Effects of Hyperthermia and Boric Acid on Skeletal Development in Rat Embryos
BACKGROUND: The individual effects of boric acid (BA) and hyperthermia on the development of the axial skeleton have previously been reported. Both cause an increased incidence of axial skeletal defects including a decrease in the total number of ribs and vertebrae. Because of the similarity in the effects of the two agents, we examined their interaction when given in combination to pregnant rats on gestational day (GD) 10. METHODS: Dams were treated on GD10 with BA (0, 250 or 500 mg/kg) and hyperthermia (37, 41 or 42C) and allowed to deliver their pups. Doses of BA were based on results from a dose-finding study. Litters were evaluated on postnatal days (PND) 1 and 3 for number, sex, and weight of pups. On PND3, pups were examined externally and viscerally, and double-stained for skeletal evaluation. RESULTS: A dose-dependent, statistically significant increase in fetal skeletal defects was seen on PND 3 with BA or hyperthermia alone and in combination. Defects included rib and vertebral fusions, split vertebral centra in the thoracic and lumbar areas, and a decrease in the total number of ribs and vertebrae. The incidence of these defects was significantly greater when BA and hyperthermia were combined than when either was administered alone. CONCLUSIONS: The increased incidence of segmental defects resulting from the combination of hyperthermia and BA compared to individual exposures indicates a synergistic effect of the two agents in combination on skeletal defects.