Increases in discontinuous rib cartilage and fused carpal bone in rat fetuses exposed to the teratogens, busulfan, acetazolamide, vitamin A, and ketoconazole.

Skeletal changes induced by treatment of pregnant rats with four potent teratogens, busulfan, acetazolamide, vitamin A palmitate, and ketoconazole, were evaluated using AlizarinRed S and Alcian Blue double-staining to investigate the relationship between drug-induced skeletal malformations and cartilaginous changes in the fetuses. Pregnant rats (N = 8/group) were treated once or twice between gestation days (GDs) 10 to 13 with busulfanat doses of 3, 10, or 30 mg/kg; acetazolamideat 200, 400, or 800 mg/kg; vitamin A palmitateat 100,000, 300,000, or 1,000,000 IU/kg; or ketoconazoleat doses of 10, 30, or 100 mg/kg. Uterine evaluations and fetal external and skeletal examinations were conducted on GD 20. Marked skeletal abnormalities in ribs and hand/ forelimbbones such as absent/ short/bent ribs, fused rib cartilage, absent/fused forepaw phalanx, and misshapen carpal boneswere induced at the mid- and high-doses of busulfanand acetazolamideand at the high-dose of vitamin A palmitateand ketoconazole. ...