PAFT Programme for Alternative Fluorocarbon Toxicity Testing

HCFC-141b is one in a series of fluorocarbon alternatives being tested by the Programme for Alternative Fluorocarbon Toxicity Testing (PAFT). HCFC-14lb is primarily an alternative to CFC-11 as a foam-blowing agent, but may also be used as a solvent in cleaning applications.

Summary of Testing Results HCFC-141b has low acute and subchronic inhalation toxicity. HCFC-141b caused an increased incidence of benign, but not life-threatening, tumours in animals following long-term exposure to high concentrations. HCFC-141b is not a developmental toxicant. HCFC-141b does not affect reproductive performance. HCFC-141b is not genotoxic.

Data from acute toxicity studies demonstrated that HCFC-141b has very low acute toxicity. HCFC-141b is not a skin irritant and is only a mild eye irritant. Skin application of HCFC-141b at high doses (2,000 mg/kg body weight) produces no adverse effects. Oral administration of HCFC-141b at high doses (5,000 mg/kg body weight) does not cause any mortality. Therefore, the oral LD50 is greater than 5,000 mg/kg body weight. HCFC-141b also has very low acute inhalation toxicity as measured by the concentration that causes 50% mortality in experimental animals, the LC50. The 4-hour exposure LC50 for HCFC-141b is 62,000 ppm in rats. Anaesthetic-like effects are observed at high concentrations.

As with many other halocarbons and hydrocarbons, inhalation of HCFC-141b 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 with HCFC-141b at approximately 5,000 ppm, a level well above expected exposures. Similarly, 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-141b. In these studies, only slight changes in clinical chemistry parameters (e.g., cholesterol) and slight anaesthetic-like effects were observed. No other effects were evident in any of these studies at concentrations of up to 20,000 ppm. The no-observed-effect level (NOEL) in these studies was about 8,000 ppm.

A two-year inhalation study with HFC-141b was conducted at exposure concentrations of 0, 1,500, 5,000 and 20,000 ppm. During the study, no significant adverse effects were noted, although at the highest concentations, slightly lower body weights were observed in male rats. Except for the testis of male rats, no grossly visible or microscopic changes were noted in any of the HCFC-141b treated animals. In the testis, an increase in hyperplasia (cell growth) and benign tumours of Leydig cells was observed in the 5,000 and 20,000 ppm groups. No malignant tumours attributable to HCFC-141b were observed. An independent review of the pathology findings supported these conclusions. None of the benign tumours were life- shortening, and all occurred near the end of the study. No effects were observed at lower concentrations in this two-year study; the NOEL was 1,500 ppm.

Several genetic toxicity studies have also been completed with HCFC-141b. Based on the evidence from all in vitro and in vivo studies, HCFC-141b is not mutagenic. Studies conducted with HCFC-141b included Ames, in vitro chromosomal aberration with human lymphocytes, and mouse micronucleus. HCFC-141b was active only at very high exposures in the Chinese Hamster ovary chromosomal aberration study. However, the overall evidence suggests that HCFC-141b is not genotoxic.

The results from developmental toxicity studies with HCFC-141b show that this material does not have embryotoxic effects in rats and rabbits at inhalation concentrations of 8,000 ppm and 1,400 ppm, respectively. In studies conducted in rats (at levels up to 20,000 ppm) and in rabbits (at levels up to 12,600 ppm), no teratogenic effects were seen. In a reproduction study, results suggest that HCFC-141b caused a slight reduction in litter size and total litter weight at 20,000 ppm. The NOEL was 8,000 ppm for the pups, and 2,000 ppm for the adults.

Metabolism studies suggest that HCFC-141b is oxidatively metabolized, although the rate of metabolism appears to be low.

The testing of HCFC-141b under PAFT II has been completed. The results are summarized in the sidebar above.

An exposure limit of 500 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