title: Prioritizing Environmental Chemicals for Obesity and Diabetes Outcomes Research: A Screening Approach Using ToxCast™ High-Throughput Data.
abstract: Diabetes and obesity are major threats to public health in the United States and abroad. Understanding the role that chemicals in our environment play in the development of these conditions is an emerging issue in environmental health, although identifying and prioritizing chemicals for testing beyond those already implicated in the literature is challenging. This review is intended to help researchers generate hypotheses about chemicals that may contribute to diabetes and to obesity-related health outcomes by summarizing relevant findings from the U.S. Environmental Protection Agency (EPA) ToxCast™ high-throughput screening (HTS) program.
  
  
  
  Our aim was to develop new hypotheses around environmental chemicals of potential interest for diabetes- or obesity-related outcomes using high-throughput screening data.
  
  
  
  We identified ToxCast™ assay targets relevant to several biological processes related to diabetes and obesity (insulin sensitivity in peripheral tissue, pancreatic islet and β cell function, adipocyte differentiation, and feeding behavior) and presented chemical screening data against those assay targets to identify chemicals of potential interest.
  
  
  
  The results of this screening-level analysis suggest that the spectrum of environmental chemicals to consider in research related to diabetes and obesity is much broader than indicated by research papers and reviews published in the peer-reviewed literature. Testing hypotheses based on ToxCast™ data will also help assess the predictive utility of this HTS platform.
  
  
  
  More research is required to put these screening-level analyses into context, but the information presented in this review should facilitate the development of new hypotheses.
  
  
  
  Auerbach S, Filer D, Reif D, Walker V, Holloway AC, Schlezinger J, Srinivasan S, Svoboda D, Judson R, Bucher JR, Thayer KA. 2016. Prioritizing environmental chemicals for obesity and diabetes outcomes research: a screening approach using ToxCast™ high-throughput data. Environ Health Perspect 124:1141-1154; http://dx.doi.org/10.1289/ehp.1510456.
authors.affiliation: Division of the National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Auerbach
authors.forename: Dayne
authors.initials: D
authors.lastname: Filer
authors.forename: David
authors.initials: D
authors.lastname: Reif
authors.forename: Vickie
authors.initials: V
authors.lastname: Walker
authors.forename: Alison C
authors.initials: AC
authors.lastname: Holloway
authors.forename: Jennifer
authors.initials: J
authors.lastname: Schlezinger
authors.forename: Supriya
authors.initials: S
authors.lastname: Srinivasan
authors.forename: Daniel
authors.initials: D
authors.lastname: Svoboda
authors.forename: Richard
authors.initials: R
authors.lastname: Judson
authors.forename: John R
authors.initials: JR
authors.lastname: Bucher
authors.forename: Kristina A
authors.initials: KA
authors.lastname: Thayer
mesh_terms: D016208:Databases, Factual; D003920:Diabetes Mellitus / Q000139:chemically induced* / Q000453:epidemiology; D004777:Environment; D004781:Environmental Exposure / Q000706:statistics & numerical data*; D004785:Environmental Pollutants / Q000592:standards / Q000633:toxicity*; D057166:High-Throughput Screening Assays; D006801:Humans; D009765:Obesity / Q000139:chemically induced* / Q000453:epidemiology; D017063:Outcome Assessment, Health Care; D018570:Risk Assessment; D014481:United States; D014484:United States Environmental Protection Agency
chemical_list: D004785:Environmental Pollutants