Teratologic Evaluation of Alpha-Methyldopa (CAS No. 555-30-6) Administered to CD-1 Mice on Gestational Days 6 through 17

摘要

Alpha-Methyldopa (MD), a widely used antihypertensive, was evaluated for toxic and teratogenic effects in timed-pregnant CD-1 mice exposed to MD on gestational days (gd) 6 through 17 and sacrificed on gd 17. 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 addition to the teratology study, a preliminary evaluation of perinatal survival and postnatal growth to postnatal day 21 of mouse pups exposed in utero to MD on gd 6-17 and fostered to untreated mothers was also conducted. In this preliminary perinatal and postnatal evaluation, MD was administered in corn oil by gavage at doses of 0, 100, 250, 500, or 750 mg/kg/day to timed-mated females (6-7 per group) on gestational days (gd) 6 through 17. MD had no significant adverse effect on live litter size, survival and growth of live pups to pnd 4, or pup survival and growth to pnd 21. Evaluation of pup relative liver, heart, and brain weight on pnd 21 indicated that liver and heart weight were unaffected, but suggested that in utero exposure to MD at doses of 250 mg/kg/day and above may result, in the postnatal period, in depressed brain growth relative to body growth.