Morris I D, Williams L M
J Pharm Pharmacol. 1980 Jan;32(1):35-8. doi: 10.1111/j.2042-7158.1980.tb12841.x.
(+/-)alpha-Chlorohydrin (80 mg kg-1) given by mouth to group-housed adult male Sprague Dawley rats produced an increase in the weight of the kidneys which persisted for at least 7 days, but there were no deaths. This dose administered to Sprague Dawley rats caged singly killed 3 out of 8 animals. The toxicity was studied in more detail using Wistar rats caged singly in metabolic cages. 4 out of 9 animals died with oliguria and anuria after 120 mg kg-1 (+/-)alpha-chorohydrin, 100 and 120 mg kg-1 (in the surviving animals), produced a loss in appetite and body weight, proteinuria, a dose-related diuresis and an increased water intake. Urinary glucose was dramatically elevated after 100 mg kg-1 but after 120 mg kg-1 the glucosuria was not as marked. By day 7 all parameters were returning to their pre-injection values. A dose of 80 mg kg-1 had no effect upon any of the parameters studied. The results are discussed in relation to the basic biochemical mechanism by which the drug exerts its antifertility action, which is achieved at much lower doses.
给成群饲养的成年雄性斯普拉格-道利大鼠经口给予(±)α-氯醇(80毫克/千克),可使肾脏重量增加,且这种增加至少持续7天,但无死亡发生。给单独饲养在笼中的斯普拉格-道利大鼠给予此剂量时,8只动物中有3只死亡。使用单独饲养在代谢笼中的Wistar大鼠对毒性进行了更详细的研究。给予120毫克/千克(±)α-氯醇后,9只动物中有4只死于少尿和无尿,100毫克/千克和120毫克/千克(在存活动物中)导致食欲和体重下降、蛋白尿、剂量相关的利尿以及水摄入量增加。给予100毫克/千克后尿糖显著升高,但给予120毫克/千克后糖尿并不那么明显。到第7天,所有参数均恢复到注射前的值。80毫克/千克的剂量对所研究的任何参数均无影响。结合该药物发挥抗生育作用的基本生化机制对结果进行了讨论,该药物在低得多的剂量下即可实现抗生育作用。