LOSS OF SKELETAL INTEGRITY IN RAT FETUSES FROM DAMS TREATED WITH HISTAMINE H1 ANTAGONISTS

Pregnant Lister Hooded rats were dosed orally with chlorocyclizine (60 mg/kg), promethazine (5 and 10 mg/kg) or doxylamine (500 and 750 mg/k g) (histamine H-1 antagonists prescribed for nausea of pregnancy) over the period of organogenesis (days 7-13). Fetuses were removed by caes arian section on day 21 and stained with Alizarin Red S and Alcian Blu e for calcified bone and cartilage respectively. There were no signifi cant differences in fetal size with any of the treatments; however, al l 3 antagonists caused dose-dependent loss of skeletal integrity and m arked fragility compared to the controls. By dosing dams on selected d ays, skeletal fragility was seen in all fetuses; the most marked effec ts occurring after dosing on days 10-12. Prolonging the gestation peri od with progesterone (10 mg/dam orally) resulted in normal sekeletal c alcification but fetuses were still very fragile. Therefore, histamine H, antagonists may interfere with the development of rat fetal joints .