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对苯二酚在F344/N大鼠和B6C3F1小鼠中的毒性和致癌性。

Toxicity and carcinogenicity of hydroquinone in F344/N rats and B6C3F1 mice.

作者信息

Kari F W, Bucher J, Eustis S L, Haseman J K, Huff J E

机构信息

National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.

出版信息

Food Chem Toxicol. 1992 Sep;30(9):737-47. doi: 10.1016/0278-6915(92)90075-v.

Abstract

Toxicology and carcinogenesis studies were conducted by administering hydroquinone (more than 99% pure) by gavage to groups of F344/N rats and B6C3F1 mice of each sex for 14 days, 13 wk or 2 yr. 14-day studies were conducted by administering hydroquinone in corn oil to rats at doses ranging from 63 to 1000 mg/kg body weight and to mice at doses ranging from 31 to 500 mg/kg, 5 days/wk. In the 13-wk studies, doses for rats and mice ranged from 25 to 400 mg/kg. At those doses showing some indication of toxicity in the 14-day and 13-wk studies, the central nervous system, forestomach and liver were identified as target organs in both species and renal toxicity was observed in rats. Based on these results, 2-yr studies were conducted by administering 0, 25 or 50 mg hydroquinone/kg in deionized water by gavage to groups of 65 rats of each sex, 5 days/wk. Groups of 65 mice of each sex were given 0, 50 or 100 mg/kg on the same schedule. 10 rats and 10 mice from each group were killed and evaluated after 15 months. Mean body weights of high-dose male rats and high-dose mice were approx. 5-14% lower than those of controls during the second half of the study. No differences in survival were observed between dosed and control groups of rats or mice. Nearly all male rats and most female rats in all vehicle control and exposed groups had nephropathy, which was judged to be more severe in high-dose male rats. Hyperplasia of the renal pelvic transitional epithelium and renal cortical cysts were increased in male rats. Tubular cell hyperplasia of the kidney was seen in two high-dose male rats, and renal tubular adenomas were seen in 4/55 low-dose and 8/55 high-dose male rats; none was seen in vehicle controls or in female rats. Mononuclear cell leukaemia in female rats occurred with increased incidences in the dosed groups (vehicle control, 9/55; low dose, 15/55; high dose, 22/55). Compound-related lesions observed in the liver of high-dose male mice included anisokaryosis, syncytial alteration and basophilic foci. The incidences of hepatocellular neoplasms, primarily adenomas, were increased in dosed female mice (3/55; 16/55; 13/55). Follicular cell hyperplasia of the thyroid gland was increased in dosed mice.(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

毒理学和致癌性研究通过对每组F344/N大鼠和B6C3F1小鼠(雌雄各半)经口灌胃给予对苯二酚(纯度大于99%)进行,持续14天、13周或2年。14天的研究中,将对苯二酚溶于玉米油中,以63至1000mg/kg体重的剂量给予大鼠,以31至500mg/kg的剂量给予小鼠,每周给药5天。在13周的研究中,大鼠和小鼠的剂量范围为25至400mg/kg。在14天和13周的研究中,在显示出一定毒性迹象的剂量下,两个物种的中枢神经系统、前胃和肝脏均被确定为靶器官,并且在大鼠中观察到肾毒性。基于这些结果,进行了2年的研究,通过经口灌胃给予每组65只雌雄大鼠0、25或50mg对苯二酚/kg,每周给药5天,溶于去离子水中。每组65只雌雄小鼠按相同给药方案给予0、50或100mg/kg。在15个月后,处死每组中的10只大鼠和10只小鼠并进行评估。在研究的后半期,高剂量雄性大鼠和高剂量小鼠的平均体重比对照组低约5 - 14%。在给药组和对照组的大鼠或小鼠之间未观察到存活率的差异。在所有赋形剂对照组和暴露组中,几乎所有雄性大鼠和大多数雌性大鼠都患有肾病,高剂量雄性大鼠的肾病被认为更严重。雄性大鼠肾盂移行上皮增生和肾皮质囊肿增加。在两只高剂量雄性大鼠中观察到肾小管细胞增生,在4/55低剂量和8/55高剂量雄性大鼠中观察到肾小管腺瘤;在赋形剂对照组或雌性大鼠中未观察到。雌性大鼠单核细胞白血病在给药组中的发生率增加(赋形剂对照组,9/55;低剂量组,15/55;高剂量组,22/55)。在高剂量雄性小鼠肝脏中观察到的与化合物相关的病变包括核大小不等、合胞体改变和嗜碱性灶。给药雌性小鼠中肝细胞肿瘤(主要是腺瘤)的发生率增加(3/55;16/55;13/55)。给药小鼠甲状腺滤泡细胞增生增加。(摘要截短至400字)

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