Chronic toxicity and carcinogenicity of semicarbazide hydrochloride in Wistar Hannover GALAS rats

We performed a combined study to determine the chronic toxicity and carcinogenicity of semicarbazide hydrochloride (SEM-HCl). Male and female Wistar Hannover GALAS rats were fed a diet containing SEM-HCl at 0, 10, 50, and 250 ppm for 52 weeks (10 rats/sex/group) or for 104 weeks (50 rats/sex/group). Enlargement of the knee joints was apparent in both sexes at 250 ppm. Reduced body weight was observed at 250 ppm from week 76 only in males. SEM-HCl exerted no toxic effects on hematology, serum biochemistry, or organ weights. Histopathologically, disarrangement of chondrocytes accompanied by increased connective tissues, and degeneration of articular cartilage were found in males at 50 ppm and above and in females at 250 ppm. Mild changes in the elastic laminae were observed at 250 ppm for both sexes in the chronic toxicity study. There were no significant intergroup differences in the incidences or types of any tumors. Taken together, toxicological effects of chronic exposure to SEM-HCI mainly occurred in the bone, cartilage, and aorta. Based on histopathological findings, the no-observed-adverse-effect-level was 10 ppm in males and 50 ppm in females (equal to 0.6 mg/kg/day in males and 3.9 mg/kg/day in females). SEM-HCl was not carcinogenic in rats.