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 chemicalsmore »
- Univ. of California, Davis, CA (United States)
- Technical Univ. of Denmark, Lyngby (Denmark). Quantitative Sustainability Assessment Div.; Univ. of Michigan, Ann Arbor, MI (United States). Dept. of Environmental Health Sciences.
- ARC Arnot Research and Consulting, Toronto, Ontario (Canada); Univ. of Toronto, Ontario (Canada). Dept. of Physical and Environmental Sciences and Dept. of Pharmacology and Toxicology.
- The Hamner Institutes for Health Sciences, Research Triangle Park, NC (United States)
- Univ. of Michigan, Ann Arbor, MI (United States). Dept. of Environmental Health Sciences.
- Technical Univ. of Denmark, Lyngby (Denmark). Quantitative Sustainability Assessment Div.
- Harvard Univ., Cambridge, MA (United States). Harvard School of Public Health and School of Engineering and Applied Sciences.
- Lawrence Berkeley National Lab., CA (United States). Environmental Energy Technologies Div.; Univ. of California, Berkeley (United States). School fo Public Health.
- Publication Date:
- Grant/Contract Number:
- Accepted Manuscript
- Journal Name:
- Environmental Science and Technology
- Additional Journal Information:
- Journal Volume: 49; Journal Issue: 11; Journal ID: ISSN 0013-936X
- American Chemical Society (ACS)
- Research Org:
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
- Sponsoring Org:
- American Chemistry Council
- Country of Publication:
- United States
- 63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
- OSTI Identifier: