Assessment of estrogenicity by using the delayed implanting rat model and examples.
Endocrine disrupting chemicals have recently drawn increased interest. The delayed implanting rat model is a method that can identify and quantify the estrogenic activity of a chemical. In rats hypophysectomized after breeding, the administration of progesterone delays embryo implantation, and exposure to one dose of an estrogenic substance initiates implantation. Although methoxychlor was ineffective at dosages below 400 mg/kg when given by injection, the administration of the chemical by gavage resulted in an increase in the percent of fertilized rats exhibiting implantation sites. These results were statistically significant at dosages of 50, 100, 200, and 300 mg methoxychlor/kg. When bisphenol A was administered, by subcutaneous injection, dosages of 50, 100, and 200 mg/kg induced implantation. Only the 400 mg/kg dose of 4-tert-octylphenol was effective. Doses of beta-sitosterol up to 30 mg/kg failed to initiate implantation. These data confirm previous evidence of the availability of this model for evaluating estrogenic activity and provide estimates of the estrogenic potencies of several environmentally important chemicals.
Cummings
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AM
Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. cummings.audrey@epa.gov
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D000284:Administration, Oral; D000818:Animals; D001559:Benzhydryl Compounds; D001755:Blastocyst / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D010065:Embryo Implantation, Delayed / Q000187:drug effects* / Q000502:physiology; D047108:Embryonic Development; D004968:Estrogens, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D004970:Estrone / Q000494:pharmacology; D005260:Female; D005306:Fertilization / Q000187:drug effects; D007016:Hypophysectomy; D007279:Injections, Subcutaneous; D008297:Male; D008731:Methoxychlor / Q000494:pharmacology; D010636:Phenols / Q000494:pharmacology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism; D012855:Sitosterols / Q000494:pharmacology; D015262:Xenobiotics / Q000008:administration & dosage / Q000494:pharmacology*; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D004968:Estrogens, Non-Steroidal; D004970:Estrone; D008731:Methoxychlor; D010636:Phenols; D011960:Receptors, Estrogen; D012855:Sitosterols; D015262:Xenobiotics; C025473:gamma-sitosterol; C105260:4-tert-octylphenol; C006780:bisphenol A; D000098826:Bisphenol A Compounds