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.

A study of knowledge, attitude and practices regarding hair dye use among general population

“…The safety of hair dyes is being under continuous surveillance for the last many years. Hair dyes include a variety of coloring agents such as 2,7-naphthalenediol, 2 -aminomethyl-p aminophenol hydrochloride, 2-chloro-p-phenylenediamine and p-phenylenediamine which have been implicated in the etiology of various disorders [5]. Numerous researchers have reported life threatening adverse effects like renal toxicity and angioedema with their use apart from allergic contact dermatitis, whereas, a few studies have also linked hair dye use with the development of certain malignancies.…”

Self‐testing for contact sensitization to hair dyes – scientific considerations and clinical concerns of an industry‐led screening programme

“…Hair dyes are composed of a variety of chemicals, including strong skin sensitizers such as p-phenylenediamine (PPD) and toluene-2,5-diamine (p-toluenediamine, PTD) (7)(8)(9)(10). Contact allergy to PPD is fairly frequent among dermatitis patients, and the prevalence seems to be higher in central and southern Europe than in northern Europe (11)(12)(13).…”

A critique of the EC’s expert (draft) reports on the status of alternatives for cosmetics testing to meet the 2013 deadline

“…REACH; each model has to be validated TOPS-MODE used to screen 229 hair dyes according to OECD principles. (Søsted et al, 2004). CAESAR made 90% correct predictions on 42 chemicals (Chaundry et al, 2010).…”