© 1987 Oxford University Press
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Embryotoxicity and Fetotoxicity of Orally Administered Tridiphane in Mice and Rats
Mammalian and Environmental Toxicology Research Laboratory, Health and Environmental Sciences, Dow Chemical USA Midland, Michigan 48674
Embryotoxicity and Fetotoxicity of Orally Administered Tridiphane in Mice and Rats. HANLEY, T. R., Jr., JOHN-GREENE, J. A., HAYES, W. C., and RAO, K. S. (1987). Fundam. Appl. Toxicol. 8, 179–187. 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. Slight fetotoxicity (increased skeletal variants) was observed in mice at 75 mg/kg, a dose which also produced a significant elevation of liver weight in the maternal animal. In rats, slight fetotoxicity was observed at the maternally toxic dose of 200 mg/kg/day, and very slight fetotoxicity at 100 mg/kg/day. Neither test species showed evidence of significant developmental toxicity at dose levels which were not toxic to the dam. Thus, the no observed effect levels (NOELs) for tridiphane under these test conditions were 25 and 30 mg/kg/day for mice and rats, respectively.