Evaluation of the genotoxicity potential and chronic inhalation toxicity of 1,1-dichloro-1-fluoroethane (HCFC-141 b)

• Published in: Food and chemical toxicology Vol. 33; no. 6; pp. 491 - 500
• Main Authors: Millischer, R.-J., de Rooij, C.G., Rush, G.M., Farr, C.H., Ben-Dyke, R., Hardy, C.J., Lewis, D.J., Hodson-Walker, G.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-06-1995; New York, NY Elsevier Science; Published by Elsevier Ltd
• Subjects: Administration, Inhalation; Animals; Biological and medical sciences; Body Weight; Carcinogens - toxicity; Chemical and industrial products toxicology. Toxic occupational diseases; Chlorofluorocarbons - toxicity; Chlorofluorocarbons, Ethane; CHO Cells; Chromosome Aberrations; Cricetinae; Escherichia coli; ethane; Female; fluorides; genetics; Humans; inhalation; Male; Medical sciences; mice; Micronucleus Tests; mutagenicity; Mutagenicity Tests; Mutagens - toxicity; Rats; Rats, Sprague-Dawley; Risk Assessment; Salmonella typhimurium; Time Factors; Toxicology; Various organic compounds; PCE; IPCS; PNE; NOAEL; PAFT; CHO; HPRT; LH; ECETOC; AIHA; Endocrinopathy; CFC fluid; Rat; Mutagenicity testing; Toxicity; Rodentia; Fluorocarbon; Halocarbon; In vitro; Inhalation; In vivo; Vertebrata; Mammalia; Carcinogenicity testing; Animal; Substitute; Male genital diseases
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/0278-6915(95)00015-T

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
Salmonella typhimurium were negative in all tester strains.
In vitro chromosomal 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 previously reported genotoxicity testing, HCFC-141b is considered non-genotoxic. 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 (increased from 15,000 ppm after 17 wk of exposure). No exposure-related effects of toxicological significance were noted with respect to survival, clinical signs, ophthalmoscopy, haematology, clinical chemistry, urinalysis or organ weight analysis. Reduced food intake and body weight gain were noted in both sexes of the 15,000 ppm group during the first 16 wk; thereafter, body weight gains in all groups were similar although the intergroup differences in body weight remained evident. Reduced food intake persisted in both sexes through wk 52 and in females during the second year of exposure. Treatment-related effects on macroscopic pathology were confined to increased incidences of testicular masses and altered appearance. Microscopic pathology examinations confirmed the testes as the target organ with findings of increased incidences of benign interstitial cell tumours and hyperplasia at 5000 and 20,000 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 and of little significance for the assessment of human health effects.