Chronic toxicity, oncogenicity, and mutagenicity studies with chlorotetrafluoroethane (HCFC-124).
Drug Chem Toxicol
; 21(4): 417-47, 1998 Nov.
Article
em En
| MEDLINE
| ID: mdl-9839154
The chronic toxicity, oncogenicity, and mutagenicity of chlorotetrafluoroethane (HCFC-124) were evaluated. In the chronic toxicity/oncogenicity study, male and female rats were exposed to 0, 2000, 10,000, or 50,000 ppm HCFC-124 for 6 hr/day, 5 days/week, for 2 years. Body weights were obtained weekly during the first three months of the study and every other week for the remainder of the study. Food consumption was determined weekly. Clinical signs of toxicity were monitored throughout the study. An ophthalmological examination was performed on all animals prior to study start, and all surviving rats were examined at approximately 3, 12, and 24 months after study start. Clinical pathology was evaluated at 3, 6, 12, 18, and 24 months. An interim termination was conducted at 12 months. All surviving rats were necropsied at 24 months. A complete set of tissues was collected for microscopic examination, and selected tissues were weighed. There were no compound-related, adverse effects on body weight, food consumption, survival, clinical signs of toxicity, ophthalmoscopically observable ocular lesions, serum hormone concentrations, or clinical pathology parameters at any exposure concentration in either male or female rats. Compared to controls, urine fluoride was increased in males and females at all exposure concentrations, and plasma fluoride was increased in females at all exposure concentrations. Excretion of fluoride represents conversion of the parent molecule, and as such is not considered to be an adverse effect. There were no toxicologically significant, compound-related organ weight changes or gross or microscopic findings in male or female rats at any of the exposure concentrations tested. HCFC-124 was not toxic or carcinogenic in rats of either sex after inhalation exposure at concentrations of up to 50,000 ppm in this two-year chronic toxicity/oncogenicity study. After exposure to HCFC-124 for six hours per day, five days per week, for 24 months, the no-observed-adverse-effect level for male and female rats was 50,000 ppm. HCFC-124 was not mutagenic in Salmonella typhimurium strains TA1535, TA97, TA98, and TA100 with and without activation when evaluated at concentrations up to 60% HCFC-124 for 48 hours. No evidence of clastogenic activity was observed in cultured human lymphocytes at atmospheric concentrations up to 100% HCFC-124 for 3 hours, with and without metabolic activation. In vivo, no micronuclei were induced in mouse bone marrow cells following exposure of mice to concentrations of 99,000 ppm HCFC-124 6 hours/day for 2 days.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Clorofluorcarbonetos de Metano
Limite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Drug Chem Toxicol
Ano de publicação:
1998
Tipo de documento:
Article
País de afiliação:
Estados Unidos
País de publicação:
Estados Unidos