dinitrobenzenes and Fetal-Growth-Retardation

The teratogenic potential of the fungicide dinocap was evaluated in CD-1 mice. Pregnant mice were dosed by intubation with dinocap in corn oil on gestation days 7-16. Doses used were 0, 5, 10, 20, 40, 80, and 120 mg/kg/day, based on day 6 weight. Dams were killed on day 18, at which time fetuses were counted, weighed, and preserved for necropsy or skeletal examination. The highest dose killed 80% of the dams dosed, while 29% of the dams in the 80 mg/kg group died during dosing. There was no dose-related maternal mortality at lower doses. Net maternal weight gain was affected only at 80 mg/kg/day. There were no live fetuses at 120 mg/kg/day. The number of live fetuses per litter was decreased and resorptions increased at 80 mg/kg. Dose-related decreases in gravid uterus weight and fetal weight were significant at all doses of dinocap. Cleft palate was found in fetuses at 5(1/234; 0.4%), 20(46/195; 23.6%), 40(140/185; 75.5%), and 80(63/85; 74.1%) mg/kg/day. There was a dose-related increase in supernumerary ribs and a low frequency of exencephaly and umbilical hernia at high doses. This study shows that dinocap is teratogenic in the CD-1 mouse at doses well below those causing maternal toxicity.

Topics: Animals; Body Weight; Dinitrobenzenes; Dose-Response Relationship, Drug; Female; Fetal Growth Retardation; Fungicides, Industrial; Mice; Nitrobenzenes; Pregnancy; Teratogens