Teratology and Carbonic Anhydrase Inhibition

FIVE years ago, Layton and Hallesy¹ reported that rats fed acetazolamide in the diet during pregnancy gave birth to offspring in which about 36% had a peculiar but specific postaxial defect confined mainly to the right forepaw. The most common lesion was absence of the fourth and fifth digits and the corresponding metacarpals. At that time, it was not clear to me whether this was due to carbonic anhydrase inhibition or some unknown effect of acetazolamide.² More recently, we have clarified this point, since it appears that all the potent carbonic anhydrase inhibitors, ethoxzolamide,³ dichlorphenamide,⁴ methazolamide, and benzolamide (unpublished data by W.M. Layton, W.J. Scott, and T.H.M.) cause identical lesions. The high doses (0.2% to 0.6% in the diet, or several hundred milligrams per kilograms per day) used by Layton and Hallesy¹ were necessary because of their drug-diet method and the relatively short half life