Risk-based high-throughput chemical screening and prioritization using exposure models and in vitro bioactivity assays

Hyeong Moo Shin, Alexi Ernstoff, Jon A. Arnot, Barbara A. Wetmore, Susan A. Csiszar, Peter Fantke, Xianming Zhang, Thomas E. McKone, Olivier Jolliet, Deborah H Bennett

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)6760-6771
Number of pages12
JournalEnvironmental Science and Technology
Volume49
Issue number11
DOIs
StatePublished - Jun 2 2015

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bioactivity
prioritization
Bioactivity
Assays
Screening
Throughput
assay
Organic Chemicals
chemical
exposure
screening
Extrapolation
food intake
Chemical properties
Dosimetry
chemical property
Health

ASJC Scopus subject areas

  • Chemistry(all)
  • Environmental Chemistry

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Risk-based high-throughput chemical screening and prioritization using exposure models and in vitro bioactivity assays. / Shin, Hyeong Moo; Ernstoff, Alexi; Arnot, Jon A.; Wetmore, Barbara A.; Csiszar, Susan A.; Fantke, Peter; Zhang, Xianming; McKone, Thomas E.; Jolliet, Olivier; Bennett, Deborah H.

In: Environmental Science and Technology, Vol. 49, No. 11, 02.06.2015, p. 6760-6771.

Research output: Contribution to journalArticle

Shin, HM, Ernstoff, A, Arnot, JA, Wetmore, BA, Csiszar, SA, Fantke, P, Zhang, X, McKone, TE, Jolliet, O & Bennett, DH 2015, 'Risk-based high-throughput chemical screening and prioritization using exposure models and in vitro bioactivity assays', Environmental Science and Technology, vol. 49, no. 11, pp. 6760-6771. https://doi.org/10.1021/acs.est.5b00498
Shin, Hyeong Moo ; Ernstoff, Alexi ; Arnot, Jon A. ; Wetmore, Barbara A. ; Csiszar, Susan A. ; Fantke, Peter ; Zhang, Xianming ; McKone, Thomas E. ; Jolliet, Olivier ; Bennett, Deborah H. / Risk-based high-throughput chemical screening and prioritization using exposure models and in vitro bioactivity assays. In: Environmental Science and Technology. 2015 ; Vol. 49, No. 11. pp. 6760-6771.
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