Michael H. Dong MPH, DrPA, PhD readings Human Exposure Assessment I (7th of 10 Lectures on Toxicologic Epidemiology)

Taken in the early ’90s, when desktop computers were still a luxury.

Learning Objectives Learn the definition, the purpose, and the function of human exposure assessment (HEA). Appreciate the dynamics and complexity of HEA. Study the basic techniques, the advantages, and the limitations of human biological monitoring.

Performance Objectives Able to define the key concepts and terms used throughout this lecture. To outline the advantages and limitations of human biological monitoring (HBM) in human exposure assessment. To explain why HBM cannot be performed for every agent or for every exposure scenario available.

Key Terms/Concepts Exposure assessment and exposure measurement are different processes. Exposure - the contact between an agent and a human’s outer boundary (the skin, the lung, etc.). Applied dose - the amount of the agent present at these outer boundaries. Internal dose - the total amount of the agent available or present in the body.

Toxicologists in Human Exposure Assessment HEA in toxicology textbooks is incomplete and fragmented, often as part of a chapter on risk assessment. Toxicologists are better trained to use animal models and bioassays. They have been working indirectly with those involved in HEA.

Epidemiologists in Human Exposure Assessment HEA is covered more fully in epidemiology textbooks, in part because it is performed mainly for environmental contaminants. HEA is not appealing to those epidemiologists who are more involved in etiology testing.

Simplified Complexity of Human Exposure Assessment (click for larger image)click for larger image Air Water Food Soil Surface Dietary Ingestion Dermal Inhalation

Case 1. Child Exposure at the Playground InhalationDietary IngestionDermal

Case 2. Swimmer Exposure at the Pool InhalationDietary IngestionDermal

Case 3. Harvester Exposure at the Field InhalationDietary IngestionDermal

Case 4. Applicator Exposure at the Field InhalationDietary IngestionDermal

Approaches to Human Exposure Assessment Two approaches to estimating the total daily exposure: indirect (IMM) and direct (DMM) measurement methods. IMM will be covered in the next lecture; DMM involve some form of human biological monitoring (HBM). HBM supposedly provides an estimate of the internal or aggregate dose.

Prerequisite of Human Biological Monitoring HBM relies on a knowledge of the chemical’s pharmacokinetics including absorption, elimination, disposition, etc. These kinetics can be used to estimate the percent recovery of the chemical. Numerous confounding factors and considerations are involved in HBM.

Example Calculation of Biomonitoring Data As illustrated here, absorbed dose can be back-calculated from a knowledge of its urinary (or other fluid) recovery. This type of back-calculation becomes more complicated if nonbolus dose (e.g., from dermal exposure) is considered. More technical considerations and procedures for human biological monitoring have been documented.

Advantages of Human Biological Monitoring Reduces uncertainties with animal dermal absorption and with other extrapolations. Reduces uncertainty with exposure events occurring concurrently. Has the ability to determine the efficiency of various protective measures (e.g., respirator, gloves).

Limitations of Human Biological monitoring HBM per se is not route-specific; hence not quite as useful for risk mitigation. The analysis and the handling of fluid samples require special care. Although urine collection seems to be less invasive, correction for incomplete urine excretion can be difficult. Pharmacokinetics data are often from studies using animals as test subjects.

Complications With Using HBM Data The chemical’s half-life in the human body is critical to the interpretation and use of human biological monitoring (HBM) data. The exposure history of the test subject must also be considered with care. Adjustment for percent recovery may or may not be necessary depending on the patterns of repeated exposures.

Impact of the Analytical Method Used Poor sensitivity or specificity can easily under- or over-estimate the (urinary) recovery 2- to 3-fold. As spot urine sample results are more practical, there are often problems with interpreting the urinary creatinine levels that are used to gauge the correction to a 24-hour or longer urine output.

Epidemiologists’ Superior Role in HEA Human exposure assessment (HEA) is a prerequisite of environmental and occupational epidemiology. Epidemiologists deal with human test subjects more often than toxicologists do. Epidemiologists are relatively more quantitatively oriented and trained.

Overview of Next Lecture Human Exposure Assessment II In many cases, indirect measurement methods (IMM) are necessary, which along with some exposure assessment models will be covered in the next lecture. IMM each typically consists of: (1) human contact; and (2) environmental concentrations.