Embryotoxicity and fetotoxicity of orally administered tridiphane in mice and rats.
Tridiphane [2-(3,5-dichlorophenyl)-2-(2,2,2-trichloroethyl)oxirane], a broad-leaf herbicide, was evaluated for its potential effects on mouse and rat embryonal and fetal development. Pregnant CF-1 mice were given 0, 25, 75, or 250 mg tridiphane/kg/day on Days 6 through 15 of gestation. Significant maternal toxicity was observed in both the 75- and 250-mg/kg/day dose groups. An increased percentage of females given 250 mg/kg/day showed implantation sites only after staining of the uterus, suggesting a toxic effect on the embryo during the early stages of development, possibly secondary to maternal toxicity. Increases in some skeletal variants were noted at the 75-mg/kg dose level; however, a teratogenic effect was not observed. An additional group of mice was given 250 mg/kg/day on Days 8 through 15 of gestation. Maternal toxicity was also observed among these mice as manifested by significantly elevated (+50%) liver weight; however, there was a substantial increase in the number of females with full-term litters following this shorter dosing period. An increase in the occurrence of cleft palate in these offspring associated with low fetal body weights was also observed. Pregnant Sprague-Dawley rats were given 0, 30, 100, or 200 mg/kg/day of tridiphane on Days 6 through 15 of gestation. Maternal toxicity was observed among rats given 200 mg/kg. Increased incidences of two minor skeletal variants, lumbar spurs and extra ribs, were observed in the 200-mg/kg/day dose group, and an increase in lumbar spurs was observed at 100 mg/kg/day. Thus, tridiphane was embryotoxic and induced cleft palate in mice only at the maternally toxic dose level of 250 mg/kg/day.(ABSTRACT TRUNCATED AT 250 WORDS)
D000014:Abnormalities, Drug-Induced / Q000473:pathology*; D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004622:Embryo, Mammalian / Q000187:drug effects; D004852:Epoxy Compounds / Q000008:administration & dosage / Q000633:toxicity*; D004988:Ethers, Cyclic / Q000633:toxicity*; D005260:Female; D005313:Fetal Death; D005327:Fetal Resorption; D005333:Fetus / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000473:pathology; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D013723:Teratogens / Q000633:toxicity*
D004852:Epoxy Compounds; D004988:Ethers, Cyclic; D013723:Teratogens; C051460:tridiphane