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Ryo Ohta - One of the best experts on this subject based on the ideXlab platform.
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evaluation of a liver micronucleus assay in young rats iv a study using a double dosing single sampling method by the collaborative study group for the micronucleus test csgmt japanese environmental mutagen society jems mammalian mutagenicity study g
Mutation Research-genetic Toxicology and Environmental Mutagenesis, 2010Co-Authors: Hironao Takasawa, Hiroshi Suzuki, Izumi Ogawa, Yasushi Shimada, Kazuo Kobayashi, Yukari Terashima, Hirotaka Matsumoto, Keiyu Oshida, Ryo Ohta, Tadashi ImamuraAbstract:A collaborative study was conducted to evaluate whether a liver micronucleus assay using four-week-old male F344 rats can be used to detect genotoxic rat hepatocarcinogens using double-dosing with a single-sampling 4 days after the second dose. The assay methods were thoroughly validated by the seven laboratories involved in the study. Seven chemicals, 2,4-diaminotoluene, diethyl nitrosamine, p-dimethylaminoazobenzene, 1,2-dimethylhydrazine dihydrochloride, 2,4-dinitrotolunene, 2,6-Dinitrotoluene and mitomycin C, known to produce positive responses in the single-dosing/triple-sampling method were selected for use in the present study, and each chemical was examined in two laboratories with the exception of 2,4-dinitrotolunene. Although several of the compounds were examined at lower doses for reasons of toxicity than in the single-dosing/triple-sampling method, all chemicals tested in the present study induced micronuclei in liver cells indicating a positive result. These findings suggest that the liver micronucleus assay can be used in young rats to detect genotoxic rat hepatocarcinogens using a double-dosing/single-sampling procedure. Further, the number of animals used in the liver micronucleus assay can be reduced by one-third to a half by using the double-dosing/single-sampling method. This reduction in animal numbers also has significant savings in time and resource for liver perfusion and hepatocyte isolation.
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evaluation of a liver micronucleus assay in young rats iii a study using nine hepatotoxicants by the collaborative study group for the micronucleus test csgmt japanese environmental mutagen society jems mammalian mutagenicity study group mms
Mutation Research-genetic Toxicology and Environmental Mutagenesis, 2010Co-Authors: Hironao Takasawa, Hiroshi Suzuki, Izumi Ogawa, Yasushi Shimada, Kazuo Kobayashi, Yukari Terashima, Hirotaka Matsumoto, Keiyu Oshida, Chinami Aruga, Ryo OhtaAbstract:Abstract We have been investigating a liver micronucleus assay to detect genotoxic chemicals using young rats for several years, and had established its advantages with respect to using autonomous proliferation of young rat hepatocytes. Nine chemicals known to induce hepatotoxic effects such as necrosis (2,6-dinitrotolune, bromobenzene, isoniazid, phenacetin, allyl alcohol and thioacetamide), cholestasis (chlorpromazine hydrochloride and α-naphthyl isothiocyanate) and oxidative stress (clofibrate) were selected for this study. A liver micronucleus assay was conducted in 4-week-old male F344 rats using two or three dose levels of test chemicals given orally by gavage to evaluate the compound's ability to induce micronucleated hepatocytes. Several of these test chemicals were additionally examined in a peripheral blood micronucleus assay conducted concurrently and in the same animals. The genotoxic rodent hepatocarcinogen, 2,6-Dinitrotoluene showed a positive result in the liver micronucleus assay, but the nongenotoxic hepatocarcinogens, clofibrate and thioacetamide gave negative responses. Bromobenzene, known to produce DNA adducts but is noncarcinogenic in rodent liver, was judged equivocal in this assay. α-Naphthyl isothiocyanate is noncarcinogenic and showed negative response in the liver. The other four chemicals, known to be either noncarcinogenic or carcinogenic in other non-liver target organs, showed negative results in the liver micronucleus assay. Based on the results in the present study and previous report described above, it was concluded that this technique is able to effectively predict genotoxic rodent hepatocarcinogenicity, and does not give false positives due to hepatotoxicity.
Hironao Takasawa - One of the best experts on this subject based on the ideXlab platform.
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evaluation of a liver micronucleus assay in young rats iv a study using a double dosing single sampling method by the collaborative study group for the micronucleus test csgmt japanese environmental mutagen society jems mammalian mutagenicity study g
Mutation Research-genetic Toxicology and Environmental Mutagenesis, 2010Co-Authors: Hironao Takasawa, Hiroshi Suzuki, Izumi Ogawa, Yasushi Shimada, Kazuo Kobayashi, Yukari Terashima, Hirotaka Matsumoto, Keiyu Oshida, Ryo Ohta, Tadashi ImamuraAbstract:A collaborative study was conducted to evaluate whether a liver micronucleus assay using four-week-old male F344 rats can be used to detect genotoxic rat hepatocarcinogens using double-dosing with a single-sampling 4 days after the second dose. The assay methods were thoroughly validated by the seven laboratories involved in the study. Seven chemicals, 2,4-diaminotoluene, diethyl nitrosamine, p-dimethylaminoazobenzene, 1,2-dimethylhydrazine dihydrochloride, 2,4-dinitrotolunene, 2,6-Dinitrotoluene and mitomycin C, known to produce positive responses in the single-dosing/triple-sampling method were selected for use in the present study, and each chemical was examined in two laboratories with the exception of 2,4-dinitrotolunene. Although several of the compounds were examined at lower doses for reasons of toxicity than in the single-dosing/triple-sampling method, all chemicals tested in the present study induced micronuclei in liver cells indicating a positive result. These findings suggest that the liver micronucleus assay can be used in young rats to detect genotoxic rat hepatocarcinogens using a double-dosing/single-sampling procedure. Further, the number of animals used in the liver micronucleus assay can be reduced by one-third to a half by using the double-dosing/single-sampling method. This reduction in animal numbers also has significant savings in time and resource for liver perfusion and hepatocyte isolation.
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evaluation of a liver micronucleus assay in young rats iii a study using nine hepatotoxicants by the collaborative study group for the micronucleus test csgmt japanese environmental mutagen society jems mammalian mutagenicity study group mms
Mutation Research-genetic Toxicology and Environmental Mutagenesis, 2010Co-Authors: Hironao Takasawa, Hiroshi Suzuki, Izumi Ogawa, Yasushi Shimada, Kazuo Kobayashi, Yukari Terashima, Hirotaka Matsumoto, Keiyu Oshida, Chinami Aruga, Ryo OhtaAbstract:Abstract We have been investigating a liver micronucleus assay to detect genotoxic chemicals using young rats for several years, and had established its advantages with respect to using autonomous proliferation of young rat hepatocytes. Nine chemicals known to induce hepatotoxic effects such as necrosis (2,6-dinitrotolune, bromobenzene, isoniazid, phenacetin, allyl alcohol and thioacetamide), cholestasis (chlorpromazine hydrochloride and α-naphthyl isothiocyanate) and oxidative stress (clofibrate) were selected for this study. A liver micronucleus assay was conducted in 4-week-old male F344 rats using two or three dose levels of test chemicals given orally by gavage to evaluate the compound's ability to induce micronucleated hepatocytes. Several of these test chemicals were additionally examined in a peripheral blood micronucleus assay conducted concurrently and in the same animals. The genotoxic rodent hepatocarcinogen, 2,6-Dinitrotoluene showed a positive result in the liver micronucleus assay, but the nongenotoxic hepatocarcinogens, clofibrate and thioacetamide gave negative responses. Bromobenzene, known to produce DNA adducts but is noncarcinogenic in rodent liver, was judged equivocal in this assay. α-Naphthyl isothiocyanate is noncarcinogenic and showed negative response in the liver. The other four chemicals, known to be either noncarcinogenic or carcinogenic in other non-liver target organs, showed negative results in the liver micronucleus assay. Based on the results in the present study and previous report described above, it was concluded that this technique is able to effectively predict genotoxic rodent hepatocarcinogenicity, and does not give false positives due to hepatotoxicity.
Joseph B. Hughes - One of the best experts on this subject based on the ideXlab platform.
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Determination of 2,4- and 2,6-Dinitrotoluene biodegradation limits.
Chemosphere, 2011Co-Authors: Sung-soo Han, Sachiyo T. Mukherji, Angela Rice, Joseph B. HughesAbstract:This study was carried out to explore the lowest achievable Dinitrotoluene (DNT) isomer concentrations that would support sustained growth of DNT degrading microorganisms under an aerobic condition. Studies were conducted using suspended (chemostat) and attached growth (column) systems. The biodegradation limits for 2,4-Dinitrotoluene chemostat and column system were 0.054 ± 0.005 and 0.057 ± 0.008 μM, respectively, and for 2,6-Dinitrotoluene, the limits for chemostat and column system were 0.039 ± 0.005 and 0.026 ± 0.013 μM, respectively. The biodegradation limits determined in this study are much lower than the regulatory requirements, inferring that bacterial ability to metabolize DNT does not preclude applications of bioremediation (including natural attenuation) for DNT contaminated media.
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Modeling Aerobic Bioremediation of 2,4-Dinitrotoluene in a Bioslurry Reactor
Environmental Engineering Science, 2005Co-Authors: Rebecca C. Daprato, Jim C. Spain, Chunlong Zhang, Joseph B. HughesAbstract:In a previous study, pilot-scale bioslurry reactors were used to treat soils contaminated with high levels of 2,4-Dinitrotoluene (DNT). The study showed that DNT could be remediated rapidly, but co...
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Toxic Effects of Hydroxylamino Intermediates from Microbial Transformation of Trinitrotoluene and Dinitrotoluenes on Algae Selenastrum capricornutum
Bulletin of Environmental Contamination and Toxicology, 2000Co-Authors: M. G. Tadros, A. Crawford, A. Mateo-sullivan, C. Zhang, Joseph B. HughesAbstract:Trinitrotoluene (TNT) has been used extensively as an explosive since 1902. As a result of the production, purification, and loading at the ammunition plants, explosives contamination of soil and groundwater has become an enormous problem in the U.S. and worldwide. Among the various types of explosives, TNT and its major by-products, 2,4-Dinitrotoluene (24DNT) and 2,6-Dinitrotoluene (26DNT), are the most important contaminants in terms of volume and impact on the aquatic environment. They are all listed as the priority pollutants by the U.S. Environmental Protection Agency (Keith and Telliard 1979).
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Slurry-Phase Biological Treatment of 2,4-Dinitrotoluene and 2,6-Dinitrotoluene: Role of Bioaugmentation and Effects of High Dinitrotoluene Concentrations
Environmental Science & Technology, 2000Co-Authors: Chunlong Zhang, Shirley F. Nishino, Joseph B. Hughes, Jim C. SpainAbstract:A pilot-scale study was conducted to evaluate the use of aerobic slurry reactors to treat soils that were highly contaminated with 2,4-Dinitrotoluene (2,4-DNT) and 2,6-Dinitrotoluene (2,6-DNT). Con...
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Stability of hydroxylamino- and amino-intermediates from reduction of 2,4,6-trinitrotoluene, 2,4-Dinitrotoluene, and 2,6-Dinitrotoluene
Biotechnology Letters, 2000Co-Authors: Chuan Yue Wang, Dandan Zheng, Joseph B. HughesAbstract:Hydroxylamines, produced as intermediates in the reductive metabolism of 2,4,6-trinitrotoluene, 2,4-Dinitrotoluene, and 2,6-Dinitrotoluene between nitroaromatic parent compounds and corresponding amines, were unstable in aqueous solution in the presence of O2. Reactions of hydroxylamines to compounds other than amines may be the major cause of poor mass balance observations in bioremediation systems where only aminated products are monitored. Results demonstrate the formation of azoxy compounds as products of abiotic aryl-hydroxylamine reactions.
Tadashi Imamura - One of the best experts on this subject based on the ideXlab platform.
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evaluation of a liver micronucleus assay in young rats iv a study using a double dosing single sampling method by the collaborative study group for the micronucleus test csgmt japanese environmental mutagen society jems mammalian mutagenicity study g
Mutation Research-genetic Toxicology and Environmental Mutagenesis, 2010Co-Authors: Hironao Takasawa, Hiroshi Suzuki, Izumi Ogawa, Yasushi Shimada, Kazuo Kobayashi, Yukari Terashima, Hirotaka Matsumoto, Keiyu Oshida, Ryo Ohta, Tadashi ImamuraAbstract:A collaborative study was conducted to evaluate whether a liver micronucleus assay using four-week-old male F344 rats can be used to detect genotoxic rat hepatocarcinogens using double-dosing with a single-sampling 4 days after the second dose. The assay methods were thoroughly validated by the seven laboratories involved in the study. Seven chemicals, 2,4-diaminotoluene, diethyl nitrosamine, p-dimethylaminoazobenzene, 1,2-dimethylhydrazine dihydrochloride, 2,4-dinitrotolunene, 2,6-Dinitrotoluene and mitomycin C, known to produce positive responses in the single-dosing/triple-sampling method were selected for use in the present study, and each chemical was examined in two laboratories with the exception of 2,4-dinitrotolunene. Although several of the compounds were examined at lower doses for reasons of toxicity than in the single-dosing/triple-sampling method, all chemicals tested in the present study induced micronuclei in liver cells indicating a positive result. These findings suggest that the liver micronucleus assay can be used in young rats to detect genotoxic rat hepatocarcinogens using a double-dosing/single-sampling procedure. Further, the number of animals used in the liver micronucleus assay can be reduced by one-third to a half by using the double-dosing/single-sampling method. This reduction in animal numbers also has significant savings in time and resource for liver perfusion and hepatocyte isolation.
Hiroshi Suzuki - One of the best experts on this subject based on the ideXlab platform.
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evaluation of a liver micronucleus assay in young rats iv a study using a double dosing single sampling method by the collaborative study group for the micronucleus test csgmt japanese environmental mutagen society jems mammalian mutagenicity study g
Mutation Research-genetic Toxicology and Environmental Mutagenesis, 2010Co-Authors: Hironao Takasawa, Hiroshi Suzuki, Izumi Ogawa, Yasushi Shimada, Kazuo Kobayashi, Yukari Terashima, Hirotaka Matsumoto, Keiyu Oshida, Ryo Ohta, Tadashi ImamuraAbstract:A collaborative study was conducted to evaluate whether a liver micronucleus assay using four-week-old male F344 rats can be used to detect genotoxic rat hepatocarcinogens using double-dosing with a single-sampling 4 days after the second dose. The assay methods were thoroughly validated by the seven laboratories involved in the study. Seven chemicals, 2,4-diaminotoluene, diethyl nitrosamine, p-dimethylaminoazobenzene, 1,2-dimethylhydrazine dihydrochloride, 2,4-dinitrotolunene, 2,6-Dinitrotoluene and mitomycin C, known to produce positive responses in the single-dosing/triple-sampling method were selected for use in the present study, and each chemical was examined in two laboratories with the exception of 2,4-dinitrotolunene. Although several of the compounds were examined at lower doses for reasons of toxicity than in the single-dosing/triple-sampling method, all chemicals tested in the present study induced micronuclei in liver cells indicating a positive result. These findings suggest that the liver micronucleus assay can be used in young rats to detect genotoxic rat hepatocarcinogens using a double-dosing/single-sampling procedure. Further, the number of animals used in the liver micronucleus assay can be reduced by one-third to a half by using the double-dosing/single-sampling method. This reduction in animal numbers also has significant savings in time and resource for liver perfusion and hepatocyte isolation.
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evaluation of a liver micronucleus assay in young rats iii a study using nine hepatotoxicants by the collaborative study group for the micronucleus test csgmt japanese environmental mutagen society jems mammalian mutagenicity study group mms
Mutation Research-genetic Toxicology and Environmental Mutagenesis, 2010Co-Authors: Hironao Takasawa, Hiroshi Suzuki, Izumi Ogawa, Yasushi Shimada, Kazuo Kobayashi, Yukari Terashima, Hirotaka Matsumoto, Keiyu Oshida, Chinami Aruga, Ryo OhtaAbstract:Abstract We have been investigating a liver micronucleus assay to detect genotoxic chemicals using young rats for several years, and had established its advantages with respect to using autonomous proliferation of young rat hepatocytes. Nine chemicals known to induce hepatotoxic effects such as necrosis (2,6-dinitrotolune, bromobenzene, isoniazid, phenacetin, allyl alcohol and thioacetamide), cholestasis (chlorpromazine hydrochloride and α-naphthyl isothiocyanate) and oxidative stress (clofibrate) were selected for this study. A liver micronucleus assay was conducted in 4-week-old male F344 rats using two or three dose levels of test chemicals given orally by gavage to evaluate the compound's ability to induce micronucleated hepatocytes. Several of these test chemicals were additionally examined in a peripheral blood micronucleus assay conducted concurrently and in the same animals. The genotoxic rodent hepatocarcinogen, 2,6-Dinitrotoluene showed a positive result in the liver micronucleus assay, but the nongenotoxic hepatocarcinogens, clofibrate and thioacetamide gave negative responses. Bromobenzene, known to produce DNA adducts but is noncarcinogenic in rodent liver, was judged equivocal in this assay. α-Naphthyl isothiocyanate is noncarcinogenic and showed negative response in the liver. The other four chemicals, known to be either noncarcinogenic or carcinogenic in other non-liver target organs, showed negative results in the liver micronucleus assay. Based on the results in the present study and previous report described above, it was concluded that this technique is able to effectively predict genotoxic rodent hepatocarcinogenicity, and does not give false positives due to hepatotoxicity.