Combined repeated-dose and reproductive/developmental toxicity screening test of 3-amino-5-mercapto-1,2,4-triazole in rats
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- Kikuchi Junichi
- CERI Hita, Chemicals Evaluation and Research Institute
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- Aso Sunao
- CERI Hita, Chemicals Evaluation and Research Institute
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- Koga Takayuki
- CERI Hita, Chemicals Evaluation and Research Institute
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- Miyata Katsumi
- CERI Hita, Chemicals Evaluation and Research Institute
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- Hoshuyama Satsuki
- CERI Hita, Chemicals Evaluation and Research Institute
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- Kusune Yuji
- CERI Hita, Chemicals Evaluation and Research Institute
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- Yoshida Tomohiko
- CERI Kurume
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- Hasegawa Ryuichi
- CERI, Chemical Biotesting Center
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- Ajimi Shozo
- CERI Hita, Chemicals Evaluation and Research Institute
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- Furukawa Kotaro
- CERI Hita, Chemicals Evaluation and Research Institute
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抄録
The substance 3-amino-5-mercapto-1,2,4-triazole (AMT, CAS No. 16691-43-3) was daily administered by gavage to Crl:CD (SD)IGS rats at doses of 0 (control), 10, 50, and 250 mg/kg bw/day. Males (12/group) were treated for a total of 42 days beginning 14 days before mating. Females (12/group) were treated beginning 14 days before mating to day 4 of lactation throughout the mating and gestation periods. No deaths occurred in males but three females died on day 23 of gestation at 250 mg/kg/day. Only temporary decreases in body weight and food intake were found in both sexes at 250 mg/kg/day. There were no considerable changes in general appearance, the functional battery tests, biochemical analysis or urinalysis. Anemia was observed in both sexes at 250 mg/kg/day. The relative weight of thyroid glands was significantly increased in both sexes at 250 mg/kg/day and hypertrophy of thyroid follicular cells was observed in 50 and 250 mg/kg/day males and 250 mg/kg/day females. As this effect on thyroid glands was considered to be the major toxicity, the possible mechanism was discussed comparing with the toxicity of structural similar analogs. Other histopathological changes in males were hypertrophy of centrilobular hepatocytes at 250 mg/kg/day, and anterior pituitary glands at 50 mg/kg/day and more. Vacuolization in renal tubular epithelium of females was observed at 50 and 250 mg/kg/day. For reproduction, the gestation period was prolonged and the delivery index was decreased at 250 mg/kg/day. The number of pups born and the birth index were also reduced. It was thus concluded that the NOAEL for repeated-dose toxicity was 10 mg/kg/day based on the thyrotoxicity and renal toxicity, and that the NOAEL for reproductive/developmental toxicity was 50 mg/kg/day based on the reduced number of offspring, etc.
収録刊行物
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- The Journal of Toxicological Sciences
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The Journal of Toxicological Sciences 38 (5), 759-773, 2013
一般社団法人 日本毒性学会
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詳細情報 詳細情報について
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- CRID
- 1390001204906162560
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- NII論文ID
- 10031191735
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- NII書誌ID
- AN00002808
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- COI
- 1:CAS:528:DC%2BC3sXhslyitbrI
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- ISSN
- 18803989
- 03881350
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- NDL書誌ID
- 024934300
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- PubMed
- 24067724
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可