The inhalation exposure of carbon tetrachloride promote rat liver carcinogenesis in a medium-term liver bioassay.
The potential of carbon tetrachloride (CCl4) to induce pre-neoplastic lesions in rat liver using a medium-term liver assay (Ito method) for the prediction of carcinogenicity was examined by nose-only inhalation exposure of male rats (15/group) to CCl4 vapor at concentrations of 0, 1, 5, 25, 125 ppm for 6h/day, 6 day/week, for a period of 6 weeks. The numbers and area of glutathione S-transferase placental (GST-P) positive foci were then determined. Additionally, other histopathological observations on the livers were recorded and serum chemical parameters and CCl4 concentrations in blood were measured. The areas and numbers of GST-P positive foci significantly increased in the CCl4-exposed rats at 25 and 125 ppm; but not at concentrations of 1 and 5 ppm. CCl4 blood concentration 24h after initiation of exposure in the 125 ppm group remained at about 5% of the 6h maximum concentration. These data from CCl4-exposed rats clearly show that inhalation exposure can be used in the rat medium-term liver assay, the method is available for the screening of volatile chemicals and is therefore a useful tool in cancer risk assessment. This is the first report of the use of inhalation exposure in this medium-term predictive assay.
Tsujimura
Kazunari
K
Hita laboratory, Chemicals Evaluation and Research Institute, 3-822 Ishii-machi, Hita City, Oita 877-0061, Japan. tsujimura-kazunari@2ceri.jp
Ichinose
Fumio
F
Hara
Takaharu
T
Yamasaki
Kanji
K
Otsuka
Masanori
M
Fukushima
Shoji
S
D000818:Animals; D001681:Biological Assay; D001835:Body Weight / Q000187:drug effects; D002251:Carbon Tetrachloride / Q000097:blood / Q000633:toxicity*; D015197:Carcinogenicity Tests / Q000379:methods; D002273:Carcinogens / Q000493:pharmacokinetics / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D051549:Glutathione S-Transferase pi / Q000378:metabolism; D007150:Immunohistochemistry; D019570:Inhalation Exposure; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011237:Predictive Value of Tests; D051381:Rats; D011916:Rats, Inbred F344
D002273:Carcinogens; D002251:Carbon Tetrachloride; D051549:Glutathione S-Transferase pi; C496558:Gstp1 protein, rat