Chemistry Services Supporting the Division of Translational Toxicology

National Institute Of Environmental Health Sciences

Investigators

Linked publications & trials

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 (e.g., NTA) 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. In support of a project investigating toxicity of brominated azo dyes (e.g., Disperse Orange 61, Disperse Blue 373, and Disperse Violet 93) using in vivo and invitro toxicity assays various chemistry support activities including chemical procurement, characterization, formulation development and formulation support, and biosample method development activities were either completed or ongoing. TK studies following exposure of rodents to thallium (1) sulfate via feed and drinking water were ongoing to bridge the toxicology study findings from thallium (1) sulfate drinking water studies to feed exposures. In support of a class study of investigating potential adverse effects of para phenylenediamines (PPDs) and their environmental degradation/transformation products (e.g., 6PPD-Q), a variety of PPDs and PPD-Qs were procured, characterized, and formulation method development was ongoing to support in vitro and in vivo studies. Activities were ongoing supporting a project identifying environmental contaminants (e.g., heavy metals, PFAS) using non-targeted analysis (NTA) approach (e.g., exposomics) in plasma. Multiple biosample analysis activites were completed supporting National Institute for Occupational Safety and Health projects. In support of mixtures of per- and polyfluorinated (PFAS) study investigating the effects following exposure to low/environmental levels of PFAS mixtures (environmental mixture) utilizing rodent models a project was completed to determine internal exposure to PFAS in >250 serum, plasma and liver samples. Few examples of chemistry support for other in vitro toxicity assay development are Cross platform evaluation on MPS-drug induced liver injury (DILI) model, Developmental Neurotoxicity (DNT) Phase 3. Development of hepatic models for slowly cleared environmental chemicals. Total number of chemistry activities to support the in vitro testing were > 100.