Integrated Testing Strategies for Skin Sensitization Hazard and Potency Assessment—State of the Art and Challenges

Joanna Jaworska

doi:10.3390/cosmetics3020016

Abstract

The paper provides an overview of existing Integrated Testing Strategies (ITS) for assessing hazard and potency of skin sensitization. The ITS research is active, diverse and constantly evolving as new assays are being developed and new mechanistic insights are discovered. Despite the need to assess potency, the majority of the ITS approaches developed to date assess hazard only. Reasons for this situation are analyzed and include, for example, the dynamic range of existing alternative assays versus the range of in vivo responses, but also sporadic use of kinetic information and molar units. Depending on the application, regulatory or product development, standardized and nonstandard ITS approaches will be developed. Challenges to practical applications, with focus on regulatory are discussed.

Highlights

Skin sensitization is one of the critical endpoints when assessing cosmetic ingredients’ safety.Legislative changes increasingly mandate that skin sensitization potential be assessed with non-animal methods
The AOP for skin sensitization triggered by chemicals that bind covalently to proteins [9] includes four key events (KE) that occur after a substance penetrates through the skin and is potentially transformed into active metabolites: KE1: covalent binding to skin proteins; KE2: activation of inflammatory cytokines and induction of cyto-protective genes in the keratinocyte; KE3: activation and mobilization of dendritic cells in the skin; KE4: activation and proliferation of antigen-specific T-cells
The authors argued that this work demonstrates that skin sensitization potency prediction based on data from three key events, and often less, is possible, reliable over broad chemical classes, and ready for practical applications

Summary

Introduction

Skin sensitization is one of the critical endpoints when assessing cosmetic ingredients’ safety. Similar legislation may be proposed in the United States in 2015 [2] This resulted in acceleration of mechanistic understanding of skin sensitization [3,4] and many novel promising alternatives to animal testing tests [5]. The AOP for skin sensitization triggered by chemicals that bind covalently to proteins [9] includes four key events (KE) that occur after a substance (parent chemical or abiotically transformed product) penetrates through the skin and is potentially transformed into active metabolites: KE1: covalent binding to skin proteins; KE2: activation of inflammatory cytokines and induction of cyto-protective genes in the keratinocyte; KE3: activation (induction of inflammatory cytokines and surface molecules) and mobilization of dendritic cells in the skin; KE4: activation and proliferation of antigen-specific T-cells.

ITS Approaches State of the Art

Making Decisions with ITS

Challenges to Practical Applications of ITS