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Initial hazard assessment of 1,4-dichlorobutane: Genotoxicity tests, 28-day repeated-dose toxicity test, and reproductive/developmental toxicity screening test in rats.
Regulatory Toxicology and Pharmacology ( IF 3.4 ) Pub Date : 2020-02-04 , DOI: 10.1016/j.yrtph.2020.104610
Toshime Igarashi 1 , Hiroshi Suzuki 2 , Kazuo Ushida 2 , Mariko Matsumoto 2 , Kaoru Inoue 2 , Takuya Kanno 3 , Yoshihisa Miwa 4 , Takahiro Ishii 5 , Takahiko Nagase 4 , Yoshihiro Katsumata 5 , Akihiko Hirose 2
Affiliation  

1,4-Dichlorobutane (1,4-DCB) is used as raw materials for drugs, pesticides, fragrances, and chemical fibers, and being used as a solvent. Its toxicity data was insufficient for screening assessment under the Japanese Chemical Substances Control Law. We conducted toxicity tests and hazard classification for screening assessment 1,4-DCB showed negative in the Ames test, positive in the in vitro chromosomal aberrations test with metabolic activation, and negative in the in vivo mouse bone-marrow micronucleus test. The 28-day repeated-dose toxicity study, where male and female rats were administered 1,4-DCB by gavage at 0, 12, 60, and 300 mg/kg/day, showed significant effects on the liver and pancreas from 12 mg/kg/day and kidney at 300 mg/kg/day. Based on periportal hepatocellular hypertrophy and decreased zymogen granules in pancreas, the lowest observed adverse effect level (LOAEL) of 12 mg/kg/day was obtained. The reproductive/developmental toxicity screening study, in which male and female rats were administered 1,4-DCB by gavage at dose of 0, 2.4, 12, and 60 mg/kg/day for 42-46 days, showed that the delivery index was decreased at 60 mg/kg/day without maternal toxicity. Based on the general toxicity, we classified this chemical as hazard class 2, with a D-value (Derived No Effect Level) of 0.002 mg/kg/day.

中文翻译:

1,4-二氯丁烷的初步危害评估:基因毒性试验,28天重复剂量毒性试验和大鼠生殖/发育毒性筛选试验。

1,4-二氯丁烷(1,4-DCB)用作药物,农药,香料和化纤的原料,并用作溶剂。其毒性数据不足以根据日本化学物质控制法进行筛选评估。我们进行了毒性测试和危害分类以进行筛选评估1,4-DCB在Ames测试中显示阴性,在具有代谢激活作用的体外染色体畸变测试中显示阳性,而在体内小鼠骨髓微核测试中显示阴性。这项为期28天的重复剂量毒性研究表明,雌雄大鼠分别以0、12、60和300 mg / kg / day的剂量通过管饲法对1,4-DCB给药,从12 mg起对肝脏和胰腺产生显着影响/ kg /天,肾脏为300 mg / kg /天。基于门静脉肝细胞肥大和胰腺中的酶原颗粒减少,观察到的最低不良反应水平(LOAEL)为12 mg / kg /天。生殖/发育毒性筛选研究表明,雄性和雌性大鼠分别以0、2.4、12和60 mg / kg / day的剂量灌胃1,42-46天,给药1,4-DCB,结果显示分娩指数每天减少60 mg / kg / day,而没有母体毒性。根据一般毒性,我们将此化学品分类为危险等级2,D值(无作用水平)为0.002 mg / kg / day。
更新日期:2020-02-04
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