Acetazolamide dysmelia in rats.

Acetazolamide dysmelia was induced in rat embryos by giving drug to mothers during days 9, 10 and 11 of pregnancy. With appropriate technique 100 per cent of deformed young could be produced. Individual anomalies were made up of one or more of 5 basic malformations—dislocation, reduction and supernumerary defects, syndactyly and synarthrosis. Right forepaws were invariably, left forepaws were less frequently and hindpaws were rarely involved. Most paws showed a postaxial to preaxial sequential involvement of digits, but on occasions digit 4 was more severely affected than the fifth digit. In all but 5 of 94 bilateral defects right forepaw lesions were of equal or greater severity than left forepaw lesions. The number of deformed paws and probably the severity of the paw defects were linearly related to drug dosage. Digital ray defects were accompanied by defects in the carpal bones and ulna of matching severity. During the phase of acute intoxication following drug treatment mothers lost weight and this was linearly related to the amount of drug given. The full term weight of foetuses was depressed in proportion to drug dosage but the drug displayed little if any embryolethal effect.