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J Occup Health year 2001 volume 43 number 6 page 314 - 320
Classification Original
Title Four-Week Inhalation Toxicity Study of 2,2-Dichloro-1,1,1-trifluoroethane (HCFC-123) in Guinea Pigs
Author Isamu KABE1, 2, Toru TAKEBAYASHI1, Yuji NISHIWAKI1, Tamie NAKAJIMA3,
Eiji IKEDA4, Takehito SAITO1, Shigeru TANAKA5, Hiroyuki MIYAUCHI6,
Yuichi ENDO2 and Kazuyuki OMAE1
Organization 1Department of Preventive Medicine and Public Health, School of Medicine, Keio University,
2Department of Health Administration, Furukawa Electric Co. Ltd.,
3Department of Hygiene, School of Medicine, Shinshu University,
4Department of Pathology, School of Medicine, Keio University,
5Faculty of Hygienic Technology, School of Allied Health Science, Kitasato University,
6The Association of Industrial Health
Keywords 2,2-Dichloro-1,1,1-trifluoroethane (HCFC-123), Liver toxicity, Chlorofluorocarbon substitute, Trifluoroacetic acid, Guinea pig, Inhalation, Fatty change, Peroxisome
Correspondence I. Kabe, Department of Preventive Medicine and Public Health, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
Abstract Four-Week Inhalation Toxicity Study of 2,2-Dichloro-1,1,1-trifluoroethane (HCFC-123) in Guinea Pigs: Isamu KABE, et al. Department of Preventive Medicine and Public Health, School of Medicine, Keio University-Groups of eight male Hartley guinea pigs were exposed to 30, 100 or 300 ppm 2,2-dichloro-1,1,1-trifluoroethane (HCFC-123) by inhalation for 6 hours a day for 4 wk. All the animals were sacrificed 48 h postexposure. Guinea pigs exposed to 300 ppm HCFC-123 had significantly lower body weight and the weight gain than controls, but there was no significant difference and no tendency in absolute and relative organ weight. ICDH, ALT and AST, which were the most sensitive indicators of halothane-induced liver injury, did not differ significantly between exposed groups and controls. In the 100 ppm group, a few vacuolar fatty changes in the portal area (zone I) were identified. In the 300 ppm group, severe fatty degeneration was observed in the portal and intermediate areas, partly centrilobule, and the incidence increased significantly compared to the controls. On the other hand, there was no histopathological change in the control or 30 ppm groups. No increase in any of the liver peroxisomal enzymes (AOX, PT, catalase) was seen in male guinea pigs exposed to HCFC-123. The activity of hepatic ALDH was significantly decreased in the 300 ppm exposed group, suggesting that HCFC-123 or its metabolite inhibited ALDH activity. In conclusion, inhalation exposure to 100 ppm or more of HCFC-123 for 4 wk produced nonfatal liver change in guinea pigs, namely hepatic fatty changes predominantly in the portal area (zone I) without any increase in AST, ALT or ICDH. The no-observed-adverse-effect level (NOAEL) of HCFC-123 for four wk in guinea pigs may be 30 ppm. Peroxisome proliferation, which may result in hepatocellular tumor induction, was not observed in guinea pigs exposed to HCFC-123.