Proposal for a risk assessment methodology for skin sensitization based on sensitization potency data.

In this paper, we propose a quantitative risk assessment methodology for skin sensitization aiming at the derivation of 'safe' exposure levels for sensitizing chemicals, used e.g., as ingredients in consumer products. Given the limited number of sensitizers tested in human sensitization tests, such as the human repeat-insult patch test (HRIPT) or the human maximization test (HMT), we used EC3 values from the local lymph node assay (LLNA) in mice because they provide the best quantitative measure of the skin sensitizing potency of a chemical. A comparison of LLNA EC3 values with HRIPT and HMT LOEL, and NOEL values was carried out and revealed that the EC3, expressed as area dose, can be used as a surrogate value for the human NOEL in risk assessment. The uncertainty/extrapolation factor approach was used to derive (a) an 'acceptable non-sensitizing area dose' (ANSAD) to protect non-allergic individuals against skin sensitization and (b) an 'acceptable non-eliciting area dose' (ANEAD) to protect allergic individuals against elicitation of allergic contact dermatitis. For ANSAD derivation, interspecies, intraspecies and time extrapolation factors are applied to the LLNA EC3. For ANEAD derivation, additional application of a variable sensitization-elicitation extrapolation factor is proposed. Values for extrapolation factors are derived and discussed, the proposed methodology is applied to the sensitizers methylchloroisothiazolinone/methylisothiazolinone, cinnamic aldehyde and nickel and results are compared to published risk assessments.