Risk-Based High-Throughput Chemical Screening and Prioritisation using Exposure Models and in Vitro Bioactivity Assays

During the present study, the authors presented 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. Firstly the authors obtained 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. These intake fractions were then combined 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 authors concluded that 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.

Authors: Shin HM, Ernstoff A, Arnot JA, Wetmore BA, Csiszar SA, Fantke P, Zhang X, McKone TE, Jolliet O, Bennett DH. ;Full Source: Environmental Science & Technology. 2015 Jun 2;49(11):6760-71. doi: 10.1021/acs.est.5b00498. Epub 2015 May 14. ;