P38 Quantitative structure activity relationships for fragrance aldehydes
DA Basketter, Grace Y. Patlewicz, Elena Giménez‐Arnau, J.‐P. Lepoittevin · Contact Dermatitis · 2004
Fragrance substances represent a diverse group of chemicals, some being associated with the ability to cause allergic skin reactions. In recent work, we evaluated two groups of fragrance chemicals, saturated aldehydes (aryl substituted and aliphatic aldehydes) and ?,?‐unsaturated aldehydes. QSAR models relating the LLNA EC3 values to a measure of the lipophilicity of a chemical (log P) and s*(a measure of reactivity) were developed for both sets of aldehydes. The outcome was consistent with ?,?‐unsaturated aldehydes reacting via Michael addition, whilst saturated aldehydes formed Schiff bases with proteins. In the present study we evaluated further aldehydes to test the robustness and extend the scope of the QSARs. The QSAR models were used to predict EC3 values for 4 new Michael addition aldehydes and 6 new Schiff base formers. LLNA data generated for these compounds demonstrated the original QSARs were fairly accurate but still required improvement. Development of the QSAR models has provided us with a better understanding of the potential mechanisms of action for aldehydes and hence how to avoid or limit allergy. Knowledge generated from this project is being incorporated into new/improved rules for sensitisation in the expert toxicity prediction system Deductive Estimation of Risk from Existing Knowledge (DEREK).