STUDIES TO EVALUATE THE POTENTIAL FOR ENVIRONMENTAL&THERAPEUTIC AGENTS TO INDUCE IMMUNOTOXICITY - In vivo

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The Division of Translation Toxicology (DTT) PAC Mixtures Assessment Program (PAC-MAP) provides the framework for assessing a breadth of individual polycyclic aromatic compounds (PACs), defined PAC mixtures, and complex PAC-containing environmental samples using an in vitro/short-term in vivo testing battery that includes a broad spectrum of endpoints. Select PACs have been associated with a wide range of toxicities (carcinogenicity, immunotoxicity, reproductive and developmental toxicity, neurotoxicity) and a complicated array of mechanisms of action. Many PACs have been associated with suppression of humoral immune function and immunotoxicity has been identified as an informative parameter for estimating the carcinogenic potential of PACs. As part of the potential testing battery to predict mixture effects, we have examined the potential for 13 individual PACs and 3 mixtures to modulate the antigen specific antibody response and affect bone marrow cytology. No in vivo immunotoxicology studies were started in FY23 and efforts were focused on reporting/archiving of studies conducted in previous contract years. BRT provided 2 final reports for PAC Mixtures completing the reporting of those studies. BRT completed an additional 3 draft reports for studies of the Immunotoxicity of Echinacea and Bisphenol F with final reports to be completed in contract year 10. In addition, BRT contributed leadership, data analysis and writing for 6 manuscripts, 3 of which were accepted for publication in FY23. Two manuscripts are in the NIH clearance process and several papers from the PAC-MAP studies are in preparation.