The Dermal Sensitisation Threshold- a TTC approach for allergic contact dermatitis.

The Threshold of Toxicological Concern (TTC) is a useful concept that is becoming of increasing interest as an addition to the arsenal of tools used for characterising the toxicological risk of human exposure to chemicals. Traditionally used for low level indirect additives, flavours and contaminants in foods, the TTC obviates the need for toxicological testing of chemicals where human exposure is low. Proposals have recently been made for the use of the TTC for low level ingredients in cosmetic and personal care products. However, use of the TTC is only protective for systemic toxicity endpoints, and cannot be used for local endpoints such as contact sensitisation. In this paper a probabilistic analysis of available sensitisation data, similar to that used in the development of the TTC, is presented. The incidence of sensitisers in the world of chemicals was estimated using the ELINCS (European List of Notified Chemical Substances) data set, and a distribution for sensitisation potency was established using a recently published compilation of Local Lymph Node Assay data. From the analysis of these data sets it is concluded that a Dermal Sensitisation Threshold (DST) can be established below which there is no appreciable risk of sensitisation, even for an untested ingredient. Use of a DST would preclude the need for sensitisation testing of ingredients where dermal exposure is sufficiently low.