A systematic search for structure-activity relationships of skin contact sensitizers: methodology.

A computerized resource for the systematic evaluation of the structure-activity relationships and other aspects of contact allergens is described. This resource consists of a data base of results of contact dermatitis tests and a structural classification scheme for contact allergens that is called a Structure-Activity (S/A) Tree. The data base now contains approximately 2200 test results extracted from the journal Contact Dermatitis (1975-1982) and is continually being expanded. The S/A Tree is being developed to provide an index to structure-activity relationships of contact allergens; 63 structural groups are currently indexed. Analyses of benzoquinones and gallic acid esters are presented as examples of the potential application of this resource to such problems as the identification of potential cross-reactants, appropriate test concentrations and vehicles, and the reliability of available test results.

The sensitizing capacity of the antioxidants propyl, octyl, and dodecyl gallate and some related gallic acid esters.

8 alkyl gallates, including the widely used antioxidants propyl, octyl, and dodecyl (= lauryl) gallate, have been subjected to experimental sensitization in guinea pigs. Using a modern sensitization procedure, the results showed that all gallates are moderate to strong contact sensitizers: dodecyl (= lauryl) gallate was found to be the strongest. A characteristic correlation between side chain length and mean response was observed, giving a maximum of sensitization at a length of 12 carbon atoms (dodecyl gallate). A literature review revealed that the frequency of reports of allergic contact dermatitis from antioxidants of the gallate type has increased in the last 4 years. In most cases, the moderate sensitizer propyl gallate was the source of sensitization.