posted on 2015-12-17, 08:21authored byHyeong-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
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.