Effects of hyperthermia and boric acid on skeletal development in rat embryos.

Birth Defects Res B Dev Reprod Toxicol

Division of Reproductive and Urologic Drug Products, Center for Drug Evaluation and Research, US Food and Drug Administration (FDA), Rockville, Maryland 20857, USA.

Published: June 2005

AI Article Synopsis

  • The study investigates the effects of boric acid (BA) and hyperthermia on the development of skeletal defects in rat offspring when combined during pregnancy.
  • Pregnant rats were treated with varying doses of BA and different temperatures of hyperthermia on gestational day 10, and their litters were analyzed for defects in skeletal structure on postnatal days 1 and 3.
  • Results demonstrated that both treatments increased the incidence of skeletal defects, with the combination of BA and hyperthermia leading to even more significant issues, particularly in vertebral segmentation and total vertebrae count.

Article Abstract

Background: The individual effects of boric acid (BA) and hyperthermia on the development of the axial skeleton have been reported previously. 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 GD 10 with BA (0, 250, or 500 mg/kg) and hyperthermia (37, 41, or 42 degrees C) 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, gender, 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 with even greater effects when given 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.

Conclusions: The increased incidence of skeletal defects resulting from combined exposure to hyperthermia and BA was additive for segmentation defects and synergistic for the reduction in numbers of vertebrae.

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http://dx.doi.org/10.1002/bdrb.20047DOI Listing

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