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Michael Werman - One of the best experts on this subject based on the ideXlab platform.
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Oral toxicity of the cyanobacterial toxin cylindrospermopsin in mice: Long‐term exposure to low doses
Environmental Toxicology, 2020Co-Authors: Assaf Sukenik, Michele Reisner, Shmuel Carmeli, Michael WermanAbstract:The hepatotoxin cylindrospermopsin, a sulfated-guanidinium alkaloid with substituted dioxypyrimidine (uracil) moiety, was isolated from several cyanobacteria species. The acute toxicity of cylindrospermopsin was well established based on intraperitoneal and oral exposure; however, only a few long-term subacute exposure studies were performed to permit a reliable guideline value for cylindrospermopsin in drinking water. In the study reported herein, female and male mice were exposed to cylindrospermopsin in their drinking water. Cylindrospermopsin-containing, Aphanizomenon ovalisporum (cyanobacterium)-free medium was provided as the only source of drinking water, whereas a control group was given a fresh medium for cyanobacteria as drinking water. Over a period of 42 weeks, experiment groups were exposed to cylindrospermopsin concentration, gradually increased from 100 to 550 μg L−1 (daily exposure ranged between 10 and 55 μg kg−1 day−1). Body and organ weights were recorded, and serum and hematology analyses were performed 20 and 42 weeks after the beginning of the experiment. The most pronounced effect of cylindrospermopsin was elevated hematocrit Levels in both male and female mice after 16 weeks of exposure to cylindrospermopsin. The observed changes in the hematocrit Level were accompanied by deformation of red blood cells, which were changed into acanthocyte. Based on these results, a daily cylindrospermopsin dose of 20 μg kg−1 day−1 (equivalent to 200 μg L−1) is proposed as the Lowest-Observed-Adverse-Effect Level for both male and female mice. © 2006 Wiley Periodicals, Inc. Environ Toxicol 21: 575–582, 2006.
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oral toxicity of the cyanobacterial toxin cylindrospermopsin in mice long term exposure to low doses
Environmental Toxicology, 2006Co-Authors: Assaf Sukenik, Michele Reisner, Shmuel Carmeli, Michael WermanAbstract:The hepatotoxin cylindrospermopsin, a sulfated-guanidinium alkaloid with substituted dioxypyrimidine (uracil) moiety, was isolated from several cyanobacteria species. The acute toxicity of cylindrospermopsin was well established based on intraperitoneal and oral exposure; however, only a few long-term subacute exposure studies were performed to permit a reliable guideline value for cylindrospermopsin in drinking water. In the study reported herein, female and male mice were exposed to cylindrospermopsin in their drinking water. Cylindrospermopsin-containing, Aphanizomenon ovalisporum (cyanobacterium)-free medium was provided as the only source of drinking water, whereas a control group was given a fresh medium for cyanobacteria as drinking water. Over a period of 42 weeks, experiment groups were exposed to cylindrospermopsin concentration, gradually increased from 100 to 550 μg L−1 (daily exposure ranged between 10 and 55 μg kg−1 day−1). Body and organ weights were recorded, and serum and hematology analyses were performed 20 and 42 weeks after the beginning of the experiment. The most pronounced effect of cylindrospermopsin was elevated hematocrit Levels in both male and female mice after 16 weeks of exposure to cylindrospermopsin. The observed changes in the hematocrit Level were accompanied by deformation of red blood cells, which were changed into acanthocyte. Based on these results, a daily cylindrospermopsin dose of 20 μg kg−1 day−1 (equivalent to 200 μg L−1) is proposed as the Lowest-Observed-Adverse-Effect Level for both male and female mice. © 2006 Wiley Periodicals, Inc. Environ Toxicol 21: 575–582, 2006.
Leobardo Manuel Gómez-oliván - One of the best experts on this subject based on the ideXlab platform.
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Oxidative stress induced in Hyalella azteca by an effluent from a NSAID-manufacturing plant in Mexico
Ecotoxicology, 2016Co-Authors: Karen Adriana Novoa-luna, Rubí Romero-romero, Reyna Natividad-rangel, Sandra García-medina, Catalina Martínez-vieyra, Nadia Neri-cruz, Nely Sanjuan-reyes, Marcela Galar-martínez, Leobardo Manuel Gómez-olivánAbstract:Production in the pharmaceutical industry has increased and along with it, the amount of wastewater of various characteristics and contaminant concentrations. The main chemicals in these effluents are solvents, detergents, disinfectants—such as sodium hypochlorite (NaClO)—and pharmaceutical products, all of which are potentially ecotoxic. Therefore, this study aimed to evaluate the oxidative stress induced in the amphipod Hyalella azteca by the effluent from a nonsteroidal anti-inflammatory drug (NSAID)-manufacturing plant. The median lethal concentration (72 h-LC_50) was determined and H. azteca were exposed to the lowest observed adverse effect Level (0.0732 %) for 12, 24, 48 and 72 h, and biomarkers of oxidative stress were evaluated [hydroperoxide content (HPC), lipid peroxidation (LPX), protein carbonyl content (PCC), and the activity of the superoxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)]. Statistically significant increases with respect to the control group ( P
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NSAID-manufacturing plant effluent induces geno- and cytotoxicity in common carp (Cyprinus carpio)
Science of The Total Environment, 2015Co-Authors: Nely Sanjuan-reyes, Sandra García-medina, Leobardo Manuel Gómez-oliván, Marcela Galar-martínez, Hariz Islas-flores, Edgar David González-gonzález, Jesús Daniel Cardoso-vera, Juan Manuel Jiménez-vargasAbstract:The pharmaceutical industry generates wastewater discharges of varying characteristics and contaminant concentrations depending on the nature of the production process. The main chemicals present in these effluents are solvents, detergents, disinfectants – such as sodium hypochlorite (NaClO) – and pharmaceutical products, all of which are potentially ecotoxic. Therefore, this study aimed to evaluate the geno- and cytotoxicity induced in the common carp Cyprinus carpio by the effluent emanating from a nonsteroidal anti-inflammatory drug (NSAID)-manufacturing plant. Carp were exposed to the lowest observed adverse effect Level (LOAEL, 0.1173%) for 12, 24, 48, 72 and 96 h, and biomarkers of genotoxicity (comet assay and micronucleus test) and cytotoxicity (caspase-3 activity and TUNEL assay) were evaluated. A significant increase with respect to the control group (p
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Oxidative stress in Cyprinus carpio induced by hospital wastewater in Mexico
Ecotoxicology, 2014Co-Authors: Nadia Neri-cruz, Sandra García-medina, Leobardo Manuel Gómez-oliván, Marcela Galar-martínez, Hariz Islas-flores, Juan Manuel Jiménez-vargas, María Del Socorro Romero-figueroa, Nely Sanjuan-reyesAbstract:The very wide range of activities performed in hospitals (care, diagnosis, hygiene, maintenance, research) require the use of a large variety of potentially ecotoxic substances such as surfactants, metals, disinfectants and pharmaceuticals. This study aimed to determine oxidative stress in the common carp Cyprinus carpio induced by hospital wastewater (HWW) in Mexico. The median lethal concentration (LC50) and subsequently the lowest observed adverse effect Level were determined. Carp were exposed to the latter value (0.5 %) for 24, 48, 72 and 96 h, and the following biomarkers were evaluated in gill, brain, liver and blood: hydroperoxide content (HPC), malondialdehyde (MDA) content, protein carbonyl content (PCC) and activity of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). Significant increases in HPC, MDA content and PCC were observed in exposed specimens, particularly in gill, liver and brain. SOD and CAT activity also increased in liver and brain. In conclusion, this particular HWW induces oxidative stress on C. carpio, this damage being most evident in gill, liver and brain.
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Genotoxic response and oxidative stress induced by diclofenac, ibuprofen and naproxen in Daphnia magna
Drug and Chemical Toxicology, 2014Co-Authors: Leobardo Manuel Gómez-oliván, Sandra García-medina, Marcela Galar-martínez, Hariz Islas-flores, Analleli Valdés-alanis, Nadia Neri-cruzAbstract:AbstractContext: Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used pharmaceuticals in Mexico, but there is not proper regulation on the sale, use and disposal. These drugs can enter water bodies by diverse pathways, attaining significant concentrations and inducing damage on hydrobionts. Objective: To evaluate the oxidative stress and consequent damage to genetic material induced by DCF, IBP and NPX on Daphnia magna. Methods: The acute toxicity assays were performed to 48-h by nonsteroidal anti-inflammatory drugs evaluated. A sublethal assay were done after 48 h of exposure to DCF, IBP and NPX added to water with the concentration equivalent to the lowest observed adverse effect Level (LOAEL), 9.7 mg/L for DCF, 2.9 mg/L for IBP and 0.017 mg/L for NPX. The DNA damage (comet assay) was evaluated at 12, 48 and 96 h. The oxidative biomarkers were evaluated: lipid peroxidation; protein carbonyl content; activity of the antioxidant enzymes superoxide dismutase, catalase and glutathi...
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Effect of ibuprofen exposure on blood, gill, liver, and brain on common carp (Cyprinus carpio) using oxidative stress biomarkers.
Environmental Science and Pollution Research, 2014Co-Authors: Hariz Islas-flores, Sandra García-medina, Nadia Neri-cruz, Leobardo Manuel Gómez-oliván, Marcela Galar-martínez, Octavio Dublán-garcíaAbstract:Although trace concentrations of ibuprofen (IBP) have been detected in diverse water bodies, there is currently insufficient information on the potentially deleterious effects of this xenobiotic. The present study aimed to determine whether IBP induces oxidative stress in brain, liver, gill, and blood of the common carp Cyprinus carpio. To this end, the median lethal concentration at 96 h (96-h LC50) was determined and the lowest observed adverse effect Level was established. Carp were exposed to the latter concentration (17.6 mg L−1) for 12, 24, 48, 72, and 96 h, and the following biomarkers were evaluated: lipid peroxidation (LPX) and activity of the antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase. Results indicated that LPX and antioxidant enzymes’ activity increased significantly (p < 0.05) with respect to the control group in liver, gill, and blood, while no significant differences occurred in brain. In conclusion, IBP induced oxidative stress on C. carpio, the liver being the organ most affected by this damage.
Glenn J. Leach - One of the best experts on this subject based on the ideXlab platform.
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Toxicological Study No. 75-51-YJ81-93, 4-Amino-2-Nitrotoluene (4A2NT) Oral Approximate Lethal Dose 14-day Range Finding 90-Day Subchronic Feeding Studies in Rats, August 1991-November 1993
1994Co-Authors: John T. Houpt, Glenn J. LeachAbstract:Abstract : The subchronic study examined the toxicity of 4-Amino 2-Nitrotoluene (4A2NT) in rats following oral administration in feed for 90 days. associated with the administration of 4A2NT in rats was testicular hypspermatogenesis (atrophy) a higher incidence of cardiomutagenicity, myopathy, anemia and high incidence of hepatocellular cytoplasmic vacuolization. A no observed adverse effect Level in the 90-day was not established. the Lowest-Observed-Adverse-Effect-Level in the 90-day study was 27 mg/kg/day for males and 32 mg/kg/day for females.
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4-Amino 2-Nitrotoluene (4A2NT) Oral Approximate Lethal Dose 14-day Range Finding 90-day Subchronic Feeding Studies in Rats, August 1991-November 1993
1994Co-Authors: John T. Houpt, Glenn J. LeachAbstract:Abstract : The subchronic study examined the toxicity of 4-Amino 2-Nitroluene (4A2NT) in rats following oral administration in feed for 90 days. Associated with the administration of 4A2NT in rats was testicular hypospermatogenesis (atrophy) a higher incidence of cardiomyopathy, anemia and a high incidence of hecatocellular cytoplasmic vacvolization. A no observed adverse effect Level in the 90-day study was not established. The Lowest-Observed-Adverse-Effect-Level in the 90-day study was 27 mg/kg/day for males and 32 mg/kg/day for females.
Ibrahim Chahoud - One of the best experts on this subject based on the ideXlab platform.
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A dose-response study following in utero and lactational exposure to di-(2-ethylhexyl) phthalate (DEHP): reproductive effects on adult female offspring rats.
Toxicology, 2006Co-Authors: Simone W Grande, Anderson J M Andrade, Chris E Talsness, Konstanze Grote, Andrea Golombiewski, Anja Sterner-kock, Ibrahim ChahoudAbstract:Abstract The reproductive effects of in utero and lactational exposure to di-(2-ethylhexyl) phthalate (DEHP) in adult male offspring rats were investigated. The selected endpoints included reproductive organ weights, testicular function, hormonal status, sexual behaviour and fertility. Two wide ranges of doses, low and high, were tested. Female Wistar rats were treated daily with DEHP and peanut oil (vehicle control) by gavage from gestation day 6 to lactation day 21. The low-doses were 0.015, 0.045, 0.135, 0.405 and 1.215 mg DEHP/kg body weight (bw)/day, and the high-doses were 5, 15, 45, 135 and 405 mg DEHP/kg bw/day. A reduction in daily sperm production of 19–25% in relation to control was observed in animals exposed to 15, 45, 135 and 405 mg/kg/day. Quantitation of specific cell types shows that the observed effects in daily sperm production are not related to changes in the number of Sertoli cells or their capability to support early stages spermatocytes. A low incidence of cryptorchidism was observed in DEHP exposed groups with a lowest observed adverse effect Level of 5 mg/kg/day. Serum testosterone concentration was similar to control at most doses but was significantly increased at 0.045, 0.405 and 405 mg DEHP/kg/day. In spite of this effect, the weight of seminal vesicle with coagulating glands was significantly reduced at 405 mg/kg/day. Testis, epididymis and prostate weights were similar among groups. Fertility and sexual behaviour were not affected by DEHP treatment at any dose. Overall, our results show that in utero and lactational DEHP exposure reduces daily sperm production and has the potential to induce reproductive tract abnormalities (of which cryptorchidism seems to be the most sensitive in our rat strain) in male offspring rats. The lowest observed adverse effect Levels (LOAELs) for these effects were 15 and 5 mg/kg/day, respectively. Therefore, the no observed adverse effect Level (NOAEL) for this study can be set at 1.215 mg/kg/day.
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A dose response study following in utero and lactational exposure to di-(2-ethylhexyl) phthalate (DEHP): reproductive effects on adult male offspring rats.
Toxicology, 2006Co-Authors: Anderson J M Andrade, Simone W Grande, Chris E Talsness, Christine Gericke, Konstanze Grote, Andrea Golombiewski, Anja Sterner-kock, Ibrahim ChahoudAbstract:The reproductive effects of in utero and lactational exposure to di-(2-ethylhexyl) phthalate (DEHP) in adult male offspring rats were investigated. The selected endpoints included reproductive organ weights, testicular function, hormonal status, sexual behaviour and fertility. Two wide ranges of doses, low and high, were tested. Female Wistar rats were treated daily with DEHP and peanut oil (vehicle control) by gavage from gestation day 6 to lactation day 21. The low-doses were 0.015, 0.045, 0.135, 0.405 and 1.215 mg DEHP/kg body weight (bw)/day, and the high-doses were 5, 15, 45, 135 and 405 mg DEHP/kg bw/day. A reduction in daily sperm production of 19-25% in relation to control was observed in animals exposed to 15, 45, 135 and 405 mg/kg/day. Quantitation of specific cell types shows that the observed effects in daily sperm production are not related to changes in the number of Sertoli cells or their capability to support early stages spermatocytes. A low incidence of cryptorchidism was observed in DEHP exposed groups with a lowest observed adverse effect Level of 5mg/kg/day. Serum testosterone concentration was similar to control at most doses but was significantly increased at 0.045, 0.405 and 405 mg DEHP/kg/day. In spite of this effect, the weight of seminal vesicle with coagulating glands was significantly reduced at 405 mg/kg/day. Testis, epididymis and prostate weights were similar among groups. Fertility and sexual behaviour were not affected by DEHP treatment at any dose. Overall, our results show that in utero and lactational DEHP exposure reduces daily sperm production and has the potential to induce reproductive tract abnormalities (of which cryptorchidism seems to be the most sensitive in our rat strain) in male offspring rats. The lowest observed adverse effect Levels (LOAELs) for these effects were 15 and 5 mg/kg/day, respectively. Therefore, the no observed adverse effect Level (NOAEL) for this study can be set at 1.215 mg/kg/day.
Assaf Sukenik - One of the best experts on this subject based on the ideXlab platform.
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Oral toxicity of the cyanobacterial toxin cylindrospermopsin in mice: Long‐term exposure to low doses
Environmental Toxicology, 2020Co-Authors: Assaf Sukenik, Michele Reisner, Shmuel Carmeli, Michael WermanAbstract:The hepatotoxin cylindrospermopsin, a sulfated-guanidinium alkaloid with substituted dioxypyrimidine (uracil) moiety, was isolated from several cyanobacteria species. The acute toxicity of cylindrospermopsin was well established based on intraperitoneal and oral exposure; however, only a few long-term subacute exposure studies were performed to permit a reliable guideline value for cylindrospermopsin in drinking water. In the study reported herein, female and male mice were exposed to cylindrospermopsin in their drinking water. Cylindrospermopsin-containing, Aphanizomenon ovalisporum (cyanobacterium)-free medium was provided as the only source of drinking water, whereas a control group was given a fresh medium for cyanobacteria as drinking water. Over a period of 42 weeks, experiment groups were exposed to cylindrospermopsin concentration, gradually increased from 100 to 550 μg L−1 (daily exposure ranged between 10 and 55 μg kg−1 day−1). Body and organ weights were recorded, and serum and hematology analyses were performed 20 and 42 weeks after the beginning of the experiment. The most pronounced effect of cylindrospermopsin was elevated hematocrit Levels in both male and female mice after 16 weeks of exposure to cylindrospermopsin. The observed changes in the hematocrit Level were accompanied by deformation of red blood cells, which were changed into acanthocyte. Based on these results, a daily cylindrospermopsin dose of 20 μg kg−1 day−1 (equivalent to 200 μg L−1) is proposed as the Lowest-Observed-Adverse-Effect Level for both male and female mice. © 2006 Wiley Periodicals, Inc. Environ Toxicol 21: 575–582, 2006.
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oral toxicity of the cyanobacterial toxin cylindrospermopsin in mice long term exposure to low doses
Environmental Toxicology, 2006Co-Authors: Assaf Sukenik, Michele Reisner, Shmuel Carmeli, Michael WermanAbstract:The hepatotoxin cylindrospermopsin, a sulfated-guanidinium alkaloid with substituted dioxypyrimidine (uracil) moiety, was isolated from several cyanobacteria species. The acute toxicity of cylindrospermopsin was well established based on intraperitoneal and oral exposure; however, only a few long-term subacute exposure studies were performed to permit a reliable guideline value for cylindrospermopsin in drinking water. In the study reported herein, female and male mice were exposed to cylindrospermopsin in their drinking water. Cylindrospermopsin-containing, Aphanizomenon ovalisporum (cyanobacterium)-free medium was provided as the only source of drinking water, whereas a control group was given a fresh medium for cyanobacteria as drinking water. Over a period of 42 weeks, experiment groups were exposed to cylindrospermopsin concentration, gradually increased from 100 to 550 μg L−1 (daily exposure ranged between 10 and 55 μg kg−1 day−1). Body and organ weights were recorded, and serum and hematology analyses were performed 20 and 42 weeks after the beginning of the experiment. The most pronounced effect of cylindrospermopsin was elevated hematocrit Levels in both male and female mice after 16 weeks of exposure to cylindrospermopsin. The observed changes in the hematocrit Level were accompanied by deformation of red blood cells, which were changed into acanthocyte. Based on these results, a daily cylindrospermopsin dose of 20 μg kg−1 day−1 (equivalent to 200 μg L−1) is proposed as the Lowest-Observed-Adverse-Effect Level for both male and female mice. © 2006 Wiley Periodicals, Inc. Environ Toxicol 21: 575–582, 2006.
