A framework to mitigate the risk of chemical leukoderma: Consumer products

Abstract

Chemical leukoderma is an acquired depigmentation of the skin caused by repeated exposure to specific agents damaging to epidermal melanocytes. Case reports of chemical leukoderma have been associated with some consumer products. To date, there are no well-accepted approaches for evaluating and minimizing this risk. To this end, a framework is presented that evaluates the physical and chemical characteristics of compounds associated with chemical leukoderma and employs structure-activity relationship (SAR) read-across and predictive metabolism tools to determine whether a compound is at increased risk of evoking chemical leukoderma. In addition to in silico approaches, the testing strategy includes in chemico quinone formation and in vitro melanocyte cytotoxicity assays to dimension the risk as part of an overall weight of evidence approach to risk assessment. Cosmetic ingredients raspberry ketone, undecylenoyl phenylalanine, tocopheryl succinate, p-coumaric acid, resveratrol, resveratrol dimethyl ether, sucrose dilaurate, tranexamic acid, niacinamide and caffeic acid are evaluated in this framework and compared to positive controls rhododendrol and hydroquinone. Overall, this framework is considered an important step toward mitigating the risk of chemical leukoderma for compounds used in consumer products.

Keywords: Hydroquinone; Leukoderma; Melanocyte toxicity; Quinone; Rhododendrol; SAR read-Across; Tyrosinase.