REACH alternative testing strategy for skin sensitization in practice: Fact or fiction?

Area of Science:

• Toxicology
• Chemical Safety

Background:

• The Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) Regulation mandates alternative testing strategies for skin sensitization.
• Industrial chemical safety assessments increasingly rely on non-animal testing methods.

Purpose of the Study:

• To evaluate the practical application of the REACH alternative testing strategy for skin sensitization.
• To assess the efficacy of a modified tiered approach for 50 industrial chemicals, including mono-constituent, multi-constituent, and Unknown or Variable Composition, Complex or Biological (UVCB) substances.

Main Methods:

• A tiered approach was employed, starting with in silico (Derek Nexus), Direct Peptide Reactivity Assay (DPRA), and KeratinoSens™ assays.
• Further testing involved the U-SENS™ assay for specific chemical types, with conclusions drawn from a weight of evidence approach.
• Testing strategies were adapted based on chemical complexity (mono-, multi-constituent, UVCB) and data requirements.

Main Results:

• A definitive conclusion on skin sensitization potential and potency was reached for 46% of the 50 tested substances using the non-animal strategy.
• In vivo testing remained necessary for 54% of substances due to discordant non-animal results or the need for reliable potency data.
• Validated non-animal methods currently lack sufficient skin metabolism simulation and potency indication compared to in vivo assays.

Conclusions:

• The current non-animal testing strategies show promise but require further refinement for comprehensive skin sensitization assessment.
• Significant challenges persist in testing UVCBs and multi-constituent substances, highlighting a gap in validated methods for these complex chemical categories.
• Addressing limitations in metabolism and potency assessment within non-animal assays is crucial for improving their regulatory acceptance and reducing reliance on in vivo studies.