Classification of dermal sensitizers under the globally harmonized system of classification and labelling of chemicals (GHS): A critical review of the principles and current challenges

The Globally Harmonized System (GHS) is a crucial framework for chemical hazard communication, especially in protecting workers from skin sensitizers. A critical assessment of the principles, issues, and challenges around classification of skin sensitization in GHS is warranted. Classification of dermal sensitizers relies on a weight of evidence (WoE) approach that incorporates human, animal, and non-test data. However, current testing methods have limitations in sensitivity, specificity, and predictive accuracy. Current test methods take into account the issue of potency and thresholds for sensitization. However, the focus on induction thresholds rather than induction and elicitation thresholds may create a gap in protecting already sensitized individuals since elicitation thresholds are in some cases lower than induction thresholds. While the sensitization process may take weeks or years, current test methods are largely acute in nature, potentially incapable of identifying all (chronic) sensitizers. Moreover, current methods used for classification of skin sensitizers only take into account the dermal route, whereas some chemicals may cause dermal sensitization through other routes, which presents a significant limitation, especially when considering non-animal testing methods. Finally, lack of UV irradiation in current methods may inadvertently miss potential photosensitizers, which may result in misclassification. Continuous refinement of testing methods and integrating novel approaches are essential to improve GHS classifications for skin sensitizers.