The direct peptides are the protein molecules that initiate the chain reactions that produce adducts in the skin and elicit the symptoms associated with sensitization. Although their direct pharmacological action is not fully understood, it has been shown that they act through the interaction with adrenergic receptors, and that they are involved in the modulation of neurotransmitter function.
In the DPRA-cys and kDPRA, the reactivity of the chemical to the cysteine peptide is assessed by measuring the percentage depletion (DP) of the peptide. The DP values generated are mathematically analysed to give the reactivity parameter logkmax, which is used to assign chemicals into UN GHS potency classes 1A or 1B/NS based on whether their kDPRA logkmax is greater than or less than -2. Both assays have significant limitations, mainly resulting from the fact that they do not assess the chemical’s potency and are based on an implicit assumption that the potency of a chemical is simply a single increasing function of its reactivity to the peptide.
Phthalic and trimellitic anhydrides are a very good illustration of why this implicit assumption is not valid. These anhydrides have high reactivity to the cysteine peptide, producing a significant level of adduct depletion in a short time period. However, the adduct is quickly hydrolysed and regenerates its sulphur nucleophile. This demonstrates that the DP value does not represent the reactivity of the anhydride to the peptide but, rather, its reactivity to the thioester formed by the reaction with the cysteine peptide.