EVALUATION OF THE GENOTOXICITY POTENTIAL AND CHRONIC INHALATION TOXICITY OF 1,1-DICHLORO-1-FLUOROETHANE (HCFC-141B)

A battery of in vitro and in vivo tests were conducted on HCFC-141b as a vapour. Bacterial gene mutation assays with Escherichia coli and Sa lmonella typhimurium were negative in all tester strains. In vitro chr omosomal aberration assays were positive on CHO cells but negative on human lymphocytes. Moreover, HCFC-141b was negative in vivo in a mouse micronucleus inhalation assay. On the basis of these data and previou sly reported genotoxicity testing, HCFC-141b is considered non-genotox ic. Groups of 80 male and 80 female Sprague-Dawley rats were exposed, by inhalation (6 hr/day, 5 days/wk) to vapours of HCFC-141b for 104 wk at target concentrations of 0 (control), 1500, 5000 and 20,000 ppm (i ncreased from 15,000 ppm after 17 wk of exposure). No exposure-related effects of toxicological significance were noted with respect to surv ival, clinical signs, ophthalmoscopy, haematology, clinical chemistry, urinalysis or organ weight analysis. Reduced food intake and body wei ght gain were noted in both sexes of the 15,000 ppm group during the f irst 16 wk; thereafter, body weight gains in all groups were similar a lthough the intergroup differences in body weight remained evident. Re duced food intake persisted in both sexes through wk 52 and in females during the second year of exposure. Treatment-related effects on macr oscopic pathology were confined to increased incidences of testicular masses and altered appearance. Microscopic pathology examinations conf irmed the testes as the target organ with findings of increased incide nces of benign interstitial cell tumours and hyperplasia at 5000 and 2 0,000 ppm. The no-observable-adverse-effect level (NOAEL) was 1500 ppm . The testicular changes at high exposure levels were considered to be due to a change of the senile hormonal imbalance in geriatric rats an d of little significance for the assessment of human health effects.