Twenty-six-week oral toxicity of diheptyl phthalate with special emphasis on its induction of liver proliferative lesions in male F344 rats
スポンサーリンク
概要
- 論文の詳細を見る
The 26-week oral toxicity of diheptyl phthalate (DHP), a peroxisome proliferator-activated receptor α (PPARα) agonist, with special emphasis on the potential induction of hepatocellular proliferative lesions was investigated in this study. DHP was administered to male F344 rats via gavage at 0 (control), 1,000 or 2,000 mg/kg/day for 26 weeks. Body weight gain was significantly lower, whereas food and water consumption was significantly higher in DHP-treated rats compared with controls. DHP-treated rats exhibited decreases in blood triglyceride, total cholesterol, phospholipid and glucose levels, which were likely related to biological effects of the PPARα agonist. Absolute and relative organ weights of the livers with pale brown discoloration and dark brown spots significantly increased in DHP-treated rats. Histopathological examinations revealed remarkable diffuse hypertrophy of hepatocytes with ground-glass appearance, intracytoplasmic inclusion bodies and/or vacuolation in the DHP-treated groups. These findings were associated with increases in serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and γ-glutamyltranspeptidase. The number and area of glutathione S-transferase placental form positive foci, a marker of hepatocellular preneoplastic lesions in rats, significantly increased in DHP-treated groups. Additionally, proliferating cell nuclear antigen positive liver cell counts in DHP-treated groups were significantly higher than those of the controls. Testicular alterations were not detected histopathologically, whereas absolute and relative prostate weights significantly decreased at both doses. These results indicate that DHP induces liver pre-neoplastic foci, and suggest the possibility that DHP is a possible genotoxic carcinogen in the liver of rats.
- 一般社団法人 日本毒性学会の論文
一般社団法人 日本毒性学会 | 論文
- No carcinogenicity of ethyl tertiary-butyl ether by 2-year oral administration in rats
- Genotoxicity evaluation of chlorpyrifos: a gender related approach in regular toxicity testing
- Induction of the fatty acid 2-hydroxylase (FA2H) gene by Δ9-tetrahydrocannabinol in human breast cancer cells
- Increased production of reactive oxygen species by the vacuolar-type (H+)-ATPase inhibitors bafilomycin A1 and concanamycin A in RAW 264 cells
- Evaluation of cytotoxic potential of cored soft contact lenses with adsorbed active ingredients from over-the-counter eye drops