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20190715 - Establishment of a Reference Chemical Database to Evaluate In Vitro and In Silico Approaches to assess Respiratory Sensitization to Facilitate Development of IATA (ICTXV)
Citation:
Sullivan, K., N. Baker, S. Cochrane, S. Enoch, J. Ezendam, G. Patlewicz, E. Roggen, R. Settivari, AND K. Sewald. 20190715 - Establishment of a Reference Chemical Database to Evaluate In Vitro and In Silico Approaches to assess Respiratory Sensitization to Facilitate Development of IATA (ICTXV). The International Union of Toxicology International Congress of Toxicology XV (ICTXV), Honolulu, Hawaii, July 15 - 18, 2019.
Impact/Purpose:
Abstract submitted to the International Union of Toxicology International Congress of Toxicology XV (ICTXV) held July 2019. This presentation outlines our approach to build a comprehensive database which would serve as a list of reference chemicals to facilitate the assessment of testing approaches. The resulting chemical list, which will be shared with regulatory agencies and the public, is an important step towards the assessment of potential test methods and the creation of internationally-harmonized integrated approaches for the detection of chemical respiratory sensitizers.
Description:
Currently no single method or strategy is generally accepted for the detection of respiratory sensitizers, despite public health and regulatory needs. An Adverse Outcome Pathway (AOP) for respiratory tract sensitization by low molecular weight organic chemicals has been published and is proceeding through the Organization for Economic Cooperation and Development review process. The AOP identified several promising in vitro and in silico test methods and combinations thereof which could form the bases for Integrated Approaches to Testing and Assessment (IATA); however most of these have only been assessed with a few well-known respiratory sensitizers (e.g., toluene diisocyanate or trimellitic anhydride). This presentation outlines our approach to build a comprehensive database which would serve as a list of reference chemicals to facilitate the assessment of testing approaches. We aim to cover a range of chemical classes and include “challenging” chemicals, such as respiratory sensitizers thought to elicit effects through dermal exposure and those for which specific-IgE has not been detected in humans. We first conducted a review of established structure-based profilers, recent literature, and human clinical reports, focusing on data verified in humans for translatability to human health outcomes. To allow for a weight of evidence analysis, we are collecting all data but qualifying the data to reflect quality. We are also making use of the Abstract Sifter literature review tool (Baker et al., 2007) to identify additional potential respiratory sensitizers. Briefly, a set of PubMed MeSH terms describing adverse effects (AEs) for 92 known sensitizers was used to query a large database of chemicals and AEs, yielding over 7000 chemicals of potential interest. Work is ongoing to identify query terms which yield the most relevant papers. The resulting chemical list, which will be shared with regulatory agencies and the public, is an important step towards the assessment of potential test methods and the creation of internationally-harmonized integrated approaches for the detection of chemical respiratory sensitizers. This does not necessarily represent U.S. EPA policy.