sabine U; Ault, Andrew P; O'Shaughnessy, Patrick T; Grassian, Vicki H; Thorne, Peter S

2014-04-01

Although ZnO nanoparticles (NPs) are used in many commercial products and the potential for human exposure is increasing, few in vivo studies have addressed their possible toxic effects after inhalation. We sought to determine whether ZnO NPs induce pulmonary toxicity in mice following sub-acute or sub-chronic inhalation exposure to realistic exposure doses. Mice (C57Bl/6) were exposed to well-characterized ZnO NPs (3.5 mg/m3, 4 hr/day) for 2 (sub-acute) or 13 (sub-chronic) weeks and necropsied immediately (0 wk) or 3 weeks (3 wks) post exposure. Toxicity was assessed by enumeration of total and differential cells, determination of total protein, lactate dehydrogenase activity and inflammatory cytokines in bronchoalveolar lavage (BAL) fluid as well as measurements of pulmonary mechanics. Generation of reactive oxygen species was assessed in the lungs. Lungs were evaluated for histopathologic changes and Zn content. Zn concentration in blood, liver, kidney, spleen, heart, brain and BAL fluid was measured. An elevated concentration of Zn2+ was detected in BAL fluid immediately after exposures, but returned to baseline levels 3 wks post exposure. Dissolution studies showed that ZnO NPs readily dissolved in artificial lysosomal fluid (pH 4.5), but formed aggregates and precipitates in artificial interstitial fluid (pH 7.4). Sub-acute exposure to ZnO NPs caused an increase of macrophages in BAL fluid and a moderate increase in IL-12(p40) and MIP-1α, but no other inflammatory or toxic responses were observed. Following both sub-acute and sub-chronic exposures, pulmonary mechanics were no different than sham-exposed animals. Our ZnO NP inhalation studies showed minimal pulmonary inflammation, cytotoxicity or lung histopathologic changes. An elevated concentration of Zn in the lung and BAL fluid indicates dissolution of ZnO NPs in the respiratory system after inhalation. Exposure concentration, exposure mode and time post exposure played an important role in the toxicity

Relative oral efficacy and acute toxicity of hydroxypyridin-4-one iron chelators in mice

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

Porter, J.B.; Morgan, J.; Hoyes, K.P.

1990-12-01

The relationship between the oral efficacy and the acute toxicity of hydroxypyridin-4-one iron chelators has been investigated to clarify structure-function relationships of these compounds in vivo and to identify compounds with the maximum therapeutic safety margin. By comparing 59Fe excretion following oral or intraperitoneal administration of increasing doses of each chelator to iron-overloaded mice, the most effective compounds have been identified. These have partition coefficients (Kpart) above 0.3 in the iron-free form with a trend of increasing oral efficacy with increasing Kpart values (r = .6). However, this is achieved at a cost of increasing acute toxicity, as shown bymore » a linear correlation between 59Fe excretion increase per unit dose and 1/LD50 (r = .83). A sharp increase in the LD50 values is observed for compounds with Kpart values above 1.0, suggesting that such compounds are unlikely to possess a sufficient therapeutic safety margin. Below a Kpart of 1.0, acute toxicity is relatively independent of lipid solubility. All the compounds are less toxic by the oral route than by the intraperitoneal route, although iron excretion is not significantly different by these two routes. At least five compounds (CP51, CP94, CP93, CP96, and CP21) are more effective orally than the same dose of intraperitoneal desferrioxamine (DFO) (P less than or equal to .02) or orally administered L1(CP20) (P less than or equal to .02).« less

Proton Therapy for Spinal Ependymomas: Planning, Acute Toxicities, and Preliminary Outcomes

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

Amsbaugh, Mark J.; Grosshans, David R., E-mail: dgrossha@mdanderson.org; McAleer, Mary Frances

2012-08-01

Purpose: To report acute toxicities and preliminary outcomes for pediatric patients with ependymomas of the spine treated with proton beam therapy at the MD Anderson Cancer Center. Methods and Materials: Eight pediatric patients received proton beam irradiation between October 2006 and September 2010 for spinal ependymomas. Toxicity data were collected weekly during radiation therapy and all follow-up visits. Toxicities were graded according to the Common Terminology Criteria for Adverse Events version 3.0. Results: All patients had surgical resection of the tumor before irradiation (7 subtotal resection and 1 gross total resection). Six patients had World Health Organization Grade I ependymomas,more » and two had World Health Organization Grade II ependymomas. Patients had up to 3 surgical interventions before radiation therapy (range, 1-3; median, 1). Three patients received proton therapy after recurrence and five as part of their primary management. The entire vertebral body was treated in all but 2 patients. The mean radiation dose was 51.1 cobalt gray equivalents (range, 45 to 54 cobalt gray equivalents). With a mean follow-up of 26 months from the radiation therapy start date (range, 7-51 months), local control, event-free survival, and overall survival rates were all 100%. The most common toxicities during treatment were Grade 1 or 2 erythema (75%) and Grade 1 fatigue (38%). No patients had a Grade 3 or higher adverse event. Proton therapy dramatically reduced dose to all normal tissues anterior to the vertebral bodies in comparison to photon therapy. Conclusion: Preliminary outcomes show the expected control rates with favorable acute toxicity profiles. Proton beam therapy offers a powerful treatment option in the pediatric population, where adverse events related to radiation exposure are of concern. Extended follow-up will be required to assess for late recurrences and long-term adverse effects.« less

Surfactant volume is an essential element in human toxicity in acute glyphosate herbicide intoxication.

PubMed

Seok, Su-Jin; Park, Jae-Seok; Hong, Joong-Rock; Gil, Hyo-Wook; Yang, Jong-Oh; Lee, Eun-Young; Song, Ho-Yeon; Hong, Sae-Yong

2011-12-01

Glyphosate, one of the most commonly used herbicides worldwide, has been considered as minimally toxic to humans. However, clinical toxicologists occasionally encounter cases of severe systemic toxicity. The purpose of this study was to determine the effect of glyphosate-surfactants ("glyphosate-surfactant toxicity") in patients with acute glyphosate intoxication. In all, 107 patients (69 men and 38 women, aged 52.3 ± 15.5 years) with acute glyphosate intoxication were enrolled in this study. From their medical records, we identified the formulation of ingested glyphosate products and derived clinical parameters, which focused on clinical outcome, admission days, duration in the intensive care unit, development of respiratory failure, cardiovascular deterioration, renal failure, altered mental status, and convulsions. The effect of surfactants on clinical complications was also assessed. For surfactant ingestion volumes of 8 mL, the incidence of clinical complications was (in rank order) as follows: hypotension, 47.1%; mental deterioration, 38.6%; respiratory failure, 30.0%; acute kidney injury, 17.1%; and arrhythmia, 10.0%. These complications were influenced by the volume of surfactant and not the type of surfactant-ingredient in the herbicide product. Two patients died of refractory shock, metabolic acidosis, and respiratory failure. However, the final clinical outcomes of the surviving patients were benign, and cardiovascular, respiratory, kidney, and mental functions were fully restored to normal levels. Our results indicate that treatment of patients with acute glyphosate herbicide intoxication should take into account the volume and not the type of surfactants in herbicide formulations.

Acute and joint toxicity of three agrochemicals to Chinese tiger frog (Hoplobatrachus chinensis) tadpoles

PubMed Central

WEI, Li; SHAO, Wei-Wei; DING, Guo-Hua; FAN, Xiao-Li; YU, Miao-Ling; LIN, Zhi-Hua

2014-01-01

We studied acute and joint toxicity of three different agrochemicals (chlorantraniliprole, flubendiamide-abamectin and penoxsulam) to Chinese tiger frog (Hoplobatrachus chinensis) tadpoles with the method of stability water tests. Results showed that the three agrochemicals increased tadpole mortality. For acute toxicity, the LC50 values after 24, 48 and 72 h of chlorantraniliprole, flubendiamide-abamectin and penoxsulam exposure were 5.37, 4.90 and 4.68 mg/L; 0.035, 0.025 and 0.021 mg/L; 1.74, 1.45 and 1.29 mg/L, respectively. The safety concentrations (SC) of chlorantraniliprole, flubendiamide-abamectin and penoxsulam to the tadpoles were 1.23, 0.30 and 0.003 mg/L, respectively. Based on these findings, chlorantraniliprole and penoxsulam were moderately toxic, while flubendiamide-abamectin was highly toxic. All pairwise joint toxicity tests showed moderate toxicity. The LC50 values after 24, 48 and 72 h of exposure were 7.08, 6.61 and 6.03 mg/L for chlorantraniliprole+penoxsulam, with corresponding values of 2.455, 2.328 and 2.183 mg/L for chlorantraniliprole+flubendiamide-abamectin, and 1.132, 1.084 and 1.050 mg/L for penoxsulam+flubendiamide-abamectin, with safe concentrations of 1.73, 0.63 and 0.30 mg/L, respectively. For toxic evaluations of pairwise combinations of the three agrochemicals, only the joint toxicity of chlorantraniliprole and flubendiamide-abamectin after 24 h was found to be synergistic, whereas all other tests were antagonistic. Our findings provide valuable information on the toxic effects of agrochemicals on amphibians and how various types of agrochemicals can be reasonably used in agricultural areas. PMID:25017745

Acute and joint toxicity of three agrochemicals to Chinese tiger frog (Hoplobatrachus chinensis) tadpoles.

PubMed

Wei, Li; Shao, Wei-Wei; Ding, Guo-Hua; Fan, Xiao-Li; Yu, Miao-Ling; Lin, Zhi-Hua

2014-07-01

We studied acute and joint toxicity of three different agrochemicals (chlorantraniliprole, flubendiamide-abamectin and penoxsulam) to Chinese tiger frog (Hoplobatrachus chinensis) tadpoles with the method of stability water tests. Results showed that the three agrochemicals increased tadpole mortality. For acute toxicity, the LC50 values after 24, 48 and 72 h of chlorantraniliprole, flubendiamide-abamectin and penoxsulam exposure were 5.37, 4.90 and 4.68 mg/L; 0.035, 0.025 and 0.021 mg/L; 1.74, 1.45 and 1.29 mg/L, respectively. The safety concentrations (SC) of chlorantraniliprole, flubendiamide-abamectin and penoxsulam to the tadpoles were 1.23, 0.30 and 0.003 mg/L, respectively. Based on these findings, chlorantraniliprole and penoxsulam were moderately toxic, while flubendiamide-abamectin was highly toxic. All pairwise joint toxicity tests showed moderate toxicity. The LC50 values after 24, 48 and 72 h of exposure were 7.08, 6.61 and 6.03 mg/L for chlorantraniliprole+penoxsulam, with corresponding values of 2.455, 2.328 and 2.183 mg/L for chlorantraniliprole+flubendiamide-abamectin, and 1.132, 1.084 and 1.050 mg/L for penoxsulam+flubendiamide-abamectin, with safe concentrations of 1.73, 0.63 and 0.30 mg/L, respectively. For toxic evaluations of pairwise combinations of the three agrochemicals, only the joint toxicity of chlorantraniliprole and flubendiamide-abamectin after 24 h was found to be synergistic, whereas all other tests were antagonistic. Our findings provide valuable information on the toxic effects of agrochemicals on amphibians and how various types of agrochemicals can be reasonably used in agricultural areas.

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

PubMed

Pérez, Sara; Beiras, Ricardo

2010-01-01

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

Small Microbial Three-Electrode Cell Based Biosensor for Online Detection of Acute Water Toxicity.

PubMed

Yu, Dengbin; Zhai, Junfeng; Liu, Changyu; Zhang, Xueping; Bai, Lu; Wang, Yizhe; Dong, Shaojun

2017-11-22

The monitoring of toxicity of water is very important to estimate the safety of drinking water and the level of water pollution. Herein, a small microbial three-electrode cell (M3C) biosensor filled with polystyrene particles was proposed for online monitoring of the acute water toxicity. The peak current of the biosensor related with the performance of the bioanode was regarded as the toxicity indicator, and thus the acute water toxicity could be determined in terms of inhibition ratio by comparing the peak current obtained with water sample to that obtained with nontoxic standard water. The incorporation of polystyrene particles in the electrochemical cell not only reduced the volume of the samples used, but also improved the sensitivity of the biosensor. Experimental conditions including washing time with PBS and the concentration of sodium acetate solution were optimized. The stability of the M3C biosensor under optimal conditions was also investigated. The M3C biosensor was further examined by formaldehyde at the concentration of 0.01%, 0.03%, and 0.05% (v/v), and the corresponding inhibition ratios were 14.6%, 21.6%, and 36.4%, respectively. This work provides a new insight into the development of an online toxicity detector based on M3C biosensor.

Size- and coating-dependent cytotoxicity and genotoxicity of silver nanoparticles evaluated using in vitro standard assays.

PubMed

Guo, Xiaoqing; Li, Yan; Yan, Jian; Ingle, Taylor; Jones, Margie Yvonne; Mei, Nan; Boudreau, Mary D; Cunningham, Candice K; Abbas, Mazhar; Paredes, Angel M; Zhou, Tong; Moore, Martha M; Howard, Paul C; Chen, Tao

2016-11-01

The physicochemical characteristics of silver nanoparticles (AgNPs) may greatly alter their toxicological potential. To explore the effects of size and coating on the cytotoxicity and genotoxicity of AgNPs, six different types of AgNPs, having three different sizes and two different coatings, were investigated using the Ames test, mouse lymphoma assay (MLA) and in vitro micronucleus assay. The genotoxicities of silver acetate and silver nitrate were evaluated to compare the genotoxicity of nanosilver to that of ionic silver. The Ames test produced inconclusive results for all types of the silver materials due to the high toxicity of silver to the test bacteria and the lack of entry of the nanoparticles into the cells. Treatment of L5718Y cells with AgNPs and ionic silver resulted in concentration-dependent cytotoxicity, mutagenicity in the Tk gene and the induction of micronuclei from exposure to nearly every type of the silver materials. Treatment of TK6 cells with these silver materials also resulted in concentration-dependent cytotoxicity and significantly increased micronucleus frequency. With both the MLA and micronucleus assays, the smaller the AgNPs, the greater the cytotoxicity and genotoxicity. The coatings had less effect on the relative genotoxicity of AgNPs than the particle size. Loss of heterozygosity analysis of the induced Tk mutants indicated that the types of mutations induced by AgNPs were different from those of ionic silver. These results suggest that AgNPs induce cytotoxicity and genotoxicity in a size- and coating-dependent manner. Furthermore, while the MLA and in vitro micronucleus assay (in both types of cells) are useful to quantitatively measure the genotoxic potencies of AgNPs, the Ames test cannot.

Sub-chronic (13-week) oral toxicity study, preceded by an in utero exposure phase and genotoxicity studies with fish source phosphatidylserine in rats.

PubMed

Lifshitz, Y; Levi, L; Eyal, I; Cohen, T; Tessler, S

2015-12-01

The safety of fish phosphatidylserine (PS) conjugated to DHA (InCog™) was examined in a series of toxicology studies as first step to support future use in infants and general population using in vitro genotoxicity tests and in a sub-chronic toxicity study with an in-utero exposure phase. PS is a major lipid in the cell membrane, active in various membrane-mediated processes. PS-DHA, present in human milk, has been suggested to be important for early brain development. Rats were exposed to diets containing 1.5%, 3% or 4.5% InCog or two control diets. Parental (F0) animals were fed throughout mating, gestation and lactation. Subsequently, a subchronic, 13-week study was conducted on the F1 animals followed by 4 weeks of recovery. The genotoxicity tests showed no mutagenicity potential. No significant toxicological findings were found in the F0 rats or the F1 pups. In the 13-weeks study, an increase in the presence of renal minimal-mild multifocal corticomedullary mineralization was noted in nine females of the high-dose group. This change was not associated with any inflammatory or degenerative changes in the kidneys. The no-observed-adverse-effect level (NOAEL) in the present study was placed at 3% in the diet (mid-dose group), equivalent to an overall intake of at least 2.1 g InCog/kg bw/day in the F1 generation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Toxicity assessment and modelling of Moringa oleifera seeds in water purification by whole cell bioreporter.

PubMed

Al-Anizi, Ali Adnan; Hellyer, Maria Theresa; Zhang, Dayi

2014-06-01

Moringa oleifera has been used as a coagulation reagent for drinking water purification, especially in developing countries such as Malawi. This research revealed the cytoxicity and genotoxicity of M. oleifera by Acinetobacter bioreporter. The results indicated that significant cytoxicity effects were observed when the powdered M. oleifera seeds concentration is from 1 to 50 mg/L. Through direct contact, ethanolic-water extraction and hexane extraction, the toxic effects of hydrophobic and hydrophilic components in M. oleifera seeds were distinguished. It suggested that the hydrophobic lipids contributed to the dominant cytoxicity, consequently resulting in the dominant genotoxicity in the water-soluble fraction due to limited dissolution when the M. oleifera seeds granule concentration was from 10 to 1000 mg/L. Based on cytoxicity and genotoxicity model, the LC50 and LC90 of M. oleifera seeds were 8.5 mg/L and 300 mg/L respectively and their genotoxicity was equivalent to 8.3 mg mitomycin C per 1.0 g dry M. oleifera seed. The toxicity of M. oleifera has also remarkable synergistic effects, suggesting whole cell bioreporter as an appropriate and complementary tool to chemical analysis for environmental toxicity assessment. Copyright © 2014 Elsevier Ltd. All rights reserved.

Handbook of acute toxicity of chemicals to fish and aquatic invertebrates : summaries of toxicity tests conducted at Columbia National Fisheries Research Laboratory, 1965-78

USGS Publications Warehouse

Johnson, W. Waynon; Finley, Mack T.

1980-01-01

Acute toxicity is a major subject of research at Columbia National Fisheries Research Laboratory for evaluating the impact of toxic chemicals on fishery resources. The Laboratory has played a leading role in developing research technology for toxicity testing and data interpretation. In 1965-78, more than 400 chemicals were tested against a variety of invertebrates and fish species representative of both cold- and warm-water climates.The use of acute toxicity tests for assessing the potential hazard of chemical contaminants to aquatic organisms is well documented (Boyd 1957; Henderson et al. 1960; Sanders and Cope 1966; Macek and McAllister 1970). Static acute toxicity tests provide rapid and (within limits) reproducible concentration-response curves for estimating toxic effects of chemicals on aquatic organisms. These tests provide a database for determining relative toxicity of a large number of chemicals to a variety of species and for estimating acute effects of chemical spills on natural aquatic systems; they also assist in determining priority and design of additional toxicity studies.Acute toxicity tests usually provide estimates of the exposure concentration causing 50% mortality (LC50) to test organisms during a specified period of time. For certain invertebrates, the effective concentration is based on immobilization, or some other identifiable endpoint, rather than on lethality. The application of the LC50 has gained acceptance among toxicologists and is generally the most highly rated test for assessing potential adverse effects of chemical contaminants to aquatic life (Brungs and Mount 1978; American Institute for Biological Sciences 1978a).The literature contains numerous papers dealing with the acute toxicity of chemicals to freshwater organisms. However, there is a tremendous need for a concise compendium of toxicity data covering a large variety of chemicals and test species. This Handbook is a compilation of a large volume of acute toxicity data

Comparative acute toxicity of neonicotinoid and pyrethroid insecticides to non-target crayfish (Procambarus clarkii) associated with rice-crayfish crop rotations.

PubMed

Barbee, Gary C; Stout, Michael J

2009-11-01

Most insecticides used to control rice water weevil (Lissorhoptrus oryzophilus Kuscel) infestations are pyrethroids. However, pyrethroids are highly toxic to non-target crayfish associated with rice-crayfish crop rotations. One solution to the near-exclusive reliance on pyrethroids in a rice-crayfish pest management program is to incorporate neonicotinoid insecticides, which are insect specific and effective against weevils but not extremely toxic to crayfish. This study aimed to take the first step to assess neonicotinoids as alternatives to pyrethroids in rice-crayfish crop rotations by measuring the acute toxicities of three candidate neonicotinoid insecticides, clothianidin, dinotefuran and thiamethoxam, to juvenile Procambarus clarkii (Girard) crayfish and comparing them with the acute toxicities of two currently used pyrethroid insecticides, lambda-cyhalothrin and etofenprox. Neonicotinoid insecticides are at least 2-3 orders of magnitude less acutely toxic (96 h LC(50)) than pyrethroids to juvenile Procambarid crayfish: lambda-cyhalothrin (0.16 microg AI L(-1)) = etofenprox (0.29 microg AI L(-1)) > clothianidin (59 microg AI L(-1)) > thiamethoxam (967 microg AI L(-1)) > dinotefuran (2032 microg AI L(-1)). Neonicotinoid insecticides appear to be much less hazardous alternatives to pyrethroids in rice-crayfish crop rotations. Further field-level neonicotinoid acute and chronic toxicity testing with crayfish is needed. (c) 2009 Society of Chemical Industry.

Comparative cytotoxic and genotoxic potential of 13 drinking water disinfection by-products using a microplate-based cytotoxicity assay and a developed SOS/umu assay.

PubMed

Zhang, Shao-Hui; Miao, Dong-Yue; Tan, Li; Liu, Ai-Lin; Lu, Wen-Qing

2016-01-01

The implications of disinfection by-products (DBPs) present in drinking water are of public health concern because of their potential mutagenic, carcinogenic and other toxic effects on humans. In this study, we selected 13 main DBPs found in drinking water to quantitatively analyse their cytotoxicity and genotoxicity using a microplate-based cytotoxicity assay and a developed SOS/umu assay in Salmonella typhimurium TA1535/pSK1002. With the developed SOS/umu test, eight DBPs: 3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-fura3-chloro-4-(dichloromethyl)-5-hydroxy-2-[5H]-furanone (MX), dibromoacetonitrile (DBN), iodoacetic acid (IA), bromochloroacetonitrile (BCN), bromoacetic acid (BA), trichloroacetonitrile (TCN), dibromoacetic acid (DBA) and dichloroacetic acid (DCA) were significantly genotoxic to S. typhimurium. Three DBPs: chloroacetic acid (CA), trichloroacetic acid (TCA) and dichloroacetonitrile (DCN) were weakly genotoxic, whereas the remaining DBPs: chloroacetonitrile (CN) and chloral hydrate (CH) were negative. The rank order in decreasing genotoxicity was as follows: MX > DBN > IA > BCN > BA > TCN > DBA > DCA > CA, TCA, DCN > CN, CH. MX was approximately 370 000 times more genotoxic than DCA. In the microplate-based cytotoxicity assay, cytotoxic potencies of the 13 DBPs were compared and ranked in decreasing order as follows: MX > IA > DBN > BCN > BA > TCN > DCN > CA > DCA > DBA > CN > TCA > CH. MX was approximately 19 200 times more cytotoxic than CH. A statistically significant correlation was found between cytotoxicity and genotoxicity of the 13 DBPs in S. typhimurium. Results suggest that microplate-based cytotoxicity assay and the developed SOS/umu assay are feasible tools for analysing the cytotoxicity and genotoxicity of DBPs, particularly for comparing their toxic intensities quantitatively. © The Author 2015. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e

In vivo genotoxicity evaluation of an artichoke (Cynara scolymus L.) aqueous extract.

PubMed

Zan, Meriele A; Ferraz, Alexandre B F; Richter, Marc F; Picada, Jaqueline N; de Andrade, Heloisa H R; Lehmann, Mauricio; Dihl, Rafael R; Nunes, Emilene; Semedo, Juliane; Da Silva, Juliana

2013-02-01

The Cynara scolymus (artichoke) is widely consumed as tea or food and shows important therapeutic properties. However, few studies have assessed the possible toxic effects of artichoke extracts. This study evaluates genotoxic and mutagenic activities of artichoke leaf aqueous extract in mice using the comet assay and the micronucleus test. Leaf extracts were given by gavage (500 mg/kg, 1000 mg/kg, and 2000 mg/kg) for 3 consecutive days. Extract composition was investigated using phytochemical screening and high-performance liquid chromatography (HPLC). In addition, antioxidant capacity was analyzed through the diphenyl-picrylhydrazyl (DPPH) and xanthine oxidase assay. Phytochemical screening detected the presence of phenolic compounds, flavonoids, and saponins. HPLC analyses indicated the presence of chlorogenic acid, caffeic acid, isoquercetrin, and rutin. Extracts showed a dose-dependent free radical scavenging effect of DPPH and an inhibitory effect of xanthine oxidase. The genotoxic results showed that leaf extracts did not increase micronuclei in peripheral blood cells. Compared to the control group, a significant increase in comet assay values was observed only in bone marrow of group treated with 2000 mg/kg, the highest dose tested, indicating that artichoke tea should be consumed with moderation. This is the first report of in vivo mutagenic and genotoxic evaluation with C. scolymus. The present study revealed leaf aqueous extract from artichoke shows lack of mutagenicity in vivo, and low genotoxicity and antioxidant activity; indicating that artichoke tea should be consumed with moderation. © 2013 Institute of Food Technologists®

Influence of pH on the acute toxicity of ammonia to juvenile freshwater mussels (fatmucket, Lampsills siliquoidea)

USGS Publications Warehouse

Wang, N.; Erickson, R.J.; Ingersoll, C.G.; Ivey, C.D.; Brunson, E.L.; Augspurger, T.; Barnhart, M.C.

2008-01-01

The objective of the present study was to evaluate the influence of pH on the toxicity of ammonia to juvenile freshwater mussels. Acute 96-h ammonia toxicity tests were conducted with 10-d-old juvenile mussels (fatmucket, Lampsilis siliquoidea) at five pH levels ranging from 6.5 to 9.0 in flow-through diluter systems at 20??C. Acute 48-h tests with amphipods (Hyalella azteca) and 96-h tests with oligochaetes (Lumbriculus variegatus) were conducted concurrently under the same test conditions to determine the sensitivity of mussels relative to these two commonly tested benthic invertebrate species. During the exposure, pH levels were maintained within 0.1 of a pH unit and ammonia concentrations were relatively constant through time (coefficient of variation for ammonia concentrations ranged from 2 to 30% with a median value of 7.9%). The median effective concentrations (EC50s) of total ammonia nitrogen (N) for mussels were at least two to six times lower than the EC50s for amphipods and oligochaetes, and the EC50s for mussels decreased with increasing pH and ranged from 88 mg N/L at pH 6.6 to 0.96 mg N/L at pH 9.0. The EC50s for mussels were at or below the final acute values used to derive the U.S. Environmental Protection Agency's acute water quality criterion (WQC). However, the quantitative relationship between pH and ammonia toxicity to juvenile mussels was similar to the average relationship for other taxa reported in the WQC. These results indicate that including mussel toxicity data in a revision to the WQC would lower the acute criterion but not change the WQC mathematical representation of the relative effect of pH on ammonia toxicity. ?? 2008 SETAC.

Is senna laxative use associated to cathartic colon, genotoxicity, or carcinogenicity?

PubMed

Morales, M A; Hernández, D; Bustamante, S; Bachiller, I; Rojas, A

2009-01-01

Due to their natural origin, apparent low oral toxicity, effectiveness, and accessibility without a medical prescription, the anthranoid laxatives are a popular remedy for constipation and are frequently used abusively. Therefore, it is important to characterize its harmful and/or toxic effects. The sennosides, main active metabolites of senna, exhibit a very low toxicity in rats, and its genotoxic activity in bacterial strains as well as mammal cells was classified as weak in those cases where it was shown to be significant. The toxicological and mutagenic status of the crude extract of senna, however, is not as well characterized, and it is necessary to do so since it is frequently, and at the same time incorrectly, believed that the chronic use of anthranoid laxatives is a risk factor for the development of colorectal cancer. The objective of this article was to review the information that arises in various scientific medical databases using key words such as senna, sen, Senna alexandrina, Cassia angustifolia, sennosides, laxative toxicity, mainly ISI and non-ISI articles of journals with an editorial committee. Web pages of products or companies that publicize or commercialize this type of laxative were not included. This analysis establishes that (1) there is no convincing evidence that the chronic use of senna has, as a consequence, a structural and/or functional alteration of the enteric nerves or the smooth intestinal muscle, (2) there is no relation between long-term administration of a senna extract and the appearance of gastrointestinal tumors or any other type in rats, (3) senna is not carcinogenic in rats even after a two-year daily dose of up to 300 mg/kg/day, and (4) the current evidence does not show that there is a genotoxic risk for patients who take laxatives containing senna extracts or sennosides.

Is Senna Laxative Use Associated to Cathartic Colon, Genotoxicity, or Carcinogenicity?

PubMed Central

Morales, M. A.; Hernández, D.; Bustamante, S.; Bachiller, I.; Rojas, A.

2009-01-01

Due to their natural origin, apparent low oral toxicity, effectiveness, and accessibility without a medical prescription, the anthranoid laxatives are a popular remedy for constipation and are frequently used abusively. Therefore, it is important to characterize its harmful and/or toxic effects. The sennosides, main active metabolites of senna, exhibit a very low toxicity in rats, and its genotoxic activity in bacterial strains as well as mammal cells was classified as weak in those cases where it was shown to be significant. The toxicological and mutagenic status of the crude extract of senna, however, is not as well characterized, and it is necessary to do so since it is frequently, and at the same time incorrectly, believed that the chronic use of anthranoid laxatives is a risk factor for the development of colorectal cancer. The objective of this article was to review the information that arises in various scientific medical databases using key words such as senna, sen, Senna alexandrina, Cassia angustifolia, sennosides, laxative toxicity, mainly ISI and non-ISI articles of journals with an editorial committee. Web pages of products or companies that publicize or commercialize this type of laxative were not included. This analysis establishes that (1) there is no convincing evidence that the chronic use of senna has, as a consequence, a structural and/or functional alteration of the enteric nerves or the smooth intestinal muscle, (2) there is no relation between long-term administration of a senna extract and the appearance of gastrointestinal tumors or any other type in rats, (3) senna is not carcinogenic in rats even after a two-year daily dose of up to 300 mg/kg/day, and (4) the current evidence does not show that there is a genotoxic risk for patients who take laxatives containing senna extracts or sennosides. PMID:20107583

Potential genotoxic effects of melted snow from an urban area revealed by the Allium cepa test.

PubMed

Blagojević, Jelena; Stamenković, Gorana; Vujosević, Mladen

2009-09-01

The presence of well-known atmospheric pollutants is regularly screened for in large towns but knowledge about the effects of mixtures of different pollutants and especially their genotoxic potential is largely missing. Since falling snow collects pollutants from the air, melted snow samples could be suitable for evaluating potential genotoxicity. For this purpose the Allium cepa anaphase-telophase test was used to analyse melted snow samples from Belgrade, the capital city of Serbia. Samples of snow were taken at two sites, characterized by differences in pollution intensity, in three successive years. At the more polluted site the analyses showed a very high degree of both toxicity and genotoxicity in the first year of the study corresponding to the effects of the known mutagen used as the positive control. At the other site the situation was much better but not without warning signals. The results showed that standard analyses for the presence of certain contaminants in the air do not give an accurate picture of the possible consequences of urban air pollution because the genotoxic potential remains hidden. The A. cepa test has been demonstrated to be very convenient for evaluation of air pollution through analyses of melted snow samples.

Partial Life-Cycle and Acute Toxicity of Perfluoroalkyl Acids to Freshwater Mussels

EPA Science Inventory

Freshwater mussels are among the most sensitive aquatic organisms to many contaminants and have complex life-cycles that include several distinct life stages with unique contaminant exposure pathways. Standard acute (24–96 h) and chronic (28 d) toxicity tests with free larva (glo...

Safety Assessment of Ocimum Basilicum Hydroalcoholic Extract in Wistar Rats: Acute and Subchronic Toxicity Studies

PubMed Central

Rasekh, Hamid Reza; Hosseinzadeh, Leila; Mehri, Soghra; Kamli-Nejad, Mohammad; Aslani, Majid; Tanbakoosazan, Farahnaz

2012-01-01

Objective(s) Ocimum basilicum L. is widely used in folk medicine of many countries including . Both O. basilicum and its oil extract have received considerable attention for their potential medicinal properties, but there are a few reports about possible toxicity of this plant. Therefore, in the present study, acute and subchronic toxicity of O. basilicum hydroalcohlic extract have been evaluated in Wistar rats. Materials and Methods For the acute toxicity assessment, five groups of 10 animals (5 male, 5 female) received four different single dose of extract orally, the animals were, then, kept under observation for 14 days. For subchronic toxicity, the animals were divided into four groups (5 male, 5 female) and were gavaged daily by 50, 200 and 500 mg/kg of extract. Mortality, clinical signs, body weight changes, food and water consumption, and hematological and biochemical parameters were monitored during the study period. On the 45th day, animals were sacrificed and gross findings, weight of liver and left kidney and liver histological markers were assessed. Results The results of acute study indicated that LD50 of O. basilicum is higher than 5 mg/kg. In subchronic study, no adverse effects were observed on serum parameters in male and female rats. The hematological results showed a reduction in the hematocrit, platelets and RBC in both sexes. No abnormalities were observed in other parameters. Conclusion Based on the results of this study, present data suggest that hematologic system could serve as a target organ in oral toxicity of this plant. PMID:23493182

Assessing deep and shallow learning methods for quantitative prediction of acute chemical toxicity.

PubMed

Liu, Ruifeng; Madore, Michael; Glover, Kyle P; Feasel, Michael G; Wallqvist, Anders

2018-05-02

Animal-based methods for assessing chemical toxicity are struggling to meet testing demands. In silico approaches, including machine-learning methods, are promising alternatives. Recently, deep neural networks (DNNs) were evaluated and reported to outperform other machine-learning methods for quantitative structure-activity relationship modeling of molecular properties. However, most of the reported performance evaluations relied on global performance metrics, such as the root mean squared error (RMSE) between the predicted and experimental values of all samples, without considering the impact of sample distribution across the activity spectrum. Here, we carried out an in-depth analysis of DNN performance for quantitative prediction of acute chemical toxicity using several datasets. We found that the overall performance of DNN models on datasets of up to 30,000 compounds was similar to that of random forest (RF) models, as measured by the RMSE and correlation coefficients between the predicted and experimental results. However, our detailed analyses demonstrated that global performance metrics are inappropriate for datasets with a highly uneven sample distribution, because they show a strong bias for the most populous compounds along the toxicity spectrum. For highly toxic compounds, DNN and RF models trained on all samples performed much worse than the global performance metrics indicated. Surprisingly, our variable nearest neighbor method, which utilizes only structurally similar compounds to make predictions, performed reasonably well, suggesting that information of close near neighbors in the training sets is a key determinant of acute toxicity predictions.

Presentations to an urban emergency department in Bern, Switzerland associated with acute recreational drug toxicity.

PubMed

Liakoni, Evangelia; Müller, Sabine; Stoller, Adrian; Ricklin, Meret; Liechti, Matthias E; Exadaktylos, Aristomenis K

2017-03-07

Although the recreational use of psychoactive substances is common there is only limited systematic collection of data on acute drug toxicity or hospital presentations. Currently, data from Switzerland are only available from the University Hospital of Basel. The present study aimed to describe the presentations due to recreational drug use at an emergency department in Bern, Switzerland during a 4 year period. Retrospective analysis of cases presenting from May 2012 to April 2016 at the emergency department of the University Hospital of Bern, Switzerland, with symptoms/signs consistent with acute toxicity of recreational drug use. The cases were retrieved using a comprehensive full-text search algorithm of the electronic health records. Isolated ethanol intoxications were excluded. During the study period, 503 of the 157,328 emergency department attendances were directly related to acute toxicity of substances used recreationally. The mean patient age was 33 years (range 16-74), 68% were male. Alcohol co-ingestion was reported in 54% of the cases, and use of more than one recreational drug in 37% of the cases. Most presentations were related to cocaine (29%), cannabis (26%), heroin (20%) and benzodiazepines/sedatives (18%). Urine drug screening immunoassay was available in 277 cases (55%). The most frequently detected substances were cannabis (29%), cocaine (22%), benzodiazepines (21%) and opioids excluding methadone (20%). There were only two intoxications with novel psychoactive substances (NPSs): One with methylone and one with 2,5-dimethoxy-4(n)-propylphenethylamine (2C-P). The majority of patients (58%) displayed impaired consciousness (Glasgow Coma Scale (GCS) <15) upon presentation and/or pre-hospital; 21% were unconscious (GCS <8). Other frequent symptoms were agitation (36%), tachycardia (29%), and anxiety (24%). Severe complications included two fatalities, three acute myocardial infarctions, two intracranial haemorrhages, as well as psychosis and

Effects of a long-acting mutant bacterial cocaine esterase on acute cocaine toxicity in rats

PubMed Central

Collins, Gregory T.; Zaks, Matthew E.; Cunningham, Alyssa R.; St. Clair, Carley; Nichols, Joseph; Narasimhan, Diwahar; Ko, Mei-Chuan; Sunahara, Roger K.; Woods, James H.

2011-01-01

Background A longer acting, double mutant bacterial cocaine esterase (CocE T172R/G173Q; DM CocE) has been shown to protect mice from cocaine-induced lethality, inhibit the reinforcing effects of cocaine in rats, and reverse cocaine’s cardiovascular effects in rhesus monkeys. The current studies evaluated the effectiveness of DM CocE to protect against, and reverse cocaine’s cardiovascular, convulsant, and lethal effects in male and female rats. Methods Pretreatment studies were used to determine the effectiveness and in vivo duration of action for DM CocE to protect rats against the occurrence of cardiovascular changes, convulsion and lethality associated with acute cocaine toxicity. Posttreatment studies were used to evaluate the capacity of DM CocE to rescue rats from the cardiovascular and lethal effects of large doses of cocaine. In addition, male and female rats were studied to determine if there were any potential effects of sex on the capacity of DM CocE to protect against, or reverse acute cocaine toxicity in rats. Results Pretreatment with DM CocE dose-dependently protected rats against cocaine-induced cardiovascular changes, convulsion and lethality, with higher doses active for up to 4 hrs, and shifting cocaine-induced lethality at least 10-fold to the right. In addition to dose-dependently recovering rats from an otherwise lethal dose of cocaine, post-treatment with DM CocE also reversed the cardiovascular effects of cocaine. There were no sex-related differences in the effectiveness of DM CocE to protect against, or reverse acute cocaine toxicity. Conclusions Together, these results support the development of DM CocE for the treatment of acute cocaine toxicity. PMID:21481548

ORAL TOXICITY OF 1,3-DICHLOROPROPANE: ACUTE, SHORT-TERM, AND LONG-TERM STUDIES IN RATS

EPA Science Inventory

The objective of this investigation was to characterize the acute and short- and long-term toxic potency of orally administered 1,2-dichloropropane (DCP). In the acute and short-term studies, male rats of 250-300 g were gavaged with 0, 100, 250, 500, or 1000 mg DCP/kg in corn oil...

Cyto-genotoxicity and oxidative stress in common carp (Cyprinus carpio) exposed to a mixture of ibuprofen and diclofenac.

PubMed

Islas-Flores, Hariz; Manuel Gómez-Oliván, Leobardo; Galar-Martínez, Marcela; Michelle Sánchez-Ocampo, Esmeralda; SanJuan-Reyes, Nely; Ortíz-Reynoso, Mariana; Dublán-García, Octavio

2017-05-01

Thirty million people worldwide consume each day nonsteroidal anti-inflammatory drugs (NSAIDs), a heterogeneous group of pharmaceuticals used for its analgesic, antipyretic, and anti-inflammatory properties. Recent studies report high NSAID concentrations in wastewater treatment plant effluents, in surface, ground, and drinking water, and in sediments. NSAIDs are also known to induce toxicity on aquatic organisms. However, toxicity in natural ecosystems is not usually the result of exposure to a single substance but to a mixture of toxic agents, yet only a few studies have evaluated the toxicity of mixtures. The aim of this study was to evaluate the toxicity induced by diclofenac (DCF), ibuprofen (IBP), and their mixture on a species of commercial interest, the common carp Cyprinus carpio. The median lethal concentration of IBP and DCF was determined, and oxidative stress was evaluated using the following biomarkers: lipid peroxidation and activity of the antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase. Cyto-genotoxicity was evaluated by micronucleus test, comet assay, and the specific activity of caspase-3. Results show that DCF, IBP, and a mixture of these pharmaceuticals induced free radical production, oxidative stress and cyto-genotoxicity in tissues of C. carpio. However, a greater effect was elicited by the mixture than by either pharmaceutical alone in some biomarkers evaluated, particularly in gill. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1637-1650, 2017. © 2017 Wiley Periodicals, Inc.

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

PubMed

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

2009-12-01

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

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.

The acute toxicity of the death camas (Zigadenus species) alkaloid zygacine in mice, including the effect of methyllycaconitine coadministration on zygacine toxicity.

PubMed

Welch, K D; Panter, K E; Gardner, D R; Stegelmeier, B L; Green, B T; Pfister, J A; Cook, D

2011-05-01

Death camas (Zigadenus spp.) is a common poisonous plant on foothill rangelands in western North America. The steroidal alkaloid zygacine is believed to be the primary toxic component in death camas. Poisonings on rangelands generally occur in the spring when death camas is abundant, whereas other more desirable forage species are limited in availability. In most cases where livestock are poisoned by plants in a range setting, there is more than one potential poisonous plant in that area. One common poisonous plant that is often found growing simultaneously in the same area as death camas is low larkspur (Delphinium nuttallianum). Consequently, the objectives of this study were to conduct acute toxicity studies in mice and to determine if coadministration of low larkspur will exacerbate the toxicity of death camas. We first characterized the acute toxicity of zygacine in mice. The LD(50) of zygacine administered intravenously (i.v.) and orally was 2.0 ± 0.2 and 132 ± 21 mg/kg, respectively. The rate of elimination of zygacine from whole blood was determined to be 0.06 ± 0.01/min, which corresponds to an elimination half-life of 13.0 ± 2.7 min. The i.v. LD(50) of total alkaloid extracts from a Utah and a Nevada collection were 2.8 ± 0.8 and 2.2 ± 0.3 mg/kg, respectively. The i.v. LD(50) of methyllycaconitine (MLA), a major toxic alkaloid in low larkspur, was 4.6 ± 0.5 mg/kg, whereas the i.v. LD(50) of a 1:1 mixture of MLA and zygacine was 2.9 ± 0.7 mg/kg. The clinical signs in mice treated with this mixture were very similar to those of mice treated with zygacine alone, including the time of onset and death. These results suggest that there is an additive effect of coadministering these 2 alkaloids i.v. in mice. The results from this study increase knowledge and understanding regarding the acute toxicity of death camas. As combined intoxications are most likely common, this information will be useful in further developing management recommendations for

Preclinical Toxicological Evaluation of IDM01: The Botanical Composition of 4-Hydroxyisoleucine- and Trigonelline-based Standardized Fenugreek Seed Extract.

PubMed

Deshpande, Pallavi O; Mohan, Vishwaraman; Thakurdesai, Prasad Arvind

2017-01-01

To evaluate acute oral toxicity (AOT), subchronic (90-day repeated dose) toxicity, mutagenicity, and genotoxicity potential of IDM01, the botanical composition of 4-hydroxyisoleucine- and trigonelline-based standardized fenugreek ( Trigonella foenum-graecum L) seed extract in laboratory rats. The AOT and subchronic (90-day repeated dose) toxicity were evaluated using Sprague-Dawley rats as per the Organisation for Economic Co-operation and Development (OECD) guidelines No. 423 and No. 408, respectively. During the subchronic study, the effects on body weight, food and water consumption, organ weights with hematology, clinical biochemistry, and histology were studied. The mutagenicity and genotoxicity of IDM01 were evaluated by reverse mutation assay (Ames test, OECD guideline No. 471) and chromosome aberration test (OECD guideline No. 473), respectively. The IDM01 did not show mortality or treatment-related adverse signs during acute (limit dose of 2000 mg/kg) and subchronic (90-day repeated dose of 250, 500, and 1000 mg/kg with 28 days of recovery period) administration. The IDM01 showed oral median lethal dose (LD50) >2000 mg/kg during AOT study. The no-observed adverse effect level (NOAEL) of IDM01 was 500 mg/kg. IDM01 did not show mutagenicity up to a concentration of 5000 μg/plate during Ames test and did not induce structural chromosomal aberrations up to 50 mg/culture. IDM01 was found safe during preclinical acute and subchronic (90-day repeated dose) toxicity in rats without mutagenicity or genotoxicity. Acute oral toxicity, subchronic (90-day) oral toxicity, mutagenicity and genotoxicity of IDM01 (4-hydroxyisoleucine- and trigonelline-based standardized fenugreek seed extract) was evaluated.The median lethal dose, LD50, of IDM01 was more than 2000 mg/kg of body weight in rats.No observed adverse effect level (NOAEL) of IDM01 was 500 mg/kg of body weight in rats.IDM01 was found safe during acute and subchronic oral toxicity studies in rats without

Preclinical Toxicological Evaluation of IDM01: The Botanical Composition of 4-Hydroxyisoleucine- and Trigonelline-based Standardized Fenugreek Seed Extract

PubMed Central

Deshpande, Pallavi O.; Mohan, Vishwaraman; Thakurdesai, Prasad Arvind

2017-01-01

Objective: To evaluate acute oral toxicity (AOT), subchronic (90-day repeated dose) toxicity, mutagenicity, and genotoxicity potential of IDM01, the botanical composition of 4-hydroxyisoleucine- and trigonelline-based standardized fenugreek (Trigonella foenum-graecum L) seed extract in laboratory rats. Materials and Methods: The AOT and subchronic (90-day repeated dose) toxicity were evaluated using Sprague-Dawley rats as per the Organisation for Economic Co-operation and Development (OECD) guidelines No. 423 and No. 408, respectively. During the subchronic study, the effects on body weight, food and water consumption, organ weights with hematology, clinical biochemistry, and histology were studied. The mutagenicity and genotoxicity of IDM01 were evaluated by reverse mutation assay (Ames test, OECD guideline No. 471) and chromosome aberration test (OECD guideline No. 473), respectively. Results: The IDM01 did not show mortality or treatment-related adverse signs during acute (limit dose of 2000 mg/kg) and subchronic (90-day repeated dose of 250, 500, and 1000 mg/kg with 28 days of recovery period) administration. The IDM01 showed oral median lethal dose (LD50) >2000 mg/kg during AOT study. The no-observed adverse effect level (NOAEL) of IDM01 was 500 mg/kg. IDM01 did not show mutagenicity up to a concentration of 5000 μg/plate during Ames test and did not induce structural chromosomal aberrations up to 50 mg/culture. Conclusions: IDM01 was found safe during preclinical acute and subchronic (90-day repeated dose) toxicity in rats without mutagenicity or genotoxicity. SUMMARY Acute oral toxicity, subchronic (90-day) oral toxicity, mutagenicity and genotoxicity of IDM01 (4-hydroxyisoleucine- and trigonelline-based standardized fenugreek seed extract) was evaluated.The median lethal dose, LD50, of IDM01 was more than 2000 mg/kg of body weight in rats.No observed adverse effect level (NOAEL) of IDM01 was 500 mg/kg of body weight in rats.IDM01 was found safe during

Cumulative toxicity of neonicotinoid insecticide mixtures to Chironomus dilutus under acute exposure scenarios.

PubMed

Maloney, Erin M; Morrissey, Christy A; Headley, John V; Peru, Kerry M; Liber, Karsten

2017-11-01

Extensive agricultural use of neonicotinoid insecticide products has resulted in the presence of neonicotinoid mixtures in surface waters worldwide. Although many aquatic insect species are known to be sensitive to neonicotinoids, the impact of neonicotinoid mixtures is poorly understood. In the present study, the cumulative toxicities of binary and ternary mixtures of select neonicotinoids (imidacloprid, clothianidin, and thiamethoxam) were characterized under acute (96-h) exposure scenarios using the larval midge Chironomus dilutus as a representative aquatic insect species. Using the MIXTOX approach, predictive parametric models were fitted and statistically compared with observed toxicity in subsequent mixture tests. Single-compound toxicity tests yielded median lethal concentration (LC50) values of 4.63, 5.93, and 55.34 μg/L for imidacloprid, clothianidin, and thiamethoxam, respectively. Because of the similar modes of action of neonicotinoids, concentration-additive cumulative mixture toxicity was the predicted model. However, we found that imidacloprid-clothianidin mixtures demonstrated response-additive dose-level-dependent synergism, clothianidin-thiamethoxam mixtures demonstrated concentration-additive synergism, and imidacloprid-thiamethoxam mixtures demonstrated response-additive dose-ratio-dependent synergism, with toxicity shifting from antagonism to synergism as the relative concentration of thiamethoxam increased. Imidacloprid-clothianidin-thiamethoxam ternary mixtures demonstrated response-additive synergism. These results indicate that, under acute exposure scenarios, the toxicity of neonicotinoid mixtures to C. dilutus cannot be predicted using the common assumption of additive joint activity. Indeed, the overarching trend of synergistic deviation emphasizes the need for further research into the ecotoxicological effects of neonicotinoid insecticide mixtures in field settings, the development of better toxicity models for neonicotinoid mixture

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.

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.

Genotoxicity assessment of magnetic iron oxide nanoparticles with different particle sizes and surface coatings

NASA Astrophysics Data System (ADS)

Liu, Yanping; Xia, Qiyue; Liu, Ying; Zhang, Shuyang; Cheng, Feng; Zhong, Zhihui; Wang, Li; Li, Hongxia; Xiao, Kai