THE DEVELOPMENTAL TOXICITY OF BORIC-ACID IN RABBITS

Boric acid (BA), an ingredient of many pharmaceutical, cosmetic, and p esticide products, was previously shown to induce reproductive and dev elopmental toxicity in laboratory rodents. In this study, BA (0, 62.5, 125, or 250 mg/kg/day, po) was administered on Gestational Days (GD) 6-19 to New Zealand White rabbits (18-23 pregnant/group). Maternal bod y weight, food consumption, and clinical condition were monitored at r egular intervals throughout gestation. At termination (GD 30), the num bers of uterine implantations, resorptions, dead fetuses, and live fet uses were determined. Fetuses were weighed, and live fetuses examined for external, visceral, and skeletal defects. Maternal food intake dec reased during treatment at 250 mg/kg/day and increased at greater than or equal to 125 mg/kg/day after treatment. Maternal body weight (CD 9 -30), weight gain during treatment, gravid uterine weight, and number of ovarian corpora lutea decreased at 250 mg/kg/day. In contrast, mate rnal corrected gestational weight gain increased at greater than or eq ual to 125 mg/kg/day. Maternal liver weight was not affected. Relative (but not absolute) maternal kidney weight increased at 250 mg/ kg/day , and microscopic evaluation revealed no treatment-related renal patho logy. At 250 mg/kg/day, prenatal mortality was increased (90% resorpti ons/litter vs 6% for controls), the proportion of pregnant females wit h no live fetuses was increased (73% vs 0%), and live litter size was reduced (2.3 fetuses/litter vs 8.8). As a result, there were only 14 l ive fetuses (6 live litters) available for evaluation in the high-dose group, compared to 153-175 live fetuses (18-23 live litters) in the o ther groups. The percentage malformed fetuses/litter was increased at 250 mg/kg/day, primarily due to cardiovascular defects in 72% of high- dose fetuses vs 3% of controls. The most prevalent cardiovascular malf ormation (interventricular septal defect) was observed in 57% of high- dose fetuses compared to 0.6% among controls. At 250 mg/kg/day, averag e fetal body weight/litter was 92% of the average control weight (not statistically significant). In summary, no definitive maternal or deve lopmental toxicity was observed at 62.5 or 125 mg/kg/day BA. Mild mate rnal effects and severe developmental toxicity were observed at 250 mg /kg/day. (C) 1996 Society of Toxicology.