Four-Week Inhalation Toxicity Study of 2,2-Dichloro-1,1,1-trifluoroethane(HCFC-123) in Guinea Pigs

• Published in: Journal of Occupational Health 2001-11, Vol.43 (6), p.314-320
• Main Authors: Kabe, Isamu, Takebayashi, Torn, Nishiwakt, Yuji, Nakajima, Tamie, Ikeda, Eiji, Saito, Takehito, Tanaka, Shigeru, Miyauchi, Hiroyuki, Endo, Yuichi, Omae, Kazuyuki
• Format: Article
• Language: English
• Subjects: 2,2‐Dichloro‐1,1,1‐trifluoroethane (HCFC‐123); Chlorofluorocarbon substitute; Fatty change; Guinea pig; Inhalation; Liver toxicity; Peroxisome; Trifluoroacetic acid
• ISSN: 1341-9145; 1348-9585; 1348-9585
• DOI: 10.1539/joh.43.314

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-1 23 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 1OO 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. (J Occup Health 2001;43, 314-320)