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Event




Chair:

Victor Johnson, Burleson Research Technologies




Co-Chair:

Marc Pallardy, Université Paris-Saclay




Primary Endorser: Immunotoxicology Specialty Section


Endorser(s): Dermal Toxicology Specialty Section




Endorser(s): In Vitro and Alternative Methods Specialty Section


Allergic contact dermatitis is an undesired side effect observed with many products, including cosmetics, natural extracts, drugs, chemicals, and medical devices. Over the last decades, a great deal of progress has been made in the development of alternative in vitro testing strategies to assess these issues, concurrent with the mechanistic understanding provided by the adverse outcome pathway (AOP) framework. The use of animals in toxicology is under ever-increasing scrutiny, with mounting pressureto develop effective alternatives. Efforts should be devoted to developing reliable in vitro assays and integrated testing strategies capable of addressing toxicity concerns for a broad spectrum of products and chemicals. This will require a better understanding of the applicability domains of scientifically validated assays and methods that are currently being used so that chemicals can be tested appropriately in these assays to produce valid predictions. In addition, accurate definition of the applicability domains will facilitate modification and improvement of current and new assays to expand these domains, resulting in better coverage of the chemical space for prediction of sensitization potential. The purpose of this Workshop is to cover current knowledge on the applicability domains of these methods, to understand their limitations and the opportunities they offer. The session will open with a brief introduction by the session Chair followed by five presentations aimed at defining the current state of the applicability domains for in vitro approaches as well as recent progress to expand these domains. The first speaker will present the current status of an international collaboration charged with establishing international test guidelines for nonanimal testing strategies that would serve as full replacements to the animal tests for skin sensitization. The approach includes using the current nonanimal methods within their applicability domains to model skin sensitization. The second speaker will define the applicability domains and limitation for the individual OECD Test Guidelines 442c, 442d, and 442e, which address chemical peptide reactivity, keratinocyte activation, and dendritic cell activation, respectively. A complete understanding of the influence of chemistry on these factors is critical for accurate predictions and improvement of current approaches to expand the applicable chemical space that can be tested without the use of animals. The third speaker will focus on in chemico assessment of peptide reactivity, presenting a characterization of the currently validated Direct Peptide Reactivity Assay (DPRA) approach while providing insight into the novel Peroxidase Peptide Reactivity Assay (PPRA), which holds promise to expand the applicability domain of peptide reactivity assays to include pre- and pro-haptens requiring metabolism. The forth speaker will provide initial data for a novel dendritic cell activation assay, the THP-1 Activation Assay, which is being developed to expand the applicability domain of the current in vitro dendritic cell activation assays to include drugs that exhibit limited or no cytotoxicity. The final speaker will introduce the state of the art for novel in vitro approaches based on transcriptional profiling and machine learning to predict sensitization potential. These assays are showing promise for addressing issues of difficult-to-test substances including hydrophobicity, metabolism, solubility, and formulation, and the GARDskin assay will be used to illustrate the progress. Overall, this Workshop aims to better defined the applicability domains for nonanimal sensitization testing and identify progress and opportunities for expanding these domains. This Workshop represents an international collaboration between the Immunotoxicology Specialty Section of SOT and the Immunotoxicology and Chemical Allergy Specialty Section of EUROTOX in an effort to communicate and improve the science of alternative approaches for assessing potential for skin sensitization.

Session and Activity Type
Workshop Sessions

Discussion