Utilization of peptide reactivity assays for the prediction of skin sensitization

Abstract

Due to the current ban on animal testing, the need for robust and reliable animal alternative test methods is critical. Reactivity of chemical allergens with proteins has long been established as a key step in induction of skin sensitization. Based on this, two in chemico approaches have been developed: the Direct Peptide Reactivity Assay (DPRA) and the Peroxidase Peptide Reactivity Assay (PPRA). Both assays utilize synthetic peptides which contain either a single cysteine or lysine amino acid as its nucleophilic center for assessing skin sensitization potential of chemicals. Chemical reactivity is determined by using analytical methods to measure the depletion of free peptide following a 24-h incubation of test chemical and peptide. By comparing reactivity data to local lymph node assay data, prediction models have been developed for both assays. These models allow for making hazard predictions and binning a chemical into reactivity categories. The DPRA has been thoroughly evaluated for its reproducibility, transferability, and accuracy under formal validation studies. The PPRA has not yet reached validated status but is undergoing interlaboratory evaluation. Although showing good correlation to established animal models, the data obtained from both of these assays should be considered in combination with other information in the context of integrated approaches such as weight of evidence or integrated testing strategies.