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

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The 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. In particular, 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 individual PACs to modulate the antigen specific antibody response and affect bone marrow cytology. Final reports for two PAC-MAP studies, were received in FY19. Draft reports for three additional compounds, dibenzothiophene, chrysene, dibenzo(a,l)pyrene have been reviewed by the NTP and are expected to close in Q1FY20. Studies evaluating defined mixtures of PACs began in Q4FY19. Final reports have been received for the assessment of the potential systemic immunotoxicity following inhalation exposure to multiwalled carbon nanotubes in adult mice and rats, and oral exposure to sodium metavandate and NTP reporting is in progress. Developmental immunotoxicology studies on the flame retardant Tris(Chloropropyl) phosphate and the plasticizer N-Butylbenzenesulfonamide have been completed and the reports for these studies are under review.