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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

Carcinogenicity: via oral route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LOAEL
25 mg/kg bw/day
Study duration:
chronic
Species:
rat
Quality of whole database:
Adequate information is available on the component substances to characterise the carcinogenic potential of these streams.

Carcinogenicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LOAEC
960 mg/m³
Study duration:
chronic
Species:
mouse
Quality of whole database:
Adequate information is available on the component substances to characterise the carcinogenic potential of these streams.

Carcinogenicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

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: 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, 2010; 2012).

1,3-Butadiene (Classification: 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: 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: 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 selection of carcinogenicity via oral route endpoint:

Some of the component substances present (e.g. benzene, butadiene, isoprene, naphthalene) have been shown to be carcinogenic. Overall, this supports the classification of members of this category as carcinogenic.

Justification for selection of carcinogenicity via inhalation route endpoint:

Some of the component substances present (e.g. benzene, butadiene, isoprene, naphthalene) have been shown to be carcinogenic. Overall, this supports the classification of members of this category as carcinogenic.

Carcinogenicity: via oral route (target organ): other: all gross lesions and masses

Carcinogenicity: via inhalation route (target organ): cardiovascular / hematological: bone marrow

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 and are classified as Cat 1B, H350 under CLP Reg (EC) 1272/2008.

It is proposed that all remaining High Benzene Naphtha streams should be classified as follows: Cat 1A, H350 under Reg (EC) 1272/2008.