Developmental toxicity assessment of arsenic acid in mice and rabbits

To evaluate potential effects of exposure to inorganic arsenic throughout m ajor organogenesis, CD-1 mice and New Zealand White rabbits were gavaged wi th; arsenic acid dosages of 0, 7.5, 24, or 48 mg/kg/d on gestation days (GD ) 6 through 15 (mice) or 0, 0.19, 0.75, or 3.0 mg/kg/d on GD 6 through 18 ( rabbits) and examined at sacrifice (GD 18, mice; GD 29, rabbits) for eviden ce of toxicity. Two high-dose mice died, and survivors at the high and inte rmediate doses had decreased weight gains. High-dose-group fetal weights we re decreased; no significant decreases in fetal weight or increases in pren atal mortality were seen at other dosages. Similar incidences of malformati ons occurred in all groups of mice, including controls. At the high dose in rabbits, seven does died or became moribund, and prenatal mortality was in creased; surviving does had signs of toxicity, including decreased body wei ght. Does given lower doses appeared unaffected. Petal weights were unaffec ted by treatment, and there were no effects at other doses. These data reve aled an absence of dose-related effects in both species at arsenic exposure s that were not maternally toxic. In mice, 7.5 mg/kg/d was the maternal No- Observed-Adverse-Effect-Level (NOAEL); the developmental toxicity NOAEL, wh ile less well defined, was judged to be 7.5 mg/kg/d. In rabbits, 0.75 mg/kg /d was the NOAEL for both maternal and developmental toxicity. (C) 1998 Els evier Science Inc.