Risk-Based High-Throughput Chemical Screening and Prioritization using Exposure Models and in Vitro Bioactivity Assays.
We present a risk-based high-throughput screening (HTS) method to identify chemicals for potential health concerns or for which additional information is needed. The method is applied to 180 organic chemicals as a case study. We first obtain information on how the chemical is used and identify relevant use scenarios (e.g., dermal application, indoor emissions). For each chemical and use scenario, exposure models are then used to calculate a chemical intake fraction, or a product intake fraction, accounting for chemical properties and the exposed population. We then combine these intake fractions with use scenario-specific estimates of chemical quantity to calculate daily intake rates (iR; mg/kg/day). These intake rates are compared to oral equivalent doses (OED; mg/kg/day), calculated from a suite of ToxCast in vitro bioactivity assays using in vitro-to-in vivo extrapolation and reverse dosimetry. Bioactivity quotients (BQs) are calculated as iR/OED to obtain estimates of potential impact associated with each relevant use scenario. Of the 180 chemicals considered, 38 had maximum iRs exceeding minimum OEDs (i.e., BQs > 1). For most of these compounds, exposures are associated with direct intake, food/oral contact, or dermal exposure. The method provides high-throughput estimates of exposure and important input for decision makers to identify chemicals of concern for further evaluation with additional information or more refined models.
†Department of Public Health Sciences, University of California, Davis, California 95616, United States.
Hyeong-Moo
HM
Shin
‡Quantitative Sustainability Assessment Division, Department of Management Engineering, Technical University of Denmark, Kgs. Lyngby 2800, Denmark.|§Department of Environmental Health Sciences, University of Michigan, Ann Arbor, Michigan 48109, United States.
Alexi
A
Ernstoff
∥ARC Arnot Research and Consulting, Toronto, Ontario M4M 1W4 , Canada.|⊥Department of Physical and Environmental Sciences, University of Toronto, Scarborough, Toronto, Ontario M1C 1A4, Canada.|#Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Jon A
JA
Arnot
∇The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina 27709, United States.
Barbara A
BA
Wetmore
§Department of Environmental Health Sciences, University of Michigan, Ann Arbor, Michigan 48109, United States.
Susan A
SA
Csiszar
‡Quantitative Sustainability Assessment Division, Department of Management Engineering, Technical University of Denmark, Kgs. Lyngby 2800, Denmark.
Peter
P
Fantke
○Harvard School of Public Health and School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, United States.
Xianming
X
Zhang
◆Environmental Energy Technologies Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720 , United States.|¶School of Public Health, University of California, Berkeley, California 94720, United States.
Thomas E
TE
McKone
§Department of Environmental Health Sciences, University of Michigan, Ann Arbor, Michigan 48109, United States.
Olivier
O
Jolliet
†Department of Public Health Sciences, University of California, Davis, California 95616, United States.
Deborah H
DH
Bennett
D001681:Biological Assay; D019992:Databases as Topic; D004781:Environmental Exposure; D004784:Environmental Monitoring; D057166:High-Throughput Screening Assays / Q000379:methods*; D008962:Models, Theoretical; D018570:Risk Assessment