Evaluation of the genotoxicity potential and chronic inhalation toxicity of 1,1-dichloro-1-fluoroethane (HCFC-141 b)

Abstract

A battery of in vitro and in vivo tests were conducted on HCFC-141b as a vapour. Bacterial gene mutation assays with Escherichia coli and Salmonella typhimurium were negative in all tester strains. In vitro chromosomal aberration assays were positive on CHO cells but negative on human lymphocytes. Moreover, HCFC-141b was negative in vivo in a mouse micronucleus inhalation assay. On the basis of these data and previously reported genotoxicity testing, HCFC-141b is considered non-genotoxic. Groups of 80 male and 80 female Sprague-Dawley rats were exposed, by inhalation (6 hr/day, 5 days/wk) to vapours of HCFC-141b for 104 wk at target concentrations of 0 (control), 1500, 5000 and 20,000 ppm (increased from 15,000 ppm after 17 wk of exposure). No exposure-related effects of toxicological significance were noted with respect to survival, clinical signs, ophthalmoscopy, haematology, clinical chemistry, urinalysis or organ weight analysis. Reduced food intake and body weight gain were noted in both sexes of the 15,000 ppm group during the first 16 wk; thereafter, body weight gains in all groups were similar although the intergroup differences in body weight remained evident. Reduced food intake persisted in both sexes through wk 52 and in females during the second year of exposure. Treatment-related effects on macroscopic pathology were confined to increased incidences of testicular masses and altered appearance. Microscopic pathology examinations confirmed the testes as the target organ with findings of increased incidences of benign interstitial cell tumours and hyperplasia at 5000 and 20,000 ppm. The no-observable-adverse-effect level (NOAEL) was 1500 ppm. The testicular changes at high exposure levels were considered to be due to a change of the senile hormonal imbalance in geriatric rats and of little significance for the assessment of human health effects.

Rodent Leydig Cell Tumorigenesis: A Review of the Physiology, Pathology, Mechanisms, and Relevance to Humans

“…In a 2-year inhalation study, male and female Sprague-Dawley (CD) rats were exposed to atmospheres containing 0, 1500, 5000, or 20,000 ppm HCFC-141b for 6 h/d, 5 d/week (Turnbull et al, 1994;Millischer et al, 1995). There was a significant increase in the incidence of LCTs in the 5000 and 20,000 ppm HCFC-141b groups.…”

“…The incidences for LCTs were 4.3% (3/70), 5.7% (4/70), 20% (14/70), and 17.1% (12/70) in the 0, 1500, 5000, and 20,000 ppm HCFC-141b groups, respectively. HCFC-141b was judged to be nongenotoxic based on negative results from a battery of in vitro and in vivo genotoxicity tests (Hodson-Walker et al, 1993;Millischer et al, 1995).…”

Chemical Exposure Guidance Levels Consistency, Integrity and Public Trust

“…If we compare the TLV committee membership to the WEEL committee membership, we see that both have representation from government Boron tri uoride -ERPG-3 (lethal threshold) Woudenberg approach (11) Level Support 50 mg/m 3 1 100 mg/m 3 8 150 mg/m 3 1 and industry. However, membership in the TLV committee is derived predominantly from academia, while membership in the WEEL committee comes predominantly from industry.…”

“…(1) In contrast, the four-hour LC 50 for dichloro uoroethane is 62,000 PPM, (2) yet daily six-hour exposures to 20,000 PPM ve days per week for two years had no effect on survival and only a marginal effect on body weight. (3) Where one wants to extrapolate exposure levels over short time intervals, it is again important to understand the mechanism of toxic action. If the substance demonstrates primarily an irritant effect, it will be relatively insensitive to time.…”

Toxicological Evaluations of Alternative Fluorocarbons

“…A noobservable-eect-level (NOEL) for these studies was determined to be 50,000 ppm (Table 5) 12 . It was also not active in the human lymphocyte chromosome aberration assay up to 35%, in the in vivo mouse micronucleus assay up to 35%, and the HGPRT-V79 assay up to 36,000 ppm 17 . It was not active in a series of genetics studies.…”