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短期给予α-氯醇对雄性斯普拉格-道利大鼠生殖毒性参数的影响。

Effects of short-term administration of alpha-chlorohydrin on reproductive toxicity parameters in male Sprague-Dawley rats.

作者信息

Yamada T, Inoue T, Sato A, Yamagishi K, Sato M

机构信息

Development Research Laboratories, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.

出版信息

J Toxicol Sci. 1995 Aug;20(3):195-205. doi: 10.2131/jts.20.195.

Abstract

alpha-Chlorohydrin (alpha-CH) was administered orally at doses of 0, 2 or 8 mg/kg/day for 2 weeks to Sprague-Dawley male rats. At the end of the administration period or 2 weeks after withdrawal (one group also treated with 8 mg/kg for 4 weeks), males were mated (treatment with alpha-CH was continued throughout the mating period of 2 weeks) with untreated females, and underwent examination, including assessment of sperm, to determine fertility. No significant treatment-associated changes were observed in terms of body weight, food consumption, or weights of the testes, epididymides or prostate in either the 2 or the 8 mg/kg group. Although there were no significant differences in sperm number, viability or maturation rate between either of the treated groups and the control group, sperm motility in the 8 mg/kg group observed after 2 hours incubation and sperm activity in groups treated with 8 mg/kg observed immediately after collection or after 2 hours incubation, as well as in the 2 mg/kg observed after 2 hours of incubation were significantly decreased. Two weeks after withdrawal (8 mg/kg group only), sperm motility and activity were no longer decreased. Histopathological examination of the testes after 4 weeks of alpha-CH administration disclosed no abnormalities on staining with Hematoxylin-Eosin after fixation in Bouin's solution. All treated male rats copulated with untreated females, but no pregnancy resulted from mating in the 8 mg/kg continuous administration case. There were no significant differences between the control and 2 mg/kg groups in numbers of corpora lutea and implantations in animals becoming pregnant. Two weeks after withdrawal, male rats treated with 8 mg/kg copulated and impregnated females. These findings suggest that evaluation of male fertility is possible within or following a 2-week treatment period for compounds like alpha-CH which have no toxicological, histopathological or sperm morphological effects, and that the use of several parameters for sperm examination is important in determining male fertility.

摘要

将α-氯醇(α-CH)以0、2或8毫克/千克/天的剂量口服给予雄性Sprague-Dawley大鼠,持续2周。在给药期结束时或停药2周后(一组还用8毫克/千克治疗4周),雄性大鼠与未处理的雌性大鼠交配(在2周的交配期内持续用α-CH治疗),并接受包括精子评估在内的检查以确定生育能力。在2毫克/千克或8毫克/千克组中,在体重、食物消耗或睾丸、附睾或前列腺重量方面未观察到与治疗相关的显著变化。尽管两个治疗组与对照组之间在精子数量、活力或成熟率方面没有显著差异,但在孵育2小时后观察到的8毫克/千克组的精子活力以及在采集后或孵育2小时后观察到的8毫克/千克处理组的精子活性,以及在孵育2小时后观察到的2毫克/千克组的精子活性均显著降低。停药2周后(仅8毫克/千克组),精子活力和活性不再降低。在以Bouin氏液固定并用苏木精-伊红染色后,对给予α-CH 4周后的睾丸进行组织病理学检查未发现异常。所有处理过的雄性大鼠都与未处理的雌性大鼠交配,但在8毫克/千克持续给药的情况下交配未导致怀孕。在怀孕的动物中,对照组和2毫克/千克组在黄体数量和着床数量方面没有显著差异。停药2周后,用8毫克/千克处理的雄性大鼠与雌性大鼠交配并使其受孕。这些发现表明,对于像α-CH这样没有毒理学、组织病理学或精子形态学影响的化合物,在2周治疗期内或之后评估雄性生育能力是可能的,并且在确定雄性生育能力时使用多个精子检查参数很重要。

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