Copyright 2002 Marc Rigas Issues in Exposure Assessment Marc L. Rigas, Ph.D. National Exposure Research Laboratory, U.S. Environmental Protection Agency.
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Copyright 2002 Marc Rigas Issues in Exposure Assessment Marc L. Rigas, Ph.D. National Exposure Research Laboratory, U.S. Environmental Protection Agency This work has been prepared by the Environmental Protection Agency through its Office of Research and Development. It has been subject to Agency review and approved for presentation. Mention of trade names does not constitute endorsement or recommendation for use.
Copyright 2002 Marc Rigas Acknowledgements Jerry Blancato, Ph.D. (EPA) Elaine Cohen Hubal, Ph.D. (EPA) Miles Okino, Ph.D. (EPA) Clifford Weisel, Ph.D. –Environmental and Occupational Health Sciences Institute, Rutgers University
Copyright 2002 Marc Rigas Outline Organization of EPA Basic definitions regarding exposure Why do exposure assessment? Example: Current project
Copyright 2002 Marc Rigas DEFINITIONS Exposure –The contact with a chemical, biological, or physical agent at the boundary of the body over a specified time. Exposure Route –How a substance contacts the body and results in an internal dose (inhalation, ingestion, dermal penetration). Boundaries of the body –By ExposureRoute: For inhalation, could be the tissue in the lung separating air from blood. For ingestion, the layer of cells, lining the gastrointestinal tract.
Copyright 2002 Marc Rigas DEFINITIONS (cont.) Exposure Pathway –How a substance moves from the source to the receptor (in this case, people). Dose –Internal Dose: the amount of a substance crossing one of the route barriers into the body –Biologically-effective dose: the amount of a substance reaching a target organ.
Copyright 2002 Marc Rigas Why assess exposure? (Isn’t it EASY?!) Determine factors that put segments of the population at higher risk to chemical toxicity Help establish dose-response relationships in the “real world” Hazard = Toxicity x Exposure
Copyright 2002 Marc Rigas Uses of Exposure Assessment in Risk Assessment Used to estimate internal dose which, with dose response data (usually in animals), is used to estimate risk. For risk-based regulations, provides the link to emissions (point source, consumer products, area sources). Evaluation of efficacy of cleanup (risk to most exposed subgroup). Hazard Identification Dose-response assessment Exposure Assessment Risk Characterization Risk Communication
Copyright 2002 Marc Rigas From: Paustenbach, DJ. (2000) The practice of exposure assessment: a state-of-the-art review. J Toxicol Env Health, 3:179-291
Copyright 2002 Marc Rigas Use Exposure Assessment for Status and Trends Determine exposure at a particular place and time as well as trends over time. Provide a profile of a population or a population segment. Establish effectiveness of risk mitigation strategy (regulations).
Copyright 2002 Marc Rigas Exposure Assessment in Epidemiology A goal of epidemiology is to establish a dose-response relationship to a contaminant and to identify an exposed population. Improve the chances of identifying a valid dose-response relationship. Reduces misclassification in epidemiological studies.
Copyright 2002 Marc Rigas Use of Exposure Assessment in Epidemiology Case-Control studies: relates disease incidence to exposure by comparing health outcomes in a group that has exposure and one that doesn’t Biomarkers Reconstruction based on questionnaire –Questions asked concerning activities or locations that may result in exposure
Copyright 2002 Marc Rigas Population based studies Exposure reconstruction or assignment of exposure classification (i.e., high, medium, low) Personal monitoring –I.e. collect water at home along with water use information –Time period? Latency? Exposure modeling –Assess individual exposure OR generate a population base distribution for boundaries on risk assessment.
Copyright 2002 Marc Rigas Absorbed Dose Estimation From Biomarker Measurements Spot UrineTotal Urine with BloodTotal Urine Collect 3 spot urine samples: before the application event, 1 day after, and 3 days after. Collect total urine during study, blood at beginning and end of study period Collect total urine for 24 hours before, and 5 days after application event. Simplest collection protocolHigh burden placed on the subject Incorporate time-activity data Assume no other exposure occurs after the monitored event Assume a reliable PK model exists for compound Assume blood/body partitioning is known Assume half-life can determine the fraction of absorbed dose excreted by end of collection Exposure profiles modeled from time-activity data Assume background exposure before app. Highest model uncertaintyLeast model uncertainty
Copyright 2002 Marc Rigas Dose Reconstruction from Spot Urine Samples Concentration (U c ) Average Urinary Excretion Rate Absorbed Dose (D a ) U c is related toby the volume of the void (V u ) and time since last urination This observable quantity is related to the absorbed dose by the solution of the linear PK model: where the body compartment concentration (C i ) is given by:
Copyright 2002 Marc Rigas Model Uncertainty: Ranges in Total Absorbed Oral Dose Estimation Total Absorbed Chlorpyrifos Dose Spot urine w/ sample volume and time Ideal total urineIdeal total urine w/ Blood : g/kg body weight 2.0 – 10.22.6 – 8.92.6 – 8.0 Ideal total urine schemes assume that no exposure to chlorpyrifos occurred after studied event and that the blood/body partitioning is known exactly. Ideal total urine uncertainty will approach the w/blood uncertainty as collection period extended past 5 days