Developmental Toxicity NOAEL and Postnatal Recovery in Rats Fed Boric Acid during Gestation

Abstract

Boric acid (BA), an essential plant micronutrient, occurs naturally in fruits, vegetables, and other foods. It is widely used in the manufacture of glass, ceramics, and other products. In a prior study, gestational exposure to BA was associated with developmental toxicity in the rat, including fetal growth retardation and altered skeletal morphology. In order to establish the developmental toxicity no-observed-adverse-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 gestational day (gd) 0 to gd 20. Approximately half the dams were terminated on gd 20, and the remaining dams delivered their litters. Pup growth and viability were monitored until postnatal day (pnd) 21. Dams sacrificed 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 intervals during gestation and lactation. At termination, maternal liver and right kidney were weighed, and live fetuses (gd 20) and pups (pnd 21) were weighed, sexed, and examined for morphological anomalies (external, visceral, skeletal). Maternal effects were limited to increased relative kidney weight at 0.2% BA. Viability of the offspring was unaffected. 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 (∼gd 22). The incidence of short rib XIII was increased on gd 20 at ≥0.1% BA, but only at 0.2% on pnd 21. The incidence of wavy rib was increased on gd 20 at ≥0.1% BA, but the reversibility of this effect was confirmed on pnd 21. A slight decrease in extra lumbar ribs was observed at 0.2% BA on gd 20, and extra lumbar ribs were not found in any pups on pnd 21. Thus, the developmental 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.