Abstract |
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.
|
Authors | Miwa Takahashi, Midori Yoshida, Kaoru Inoue, Tomomi Morikawa, Akiyoshi Nishikawa |
Journal | Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
(Food Chem Toxicol)
Vol. 47
Issue 10
Pg. 2490-8
(Oct 2009)
ISSN: 1873-6351 [Electronic] England |
PMID | 19616055
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Environmental Pollutants
- Semicarbazides
- carbamylhydrazine
|
Topics |
- Animals
- Aorta, Thoracic
(drug effects)
- Bone and Bones
(drug effects, pathology)
- Cartilage, Articular
(drug effects, pathology)
- Chondrocytes
(drug effects, pathology)
- Dose-Response Relationship, Drug
- Eating
(drug effects)
- Environmental Pollutants
(toxicity)
- Female
- Male
- Rats
- Rats, Wistar
- Semicarbazides
(toxicity)
- Stifle
(drug effects, pathology)
- Toxicity Tests
- Weight Gain
(drug effects)
|