Bisphenol A, a widely distributed industrial chemical used in making epoxy resins and polycarbonates, was evaluated for toxic and teratogenic effects on timed-pregnant Swiss ICR CD-l mice. BPA (O, 500, 750, 1000, and 1250 mg/kg/day) suspended in corn oil was given by gavage (10.0 mL/kg body weight) daily on gestational days 6 through 15. Timed-pregnant dams (n= 29-33/group) were sacrificed 1 day prior to parturition, the uterine contents were examined, and all fetuses were examined for external, visceral, and skeletal malformations.
During BPA treatment, dams exhibited clinical signs of toxicity including arched back, piloerection, weight loss, lethargy, rough coat, vaginal bleeding, vocalization, wheezing, and alopecia. Maternal mortality occurred at all BPA doses: 7.1%, 3.6%, 6.3%, and 18.2% for the low through high dose groups, respectively. Maternal body weight on gd 0, gd 6, and gd 11 did not differ among dosed groups. Maternal body weight was decreased in the 1250 mg/kg/day dose group on gd 15 (by 10%) and 17 (by 16%). Gravid uterine weight was depressed in the 1250 mg/kg/day dose group by 32%. Weight gain corrected for gravid uterine weight was not affected by BPA. Relative maternal liver weight (i.e., corrected for body weight) was increased at all doses (by 9%, 13%, 17%, and 25% respectively). There was a significant increase in the percentage of resorptions per litter at the high dose from a control value of 14%, to 40%. Malformation incidence was not altered by BPA. There was a 13-15% decrease in individual fetal weight, seen only at the high dose.
BPA treatment at maternally toxic dose levels produced fetal toxicity but did not alter fetal morphologic development. Based on mortality at all doses, no observed adverse effect level was established for dams. The NOAEL for fetal malformations is 1250 mg/kg/day.