The teratogenic potential of cacodylic acid in the rat and mouse

Cacodylic acid, an organic arsenical herbicide, was administered to time-pregnant albino CD rats and CD-1 mice on days 7-16 of gestation. The compound was given by gastric intubation as a solution in distilled water. Rats received 0, 7.5, 15, 30, 40, 50, or 60 mg/kg/day in 0.2 ml/day intubation volume; mice received 0, 200, 400, or 600 mg/kg/day in 0.1 ml/day. Following maternal sacrifice on day 18 (mice) and 21 (rats), fetuses were weighed and fixed for skeletal and visceral examinations. Fetal and maternal toxicity was observed in both species. In the mouse, maternal toxicity was evident at the lowest dose, while teratogenic response was confined to cleft palate at 400 and 600 mg/kg/day. The effective maternal toxic dose in the rat was 40 mg/kg/day. In this species, incidence of irregular palatine rugae, i.e., ridges that were discontinuous and/or not lying in apposition at the palatal raphe, was significantly (p less than 0.001) dose-related. The results suggest an "apparent no effect level" for this anomaly below 30 mg/kg/day.