Chemistry Services Supporting the Division of Translational Toxicology

National Institute Of Environmental Health Sciences

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Linked publications, trials & patents

Abstract

The DTT Office of the Scientific Director (OSD) establishes the vision, mission, and strategic direction of the division and provides administrative and operational support for DTT, ensuring the availability of personnel and fiscal resources to deliver on the strategic mission. This is accomplished by collaborative work across four offices. The Office of Program Operations (OPO) in OSD provides tactical support for the DTT research portfolio by coordinating and managing contract and interagency agreement research budgets and services, acquiring technical capabilities, and directing and managing the work of DTTs contract research organizations, including chemistry services contracts. Additionally, personnel in OPO serves as chemistry experts to the division designing, interpreting, and reporting data. Chemistry services required can vary from procuring and characterizing test articles (e.g., chemical agents, physical agents, complex mixtures) for in vivo (e.g., animal models) or in vitro (e.g., cell-based assays) studies, formulating test materials in suitable vehicles to administer in the test system, determining concentrations of test articles and/or metabolites in biological matrices (e.g., plasma), conducting ADME and TK studies in animal and in vitro models, to utilizing state of the art techniques to identify and quantify exposures (e.g., exposomics) and outcome (e.g., metabolomics and proteomics). Selected examples of projects designed, conducted, and/or completed during the current reporting period are given below Mixtures of polycyclic aromatic hydrocarbons and per- and polyfluorinated (PFAS) were prepared for in vitro and in vivo testing activities. A sensitive method was developed to simultaneously quantify multiple PFAS in plasma from animals dosed with these mixtures. DTT has been utilizing various in vivo, in vitro, and exploratory research (e.g., polypharmacokinetics, bioassay-guided fractionation) to generate data to aid in predicting potential adverse human health impacts of consuming botanical dietary supplements (BDS). Chemistry support for the BDS program included procuring, characterizing and formulating these r5variable complex mixtures including utilizing novel analytical techniques and approaches to characterize these materials. A TK study of alpha pinene following oral exposure in rats was completed to generate data to bridge between inhalation and oral exposures and to aid in predicting adverse human health effects. Research on 2-ethyl toluene (ET) was aimed at understanding metabolism following inhalation exposure in rodents to help explain differential toxicity between ET isomers. A pilot project was successfully completed to develop a non-targeted analysis (NTA) approach to identify environmental contaminants (i.e., exposomics) in plasma. Activities including procurement, characterization, formulation, and biosample analysis were completed supporting a 10-chemical project investigating cardiovascular toxicity. A TK study in rats were conducted to aid in the interpretation of animal toxicology study data on triphenyl phosphate, which is a flame retardant with ubiquitous human exposure. Two projects were also ongoing to generate data to aid in in vivo to in vivo extrapolation (IVIVE) conceptone focusing on in vitro disposition of xenobiotics and the other on extrapolating animal data to humans using the parallelogram approach. Activities were ongoing in support of various in vitro toxicity screening projects including, assay validationsup to 120 chemicals were procured, characterized, formulated, and shipped to collaborators.