The effects of acute alterations in maternal health status upon fetal development were assessed following exposure of pregnant CD-1 mice on day 8 of gestation to one of ten chemicals at doses calculated to exert either a low or a moderate degree of maternal lethality. The dams were killed on day 18 of gestation, and the fetuses were examined by routine teratological techniques. The chemicals were cacodylic acid, caffeine, deltamethrin, dinoseb, ethylene bisisothiocyanate sulfide (EBIS), endrin, guthion, kepone, sodium salicylate, and toxaphene. Three (cacodylic acid, EBIS, and kepone) produced dose-related increases in the incidence of dams with completely resorbed litters. Prenatal mortality in litters that contained live fetuses at term was elevated only for one chemical (cacodylic acid). Fetal weight was reduced in three instances (cacodylic acid, endrin, and guthion), while the incidence of terata was markedly elevated for two (cacodylic acid and kepone). For two other chemicals (endrin and sodium salicylate), a low incidence was found of defects that were similar to defects induced by those chemicals in other species. These effects appear to be chemospecific in nature and not the result of some indirect maternal action. Thus, maternal health status, as measured by the incidence of lethality in the treated groups and by the magnitude of maternal weight gain in surviving females, presents no simple explanation for many manifestations of fetal toxicity. However, for seven chemicals (excluding deltamethrin, EBIS, and kepone) an increased incidence of supernumerary ribs was observed. For three of these seven chemicals (caffeine, dinoseb, and toxaphene), supernumerary ribs was the only observed fetal effect. There was a significant linear inverse relationship between maternal weight gain during gestation and the incidence of extra ribs in the treated groups compared to their respective controls. Under the experimental conditions of this study, it appears that the incidence of supernumerary ribs increased in response to a nonspecific maternal toxicity.

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.

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