DEVELOPMENTAL TOXICITY NOAEL AND POSTNATAL RECOVERY IN RATS FED BORIC-ACID DURING GESTATION

Boric acid (BA), an essential plant micronutrient, occurs naturally in fruits, vegetables, and other foods. It is widely used in the manufac ture of glass, ceramics, and other products. In a prior study, gestati onal exposure to BA was associated with developmental toxicity in the rat, including fetal growth retardation and altered skeletal morpholog y. In order to establish the developmental toxicity no-observed-advers e-effect level (NOAEL) in the rat, BA (0, 0.025, 0.05, 0.075, 0.1, or 0.2% in feed) was administered to timed-mated rats (60/group) from ges tational day (gd) 0 to gd 20. Approximately half the darns were termin ated on gd 20, and the remaining dams delivered their litters. Pup gro wth and viability were monitored until postnatal day (pnd) 21. Dams sa crificed on gd 20 (pnd 21) ingested average doses of 0(0), 19(19), 36( 37), 55(56), 76(74), or 143(145) mg BA/kg/day. Maternal clinical signs , body weight, and food and water intake were measured at regular inte rvals during gestation and lactation. At termination, maternal liver a nd right kidney were weighed, and live fetuses (gd 20) and pups (pnd 2 1) were weighed, sexed, and examined for morphological anomalies (exte rnal, visceral, skeletal). Maternal effects were limited to increased relative kidney weight at 0.2% BA. Viability of the offspring was unaf fected. On gd 20, fetal body weight was 94 and 88% of controls at 0.1 and 0.2% BA, but recovery was complete at birth (similar to gd 22). Th e incidence of short rib XIII was increased on gd 20 at greater than o r equal to 0.1% BA, but only at 0.2% on pnd 21. The incidence of wavy rib was increased on gd 20 at greater than or equal to 0.1% BA, but th e reversibility of this effect was confirmed on pnd 21. A slight decre ase in extra lumbar ribs was observed at 0.2% BA on gd 20, and extra l umbar ribs were not found in any pups on pnd 21. Thus, the development al toxicity NOAEL in the rat was 0.075% BA (55 mg/kg/day) on gd 20 and 0.1% BA (74 mg/kg/day) on pnd 21. (C) 1996 Society of Toxicology