Triphenyltin as a potential human endocrine disruptor.
Organotin compounds have been implicated as reproductive toxicants and endocrine disruptors primarily through studies in aquatic organisms, with little information available in mammals. Among the organotins, aryltins have been less studied than alkyltins. Extensive data is available on mammalian developmental and reproductive toxicity of one aryltin compound, triphenyltin (TPT), from toxicity studies conducted in connection with the registration of triphenyltin hydroxide (TPTH) as a pesticide and supporting publications from the open literature. Indications of adverse functional and morphological effects on the reproductive tract of rats were reported in a dose range of 1.4-20 mg/kg/d. Gonadal histopathology (both ovaries and testes) and infertility were affected at the higher doses, while reproductive-tract cancer, smaller litter sizes, and reproductive organ weights were affected at the lower end of the dose range. In vitro studies indicate that TPT can directly activate androgen receptor-mediated transcription and inhibit enzymes that are involved in steroid hormone metabolism. These data suggest that the aryltin TPT can be active as a reproductive toxicant in mammals and may be a human endocrine disruptor.
Golub
Mari
M
California Environmental Protection Agency, Sacramento, California 95812, USA. mgolub@oehha.ca.gov
Doherty
John
J
D000818:Animals; D000890:Anti-Infective Agents / Q000009:adverse effects*; D004195:Disease Models, Animal; D005314:Embryonic and Fetal Development / Q000187:drug effects; D004703:Endocrine System / Q000187:drug effects*; D005260:Female; D006801:Humans; D007246:Infertility / Q000139:chemically induced*; D008297:Male; D008322:Mammals / Q000196:embryology; D009947:Organotin Compounds / Q000009:adverse effects*; D010053:Ovary / Q000002:abnormalities*; D010575:Pesticides / Q000633:toxicity; D051381:Rats; D013737:Testis / Q000002:abnormalities*
D000890:Anti-Infective Agents; D009947:Organotin Compounds; D010575:Pesticides; C030665:triphenyltin