ADRA.
OECD TG 442C: Amino Acid Derivative Reactivity Assay
Amino Acid Derivative Reactivity Assay (ADRA) is an in chemico method that assesses the skin sensitization hazard of chemicals.
The assay evaluates a substance’s ability to react with synthetic model amino acid derivatives containing either lysine or cysteine, providing a binary classification that identifies test substances as either skin sensitizers or non‑sensitizers.
Targeting Key Event 1 of the skin sensitization AOP
ADRA is included in OECD Test Guideline 442C and addresses Key Event 1 (KE1) of the Adverse Outcome Pathway (AOP) for skin sensitization: covalent binding to skin proteins.
For poorly soluble and complex substances, replacing DPRA
Compared to peptide-based assays such as DPRA, ADRA uses amino acid derivatives, improving both solubility and analytical robustness.
- Improved solubility handling extends applicability to poorly soluble substances and complex mixtures and UVCBs, where peptide‑based systems may be limited.
- Support for fluorescence detection alongside UV improves detection of co‑eluting components in HPLC. This is particularly beneficial for complex mixtures.
Together, these features make ADRA a well-suited KE1 metod for poorly soluble and complex substances.
As with other KE1 assays, certain limitations remain. Substances requiring metabolic activation (pro‑haptens) or containing metals fall outside the assay’s applicability domain.
*Reference: OECD TG 442C, Appendix II
Defined approaches for “difficult-to-test” substances (OECD TG 497)
For regulatory testing of “difficult-to-test” substances under Defined Approaches for Skin Sensitization (DASS, OECD TG 497), use GARD®skin as the central method and combine it with ADRA, EpiSensA, and in silico methods to tailored testing strategies:
