Teratologic Evaluation of Hydrochlorothiazide (CAS No. 58-93-5) Administered to CD-1 Mice on Gestational Days 6 through 15

摘要

Hydrochlorothiazide (HCTZ) is a widely used thiazide diuretic. HCTZ (0, 300, 1000, and 3000 mg/kg/day, po) was administered to timed-pregnant CD-1 mice on gestational days (gd) 6 through 15. At sacrifice (gd 17) confirmed-pregnant females (20-27 per group) were evaluated, and each live fetus was weighed and examined for external, visceral, and skeletal malformations. The maternal mortality rate was 0% for all dose groups. Maternal water consumption exhibited a significant upward trend with increasing dose (gd 0-6 and 15-17), but no effects were observed in maternal body weight, weight gain, kidney weight or liver weight. There were no dose-related differences in the percentage per litter or resorptions, dead fetuses, nonlive implants (i.e., dead plus resorbed) or adversely affected implants (i.e., nonlive plus malformed fetuses). Among those litters containing live fetuses, there were no differences among dose groups in the number of live fetuses/live litter, % males/live litter, or avg. fetal body weight/litter. There was a significant dose-response trend for % malformed fetuses/litter, and % females malformed/litter.