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Carcinogenicity

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Description of key information

The available data and available weight of evidence demonstrate that the C14-C20 aliphatic, 2-30% aromatics are highly unlikely to be carcinogenic and are not classifiable as carcinogens.  

Key value for chemical safety assessment

Additional information

The available data and available weight of evidence demonstrate that the C14-C20 aliphatic, 2-30% aromatics are highly unlikely to be carcinogenic and are not classifiable as carcinogens. 

 

C14-C20 aliphatic, 2-30% aromatics are not classified as dermal irritants (IUCLID section 7.3.1). Early studies that examine structurally analogous test materials, kerosene and jet fuels, were noted to promote dermal tumors in mice. It was noted that tumor development was associated with moderate to severe skin irritation. Since the materials contain very low or no polycyclic aromatic components (PAC’s), it was suggested that tumor development may have resulted from chronic skin irritation. Therefore, a series of studies were conducted to examine the effect of skin irritation on the tumorigenicity of kerosene. In studies conducted by the American Petroleum Institute (API) and CONCAWE, the absence of skin irritation resulted in no statistically significant differences in tumorigenicity between control animals and animals treated with the test materials (Craig S. Nessel, James J. Freeman, Richard C. Forgash, and Richard H. McKee 1999; CONCAWE 1991)). Accordingly, it was concluded that the tumors were the consequence of repeated dermal irritation and not kerosene or jet fuel per se. Since, C14-C20 aliphatic, 2-30% aromatics do not cause the same dermal irritation under recommended and real world use, C14-C20 aliphatic, 2-30% aromatics would not be considered a dermal tumor promoter in mice.

 

Structural analogues of the C14-C20 aliphatic, 2-30% aromatics do not produce hyperplasic or pre-neoplastic changes which are relevant to humans in oral or inhalation sub-chronic repeat-dose studies. Kidney effects were noted in male rats due to a alpha2u-globulin-mediated process that is not regarded as relevant to humans that are not relevant to humans. No test article-related lesions, including no cancer-relevant lesions, were found in examinations of the tissues of rats chronically exposed to the structurally analogous C9-C14 aliphatic, 2-30% aromatics by inhalation for 6 hours per day, 5 days per week for 13 weeks (Shell 1980).   Likewise, no test article-related lesions, including no cancer-relevant lesions, were found in examination of the tissues of rats sub-chronically exposed to JP-8 jet fuel, a structural analogue to C14-C20 aliphatic, 2-30% aromatics, by oral gavage for 7 days per week for 13 weeks (Mattie DR, Marit GB, Flemming CD, Cooper JR 1995). It is unlikely that C14-C20 aliphatic, 2-30% aromatics would cause dermal tumors.

 

C14-C20 aliphatic, 2-30% aromatics are not genotoxic and are not classifiable as mutagens based upon the results of reliable in vitro and in vivo studies. In bacterial reverse mutation studies, the C14-C20 aliphatic, 2-30% aromatics were not mutagenic in the presence or absence of metabolic activation (IUCLID section 7.6.1). In mammalian cells in vitro, and in rats in vivo there were no mutagenic, clastenogenic or aneugenic effects reported in read-across from studies on C9-C14 aliphatic, 2-25% aromatics, hydrodesulfurized kerosene, and jet fuels that included: a negative chromosome aberration (Human Peripheral Lymphocyte Chromosomal Aberration Test, Chinese Hamster Ovary Sister Chromatid Exchange Assay); and an in vivo inhalation exposure bone marrow chromosomal aberration study and micronucleus test in rats and mice (IUCLID sections 7.6.1 and 7.6.2).

 

C14–C20 aliphatic, 2 -30% aromatic hydrocarbon fluids are readily absorbed and excreted when inhaled or ingested. C14–C20 aliphatic, 2 -30% aromatic hydrocarbon fluids are poorly absorbed dermally. Bioaccumulation of C14–C20 aliphatic, 2 -30% aromatic hydrocarbon fluids is not expected.

 

The lack of genotoxicity, subchronic toxicity, dermal irritation, and the lack of bioaccumulation indicate that that the C14-C20 aliphatic, 2-30% aromatics are highly unlikely to be carcinogenic and are not classifiable as carcinogens based on the weight of evidence. 

 

Justification for classification or non-classification

These findings do not warrant the classification of C14-C20 aliphatic, 2-30% aromatic hydrocarbons as a carcinogen under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP) or under the Directive 67/518/EEC for dangerous substances and Directive 1999/45/EC for preparations.