Propene

Endpoint summary

Additional information

Bacterial Reverse Mutation Assay.   

A guideline study (OECD Guideline 471 with minor modifications to the method as the test item is a gas at ambient temperature), used dose levels of 0, 0.031, 0.063, 0.125, 0.25, and 1%, (although higher concentrations were also tested in a sighting study (Inveresk, 2003b). 5 bacterial strains (S. typhimurium TA1535, TA1537, TA98 and TA100 and E. coli WP2 uvr A pKM 101) were tested with and without metabolic activation. In only one strain (TA1535), when supplemented with metabolic activation, there was a slight increase in revertant colonies, relative to negative control cultures (to a maximum of 3x the control value in one experiment), (Inveresk, 2003a). 

 

Mammalian Cell Gene Mutation

Propene was tested in an OECD Guideline 476, In vitro Mammalian Cell Gene Mutation Test. Mouse lymphoma L5178Y cells were exposed to propene at the following concentrations - 0 (air), 2.5, 5, 10, 20 and 30% (nominal) with and without metabolic activation for trials 1 and 2. For trial 3, the concentrations were - 0 (air), 10, 20, 30, 40 and 50% (nominal) and this 3rd trial was conducted with metabolic activation. The authors reported that there was no evidence of mutagenicity in the absence of S9. However, in the presence of S9 they reported that the test material could not be classified as mutagenic or non-mutagenic (McGregor et al., 1991). In the presence of S9, some increases in mutant frequency over controls were seen. However these were small (< 2x control), were not seen in all experiments and there was limited evidence of any dose-response. The lack of reproducibility of the small increases seen and lack of reproducibility in any dose-response, even at doses as high as 50% atmosphere, indicates overall that propene showed no evidence for genotoxicity in this study.

In vivo

Micronucleus (OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Propene was evaluated in vivo for its ability to induce micronuclei (MN) in bone marrow polychromatic erythrocytes (PCEs) in male Fischer 344 (F344) rats. Groups of 8 rats were exposed to 200, 2000, or 10,000 ppm propene, clean air, or positive control substance by inhalation for 6 hours/day, 5 days/week, for a total of 20 exposures (4 weeks). Bone marrow smears were prepared immediately after sacrifice. Propene exposure did not produce any statistically significant effect on the proportion of PCEs per 1000 erythrocytes scored per animal, or on the frequency of micronucleated erythrocytes per 2000 PCE’s scored per animal. The positive control, cyclophosphamide, clearly induced an increased frequency of MN’s and a decreased ratio of PCE’s, indicating adequacy of the assay conditions to detect genotoxicity. Therefore, inhalation exposure of F344 male rats to up to 10,000 ppm propene did not cause any in vivo genotoxicity/clastogenicity as measured by increases in formation of MN’s in bone marrow (Pottenger et al., 2007).

HPRT Assay

HPRT mutant frequencies in T-lymphocytes isolated and cultured from spleens of male F344 rats exposed to propene at 200, 2000, or 10,000 ppm for 20 days, as well as negative (air only) and positive (cyclophosphamide) controls were assessed. All cloning efficiency plates and 6TG selection plates were blinded and designated by number assignments known only to appropriate contacts of this work group. The scoring of all mutant lymphocytes was consistent throughout the study as demonstrated by periodic checks on the scoring of mutant lymphocytes. All mutation frequency calculations were reviewed and in agreement with study protocols. Appropriate statistical analyses were performed on raw data. Propene did not produce an increase in HPRT mutant frequencies in splenic T-lymphocytes; the NOAEL was 10,000 ppm (Walker et al., 2004).

Overall, the weight of experimental evidence indicates that propene is not likely to be mutagenic in humans. Some limited mutagenic activity has been reported from some in vitro studies with one of five bacterial strains tested in the Ames assay (i.e.,Salmonella typhimurium strain TA1535) demonstrating a marginal increase in mutagenic activity only in the presence of S9 (Inveresk, 2003a,b). Propene has been without activity in other bacterial strains tested with and without metabolic activation. In addition, propene was not mutagenic in an in vitro mammalian cell mutation assay in L5178Y mouse lymphoma cells. In vivo a micronucleus test (Pottenger et al., 2007) and a HPRT mutation assay (Walker et al., 2004) in rats following inhalational exposure to high levels of propene, both reported negative results (Pottenger et al 2007). These studies support the negative outcome of chronic (2-year) inhalational exposure of rats and mice (NTP, 1985 & Ciliberti et al., 1988) to concentrations up to 10000 ppm (half the lower explosion limit) of propene. Taken together these studies underpin the conclusion that propene is not a genotoxic carcinogen.

Short description of key information:
Review of an extensive database indicate that propene is not genotoxic

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

There is no evidence that propene is genotoxic therefore no classification is warranted under DSD or CLP.