Biomarkers for Cumulative Risk

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The Issue | Science Objectives | Research Highlights | Impact and Outcome

The Issue

With advanced technologies, it is now possible to measure very low levels of many environmental chemicals or their metabolites in biological fluids. Although detection of a specific biomarker provides information that exposure has occurred, it often provides little information to determine whether there is a health risk, or what the levels, sources, or pathways of exposure might be. The Centers for Disease Control and Prevention (CDC) and other health researchers obtain data on a variety of biomarkers of exposure in the U.S. population through the National Health and Nutritional Examination Survey. EPA has been called on to interpret the CDC data in terms of both exposure and health outcomes.

The research outlined in this area will augment biomonitoring activities by the CDC and others by providing fundamental information to define the appropriate uses of biomarkers of exposure, determine what additional measurements and information are required to interpret biomarker data, and link the results from groups of individuals to the general population. It will provide the tools and information that will enable the Agency to use biomonitoring data to inform important public health decisions.

Science Objectives

The overall goal of this research effort is to develop the processes, tools, and information for using biomarker data to assess cumulative risks to environmental pollutants. Specific research focuses on using pharmacokinetic (PBPK) models to interpret biomarker data; understanding the biochemical and mathematical relationships among biomarkers, exposures, and internal dose for nonpersistent chemicals; and linking exposure to health effects using a systems biology approach.

Research Goals:

Develop and use PBPK models to estimate target tissue dose from biomarker measurements
Develop and use PBPK and classical pharmacokinetic models to reconstruct exposure and environmental concentration from biomarker measurements
Use mathematical and statistical methods to describe the relationship between exposure measurements and biomarker data and interpret inter- and intrapersonal differences
Develop and apply low-burden methods (i.e., saliva, breath) for collecting biomarker data
Assess the variability of biomarker measurements over time
Develop tools for guiding the collection of biomarker samples for future studies
Integrate biomarkers of susceptibility with other tools, including PBPK models, to evaluate difference in dose and health outcomes for similar exposures

Research Highlights

Advanced statistical analysis and modeling are being conducted on data from previous exposure studies to determine the relationship between a biomarker and the external measurement data, as well as the factors that impact that relationship. Results have demonstrated the importance of dietary exposures for many chemicals, the impact of activities and sources of exposure, and improvements that will be needed in various assumptions and protocols to more accurately estimate exposures and dose.
PBPK models are being developed and applied to estimate exposure and dose for a variety of chemicals, including chloropyrifos and 2,4-dichloroacetic acid. Models are being developed to refine measurement protocols for future studies.
New low-burden methods for measuring biomarkers of exposure and effect in saliva and breath are being developed and applied as a proof of concept. These methods will be applied to larger scale field studies in the future.
Cumulative exposure measurements from diesel exhaust experiments are being conducted to assess metabolic changes reflected in blood-borne and exhaled-breath biomarkers.

Impact and Outcomes

Human Health Research Contributions: