Toxicology Division, Institute of Environmental Toxicology, Joso, Ibaraki, Japan.
Developmental and Reproductive Toxicology, Drug Safety R&D, Pfizer, Inc., Groton, Connecticut, USA.
Vitam Horm. 2014;94:193-210. doi: 10.1016/B978-0-12-800095-3.00007-9.
Methoxychlor is an organochlorine pesticide having a weak estrogenicity, which is estimated to be approximately 1000- to 14,000-fold less potent to a natural ligand, 17β-estradiol. However, its active metabolite, hydroxyphenyltrichloroethane, has much more potent estrogenic activity and probably acts in the target organs of animals exposed to methoxychlor at least 100 times stronger than the parent compound. A variety of in vivo reproductive toxicity studies have shown that treatment with methoxychlor exerts typical endocrine-disrupting effects manifest as estrogenic effects, such as formation of cystic ovaries resulting in ovulation failures, uterine hypertrophy, hormonal imbalances, atrophy of male sexual organs, and deteriorations of sperm production in rats and/or mice, through which it causes serious reproductive damages in both sexes of animals at sufficient dose levels. However, methoxychlor is not teratogenic. The no-observed-adverse-effect level of methoxychlor among reliable experimental animal studies in terms of the reproductive toxicity is 10 ppm (equivalent to 0.600 mg/kg/day) in a two-generation reproduction toxicity study.
甲氧滴滴涕是一种有机氯杀虫剂，具有较弱的雌激素活性，据估计，其对天然配体 17β-雌二醇的效力约低 1000 至 14000 倍。然而，其活性代谢物羟苯基三氯乙烷具有更强的雌激素活性，并且可能在接触甲氧滴滴涕的动物的靶器官中发挥作用，其效力至少比母体化合物强 100 倍。各种体内生殖毒性研究表明，甲氧滴滴涕的处理表现出典型的内分泌干扰作用，表现为雌激素作用，例如形成导致排卵失败的囊性卵巢、子宫肥大、激素失衡、雄性性器官萎缩以及雄性和/或雌性动物的精子生成恶化，在足够剂量水平下，这会导致动物两性的严重生殖损伤。然而，甲氧滴滴涕没有致畸性。在可靠的实验动物生殖毒性研究中，甲氧滴滴涕的无观察到不良效应水平在两代生殖毒性研究中为 10 ppm（相当于 0.600 mg/kg/天）。
