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BIOMONITORING: INTERPRETATION AND USES
Citation:
SHELDON, L. S., M. K. MORGAN, AND J. D. PLEIL. BIOMONITORING: INTERPRETATION AND USES. Presented at Internation al Life Sciences Institute Annual Meeting, San Juan, PUERTO RICO, January 16 - 19, 2006.
Impact/Purpose:
1) Identify potential pathways of exposure for chemicals of interest based regulatory assumptions, product use labels and existing field study data.
2)Develop chemical or class specific PBPK/PD models suitable for biomarker analysis
3)Generate PBPK/PD model output to include simulation-based distributions of projected biomarkers from exposure time-histories.
4)Test biomarker data from human exposure field studies against the in silicoderived prior distributions of exposure to produce ?posterior? distributions.
5)Derive PK and PD dose metrics and calculate cumulative risks.
Description:
With advanced technologies, it is now possible to measure very low levels of many chemicals in biological fluids. However, the appropriate use and interpretation of biomarkers will depend upon many factors associated with the exposure, adsorption, deposition, metabolism, and elimination of these chemicals. Current ORD exposure research is directed toward developing the processes, tools, and information to put biomonitoring data into perspective for the risk assessment process, to define the appropriate uses of specific biomarkers, and to integrate biomarker measurements with exposure and internal dose. Modeling tools will be used to help select approaches for collecting biomonitoring data and to identify data gaps that limit interpretation. Measurement studies, modeling, and data analysis will be used to fill these knowledge gaps and to quantify the relationship between biomarkers, exposure, and internal dose. Modeling and advanced statistical analysis will be used to define the relationship between environmental concentrations and biomarkers. This information will be used to predict changes in biomarker concentrations that may result from changes in environmental concentrations. Research in metabonomics and genomics will allow us to develop and interpret biomarkers of effects resulting from exposures to environmental stressors and to identify sensitive phenotypes.
Results from this research program will allow the Agency to generate meaningful biomonitoring data and to make better use of the available data. Potential uses may include identifying susceptible populations, identifying emerging chemical risks, evaluating tends in exposures, conducting epidemiology studies, and evaluating the impact of risk reduction strategies.