Comparative 90-day toxicity of two decarboxylase inhibitors, benserazide and carbidopa, in the rat

The toxicity of two decarboxylase inhibitors, benserazide and carbidopa, was compared in a 90-day study in rats given doses from 32 to 260 mg/kg/day. No mortality directly caused by the drugs occurred. Late growth retardation in the high-dosage benserazide groups was apparently caused by difficulties in locomotion secondary to skeletal deformations. In the carbidopa groups, a uniform dose-dependent growth retardation was seen from the beginning. Hematological changes were not prominent. SGPT activities were decreased by both drugs after 6 weeks and more so after 12 weeks, presumably by direct inhibition. Effects on organ weights were difficult to interpret due to the serious growth retardation. No important histopathologic anomalies were seen, except in the skeleton of groups given the highest dosage of benserazide. A disturbance in enchondral bone formation caused secondary distortions in the skeleton impairing locomotion. Earlier results from separate studies suggesting a large difference between the two substances in toxicity for the rat could not be substantiated.