Ranking of hair dye substances according to predicted sensitization potency: quantitative structure–activity relationships

Abstract

Allergic contact dermatitis following the use of hair dyes is well known. Many chemicals are used in hair dyes and it is unlikely that all cases of hair dye allergy can be diagnosed by means of patch testing with p-phenylenediamine (PPD). The objectives of this study are to identify all hair dye substances registered in Europe and to provide their tonnage data. The sensitization potential of each substance was then estimated by using a quantitative structure-activity relationship (QSAR) model and the substances were ranked according to their predicted potency. A cluster analysis was performed in order to help select a number of chemically diverse hair dye substances that could be used in subsequent clinical work. Various information sources, including the Inventory of Cosmetics Ingredients, new regulations on cosmetics, data on total use and ChemId (the Chemical Search Input website provided by the National Library of Medicine), were used in order to identify the names and structures of the hair dyes. A QSAR model, developed with the help of experimental local lymph node assay data and topological sub-structural molecular descriptors (TOPS-MODE), was used in order to predict the likely sensitization potential. Predictions for sensitization potential were made for the 229 substances that could be identified by means of a chemical structure, the majority of these hair dyes (75%) being predicted to be strong/moderate sensitizers. Only 22% were predicted to be weak sensitizers and 3% were predicted to be extremely weak or non-sensitizing. Eight of the most widely used hair dye substances were predicted to be strong/moderate sensitizers, including PPD - which is the most commonly used hair dye allergy marker in patch testing. A cluster analysis by using TOPS-MODE descriptors as inputs helped us group the hair dye substances according to their chemical similarity. This would facilitate the selection of potential substances for clinical patch testing. A patch-test series with potent, frequently used, substances representing various chemical clusters is suggested. This may prove useful in diagnosing PPD-negative patients with symptoms of hair dye allergy and would provide some clinical validation of the QSAR predictions.