STRUCTURE-ACTIVITY-RELATIONSHIPS IN SKIN SENSITIZATION USING THE MURINE LOCAL LYMPH-NODE ASSAY

Murine local lymph assay node data for 106 chemicals are listed. Among these, 73 are active in the assay indicating their potential as skin sensitizing agents. Broad structure activity relationships (SAR) are s uggested based on the electrophilic theory of skin sensitization sugge sted by Landsteiner and Jacobs in 1936, and elaborated by Dupuis and B enezra in 1982. Eight classes of agent are discerned; electrophiles, p otential electrophiles after metabolism, Michael-reactive agents, benz oylating agents, ionic chemicals and miscellaneous agents. The electro philic theory cannot at present fully explain the activity of agents i n the last two classes. That fact will hopefully focus research into t heir mode of action. Some chemicals fit equally into more than one cla ss, and such agents are entered into the several classes in order not to bias the analysis. Attention is given to why not all chemicals of a class are active in the assay. It is concluded that a combination of inappropriate lipophilicity, molecular size and metabolic detoxificati on are responsible for these inactivities. Given a sufficient number o f analogues tested within each class it should be possible eventually to predict with accuracy the skin sensitizing potential of new members of the class. However, the present analysis is qualitative, not quant itative. Finally, the parallelism between sensitizing potential and mu tagenic potential for chemicals is explored further.