Registration Dossier

Toxicological information

Carcinogenicity

Currently viewing:

Administrative data

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. Resin Oils and Cyclic Dienes are considered to be carcinogens if they contain ≥0.1% benzene, 1,3-butadiene or isoprene or ≥1% naphthalene.

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 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 (EU, 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 (leukaemia) (Sathiakumar et al, 2005; Graff et al, 2005; Delzell et al, 2006; Cheng et al, 2007; Sielken et al, 2006, 2007 and 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; CLP - Category 1B, H350): When inhaled in concentrations of 70 ppm (195 mg/m3) and above, isoprene was found to induce tumours in a range of tissues including lung, liver, Harderian gland, forestomach, lymphoreticular system of male mice and in the Harderian gland and pituitary gland of female mice. No statistically significant increases in tumours were reported at a dose level of 10 ppm (28 mg/m3) (Placke et al., 1996). Inhalation by rats of concentrations above the lowest tested value of 220 ppm (613 mg/m3) caused a significantly increased incidence of mammary gland, testicular and kidney tumours in males, and mammary gland tumours in females (NTP, 1999). At the lowest dose tested, 220 ppm (613 mg/m3), a statistically significant increase in only mammary gland fibroadenoma was observed in females.

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

Resin Oils and Cyclic Dienes that contain ≤0.1% benzene, ≤0.1% 1,3-butadiene and ≤0.1% isoprene and ≤1% naphthalene are considered not to be carcinogenic and no classification is required under Dir 1999/45/EC or Reg (EC) 1272/2008.

The streams CAS numbers: 101316-62-5, 102110-15-6, 65996-79-4, 68477-50-9, 68477-54-3, 68516-20-1 and 68527-26-4 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.

For other Resin Oils and Cyclic Dienes streams classification with respect to carcinogenicity is dependent upon the concentration of benzene, 1,3-butadiene, isoprene and naphthalene as detailed below:

≥0.1% benzene or ≥0.1% 1,3-butadiene: Carcinogenic Cat 1, R45 “May cause cancer” according to Dir 1999/45/EC and Cat 1A, H350 “May cause cancer” under Reg (EC) 1272/2008.

<0.1% benzene and <0.1% 1,3-butadiene but ≥0.1% isoprene: Carcinogenic Cat 2, R45 “May cause cancer” according to Dir 1999/45/EC and Cat 1B, H350 “May cause cancer” under Reg (EC) 1272/2008.

<0.1% benzene and <0.1% 1,3-butadiene and <0.1% isoprene but ≥1% naphthalene: Carcinogenic Cat 3, R40 according to Dir 1999/45/EC “Limited evidence of carcinogenic effect” and Cat 2, H351 under Reg (EC) 1272/2008 “Suspected of causing cancer”.