Acetazolamide teratogenesis: association of maternal respiratory acidosis and ectrodactyly in C57BL/6J mice.

Exposure of C57BL/6J mice to CO2 during a critical period of gestation results in predominantly right-sided, postaxial, forelimb ectrodactyly in the offspring. The incidence and severity of CO2-induced limb malformations has been shown to be dependent on the concentration of inspired CO2, the developmental age of the embryo at exposure and the duration of CO2 exposure. Offspring of acetazolamide-treated C57BL/6J mice also display this highly specific form of ectrodactyly (Green et al., '73). Since the drug has been shown to elevate tissue CO2 tension (Mithoefer and Davis, '58), the teratogenic effect of acetazolamide may be related to induction of a hypercapnic embryonic environment.