Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5850053 | Food and Chemical Toxicology | 2014 | 11 Pages |
Abstract
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 250Â ppm for 52Â weeks (10 rats/sex/group) or for 104Â weeks (50 rats/sex/group). Enlargement of the knee joints was apparent in both sexes at 250Â ppm. Reduced body weight was observed at 250Â 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 50Â ppm and above and in females at 250Â ppm. Mild changes in the elastic laminae were observed at 250Â 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 10Â ppm in males and 50Â ppm in females (equal to 0.6Â mg/kg/day in males and 3.9Â mg/kg/day in females). SEM-HCl was not carcinogenic in rats.
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Authors
Miwa Takahashi, Midori Yoshida, Kaoru Inoue, Tomomi Morikawa, Akiyoshi Nishikawa, Kumiko Ogawa,