Boric acid is used as an insecticide and constituent of commercial products, including topically applied medicinals and cosmetics. In this study, developmental toxicity was evaluated in timed-mated Sprague-Dawley-derived (CD) rats exposed to boric acid in feed at concentrations of 0.1%, 0.2% or 0.4% on gestational days 0 to 20 (n=29/group); exposure to 0.8% dietary boric acid (n=14) was restricted to the period of major organogenesis (gd 6 to 15) in order to limit early embryolethality.
Average daily intake of boric acid was 78, 163, 330 and 539 mg/kg/day , respectively. Exposure to 0.2% and 0.4% resulted in increased maternal food intake for gd 12 to 20; water intake was increased on gd 18, to 20 at 0.4%. Food intake was decreased during treatment at 0.8% with a rebound increase on gd 15 to 18; water intake was decreased on gd 6 to 9. Other effects summarized across all dose levels included increased relative maternal liver and kidney wts. at greater than or equal to 0.2%, decreased gravid uterine weight at greater than or equal to 0.4%, decreased wt. gain during treatment and gestation at greater than or equal to 0.4%, and increased corrected body wt. gain only at 0.4%. Microscopic evaluation of maternal kidneys (10 dams/group) did not provide any definitive evidence for treatment-related renal pathology.
Average fetal body wt./litter was reduced at all doses. Prenatal mortality was increased only at 0.8%. The incidence of fetal malformations was significantly increased at greater than or equal to 0.2% dietary boric acid (2, 3, 8, 50 and 73% malformed fetuses/litter in the control through high-dose groups). The most frequently observed malformations were enlarged lateral ventricles of the brain, and agenesis or shortening of rib XIII. As an associated finding, the incidence of Lumbar I rib(s), a common variation in the CD rat, was reduced following boric acid treatment.
In conclusion, the no observed adverse effect level for maternal toxicity was 0.1% dietary boric acid and the lowest observed adverse effect level was 0.2%. Embryo/fetal toxicity occurred in all treatment groups (greater than or equal to 0.1%).