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Biomedical subjects

Michael D Sohn

Publications and source records attributed to Michael D Sohn.

3 recordsLinked to original sources

Reconstructing population exposures from dose biomarkers: inhalation of trichloroethylene (TCE) as a case study.

Physiologically based pharmacokinetic (PBPK) modeling is a well-established toxicological tool designed to relate exposure to a target tissue dose. The emergence of federal and state programs for environmental health tracking and the availability of exposure monitoring through biomarkers creates the opportunity to apply PBPK models to estimate exposures to environmental contaminants from urine, blood, and tissue samples. However, reconstructing exposures for large populations is complicated by often having too few biomarker samples, large uncertainties about exposures, and large interindividual variability. In this paper, we use an illustrative case study to identify some of these difficulties, and for a process for confronting them by reconstructing population-scale exposures using Bayesian inference. The application consists of interpreting biomarker data from eight adult males with controlled exposures to trichloroethylene (TCE) as if the biomarkers were random samples from a large population with unknown exposure conditions. The TCE concentrations in blood from the individuals fell into two distinctly different groups even though the individuals were simultaneously in a single exposure chamber. We successfully reconstructed the exposure scenarios for both subgroups - although the reconstruction of one subgroup is different than what is believed to be the true experimental conditions. We were however unable to predict with high certainty the concentration of TCE in air.

Adult↗

Standardized approach for developing probabilistic exposure factor distributions.

The effectiveness of a probabilistic risk assessment (PRA) depends on the quality and relevance of the output from exposure and risk models, which, in turn, depends on the critical inputs to the assessment. These critical inputs are often in the form of probabilistic exposure factor distributions that are derived for the given risk scenario. Deriving probabilistic distributions for model inputs can be time consuming and subjective. The absence of a standard approach for developing these distributions can result in PRAs that are inconsistent and difficult to review by regulatory agencies. We present an approach that reduces subjectivity in the distribution development process without limiting the flexibility needed to prepare relevant PRAs. The approach requires two steps. First, we analyze data pooled at a population scale to (i) identify the most robust demographic descriptors within the population for a given exposure factor, (ii) partition the data into subsets based on these variables, and (iii) construct archetypal distributions for each subpopulation. Second, we sample from these archetypal distributions according to site- or scenario-specific conditions to simulate exposure factor values and use these values to construct the scenario-specific input distribution. The archetypal distributions developed through Step 1 provide a consistent basis for developing scenario-specific distributions so risk assessors will not have to repeatedly collect and analyze raw data for each new assessment. We demonstrate the approach for two commonly used exposure factors--body weight (BW) and exposure duration (ED)--using data that are representative of the U.S. population. For these factors we provide a first set of subpopulation-based archetypal distributions and demonstrate methods for using these distributions to construct relevant scenario-specific probabilistic exposure factor distributions.

Adolescent↗

Rapidly locating and characterizing pollutant releases in buildings.

Releases of airborne contaminants in or near a building can lead to significant human exposures unless prompt response measures are taken. However, possible responses can include conflicting strategies, such as shutting the ventilation system off versus running it in a purge mode or having occupants evacuate versus sheltering in place. The proper choice depends in part on knowing the source locations, the amounts released, and the likely future dispersion routes of the pollutants. We present an approach that estimates this information in real time. It applies Bayesian statistics to interpret measurements of airborne pollutant concentrations from multiple sensors placed in the building and computes best estimates and uncertainties of the release conditions. The algorithm is fast, capable of continuously updating the estimates as measurements stream in from sensors. We demonstrate the approach using a hypothetical pollutant release in a five-room building. Unknowns to the interpretation algorithm include location, duration, and strength of the source, and some building and weather conditions. Two sensor sampling plans and three levels of data quality are examined. Data interpretation in all examples is rapid; however, locating and characterizing the source with high probability depends on the amount and quality of data and the sampling plan.

Air Pollution, Indoor↗