We have carried out animal toxicity tests of chemicals for a chemical safety program implemented by the Ministry of Economy, Trade, and Industry of Japan. Here, we tested 1-tert-butoxy-4-chlorobenzene in a combined repeat-dose and developmental and reproductive toxicity test. The test chemical was administered daily by gavage to 9-week-old Crl:CD (SD) rats at doses of 0, 20, 100, and 500 mg/kg/d. Males were treated for 42 d beginning 14 d before mating. Females were treated from 14 d before mating to day 4 of lactation. Decreased spontaneous locomotion, decreased respiratory rate, and incomplete eyelid opening were observed at 500 mg/kg/d (both sexes), but resolved within 30 min of administration, suggesting central nervous system depression. No notable changes were observed in body weight, food consumption, functional battery tests, or blood test. Increased liver weight with centrilobular or diffuse hepatocyte hypertrophy was observed at 100 and 500 mg/kg/d (both sexes). There were no biochemical or histopathological changes related to hepatotoxicity. Increased kidney weight with basophilic tubules, tubule dilatation, and increased hyaline droplets were observed in males dosed at 100 and 500 mg/kg/d. Immunohistochemical staining indicated α_2u-globulin nephropathy, a male rat-specific toxicity. Although kidney weight was also increased in females dosed at 500 mg/kg/d, it was not considered to be an adverse effect because there were no histopathological changes. Pup weights on postnatal day 0 were decreased at 500 mg/kg/d and still decreased on postnatal day 4. Our data indicated the no-observed-adverse-effect-level for repeated-dose and reproductive/developmental toxicity for 1-tert-butoxy-4-chlorobenzene was 100 mg/kg/d.

我们针对日本经济产业省实施的化学安全计划进行了化学物质动物毒性测试。在这里，我们测试了1叔-丁氧基-4-氯苯的重复剂量与发育和生殖毒性综合测试。每天通过管饲法向9周龄的Crl：CD（SD）大鼠以0、20、100和500 mg / kg / d的剂量施用测试化学品。雄性在交配前14天开始治疗42天。从交配前14天到哺乳第4天对雌性进行治疗。在500 mg / kg / d（两性）下，观察到自发运动减少，呼吸频率降低和眼睑张开不完全，但在给药后30分钟内消失，表明中枢神经系统抑制。体重，食物消耗，功能性电池测试或血液测试未见明显变化。分别以100和500 mg / kg / d（两性）观察到肝小叶或肝小叶肥大的肝脏重量增加。没有与肝毒性有关的生化或组织病理学变化。在剂量为100和500 mg / kg / d的雄性中，观察到嗜碱性肾小管肾重量增加，肾小管扩张和透明小滴增多。免疫组化染色指示为α_2U球蛋白肾病，雄性大鼠特异性毒性。尽管剂量为500 mg / kg / d的雌性肾脏重量也有所增加，但由于没有组织病理学改变，因此未将其视为不良反应。出生后第0天的幼崽体重以500 mg / kg / d下降，但出生后第4天仍下降。我们的数据表明，重复剂量和生殖/发育毒性的未观察到的不良反应水平为1-叔-丁氧基-4-氯苯为100 mg / kg / d。