Chlorodifluoromethane is rapidly equilibrated in tissues after inhalation and is eliminated from the blood in expired air with a half life of a few minutes. Over a wide range, the inhalation concentrations and blood concentrations are linearly correlated. Metabolism occurs, if at all, in only minor amounts; the toxicological activities described are unlikely to be due to the formation of reactive intermediates.
Chlorodifluoromethane has an extremely low order of acute toxicity. Atmospheric concentrations over 700,000 mg/m3 are required to produce a lethal effect.
When liquid chlorodifluoromethane is in contact with skin it causes local freezing. It is not a skin sensitiser.
Chlorodifluoromethane causes cardiac sensitisation when exposure is to concentrations approaching the LCM’.
In animal studies, chlorodifluoromethane showed no adverse effects on fertility. It was not teratogenic in rabbits in a study using conventional group sizes at doses up to 175,000 mg/m3. In initial teratogenicity studies in rats, litters from treated groups contained a low incidence of litters with foetuses with microphthalmia or anophthalmia. In a very large study in which groups of about 400 pregnant rats were exposed to 175,000 mg/m3, there was a low incidence of anophthalmia and microphthalmia combined (10 foetuses in 383 litters).
This increased incidence was statistically significant when compared to concurrent controls; however there was a considerable variation in prospective controls with incidences similar to this high dose group’s in studies conducted 6 years later. The concentration used (175,000 mg/m3) is equivalent to approximately 25% of the 4hr LC50 and there was a slight reduction in maternal body weight gain indicating maternal toxicity. It is concluded that these results are not of significance when considering the health of human beings occupationally exposed at or below recommended permissable exposure levels.
Chlorodifluoromethane is not considered to be genotoxic in viva. Most in vitro tests are negative and a positive response in the Ames test is consistent with occurrence of bacteria-specific metabolic pathways.
In studies in which rats and mice were exposed to chlorodifluoromethane for 4 – 131 wks, only minimal effects or no effects were observed. A slight decrease in body weight gain and a small increase in liver and kidney weight occurred with an exposure level of 175,000 mg/m3. The only exception was a limited study in rats, mice and rabbits which reported changes in the blood, liver, lung and nervous system in animals exposed to 49,000 mg/m3 over a ten months period; these findings were not confirmed in subsequent studies.
Chlorodifluoromethane did not produce neoplastic changes in female rats and male and female mice exposed to concentrations as high as 175,000 mg/m3. In one study in male rats, a concentration of 175,000 mg/m3 was associated with an increase in the number of fibrosarcomas and Zymbal gland tumours; these occurred late in the study and are not considered to be relevant to man. Lower concentrations (35,000 mg/m3 and below) did not increase tumour rates in this study or in any of the other studies. Overall the data do not indicate that chlorodifluoromethane constitutes a carcinogenic hazard to man.
Although the material has been used for several decades, reports on adverse health effects in man are rare and are consistent with findings in experimental animals.
Joint Assessment of Commodity Chemicals No. 9
ECETOC, October 19, 1989