Use of the modified Ames test as an indicator of the carcinogenicity of residual aromatic extracts

Report no. 12/12: Existing data demonstrate that residual aromatic extracts (RAEs) can be either carcinogenic or non-carcinogenic. CONCAWE had previously concluded that “Although limited data available indicate that some RAEs are weakly carcinogenic, it is not possible to provide a general recommendation. Classify on a case-by-case basis” (CONCAWE 2005).

Therefore CONCAWE’s Health/Toxicology Subgroup (H/TSG) has developed a proposal for the use of the modified Ames test as a short termpredictive screening tool for decisions on the classification of RAEs for carcinogenicity. The relationship between RAE chemistry and carcinogenic potential is not as well understood as it is for some other categories of substances, e.g. Other LubricantBase Oils (OLBO). However, a correlation has been found between the results of the skin carcinogenicity bioassay and the mutagenicity index (MI) obtained from the modified Ames test.

Data supporting this correlation are summarised in this report. The H/TSG confirmed that the modified Ames test can be used as a predictive screening tool and that a cut-off value can be established to make a distinction between carcinogenic and non-carcinogenic products. RAEs with a MI > 0.4demonstrated carcinogenic potential upon dermal application to mouse skin with chronic exposure. RAEs with a MI < 0.4 did not demonstrate a carcinogenic potential. To justify the use of the modified Ames test with RAEs, additional analysis of the repeatability of the test with RAEs was required. With this objective, CONCAWE sponsored a round robin study with different samples of RAEs from member companies, at three different laboratories.

The repeatability demonstrated in the round robin study with RAEs support the proposed use of the modified Ames test. As part of the tools available for use by member companies, the H/TSG proposed a standard operating procedure (SOP) (included as an Appendix to this report) on the conduct of the modified Ames test with RAEs. The H/TSG also prepared two special Oil Industry Notes (OINs) for use in cancer hazard classification. One OIN based on Dangerous Substances Directive (DSD) (OIN 9) and one based on Classification, Labelling and Packaging (CLP) regulation (OIN 10) have been adopted.