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Key value for chemical safety assessment

Additional information

Methane CAS Number 74-82-8

In vitro data

The key study is considered to be a bacterial mutation assay (NTP, 1993), a recognised core assay type for investigating mutation in vitro.

Methane was tested in a standard Ames test but using gas chambers to allow appropriate examination of a gaseous material. Salmonella typhimurium (TA1535, TA97, TA98 and TA100) was treated with methane both with and without auxiliary metabolic activation (S9). A range of doses of methane was used, and the S9 was prepared from both rat and hamster livers and added at two levels.

Methane was not mutagenic in this test system.

In vivo data

No in vivo genotoxicity data are available for methane.

Human information

There is no information indicating any adverse effects of methane.

 

Summary

Methane has been examined for mutagenicity in vitro in the Ames test using a test system that is suitable for examining gaseous materials. It was tested both in the absence and presence of different levels of S9 fractions from both rat and hamster. It was non-mutagenic in the assay. This result is what would be expected from the simple chemical structure of methane. There are no functional groups in the molecule, and it would not be expected to undergo significant metabolism to any reactive species. It carries no alerts for possible genotoxic activity based on established Structure Activity Relationship (SAR) principles ( Tennant RW and Ashby J (1991). Classification according to chemical structure, mutagenicity to Salmonella and level of carcinogenicity of a further 39 chemicals by the US National Toxicology Program.  Mutat Res 257 (3) 209-227). 

 

Ethane CAS Number 74-84-0

No data were identified. There are no functional groups in the ethane molecule, and it would not be expected to undergo significant metabolism to any reactive species. It carries no alerts for possible genotoxic activity based on established Structure Activity Relationship (SAR) principles (Tennant and Ashby, 1981). 

 

Propane CAS Number 74-98-6

In vitro data

The key study is considered to be a bacterial mutation assay (Kirwin et al, 1980), a recognised core assay type for investigating mutation in vitro.

Propane was tested in a standard Ames test but using gas chambers to allow appropriate examination of a gaseous material. Salmonella typhimurium (TA1535, TA1537, TA1538, TA98 and TA100) was treated with propane both with and without auxiliary metabolic activation from rat liver (S9). A range of doses of propane was used, up to 50% atmosphere. Propane was not mutagenic in this test system.

In vivo data

No in vivo genotoxicity data are available for propane.

Human information

There is no information indicating any adverse effects of propane.

Summary 

Propane has been examined for mutagenicity in vitro in the Ames test using a test system that is suitable for examining gaseous materials. It was tested both in the absence and presence of different levels of S9 fractions from both rat and hamster. It was non-mutagenic in the assay. This result is what would be expected from the simple chemical structure of propane. There are no functional groups in the molecule, and it would not be expected to undergo significant metabolism to any reactive species. It carries no alerts for possible genotoxic activity based on established Structure Activity Relationship (SAR) principles (Tennant and Ashby, 1981). 

 

Isobutane CAS Number 75-28-5

In vitro data

The key study is considered to be a bacterial mutation assay (Kirwin et al, 1980), a recognised core assay type for investigating mutation in vitro.

Isobutane was tested in a standard Ames test but using gas chambers to allow appropriate examination of a gaseous material. Salmonella typhimurium (TA1535, TA1537, TA1538, TA98 and TA100) was treated with isobutane both with and without auxiliary metabolic activation from rat liver (S9). A range of doses of isobutane was used, up to 50% atmosphere. Isobutane was not mutagenic in this test system.

In vivo data

No in vivo genotoxicity data are available for isobutane.

Human information

There is no information indicating any adverse effects of isobutane.

 

Summary

Isobutane has been examined for mutagenicity in vitro in the Ames test using a test system that is suitable for examining gaseous materials. It was tested both in the absence and presence of different levels of S9 fractions from both rat and hamster. It was non-mutagenic in the assay. This result is what would be expected from the simple chemical structure. There are no functional groups in the molecule, and it would not be expected to undergo significant metabolism to any reactive species. It carries no alerts for possible genotoxic activity based on established Structure Activity Relationship (SAR) principles (Tennant and Ashby, 1981). 

 

Butane CAS Number 106-97-8

In vitro data

The key studies are considered to be bacterial mutation assays (Kirwin et al 1980, NTP, 2005), and an in vitro cytogenetic assay (Safepharm, 2008). These are recognised core assay types for investigating mutation in vitro.

Butane was tested in a standard Ames test but using gas chambers to allow appropriate examination of a gaseous material (Kirwin et al 1980). Salmonella typhimurium (TA1535, TA1537, TA1538, TA98 and TA100) was treated with butane both with and without auxiliary metabolic activation from rat liver (S9). A range of doses of butane was used up to a dose of 50% atmosphere.  In a second Ames test, Salmonella typhimurium (TA1535, TA97, TA98 and TA100) was treated with butane both with and without auxiliary metabolic activation (S9). In this study, a range of doses of butane was again used, and the S9 was prepared from both rat and hamster livers and added at two levels. Butane was not mutagenic in either of these studies.

Butane was examined in an in vitro cytogenetic assay in human lymphocytes in both the absence and presence of auxiliary metabolic activation. It was tested using contained exposures to allow appropriate examination of a gaseous material. Butane was not mutagenic in this assay.

In vivo data

No in vivo genotoxicity data from mammalian systems are available for butane. Butane has been examined in the Sex Linked Recessive Lethal assay in drosophila, at a dose level of 35% atmosphere (NTP, 2005). The material was reported to give a negative response.

Human information

There is no information indicating any adverse effects of butane.

 

Summary

Butane has been examined for mutagenicity in vitro in the Ames test using a test system that is suitable for examining gaseous materials. It was tested both in the absence and presence of different levels of S9 fractions from both rat and hamster. It was non-mutagenic in the assay.   Furthermore, butane has been examined in an in vitro cytogenetic assay in human lymphocytes to current OECD guideline standards, again under exposure conditions appropriate for a gaseous material. It was negative in this assay. Butane has therefore been examined, and found to be negative, for both gene mutation and cytogenetic endpoints in vitro. This result is what would be expected from the simple chemical structure of butane. There are no functional groups in the molecule, and it would not be expected to undergo significant metabolism to any reactive species. It carries no alerts for possible genotoxic activity based on established Structure Activity Relationship (SAR) principles (Tennant and Ashby, 1981).

 

 

Petroleum gases, liquefied,

In vitro/vivo data

The major constituents are identified as propane and propene.

HLS (2009) assessed the potential inhalation toxicity of liquified petroleum gas when administered via whole-body exposures to rats for 13 weeks. The assessment included evaluations of genotoxicity parameters.

Rats were exposed for six hours per day to 0 (air control), 1000, 5000 or 10000 ppm of LPG for 5 days per week for 13 consecutive weeks (highest exposure concentration was selected for safety reasons and approximated 50% of the lower explosive limit). At the end of the treatment period, all animals were euthanized and necropsied and the incidences of micronucleated immature erythrocytes were calculated in 5 males & females per dose concentration. After 13 weeks of exposure, there were no treatment-related differences in micronucleus incidence at concentrations up to 10000 ppm, compared to the air control animals. The no observed adverse effect concentration (NOAEC) was 10000 ppm.

Summary for the category

In summary, simple short chain alkanes (i.e methane, ethane, propane, butane, isobutane) can be considered in a similar manner, and data are available for methane, propane, butane and isobutane in the Ames test, testing under exposure conditions appropriate for gaseous materials, that similarly show them to be non-mutagenic. Furthermore, butane (the C4 analogue alkane) has been examined in an in vitro cytogenetic assay in human lymphocytes to current OECD guideline standards, again under exposure conditions appropriate for a gaseous material. It was negative in this assay. The data are further supported by in vivo data on liquefied petroleum gases (major constituents identified as propane and butane). After 13 weeks of exposure of rats, there were no treatment-related differences in micronucleus incidence at concentrations up to 10000 ppm, compared to the air control animals.

The available data for the short-chain alkanes indicates no genotoxic activity across endpoints of bacterial gene mutation, in vitro clastogenicity and in vivo.


Short description of key information:
Mutagenicity data exist for the Petroleum Gases category. A review of an extensive database indicates they are not genotoxic.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

There is no evidence that members of Petroleum Gases are genotoxic therefore no classification is warranted under Dir 67/548/EEC or GHS/CLP.