Teratologic and postnatal evaluation of aniline hydrochloride in the Fischer 344 rat.

Timed-pregnant Fischer 344 rats were dosed by gavage with aniline hydrochloride (10, 30, or 100 mg/kg/day), a positive control agent (hydroxyurea, 200 mg/kg/day), or vehicle (distilled water) on gestational days (gd) 7 through 20 or gd 7 through parturition. At termination on gd 20 confirmed-pregnant dams exhibited characteristic signs of aniline HCl toxicity, i.e., methemoglobinemia, increased relative spleen weight, decreased red blood cell (RBC) count, and hematological changes indicative of increased hematopoietic activity. High-dose dams exhibited mild methemoglobinemia, increased relative spleen weight, and increased RBC size at termination on postnatal day (pnd) 30. At termination on gd 20, fetuses from aniline-treated dams exhibited increased relative liver weight and enhanced hematopoietic activity, but no evidence of an embryolethal or teratogenic effect was observed. Postnatal signs of toxicity in litters from aniline-treated dams (i.e., decreased body weight, elevated relative liver weight, and elevated relative spleen weight) were transient, and no evidence of toxicity was observed in pups surviving to pnd 60. Hydroxyurea (200 mg/kg/day) administered by gavage proved to be an excellent positive control for embryotoxicity, maternal toxicity, teratogenicity, and postnatal maturational deficits in the Fischer 344 rat. In conclusion, aniline hydrochloride was not teratogenic to Fischer 344 rats, even at maternally toxic doses; transient signs of toxicity were observed postnatally in the offspring in conjunction with mild, but persistent signs of maternal toxicity through pnd 30.