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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 data on the carcinogenicity of a number of specific components present in the streams. As all streams contain >=1% isoprene which is a category 2 genotoxic carcinogen (DPD), classification of all category streams is based on isoprene.  Additional classification is required for streams containing >=0.1% benzene and/or 1,3, -butadiene which are both classified as category 1 carcinogens (DPD).

Key value for chemical safety assessment

Additional information

There are no carcinogenicity data for any of the streams identified in the C5 non-cyclics category. Specific components that have been identified as present in some streams and shown to be carcinogenic are the marker substance, isoprene, as well as benzene and 1,3- butadiene which are present in some but not all streams.

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.

Benzene (Classification: EU - Toxic T, Carcinogen Cat 1 R45; 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; 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). Various models have established a dose response-relationship for cumulative exposure to 1,3-butadiene, especially concentrations above 100 ppm. The estimates for occupational and population human risk are based on these models.

Justification for classification or non-classification

Isoprene is present at >=1% in all streams and therefore mandatory classification as Carcinogen Cat 2 R45 under DPD with corresponding classification as Category 1B, H350 under CLP is required for all C5 non-cyclics streams.

CAS numbers 68476-55-1, 91995-41-4 and 68477-50-9 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.

CAS number 68477-35-0 is listed in Annex VI of CLP and is classified as follows Carcinogenic Cat 1, R45 according to Dir 1999/45/EC and Cat 1B, H350 under CLP Reg (EC) 1272/2008.

It is proposed that the remaining C5 non-cyclics stream (CAS 68476-43-7) should be classified as follows:Carcinogenic Cat 2, R45 according to Dir 1999/45/EC and Cat 1B, H350 under CLP Reg (EC) 1272/2008. 

If benzene or 1, 3-butadiene are present at >= 0.1% the classification should be May cause cancer Carcinogenic Cat 1, R45 according to Dir 1999/45/EC and Cat 1A, H350 under Reg (EC) 1272/2008.