Teratologic Evaluation of alpha-Methyldopa (CAS No. 555-30-6) Administered to CD Rats on Gestational Days 6 through 20

摘要

Alpha-Methyldopa (MD), a widely used antihypertensive, was evaluated for toxic and teratogenic effects in timed-pregnant CD rats exposed to MD on gestational days (gd) 6 through 20 and sacrificed on gd 20. Prior to the initiation of the teratology study, a preliminary study was conducted in order to establish appropriate doses for use in the teratology study. In the preliminary dose range-finding study, MD, suspended in corn oil, was administered by gavage to timed-pregnant CD rats at doses of 0, 100, 250, 500, 750, and 1000 mg/kg/day (6 animals/group) on gd 6 through 20. Animals were sacrificed and evaluated on gd 20. The results of the preliminary dose range-finding study indicated that the 1000 mg/kg/day dose caused 33% mortality of confirmed-pregnant dams, and was therefore unsuitable for use in the teratology study. A probit plot analysis of the mortality data from the preliminary study suggested an LD10 of 581 mg/kg/day. Accordingly, doses of 0, 50, 100, 250, and 500 mg/kg/day MD were chosen for administration in the teratology study.