Boric acid (BA) is a naturally occurring agent used in manufacturing processes and numerous consumer products. Because of the potential for both industrial and consumer exposure to boron-containing compounds, and the lack of developmental toxicity data, the National Toxicology Program evaluated the potential for boric acid to cause developmental toxicity in pregnant Swiss (CD-1) mice, Sprague-Dawley rats (n = 26-28/group), and New Zealand rabbits (n = 18-23/group). BA was provided in the feed to mice and rats at 0, 0.1, 0.2, or 0.4% throughout gestation to attain steady-state exposure as early as possible during development. Average doses (mg/kg/day) were 248, 452, or 1003 for mice, and 78, 163, or 330 in rats. A separate group of rats received 0.8% BA in the feed, or 539 mg/kg/day only on gestation days (gd) 6 to 15. Rabbits were given BA (0, 62.5, 125, or 250 mg/kg) by gavage administration on gd 6 to 19. Maternal body weight, food and/or water consumption and signs of toxicity were monitored at regular intervals. At termination, gd 17 (mice), 20 (rats), or 30 (rabbits), the uterus was examined to determine the number of resorptions, dead, or live fetuses. Fetuses were weighed and live fetuses were examined for external, visceral, and skeletal defects. Mouse darns exhibited mild renal lesions (greater than or equal to 248 mg/kg/day BA). increased water intake and relative kidney weight (1003 mg/kg/day BA), and decreased weight gain during treatment. Maternal rats exhibited increased liver and kidney weights at greater than or equal to 163 mg/kg/day BA, altered water and/or food intake at >163 mg/kg/day BA, and decreased weight gain at >330 mg/kg/day BA. In rabbits, signs of toxicity included decreased food consumption during treatment. and vaginal bleeding associated with pregnancy loss at 250 mg/kg/day. Maternal body weight (gd 9 to 30), weight gain during treatment, and gravid uterine weight decreased at 250 mg/kg/day. Relative maternal kidney weight (but not absolute weight) was increased at 250 mg/kg/day, but microscopic evaluation did not indicate any renal pathology associated with BA exposure. BA is a developmental toxicant in all three species. The lowest-observed-adverse-effect level (LOAEL) for developmental toxicity was 78 mg/kg/day for rats (fetal weight reduction), 250 mg/kg/day for rabbits (prenatal mortality and malformations), and 452 mg/kg/day for mice (fetal weight reduction). The no-observed-adverse-effect levels (NOAELs) for developmental toxicity in these species were <78 mg/kg/day (rats), 125 mg/kg/day (rabbits), and 248 mg/kg/day (mice). With regard to maternal toxicity. the rat was the most sensitive (163 mg/kg/day), while both the mouse and rabbit showed maternal toxicity at 250 mg/kg/day. Thus, developmental toxicity occurred below maternally toxic levels in the rat, and only in the presence of maternal toxicity in mice or rabbits.
