PAFT Programme for Alternative Fluorocarbon Toxicity Testing

HCFC-124 is one of a series of fluorocarbon alternatives being tested by the Programme for Alternative Fluorocarbon Toxicity Testing (PAFT). HCFC-124 is considered primarily as an alternative in specialized refrigeration systems.

Summary of Testing Results HCFC-124 has very low acute and subchronic inhalation toxicity. HCFC-124 is not tumourigenic. HCFC-124 is not a developmental toxicant. HCFC-124 is not genotoxic.

HCFC-124 has very low acute toxicity by inhalation. The lowest concentration that causes mortality in experimental animals -- the approximate lethal concentration (ALC) -- for a 4-hour exposure is between 230,000 and 300,000 ppm in rats. Similar exposure levels cause toxicity in other species, such as the guinea pig. During inhalation exposure to very high concentrations, anaesthetic-like effects, such as weakness and incoordination, are observed. The 10-minute exposure concentration that causes these effects (EC50 for nervous system effects) in experimental animals is about 140,000 ppm. Similar anaesthetic-like effects are observed with many other fluorocarbons in acute inhalation studies.

As with many other halocarbons and hydrocarbons, inhalation of HCFC-124, followed by intravenous injection of epinephrine, which simulates human stress reactions, results in a cardiac sensitization response in experimental screening studies with dogs. This cardiac sensitization response is observed at approximately 25,000 ppm of HCFC-124, a level well above expected exposures. By comparison, a cardiac sensitization response is observed with CFC-11 at approximately 5,000 ppm.

Longer term studies of up to 90 days in duration have also been conducted with HCFC-124. Only changes in clinical chemistry parameters (e.g., triglycerides) and anaesthetic-like effects were noted. These were observed only in the 90-day study. No other effects were evident in any of these studies at concentrations of up to 50,000 ppm. In a 90-day study with mice, inhalation exposures caused an increase in beta-oxidation (indicative of peroxisome proliferation) and a decrease in triglycerides. No other toxic effects were noted in this 90-day study.

A two-year inhalation study with HCFC-124 was conducted with exposure concentrations of 0, 2,000, 10,000 and 50,000 ppm. No adverse effects were noted during the study, and no compound-related grossly visible or microscopic changes were observed at any HCFC-124 exposure level. The no-observed-adverse-effect level (NOAEL) was 50,000 ppm.

Several genetic toxicity studies have also been completed with HCFC-124. Studies conducted with HCFC-124 include the Ames assay, mouse micronucleus, and in vitro chromosomal aberration with human lymphocytes. Based on the evidence from all in vitro and in vivo studies, HCFC-124 is not genotoxic.

The results from developmental toxicity studies with HCFC-124 show that this material does not have embryotoxic or teratogenic effects in rats or rabbits. At very high concentrations (e.g., 50,000 ppm), anaesthetic-like effects and reduced body weights were observed in pregnant animals. However, no fetal effects were observed at these high, maternally toxic concentrations.

HCFC-124 is oxidatively metabolized by the body following inhalation exposure, as suggested by a slight increase in urinary fluoride levels. Also, trifluoroacetic acid (TFA) has been detected following HCFC-124 administration. The rate of metabolism appears to be low.

The testing of HCFC-124 under PAFT III is now complete. The results are summarized in the sidebar above.

An exposure limit of 1,000 ppm (8-hour time-weighted average) has been recommended by the American Industrial Hygiene Association, Workplace Environmental Exposure Limit (WEEL) Committee.

As for all chemicals, PAFT recommends that exposures be kept to a practicable minimum.

September 1995

Last updated October 11, 1996