The maximization test for skin sensitization potential--updating the standard protocol and validation of a modified protocol.

Since Magnusson and Kligman (1969) first described the maximization test, for assessing skin sensitization potential, the test has been substantially validated and data have been obtained on dose-activity relationships. The original method remains acceptable for qualified risk assessment but several modified protocols have been developed to overcome problems with particular test materials. A modified maximization test is described for compounds that are not soluble in the standard vehicles and, therefore, not injectable, and for formulations, to simulate user exposure conditions. The test compounds 2,4-dinitrochlorobenzene, p-phenylenediamine, 1-(3-chlorophenyl)-3- (4-chlorophenyl)-2-pyrazoline, formaldehyde, benzocain, penicillin G, benzylsalicylate, potassium dichromate and isoeugenol, all gave positive reactions. The incidences of positive reactions varied with the sensitization potentials of the compounds. The results for the first six compounds listed above were compared with those obtained by the standard procedure and were found to be similar. We propose that testing guidelines for skin sensitization should accommodate validated modifications of existing standard procedures.