Integrated Use of Alternative Methods for Evaluating the Skin Sensitization Potencies of Five Frequently Used Preservatives in Cosmetics

In vitro skin sensitization testing methods based on the adverse outcome pathway(AOP)were used to evaluate the skin sensitization potencies of 5 commonly used preservatives.According to the"2 out of 3"principle of the integrated approaches to testing and assessment(IATA)the direct peptide reactivity assay(DPRA)and the human cell line activation test(h-CLAT)were used to detect the preservatives commonly used in cosmetics,including phenoxyethanol.methyl paraben,propyl paraben,imidazolidinyl urea and DMDM hydantoin.The DPRA and the h-CLA were carried out according to the OEC442C and 442E guidelines,respectively.The results show that.phenoxyethanol and methyl paraben are both negative in DPRA and h-CLAT while imidazolidinyl urea and DMDM hydantoin are both positive in these two tests.Propyl paraben has negative result in DPRA but positive result in h-CLAT.Therefore,imidazolidiny urea and DMDM hydantoin are sensitizers,while phenoxyethanol and methylparaben are non-sensitizers.Taken animal and human data into consideration,it is predicted that propyl paraben should be a non-sensitizer.The combination of DPRA and h-CLAT can make up for the limitations of using a single method,and it is suitable for the preliminary screening of cosmetic raw materials according to skin sensitization.