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Promises and challenges in constructing an adverse outcome pathway for chemical sensitization of the respiratory tract

: Sullivan, K.; Cochrane, S.; Enoch, S.; Kimber, I.; Patlewicz, G.; Roggen, E.; Sewald, Katherina; Ezendam, J.

ALTEX Proceedings 3 (2014), No.1, pp.55, Abstract II-1b-499
ISSN: 2194-0479
World Congress on Alternatives and Animal Use in the Life Sciences <9, 2014, Prag>
Fraunhofer ITEM ()

Increased interest in toxicological modes of action and a desire to develop mechanistically-based assays for improved characterization of toxic hazards has fueled interest in the OECD Adverse Outcome Pathway program. This program outlines and models AOPs to support the development of new regulatory tools for toxicology. One endpoint of particular regulatory interest is chemical sensitization of the respiratory tract, or chemical respiratory allergy. An expert group was formed to define an AOP for this endpoint. The group first aimed to identify commonalities and differences between chemical sensitization of the respiratory tract and skin sensitization resulting in allergic contact dermatitis. Important differences may include differential selectivity of protein binding, dendritic cell interactions, and the quality of immune responses associated with the acquisition of sensitization. However, experimental evidence confirming some of these differences may not always be available. Furthermore, determining the kinds of evidence to include in an AOP can be challenging. For example, should this AOP include relevant evidence from work with biological allergens, such as proteins? This presentation will give an overview of the AOP and discuss some challenges faced in its construction.