A ninety-day toxicity study of semicarbazide hydrochloride in Wistar Hannover GALAS rats.
A ninety-day toxicity study of semicarbazide hydrochloride (SEM-HCl) was conducted in male and female Wistar Hannover GALAS rats fed diet containing the compound at concentration of 0, 250, 500 and 1000 ppm. Suppression of body weight gain and food consumption was found in both sexes at 1000 ppm throughout the study. Enlargement and deformation of knee joints were obvious at 500 and 1000 ppm from week 3, together with deformation of the thorax and tail. Histopathologically, disarrangement of chondrocytes and fissures in the cartilage matrix were apparent at all doses tested in epiphyseal and articular cartilage. The severity of these lesions increased dose-dependently, accompanied by increased connective tissues and bone deformation at high doses. Additionally, compact bones at 1000 ppm became thin, suggesting loss of bone mass. In the thoracic aorta, the edges of elastic laminae became rough and the interlaminar spaces were altered from a fibrillar to a rod or globular appearance. No abnormalities were detected in any other organs. Taken together, toxicological effects of subchronic exposure to SEM-HCI were mainly observed in bone, cartilage and the aorta, with the no-observed-adverse-effect-level estimated from the present histopathological examination of less than 250 ppm in both sexes.
Takahashi
Miwa
M
Division of Pathology, National Institute of Health Sciences, Tokyo 158-8501, Japan. mtakahashi@nihs.go.jp
Yoshida
Midori
M
Inoue
Kaoru
K
Morikawa
Tomomi
T
Nishikawa
Akiyoshi
A
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology; D002358:Cartilage, Articular / Q000187:drug effects / Q000473:pathology; D019902:Chondrocytes / Q000187:drug effects / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012663:Semicarbazides / Q000633:toxicity*; D013264:Stifle / Q000187:drug effects / Q000473:pathology; D018675:Toxicity Tests; D015430:Weight Gain / Q000187:drug effects
D004785:Environmental Pollutants; D012663:Semicarbazides; C010059:carbamylhydrazine