PAFT Programme for Alternative Fluorocarbon Toxicity Testing

HFC-134a is one of a series of fluorocarbon alternatives being studied as part of the Programme for Alternative Fluorocarbon Toxicity Testing (PAFT). HFC-134a is being considered as an alternative for refrigeration and air conditioning, medical dose delivery systems, and as a foam blowing agent.

Summary of Testing Results HFC-134a has very low acute and subchronic inhalation toxicity. HFC-134a caused an increased incidence of benign tumours in animals following long-term exposure to high concentrations. HFC-134a is not a developmental toxicant. HFC-134a is not genotoxic.

HFC-134a has very low acute inhalation toxicity. The lowest concentration that causes mortality in rats -- the approximate lethal concentration (ALC) -- for a 4-hour exposure is greater than 500,000 ppm. Anaesthetic-like effects, such as lethargy and incoordination, are observed in rats at very high inhalation concentrations (greater than 200,000 ppm).

As with many other halocarbons and hydrocarbons, inhalation of HFC-134a 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 75,000 ppm of HFC-134a, a level well above expected exposures. By comparison, a cardiac sensitization response is observed with CFC-12 at approximately 50,000 ppm.

Longer term studies have also been conducted with HFC-134a. No significant toxicological effects were observed in rats following inhalation exposure for up to one year at concentrations up to 50,000 ppm.

At the end of the two-year inhalation study, no effects were observed in body weights, in-life measurements, clinical observations or clinical chemistry, or haematology. Except for the testis of male rats, no grossly visible or microscopic changes were observed in the any of the HFC-134a exposed rats. At 50,000 ppm, an increased incidence of hyperplasia (cell growth) and benign tumours of Leydig cells was observed on microscopic examination of the testis. No malignant tumours attributable to exposure to HFC-134a were observed. An independent review of the pathology findings supported these conclusions. None of the benign tumours were life- threatening, and all occurred near the end of the study. No effects were observed at lower concentrations in this two-year study; the no-observed-effect level (NOEL) was 10,000 ppm.

Several genetic toxicity studies with HFC-134a have been completed. These included a bacterial reverse mutation (Ames) test, an in vitro chromosomal aberration study with human lymphocytes, and a cytogenetics assay with Chinese Hamster Lung Cell (CHL). In vivo studies included cytogenetics, mouse micronucleus, and a dominant lethal study in the mouse. Evidence from all in vitro and in vivo studies clearly indicates that HFC-134a is not genotoxic. Furthermore, these data and data obtained from the two-year inhalation study suggest that the increased incidence of benign tumours observed in the two-year inhalation study is not due to an effect on genetic material.

Results from inhalation developmental toxicity studies indicate that HFC-134a does not cause teratogenic effects in rats or rabbits. At inhalation concentrations of 300,000 ppm, slight maternal toxicity and embryotoxicity, evidenced by a decrease in fetal body weights, were observed in rats. Lower fetal body weights of rats and rabbits have been observed at 50,000 ppm with slight maternal toxicity; lower maternal body weights were also observed in rats at this concentration. In an additional study, no fetal effects were observed in rabbits at inhalation concentrations of up to 40,000 ppm.

Although not metabolized to any significant extent in animals, HFC-134a is oxidatively metabolized following inhalation exposure, as suggested by a slight increase in urinary fluoride levels. However, the rate of metabolism of HFC-134a is very low, and about 99% of an inhaled dose is eliminated unchanged.

The testing of HFC-134a under PAFT I has been completed. 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