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Carcinogenicity

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Description of key information

There are no carcinogenicity data on the streams in this category  but all streams within the C4 high 1,3-butadiene category (CAS numbers; 68476-52-8, 68477-42-9, 68955-28-2, 87741-01-3, 92045-23-3) contain at least 0.1% w/w 1,3-butadiene. 1,3-Butadiene is a genotoxic human carcinogen and therefore this component substance defines the hazard for this category. The only other carcinogenicity data are on the marker substance 2-methylpropene which is not a genotoxic carcinogen and does not pose a hazard to man. Humans occupationally exposed to 1,3-butadiene are at increased risk of developing lymphohaematopoietic cancer (leukemia). 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. The available data therefore indicates that members of this category may be carcinogenic in humans.

Key value for chemical safety assessment

Additional information

All streams within the C4 high 1,3-butadiene category (CAS numbers; 68476-52-8, 68477-42-9, 68955-28-2, 87741-01-3, 92045-23-3) contain at least 0.1% w/w 1,3-butadiene and this substance drives the carcinogenicity classification for this category. 1,3-Butadiene is a genotoxic carcinogen, causing cancer at multiple sites in the mouse and lymphohaematopoietic cancer (leukemia) in occupationally exposed humans (EU RAR 2002, SCOEL 2007, Baan 2009). There are no carcinogenicity data on the streams in the C4 high 1,3-butadiene category but the presence of >=0.1% of the marker substance, 1,3-butadiene, indicates that category members are likely to be carcinogenic. Of the other component substances, butane has no carcinogenicity data and although the butene isomers (2-methylpropene) have carcinogenicity data, 2-methylpropene is not a genotoxic carcinogen and therefore this substance has no impact on the classification of the category.

CAS numbers 68955-28-2, 87741-01-3 and 92045-23-3 are already classified as Carcinogenicity Cat. 1B: H350 (May cause cancer) under GHS/CLP and it is proposed that the remaining streams (68476-52-8 and 68477-42-9) are given the same classification as 1,3-butadiene [Carc. Cat 1: R45 (May cause cancer) under Dir 1999/45/EC and Carcinogenicity Cat. 1A: H350 (May cause cancer) under GHS/CLP].

 

Specific data are as follows:

 

1,3-Butadiene: 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.

 

Butene isomers (butenes): Carcinogenicity studies carried out on 2-methylpropene in rats and mice were reported to produce an increase in thyroid follicular cell tumours (NTP 1998). The thyroid tumours occurred only in male rats at the highest exposure concentration (8000 ppm: 18,359 mg/m3) at an incidence slightly above the laboratory historical incidence in control animals and no tumours were observed in female rats or male and female mice. As the butene isomers are not genotoxic, if 2-methylpropene did cause an increase in thyroid tumors in male rats, a threshold mechanism is likely to be involved and the relevance of tumours of this type to human health is low (IARC, 1999).

 

  

Additional References:

Baan R, Grosse Y, Straif K, Secretan B, El Ghissassi F, Bouvard V, Benbrahim-Tallaa L, Guha N, Freeman C, Galichet L, Cogliano V; WHO International Agency for Research on Cancer Monograph Working Group. (2009). A review of human carcinogens--Part F: chemical agents and related occupations. Lancet Oncol. 10(12):1143-4.

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)

IARC Sci Publ. (1999). Agents that induce epithelial neoplasms of the urinary bladder, renal cortex and thyroid follicular lining in experimental animals and humans: summary of data from IARC monographs volumes 1-69.; Ed Wilbourn JD, Partensky C, Rice JM. 147,191-209.

SCOEL. (2007) Recommendation from the Scientific Committee on Occupational Exposure Limits: risk assessment for 1,3-butadiene. SCOEL/SUM/75 final (updated Feb 2007). http: //ec. europa. eu/employment_social/health_safety/docs/sum_75. pdf


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

Justification for classification or non-classification

Members of the C4 high 1,3-butadiene category contain at least 0.1% w/w 1,3-butadiene and this substance drives classification. There are sufficient data available to conclude that streams within the C4 high 1,3-butadiene category are carcinogenic. 

CAS numbers 68955-28-2, 87741-01-3 and 92045-23-3 are listed in Annex VI of CLP and are classified as follows: Carcinogenic Cat 2, R45 under Dir 1999/45/EC and Carcinogenicity Cat. 1B: H350 (May cause cancer) under GHS/CLP.

It is proposed that the remaining streams (68476-52-8 and 68477-42-9) should be classified as follows: Carc. Cat 1: R45 (May cause cancer) under Dir 1999/45/EC and Carcinogenicity Cat. 1A: H350 (May cause cancer) under GHS/CLP.