direct peptides are synthetic peptides that have an essential cysteine-containing amino acid for forming covalent, non-redox-active, disulfide linkages with the thiol groups of protein and lipid molecules. They are used as model systems for understanding how peptide hormones such as insulin and leucine enkephalin interact with neuronal structures of the central nervous system.

The kinetic direct peptide reactivity assay (kDPRA) and its cys version the DPRA-cys are OECD TG 442C in vitro skin sensitisation tests that determine the reactivity of chemicals with a synthetic cysteine-containing peptide and the resulting peptide depletion (i.e. logkmax) and assign the chemical to UN GHS potency class 1A or 1B/NC, depending on whether the kDPRA prediction is greater than or less than -2. A DPRA prediction is based on a rate constant determined from the data analysis protocol for the peptide depletion and a chemical’s reactivity with this peptide. The true rate constant, however, cannot be directly predicted from DPRA results and can only be inferred with considerable uncertainty. This limits the sensitivity and specificity of kDPRA.

It also means that chemicals that do not give stable adducts with the peptide can be wrongly predicted to be sensitisers because of their reactivity with the peptide (although a very few have a low DP value despite this). In addition, some aldehydes such as trimellitic and phthalic anhydrides as well as chlorpromazine can be classified as potent sensitisers by the kDPRA but do not give significant adducts with the peptide because they have special chemistry and are not reactive.

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