Avoiding contact allergens: from basic research to the in vitro identification of contact allergens

Abstract

Allergic contact dermatitis (ACD) is a chemical-induced inflammatory skin disease. Contact allergens are low-molecular-weight chemicals that must react with proteins in order to become immunogenic. This interaction leads to the activation of innate immune and stress responses and to the formation of antigenic epitopes for T cells which are the effector cells of ACD. Due to the multitude of chemicals that surround us in our daily life and their potential sensitizing capacity, it is crucial to identify contact sensitizers before these chemicals are used in consumer products. Appropriate in vitro assays for hazard identification are urgently needed to replace animal-based assays. The EU-wide ban on sensitization testing of cosmetic ingredients in animals is in effect since March 2009 and the necessity to test more than 30,000 already marketed chemicals for their sensitizing potential under the EU regulation REACh has intensified the worldwide efforts to replace animal testing. We summarize here the current strategies to develop a battery of assays which allows the identification of contact allergens by in vitro alternatives to animal testing. Our main focus lies on the test systems recently developed within the EU project Sens-it-iv in which we participate.

Keywords: contact dermatitis; in vitro assay; inflammation; innate immune system; skin.

Figure 1.. Steps leading to sensitization to contact allergens and in vitro assay development. In vitro assays for contact allergen identification must reproduce key steps of the sensitization phase of ACD. Skin penetration, protein modification and activation of innate immune and stress responses in the skin are followed by DC emigration and homing to skin draining lymph nodes. Contact allergens are presented on DC in the context of MHC molecules to T cells. These are primed and differentiate to effector T cells which exert their function after recruitment to the skin in the elicitation phase. The validated animal tests (GPMT, Buehler Test and LLNA) must be replaced by in vitro alternatives.

Figure 2.. Currently used terminology for categories of chemicals that cause contact dermatitis. Irritants have toxic effects on the skin and induce Irritant Contact Dermatitis (ICD) without triggering a T cell response. In contrast, contact allergens are protein-reactive haptens or pre- and pro-haptens that are converted to reactive haptens by (auto-) oxidation or metabolic activation. They activate the innate immune system due to their adjuvant effect and form antigenic T cell epitopes leading to Allergic Contact Dermatitis (ACD).