title: Reproductive toxicities of methoxychlor based on estrogenic properties of the compound and its estrogenic metabolite, hydroxyphenyltrichloroethane.
abstract: 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.
authors.affiliation: Toxicology Division, Institute of Environmental Toxicology, Joso, Ibaraki, Japan. Electronic address: aoyama@iet.or.jp.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Aoyama
authors.affiliation: Developmental and Reproductive Toxicology, Drug Safety R&D, Pfizer, Inc., Groton, Connecticut, USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Chapin
mesh_terms: D000818:Animals; D001711:Biotransformation; D052244:Endocrine Disruptors / Q000493:pharmacokinetics / Q000633:toxicity; D004785:Environmental Pollutants / Q000493:pharmacokinetics / Q000633:toxicity; D004968:Estrogens, Non-Steroidal / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D005836:Genitalia, Female / Q000187:drug effects* / Q000196:embryology / Q000254:growth & development / Q000473:pathology; D005837:Genitalia, Male / Q000187:drug effects* / Q000196:embryology / Q000254:growth & development / Q000473:pathology; D006801:Humans; D007247:Infertility, Female / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D007248:Infertility, Male / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D007306:Insecticides / Q000493:pharmacokinetics / Q000633:toxicity*; D008297:Male; D008731:Methoxychlor / Q000493:pharmacokinetics / Q000633:toxicity*; D010636:Phenols / Q000378:metabolism / Q000633:toxicity; D011247:Pregnancy; D046468:Sexual Development / Q000187:drug effects*
chemical_list: D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D004968:Estrogens, Non-Steroidal; D007306:Insecticides; D010636:Phenols; C404910:2,2-bis(4-hydroxyphenyl)-1,1,1-trichloroethane; D008731:Methoxychlor
keywords: Cystic ovary; Decreased sperm production; Endocrine disruption; Estrogenic; Hormonal imbalance; Infertility; Ovulation failure; Uterotrophic