gestation (Ferm, 1974; Ferm et al., 1971; Holmberg and Ferm, 1969). Ferm and Saxon (1971) also reported renal agenesis in hamsters treated with arsenic. Hood and Bishop (1972), studying IP injection of pregnant mice using 45 mg/kg of sodium arsenate, found a variety of malformations in the surviving fetuses.
Finally, Luego and colleagues (1969) report the case of a 17-year-old girl who ingested ''a dose" of inorganic arsenic during the third trimester of pregnancy. She gave birth to a baby weighing 1.1 kg who died 11 hours later. The child had very high levels of arsenic in the liver, brain, and kidney. This clearly shows that anionic arsenic can pass through the mammalian placental barrier. This is consistent with work by Morris and colleagues (1938).
Organic Arsenicals. Organic arsenicals appear to be stored in the placenta at high concentrations, but they appear not to cross the placental membrane with any great ease in humans, cats, or rabbits (Eastman, 1931; Underhill and Amatruda, 1923). Several studies of the teratogenicity of a variety of organic arsenicals have been completed. Sodium dimethylarsonate was given by gavage to CD rats (7.5-60 mg/kg per day) and CD-1 mice (200-600 mg/kg per day) on day 7-16 of gestation. Sacrifice of the animals on day 18 (mice) and day 21 (rats) showed that there was both maternal and fetal toxicity in both species (Rogers et al., 1981). Cleft palate was seen at the middle and highest doses in the mouse. In the rat, genesis of irregular rugae (stomach folds) was observed to be dose related. Both species had maternal toxicity at doses below the maximum.
Frost and colleagues (1964) found no teratogenic effects in feeding studies (0.01, 0.02, and 0.05 percent arsanilic acid) following seven generations of rats. Harrison and colleagues (1980) studied intravenous administration of sodium dimethylarsonate in pregnant CD-1 mice. On day 9 and 10 they observed increased fetal resorption and mortality rates, with increased incidence of skeletal malformations and exencephaly. Hamsters given 900-1,000 mg/kg of sodium dimethylarsonate on day 9, 11, and 12 of pregnancy had a significant dose-related incidence of fetal resorptions (Hood et al., 1982a,b). The same work showed that IP injection of methanearsonic acid into hamsters (500 mg/kg) also induced both fetotoxicity and teratogenicity.
The sodium salts of the methanearsonates administered by IP injection in rodents (500-1,500 mg/g) also caused maternal mortality (Harrison et al., 1980; Hood, 1985). Inorganic arsenic injected at doses of 5-15 mg/kg induced developmental defects in mice (Hood, 1972; Hood and Bishop, 1972). Finally, Willhite (1981) injected 20-100 mg/kg of methylarsonic acid or 20-100 mg of dimethylarsinic acid intravenously into golden hamsters on the eighth day of gestation. In this work there was no teratogenic response.