Four-week inhalation toxicity study of 2,2-dichloro-1,1,1-trifluoroethane (HCFC-123) in guinea pigs

Isamu Kabe, Toru Takebayashi, Yuji Nishiwaki, Tamie Nakajima, Eiji Ikeda, Takehito Saito, Shigeru Tanaka, Hiroyuki Miyauchi, Yuichi Endo, Kazuyuki Omae

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)314-320
Number of pages7
JournalJournal of Occupational Health
Volume43
Issue number6
Publication statusPublished - 2001

Fingerprint

Inhalation
Toxicity
Guinea Pigs
Liver
No-Observed-Adverse-Effect Level
Inhalation Exposure
Peroxisomes
Organ Size
2,2-dichloro-1,1,1-trifluoroethane
Gain control
Halothane
Metabolites
Catalase
Weight Gain
Tumors
Animals
Body Weight
Control Groups
Incidence
Wounds and Injuries

Keywords

  • 2,2-Dichloro-1,1,1-trifluoroethane (HCFC-123)
  • Chlorofluorocarbon substitute
  • Fatty change
  • Guinea pig
  • Inhalation
  • Liver toxicity
  • Peroxisome
  • Trifluoroacetic acid

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Toxicology

Cite this

Kabe, I., Takebayashi, T., Nishiwaki, Y., Nakajima, T., Ikeda, E., Saito, T., ... Omae, K. (2001). Four-week inhalation toxicity study of 2,2-dichloro-1,1,1-trifluoroethane (HCFC-123) in guinea pigs. Journal of Occupational Health, 43(6), 314-320.

Four-week inhalation toxicity study of 2,2-dichloro-1,1,1-trifluoroethane (HCFC-123) in guinea pigs. / Kabe, Isamu; Takebayashi, Toru; Nishiwaki, Yuji; Nakajima, Tamie; Ikeda, Eiji; Saito, Takehito; Tanaka, Shigeru; Miyauchi, Hiroyuki; Endo, Yuichi; Omae, Kazuyuki.

In: Journal of Occupational Health, Vol. 43, No. 6, 2001, p. 314-320.

Research output: Contribution to journalArticle

Kabe, I, Takebayashi, T, Nishiwaki, Y, Nakajima, T, Ikeda, E, Saito, T, Tanaka, S, Miyauchi, H, Endo, Y & Omae, K 2001, 'Four-week inhalation toxicity study of 2,2-dichloro-1,1,1-trifluoroethane (HCFC-123) in guinea pigs', Journal of Occupational Health, vol. 43, no. 6, pp. 314-320.
Kabe, Isamu ; Takebayashi, Toru ; Nishiwaki, Yuji ; Nakajima, Tamie ; Ikeda, Eiji ; Saito, Takehito ; Tanaka, Shigeru ; Miyauchi, Hiroyuki ; Endo, Yuichi ; Omae, Kazuyuki. / Four-week inhalation toxicity study of 2,2-dichloro-1,1,1-trifluoroethane (HCFC-123) in guinea pigs. In: Journal of Occupational Health. 2001 ; Vol. 43, No. 6. pp. 314-320.
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abstract = "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.",
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AU - Kabe, Isamu

AU - Takebayashi, Toru

AU - Nishiwaki, Yuji

AU - Nakajima, Tamie

AU - Ikeda, Eiji

AU - Saito, Takehito

AU - Tanaka, Shigeru

AU - Miyauchi, Hiroyuki

AU - Endo, Yuichi

AU - Omae, Kazuyuki

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