Rapid Chemical Exposure and Dose Research
EPA is responsible for ensuring the safety of thousands of chemicals. Quantitative exposure data are available for only a small fraction of registered chemicals. This type of exposure data is needed to thoroughly evaluate chemicals for potential risks to humans, wildlife and ecosystems. EPA is developing innovative methods to develop exposure estimates for thousands of chemicals to better protect human health and the environment. These innovative methods are called rapid exposure and dose assessments.
Rapid Exposure Predictions
Rapid, also called high-throughput, exposure predictions or ExpoCast provide rapid exposure estimates for thousands of chemicals. ExpoCast quickly and efficiently looks at multiple routes of exposure to provide exposure estimates. ExpoCast uses and enhances two well-known exposure models to estimate chemical exposure.
- Farfield Exposure Models
Farfield exposure models are used to predict exposure from chemicals that are released into the outdoor environment through industrial releases. ExpoCast uses “off-the-shelf” models, USEtox and RAIDAR, for estimating outdoor environment exposures. These models estimate the average amount of chemical that gets into the air, water, and soil.
- Nearfield Exposure Models
Nearfield exposure models provide estimates of exposure to chemicals used in consumer products and in-home products. The model used to estimate the range of total chemical exposures in a population is the EPA’s Stochastic Human Exposure and Dose Simulation (SHEDS) model.
- SHEDS High-throughput: Models population-level distributions of exposure to near-field chemical sources. SHEDS-HT can produce a model for thousands of chemicals. This model accounts for the multiple routes, scenarios, and pathways of exposure to understand the total exposure to these chemicals while retaining population and life stage information. SHEDS-HT is useful for the quick evaluation of many chemicals as it has broad applicability, is flexible for what inputs are allowed, and can add new chemicals easily.
- SHEDS Exit: SHEDS estimates the range of total chemical exposures in a population from different exposure pathways (inhalation, skin contact, dietary and non-dietary ingestion) over different time periods, given a set of demographic characteristics. The estimates are calculated using available data, such as dietary consumption surveys; human activity data drawn from EPA's Consolidated Human Activity Database (CHAD) Exit; and observed chemical levels in food, water, air, and on surfaces like floors and counters. Data on chemical concentrations and exposure factors used in SHEDS are based on measurements collected in EPA field studies and published literature values. SHEDS is useful for considering all exposure scenarios.
Evaluating High-throughput Exposure Predictions
EPA is currently evaluating the effectiveness of high-throughput exposure models using the Systematic Empirical Evaluation of Models (SEEM) framework. The SEEM framework includes calibration and evaluation of the models using chemical concentrations found in blood and urine samples from the National Health and Nutrition Examination Study. EPA’s high-throughput models are continually refined as more data is gathered for consumer product use, non-targeted chemical exposure screening, and from estimates for oral doses. The SEEM framework allows for the systematic evaluation of whether additional data improves the exposure predictions.
Exposure Predictions for Varying Demographics and Life Stages
When evaluating the risk of chemicals, uncertainty exists in hazard identification and exposure predictions. There is also variability in exposure due to differences in key populations. General population exposure estimates are helpful, but population specific exposure values for children, older adults, and other key populations are needed to account for group level variability.
Compared to traditional pharmacokinetic approaches, high-throughput pharmacokineticspharmacokineticsDescribes how the body affects a specific chemical after administration through the mechanisms of absorption and distribution, as well as the chemical changes of the substance in the body (e.g. by metabolic enzymes such as cytochrome P450 or glucuronosyltransferase enzymes), and the effects and routes of excretion of the metabolites of the drug. Pharmacokinetic properties of chemicals may be affected by elements such as the site of administration and the dose of the chemical. These may affect the absorption rate. Pharmacokinetics is often studied in conjunction with pharmacodynamics, the study of a chemical’s effect on the body. (HTPK) provides a more rapid and less resource intensive method for understanding these population specific differences in exposure and dose. For example, there is biological variability in the rate that a chemical is cleared from the body across different age and ethnic subpopulations due to differing amounts and activities of metabolic enzymes. This method allows you to adjust exposure models to account for these population specific susceptibilities.
Consumer Product Information
High-throughput exposure predictions use a simple indicator of consumer product use. The high-throughput exposure models are being improved by adding more refined indoor and consumer use information. More refined consumer use information is available in the EPA Chemical and Product Categories database (CPCat). The database catalogs the use of over 40,000 chemicals and their presence in different types of consumer products. The chemical use information is compiled from multiple sources while product information is gathered from publicly available Material Safety Data Sheets (MSDS).
Non-Targeted Chemical Screening
Most exposure sampling techniques are chemical-specific and designed to test for chemicals that are suspected to be present. EPA researchers are developing “Non-Targeted Screening” methods to test indoor environmental samples such as dust for all chemicals present in the samples collected from the homes.