Absence of prenatal developmental toxicity from inhaled arsenic trioxide in rats

A review of the literature revealed no published inhalational developmental toxicity studies of arsenic performed according to modern regulatory guide lines and with exposure throughout gestation. In the present study, inorgan ic arsenic, as arsenic trioxide (As+3, As2O3), was administered via whole-b ody inhalational exposure to groups of twenty-five Crl:CD(R)(SD)BR female r ats for six h per day every day, beginning fourteen days prior to mating an d continuing throughout mating and gestation. Exposures were begun prior to mating in order to achieve a biological steady state of As+3 in the dams p rior to embryonal-fetal development. In a preliminary exposure range-findin g study, half of the females that had been exposed to arsenic trioxide at 2 5 mg/m(3) died or were euthanized in extremis. In the definitive study, tar get exposure levels were 0.3, 3.0, and 10.0 mg/m(3). Maternal toxicity, whi ch was determined by the occurrence of rales, a decrease in net body weight gain, and a decrease in food intake during pre-mating and gestational expo sure, was observed only at the 10 mg/m(3) exposure level. Intrauterine para meters (mean numbers of corpora lutea, implantation sites, resorptions and viable fetuses, and mean fetal weights) were unaffected by treatment. No tr eatment-related malformations or developmental variations were noted at any exposure level. The no-observed-adverse-effect level (NOAEL) for maternal toxicity was 3.0 mg/m(3); the NOAEL for developmental toxicity was greater than or equal to 10 mg/m(3), 760 times both the time-weighted average thres hold limit value (TLV) and the permissible exposure limit (PEL) for humans. Based on the results of this study, we conclude that arsenic trioxide, whe n administered via whole-body inhalation to pregnant rats, is not a develop mental toxicant.