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

Area of Science:

• Toxicology
• Risk Assessment
• Dermatology

Background:

• The Threshold of Toxicological Concern (TTC) is used to assess chemical safety for low-level exposure.
• TTC is traditionally applied to food additives, flavors, and contaminants.
• Recent proposals extend TTC to cosmetic and personal care ingredients.

Purpose of the Study:

• To evaluate the applicability of TTC principles to dermal endpoints, specifically skin sensitisation.
• To establish a Dermal Sensitisation Threshold (DST) for untested chemical ingredients.
• To reduce the requirement for dermal sensitisation testing in low-exposure scenarios.

Main Methods:

• Probabilistic analysis of existing sensitisation data.
• Estimation of sensitiser incidence using the European List of Notified Chemical Substances (ELINCS) dataset.
• Determination of sensitisation potency distribution using Local Lymph Node Assay (LLNA) data.

Main Results:

• A Dermal Sensitisation Threshold (DST) was established.
• Below the DST, there is no significant risk of dermal sensitisation.
• The DST concept is analogous to the TTC for systemic toxicity.

Conclusions:

• A DST can be reliably determined for chemical ingredients.
• The DST can obviate the need for sensitisation testing when dermal exposure is low.
• This approach enhances chemical risk assessment for dermal endpoints.