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Toxicological information

Carcinogenicity

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Description of key information

There are no specific carcinogenicity data on any of the streams within this category. However, there are substantial data on the carcinogenicity of a number of specific components present in some streams. Of these, benzene, 1,3-butadiene, naphthalene and isoprene have been shown to be carcinogenic. High Benzene Naphtha streams are considered to be carcinogens as they contain ≥0.1% benzene and may contain up to 1% 1,3-butadiene, up to 30% naphthalene and up to 6% isoprene.

Key value for chemical safety assessment

Additional information

There is no carcinogenicity information on any of the streams identified for this category. Specific components which have been identified as present in some streams and shown to be carcinogenic in animals and/or man are benzene, 1,3-butadiene, naphthalene and isoprene:

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. 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. In the rat, fewer tumour types, mostly benign, develop at exposure concentrations of 100 to1000-times higher (EU, 2002). In humans a positive association was demonstrated between workplace exposure to butadiene in the styrene-butadiene rubber industry and lymphohaematopoietic cancer (leukaemia) (Delzell et al, 2006; Sathiakumar and Delzell, 2009; Sielken et al, 2008).

Naphthalene (Classification: EU -Harmful Xn, Carcinogen Cat 3 R40; GHS/CLP - Category 2, H352): According to the EU RAR (EU, 2003b) the limited information available in humans are considered insufficient conclude on carcinogenicity. However, naphthalene produced an increase in the incidence of respiratory epithelial adenomas and olfactory epithelial neuroblastomas (at the lowest exposure concentration of 10 ppm (50 mg/m3) in rats and an increase in the incidence of benign lung tumours (alveolar/bronchiolar adenomas) in mice. The tumours are considered to arise via a non-genotoxic mechanism and there is some uncertainty surrounding the relevance for human health. The LOAEL for carcinogenicity was considered to be 5 mg/m3.

Isoprene (Classification: EU -Toxic T, Carcinogen Cat 2 R45; GHS/CLP - Category 1B, H350): There is clear evidence of carcinogenicity of isoprene in mice, with increases in the incidence of malignant neoplasms in the liver, lung, Harderian gland and forestomach. Histiocytic sarcomas and haemangiosarcomas were also observed, together with benign tumours observed in the liver, lung, Harderian gland, forestomach and pituitary (NTP, 1999; Placke et al, 1996).

References

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

EU (2003b). European Union Risk Assessment Report: Naphthalene. http: //ecb. jrc. ec. europa. eu/DOCUMENTS/Existing-Chemicals/RISK_ASSESSMENT/REPORT/naphthalenereport020. pdf

Justification for classification or non-classification

High Benzene Naphtha streams contain ≥0.1% benzene and may contain up to 1% 1,3-butadiene, up to 30% naphthalene and up to 6% isoprene and are considered to be carcinogenic.

The majority of streams (CAS numbers:102110-55-4, 64741-47-5, 64741-84-0, 64742-83-2, 68410-96-8, 68475-70-7, 68477-53-2, 68477-55-4, 68513-69-9, 68516-20-1, 68527-23-1, 68527-26-4, 68606-10-0, 68955-29-3, 90641-13-7, 90989-41-6, 91995-50-5, 92045-57-3, 92045-61-9, 94114-03-1, 98219-47-7) are listed in Annex VI of CLP and are classified as follows Carcinogenic Cat 2, R45 according to Dir 1999/45/EC and Cat 1B, H350 under CLP Reg (EC) 1272/2008.

It is proposed that all remaining High Benzene Naphtha streams should be classified as follows: "May cause cancer" Carcinogenic Cat 1, R45 according to Dir 1999/45/EC and Cat 1A, H350 under Reg (EC) 1272/2008.