- 著者
-
Nagano Kasuke
Umeda Yumi
Saito Misae
NISHIZAWA Tomoshi
IKAWA Naoki
ARITO Heihachiro
YAMAMOTO Seigo
FUKUSHIMA Shoji
- 出版者
- 公益社団法人日本産業衛生学会
- 雑誌
- Journal of occupational health (ISSN:13419145)
- 巻号頁・発行日
- vol.49, no.4, pp.249-259, 2007-07-01
- 参考文献数
- 44
- 被引用文献数
-
3
Subchronic toxicity of carbon tetrachloride (CCl_4) was examined by inhalation exposure of F344 rats and BDF_1 mice of both sexes to 0, 10, 30, 90, 270 or 810 ppm (v/v) CCl_4 vapor for 13 wk (6 h/d and 5 d/wk). In the high exposure levels at 270 and 810 ppm, altered cell foci in the livers of both rats and mice, and fibrosis and cirrhosis in the rat liver were observed. Hematoxylin and eosin-stained altered cell foci of rats were recognized as glutathione-S-transferase placental form (GST-P) positive foci, which are preneoplactic lesions of hepatocarcinogenesis. The most sensitive endpoint of CCl_4-induced toxicity was fatty change with large droplets in rats of both sexes and male mice, and cytoplasmic globules in male mice, as well as increased relative liver weight in male rats. Those endpoints were manifested at 10 ppm and the LOAEL was determined as 10 ppn for the hepatic endpoints in rats and mice. Enhanced cytolytic release of liver transaminases into plasma in rats and mice and its close association with hepatic collapse in mice were observed at medium and high levels of inhalation exposure. Both CCl_4-induced hematotoxicity and nephrotoxicity were observed in both rats and mice, but those toxicities were manifested at higher exposure concentrations than hepatotoxicity. The LOAEL for the hepatic endpoint and the GST-P-stained altered cell foci provide relevant animal data for reconsidering the occupational exposure limit value of 5 ppm for CCl_4 and strengthen the evidence of CCl_4-induced hepatocarcinogenicity which is used in its carcinogenicity classification.