EPA-Expo-Box (A Toolbox for Exposure Assessors)
(Biomonitoring and Reverse Dosimetry)
Determining intake dose for a particular receptor population is often difficult, but reconstructing exposure using biomarker data collected through biomonitoring is one solution to the problem. Reconstruction of exposure relies on biomarker measurements and intake and uptake predictions to estimate dose levels (U.S. EPA, 2012). There are two primary approaches for converting biomarker measurements to dose or environmental levels as recommended by NRC (2006): REVERSE DOSIMETRY and FORWARD DOSIMETRY (U.S. EPA, 2012).
Biomarker data, gathered through biomonitoring, can strengthen exposure assessment.
Biomonitoring involves analyzing tissues (including blood and hair), body fluids, excreta, or exhaled air to determine contaminant or biomarker concentrations (U.S. EPA, 1992). Biomarkers are cellular, biochemical, analytical, or molecular measures obtained from biological media (e.g., tissues, cells, fluids), that can indicate exposure to a chemical (U.S. EPA, 1992). A metabolite in urine, for example, may serve as a biomarker for exposure to the parent chemical. In vitro genomic data may indicate exposure by the genetic or other cellular responses to presentation of a stimulus or toxin.
Exposure Reconstruction, illustrated by the dark blue arrows in the figure, is the process of estimating an external exposure to a chemical that is consistent with and based on biomonitoring data. This reconstructive analysis, sometimes called reverse dosimetry, can be accomplished using pharmacokinetic (PK) models. PK models combine data about physiological and metabolic processes with biomarker concentrations or other biomonitoring data to mathematically estimate exposure or dose. This reconstruction can happen only after exposure has taken place and can be used to estimate exposure based on information from an effect or outcome or a target dose. The exact sources and pathways of exposure resulting in the biomarker concentration of the chemical cannot be determined by this method.
With the appropriate PK model, exposure reconstruction has the potential to provide the most accurate estimate of total exposure.
In the opposite direction, as discussed in the Indirect Estimation Module of EPA-Expo-Box, an exposure model can be used to estimate intake dose based on media or exposure concentrations and exposure factors; from there, a PK model can "predict" biomarker concentrations by combining physiological parameters with intake dose, as illustrated above by the light blue arrows.