Hydrocarbons, C9-C10, aromatics, >1% naphthalene

Carcinogenicity

Description of key information

Hydrocarbons, C9-C10, aromatics, >1% Naphthalene are a combination of Hydrocarbons, C9 Aromatics and Hydrocarbons, C10-C12 Aromatics. Read across data is available for Hydrocarbons, C9 Aromatics and Hydrocarbons, C10-C12 Aromatics and the worst case scenario for each end point has been presented.

 

The available data and available weight of evidence demonstrate that Hydrocarbons, C9 Aromatics and Hydrocarbon, C10-C12 Aromatics are highly unlikely to be carcinogenic and are not classifiable as carcinogens. However, Naphthalene is classified as a carcinogen Category 2 (H351) under Regulation (EC) 1272/2008 on classification, labelling and packaging of substances and mixtures (CLP).

Key value for chemical safety assessment

Carcinogenicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

There is no data available for Hydrocarbons, C9-C10, aromatics, >1% Naphthalene. Hydrocarbons, C9-C10, aromatics, >1% Naphthalene are a combination of Hydrocarbons, C9 Aromatics and Hydrocarbons, C10-C12 Aromatics. Based on the negative results from read across in vitro and in vivo genotoxicity assays, and weight of evidence from read across repeat dose toxicity studies, Hydrocarbons, C9-C10, aromatics, >1% Naphthalene do not warrant classification as carcinogens under Regulation (EC) 1272/2008 on classification, labelling and packaging of substances and mixtures (CLP). However, Naphthalene, a constituent of Hydrocarbons, C9-C10, aromatics, >1% Naphthalene is classified as a carcinogen Category 2 (H351) under Regulation (EC) 1272/2008 on classification, labelling and packaging of substances and mixtures (CLP).

Additional information

Hydrocarbons, C9-C10, aromatics, >1% Naphthalene are a combination of Hydrocarbons, C9 Aromatics and Hydrocarbons, C10-C12 Aromatics. Read across data is available for Hydrocarbons, C9 Aromatics and Hydrocarbons, C10-C12 Aromatics and the worst case scenario for each end point has been presented.

 

Hydrocarbons, C9 AromaticsandHydrocarbons, C10-C12 Aromatics:

The available data and available weight of evidence demonstrate that Hydrocarbons, C9 aromatics and Hydrocarbons, C10-C12 Aromatics are highly unlikely to be carcinogenic and are not classifiable as carcinogens.

 

The weight of evidence is derived from study records reported for the C10-C12 Aromatics, and the closely related C9 Aromatic solvents and high flash aromatic naphtha. Both the C10-C12 and related C9 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, both the C10-12 and the related C9 Aromatic solvents were not mutagenic in the presence or absence of metabolic activation (See C9 Aromatics IUCLID section 7.6.1 and the same section in this IUCLID). The C10-C12 aromatics were not clastogenic or anuegenic in vivo as evidenced by a negative rat erythrocyte micronucleus study (IUCLID section 7.6.2). This is concordant with the findings that high flash aromatic naphtha is also clearly not mutagenic, clastogenic or aneugenic in mammalian cells in vitro, and in rats in vivo as evidenced by: (a) a negative mammalian gene mutation (HGPRT forward mutation specific locus) assay; (b) negative chromosome aberration tests (Chinese Hamster Ovary Chromosomal Aberration Test, Chinese Hamster Ovary Sister Chromatid Exchange Assay); and (c) anin vivoinhalation exposure bone marrow chromosomal aberration study in rats (C9 Aromatics IUCLID sections 7.6.1 and 7.6.2).

 

The C10-C12 aromatics did not produce pre-neoplastic changes in any tissues during sub-chronic (90 day) repeat dose testing (IUCLID sections 7.5.1 and 7.5.3). Likewise, the closely related C9 aromatic solvents did not produce hyperplastic or pre-neoplastic changes in any tissues in sub-chronic (90 day) and chronic (12 month) repeat-dose studies. No test article-related lesions, including no cancer-relevant lesions, were found in extensive histological examinations of the tissues of rats chronically exposed to C9 aromatic solvents by inhalation for 6 hours per day, 5 days per week for 12 months (C9 Aromatics IUCLID section 7.5.3). Likewise, no test article-related lesions, including no cancer-relevant lesions, were found in extensive histological examinations of the tissues of rats sub-chronically exposed to C9 Aromatic and C10-C12 Aromatic solvents by inhalation for ≥ 90 days (IUCLID section 7.5.3).  Similarly, subchronic oral dosing with C10-C12 aromatic solvent did not produce pre-neoplastic changes and had a NOAEL of 300 mg/Kg bw/day (IUCLID section 7.5.1).

 

Notably, studies on the metabolism of ¹⁴C-1,2,4-trimethylbenzene, a prototypical C9 aromatic compound and a close relative of the compounds present in C10-C12 aromatic solvents demonstrated that > 99% of the administered radioactivity was excreted in urine within 24 hours following oral dosing.1 Little or no tissue-bound residual radioactivity was detected in this study, demonstrating that the metabolism of the C9 aromatic molecules, and their close relatives in the C10-C12 Aromatic solvents, do not bioaccumulate and are unlikely to result in the formation of DNA adducts or other associated DNA lesions.

 

1.Huo JZ, Aldous S, Campbell K, Davies N. Distribution and metabolism of 1,2,4-trimethylbenzene (pseudocumene) in the rat. Xenobiotica1989;19:161-170.