Critical review of the relationship between IP346 and dermal carcinogenic activity

Report no. 6/16: The IP 346 method was adopted as a screening assay to predict the carcinogenicity of specific petroleum streams. Its application is based on a strong correlation with results from over 100 mouse dermal carcinogenicity studies, which were reported in a series of publications and formally documented in Concawe Report 94/51.

This correlation was used to establish the basis for defining a cancer hazard classification threshold for specific petroleum categories. It has been adopted in EU legislation through the use of note L as per the former Dangerous Substance Directive No 67/548 EC and continued in the Classification, Labelling and Packaging (CLP) Regulation (EC) No 1272/2008.

The purpose of this report is to review the current state of the science to determine if the IP 346 method continues to be fit for purpose to predict the carcinogenic potential of certain categories of petroleum streams. A systematic literature search was conducted to identify any new petroleum stream carcinogenicity studies published since 1994 that were correlated with IP 346 data.

Thirty-six new carcinogenicity study results were identified, with 29 of these on substances within the scope of the IP 346 method. With the addition of these new sample results and their complementary IP 346 test results, specificity and accuracy were not significantly changed, and most importantly, sensitivity was slightly increased to 93% for all petroleum streams, and increased to 86% for lubricant base oils.

Therefore, based on an analysis of the results of additional studies identified since publication of Concawe report 94/51, the IP 346 method and the original criteria developed in 1994 continue to be fit for purpose for the prediction of carcinogenic potential for lubricant base oils, treated distillate aromatic extracts and foots oils