Registration Dossier

Toxicological information

Carcinogenicity

Currently viewing:

Administrative data

Description of key information

No specific carcinogenicity data are available on any of the streams identified for this category or the C1-C4 alkanes. However there are substantial data on one of the main components, propene. There is no evidence of carcinogenicity of propene following evaluation in rats and mice. Benzene and 1,3–butadiene have been identified as potential specific components present in some streams and these have been shown to be carcinogenic in animals and man. 

Key value for chemical safety assessment

Additional information

There are no specific carcinogenicity data are available on any of the streams identified and also no carcinogenicity studies for any of the C1-C4 alkanes in the Other Petroleum Gases category. However, a consideration of their simple chemical structures, which have no reactive groups and carry no alerts for likely genotoxic carcinogenic activity from established Structure Activity Relationship analysis (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), together with the conclusion that C1-C4 alkanes are not genotoxic, provide a strong case for concluding that none will show any significant carcinogenic activity. 

There are data for main component propene:

Propene CAS No: 115-07-1

There was no evidence of carcinogenicity in male and female F344/N rats or in male and female B6C3F1 mice exposed to propene by inhalation at concentrations of 5000 or 10000 ppm (8,600 or 17,200 mg/m3), for 103 weeks (NTP, 1985), or in the supporting study in male and female Swiss mice at concentrations up to 5000 ppm (8,600 mg/m3), following exposure for 78 weeks, or in male and female Sprague-Dawley rats at concentrations up to 5000 ppm (8,600 mg/m3), following exposure for 104 weeks (Ciliberti et al, 1988).

 

Summary:

No specific carcinogenicity data are available on any of the streams identified for this category or the C1-C4 alkanes. However there are data on one of the main components, propene, to indicate that members of this category have low potential for carcinogenicity. Propene, like the C1-C4 alkanes, is also considered to be non-genotoxic both in vitro and in vivo, and furthermore, has carcinogenicity data in animals that provides evidence of non-carcinogenicity.

Taking all these data into account, together with the general lack of toxicity across other endpoints, it is considered that there is no justification for conducting further animal carcinogenicity studies. The above reasoning leads to the conclusion that Other Petroleum Gases category can be considered to have low concern for human carcinogenicity.

However, benzene and 1,3–butadiene have been identified as potential specific components present in some streams and these have been shown to be carcinogenic in animals and man:

Benzene

(Classification: EU -Toxic T, Carcinogen Cat 1 R45; GHS/CLP - Category 1A, H350): Long term experimental carcinogenicity bioassays have shown that benzene is a carcinogen producing a variety of tumours in animals (including lymphomas and leukaemia). Human epidemiological studies indicate a causal relationship between benzene exposure and acute non-lymphatic leukaemia (Crump, 1994; Glass et al, 2003, 2004, 2006; Rinsky et al, 2002; Schnatter, 2004).

1,3-Butadiene

(Classification: EU -Toxic T, Carcinogen Cat 1 R45; GHS/CLP - Category 1A, H350): In experimental animals, there is a marked species difference in carcinogenicity (EU RAR 2002). In the mouse, 1,3-butadiene is a potent multi-organ carcinogen. Tumours develop after short durations of exposure, at low exposure concentrations and the carcinogenic response includes rare types of tumours (NTP 1993). In the rat, fewer tumour types, mostly benign, develop at exposure concentrations of 100 to1000-times higher (Owen et al 1987). In humans a positive association was demonstrated between workplace exposure to butadiene for men employed in the styrene-butadiene rubber industry and lymphohaematopoietic cancer (leukemia) (Sathiakumar et al 2005, Graff et al 2005, Delzell et al 2006, Cheng et al 2007, Sielken et al 2006, 2007 & 2008).

 

Category streams are considered to be carcinogens if they contain ≥0.1% benzene or 1,3-butadiene.

Additional Reference:

EU RAR (2002). European Union Risk Assessment Report for 1,3-butadiene. Vol. 20. European Chemicals Bureau (http: //ecb. jrc. ec. europa. eu/DOCUMENTS/Existing-Chemicals/RISK_ASSESSMENT/REPORT/butadienereport019. pdf)

Justification for classification or non-classification

Members and main components of Other Petroleum Gases have a low potential for carcinogenicity and therefore do not warrant classification under DPD (Dir 1999/45/EC) or GHS/CLP.

Similarly, category streams that contain <0.1% benzene and 1,3-butadiene are considered not to be carcinogenic and no labelling is required under DPD (Dir 1999/45/EC) or GHS/CLP.

However it is proposed that Category streams that contain ≥0.1% benzene or 1,3-butadiene are likely to be carcinogenic to animals and humans. Some streams are already listed in Annex VI of CLP and are classified as follows Carcinogenic Cat 1, R45 according to Dir 1999/45/EC and as Carc 1B:H350 (May cause cancer) under CLP Reg (EC) 1272/2008 (see Section 3). It is proposed that all remaining streams that contain ≥0.1% benzene or 1,3-butadiene are classified as follows: Carc. Cat 1: R45 (May cause cancer) under Dir 1999/45/EC and Carcinogenicity Cat1A: H350 (May cause cancer) under CLP Reg (EC) 1272/2008.