2-Week Inhalation Toxicity Study with HCFC-122 in Rats

Abstract

Hydrochlorofluorocarbon (HCFC) 122 (1,1-difluoro-1,2,2-trichloroethane) is an intermediate in the synthesis of HCFC-123, a principal potential replacement candidate for chlorofluorocarbon (CFC) compounds in blowing agent and chiller applications. Because the possibility exists for inhalation exposure of HCFC-722 for workers, this study was conducted to assess the toxicity of repeated inhalation of sublethal concentrations of HCFC-722. Four groups of 10 male Cr1:CD BR rats were exposed 6 h/day, 5 days/wk for 2 wk to concentrations of 0, 700, 540, and 2200 ppm HCFC-122 in air. No deaths occurred that could be related to exposure to HCFC-122. Male rats exposed to 2200 ppm HCFC-122 had significantly decreased body weights at various time periods during the exposure but not during the recovery periods. In addition, rats exposed to 170 and 2200 but not 540 ppm had significantly decreased body weight gains during the exposure phase of the study. Functional observational battery (FOB) assessments of exposed and control male rats were conducted before and after exposures on exposure days 1 and 8. On the basis of these evaluations, HCFC-722 was not considered to be neurotoxic. Clinical pathological examinations revealed exposure-related decreases in mean serum concentrations of triglycerides, cholesterol, and globulin, and increases in urine fluoride for all treated groups. Rats in the 540 and 2200 ppm groups also had decreased serum concentrations of total protein and increased alanine aminotransferase (ALV activities. All clinical chemical changes were reversible following a 2-wk recovery period except urine fluoride concentrations, which remained increased in all treatment groups. Pathological examinations revealed significant decreases in mean final body weights in the 540 and 2200 groups, and increased mean relative liver weights in all treated groups relative to controls. These effects were reversible following a 2-wk recovery period. Microscopically, hepatocellular hypertrophy correlated with liver weight changes. Hypertrophy was minimal and occurred in all treated groups without a definitive dose-reesponse relationship with respect to incidence or severity All pathological changes were reversible following the 14-day recovery period. Under the conditions of this study and based on the clinical chemical and pathological parameters measured, a no-observable-effect level for male rats could not be established. The findings of treatment-related clinical chemical and pathological changes in the liver reflect the target organ toxicity.