New High Throughput Methods to Estimate Chemical Exposure

Description:

This SAP reviewed the use of EPA's ExpoCast model to rapidly estimate potential chemical exposures for prioritization and screening purposes. The focus was on bounded chemical exposure values for people and the environment for the Endocrine Disruptor Screening Program (EDSP) Universe of Chemicals. In addition to exposure, the SAP reviewed methods to extrapolate an in vivo dose from in vitro dose data. This involved presenting pharmacokinetic (PK) data for chemicals that have been run through a battery of high throughput endocrine screening assays and the methodology to use that PK information to estimate an in vivo dose. This exposure and RTK information along with high throughput in vitro bioactivity data will allow the EPA to assign a risk ranking to chemicals and prioritize them accordingly. ExpoCast is an EPA initiative to develop the necessary approaches and tools for rapidly prioritizing and screening thousands of chemicals based on the potential for human exposure. This focus for ExpoCast is distinct from many existing exposure tools that support regulatory risk assessment. Traditional exposure tools are lower throughput, requiring considerable data to make predictions of sufficient precision for a full risk assessment. ExpoCast efforts have focused on empirically assessing the uncertainty in forecasts made with limited available data, finding that in some cases even highly uncertain forecasts may be useful for prioritization and screening. In order to relate high throughput bioactivity data and rapid exposure predictions, an in vitro-in vivo extrapolation (IVIVE) via PK is needed. This IVIVE relates the in vitro compound concentrations (µM) found to be bioactive to the in vivo doses needed to produce serum concentrations equal to the in vitro concentrations. Without the time and resources necessary to generate in vivo PK data for the thousands of chemicals in the EDSP universe, high throughput pharmacokinetics (HTPK) can serve as a useful surrogate. HTPK methods were developed for pharmaceuticals to estimate therapeutic doses for clinical studies. HTPK technologies have been effective for pharmaceutical compounds and predicted concentrations are typically on the order of the measured in vivo concentrations. For non-therapeutic compounds in humans, PK data is not available and so it is essential to carefully characterize the predictive ability of the HTPK models and define the domain of applicability. High throughput exposure prediction and high throughput PK, when taken together with in vitro bioactivity profiling as a surrogate for hazard, will allow for a risk-based, rapid prioritization and screening of chemicals in the EDSP universe and beyond.

Contact: Steven Knott   (202) 564-0103   knott.steven@epa.gov  

Office: OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION

Full Record ID: 291980

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