The Exposure Concept

Overview

Exposure assessment dates back at least to the early twentieth century, and perhaps before, particularly in the fields of epidemiology, industrial hygiene, and health physics (Armstrong et al., 1991; Lioy PJ, 1990; EPA, 1992; WHO, 2000). Exposure assessment is a key component of the public health evaluation of diseases since it is often hypothesis-driven research that seeks to determine health effects of exposure to various harmful agents. In the context of assessing health effects of disaster and bioterrorism, conducting exposure assessment is a must.

Objectives

By the end of this lesson, you should be able to:

• Explain the concept of exposure including:
  • Exposure intensity
  • Exposure frequency
  • Exposure duration
  • Microenvironment, exposure pathways, and exposure routes
• Differentiate among exposure, applied dose, potential dose, internal dose, and biologically effective dose
• Identify an appropriate exposure assessment approach, choosing between point-of-contact measurement, scenario evaluation, and reconstruction

The Exposure Concept: Road Map

Note: The purpose of the Lesson Road Map is to give you an idea of what will be expected of you for this lesson. You will be directed to specific tasks as you proceed through the lesson. Each activity in the To Do: section will be identified as individual (I), team (T), graded (G).

To Read

• Lioy PJ, et al. Defining Exposure Science. J Expo Anal Environ Epidemiol 15, 2005.

• Lioy PJ and Gochfeld M. Lessons learned on environmental, occupational, and residential exposures from the attack on the World Trade Center. American Journal of Industrial Medicine 42:560-565, 2002.

To Do

In this lesson you will complete the following activities:

1. The Exposure Concept: Lesson Review Worksheet
2. Misconceptions around Human Exposure
3. 9-11 Lessons Learned

Topics

• Continuum from Emission of an Agent to a Health Effect
• Exposure Assessment
  • Concepts of Exposure, Intake, Uptake, and Dose
  • Exposure Pathways
  • Exposure Routes
  • Definitions of Applied Dose, Potential Dose, Internal Dose, and Biologically Effective Dose
  • Calculation of Doses
  • Approaches to Quantification of Exposure

Continuum from Emission of an Agent to a Health Effect

In the context of exposure assessment, an investigator needs to look at data from the source of an agent of interest to time-activity pattern data of populations under study simultaneously to identify susceptible populations (Wallace LA, 1995). Characterizing major components of the continuum of source-exposure-dose-health effects is a must (Lioy PJ, 1990). (See Figure 1 below.) For example, the source data provide a profile of agents and emission rate of agents; and time-activity pattern data tell us how each of the individuals in the population contact the agents, as well as the frequency and intensity of those contacts (EPA, 1992).

Figure 1-1: Continuum from Emission of an Agent to a Health Effect

Adapted from Lioy, 1990

 

Introduction to Exposure Assessment

Definition of Exposure Assessment

Exposure assessment is defined as the science that describes how an individual or population comes in contact with an agent, including quantification of the amount of the agent across space and time, for individuals and populations (Lioy, 1990).

Human exposure requires the “simultaneous occurrence of two events: the presence of an agent at a particular point in space and time and the presence of a person at the same location and time” (WHO, 2000). Once exposure has occurred, a continuum of biologic changes can be detected. These changes may serve as markers of the initial exposure, internal dose, biologically effective dose, altered structure or function with no ensuing pathologic effect, or potential or actual disease (EPA, 1992; WHO, 2000).

In the field of exposure assessment, the human body is regarded as having a hypothetical outer boundary which separates the inside of the body from the outside of the body (EPA, 1992). As used in this class, exposure to an agent is the contact of that agent with the outer boundary. An exposure assessment is the quantitative or qualitative evaluation of the intensity, frequency, and duration of contact, and often evaluates the rates at which an agent crosses the boundary (agent intake or uptake rates), the routes by which it crosses the boundary (e.g., oral, inhalation, dermal), and the resulting amount of the agent that actually crosses the boundary (a dose) and the amount absorbed (internal dose) (EPA, 1992; WHO 2000).  

Process of an Agent from Environment to Human Body

There are two steps in the process of an agent entering the human body: contact (exposure), followed by actual entry crossing the boundary including an absorption (EPA, 1992). The absorption leads to the availability of an amount of the agent to target organs or cells within the body (internal dose) (WHO, 2000).

The process of an agent entering the body can be described in two types, intake and uptake (EPA, 1992). Intake is a process of physical moving an agent under study through an opening in the outer boundary (usually the mouth or nose), typically through inhalation, ingestion, or drinking (WHO, 2000). In most of cases, the agent is contained in an environmental medium (e.g., air, food, or water). To estimate the amount of the agent entering into the human body focuses on the amount of the carrier medium enters (EPA, 1992). During the intake, mass transfer occurs by bulk flow, and the amount of the agent itself crossing the boundary is described as an agent intake rate (Kathryn et al., EPA, 1992). The agent intake rate is the amount of an agent crossing the outer boundary per unit time, and is the product of the exposure concentration times the ingestion or inhalation rate (Aronson et al., 2000; Backer et al., 2005). Ingestion and inhalation rates are the amount of the carrier medium crossing the boundary per unit time, such as m³ air breathed/hour, kg food ingested/day, or liters of water consumed/day (WHO, 2000). Ingestion or inhalation rate is not constant over time (Baldauf et al., 2006; Bouvier et al., 2006).

The second process is uptake. Uptake is a process of absorption of the agent through the skin or other exposed tissue such as the eye (WHO, 2000). Although the agent is often contained in a carrier medium (e.g., air, water, and, and soil), the medium itself usually is not absorbed at the same rate as the agent (Hoppin et al., 2006). Therefore, estimates of the amount of the agent crossing the boundary cannot be made in the same way as for intake (EPA, 1992). Dermal absorption is an example of direct uptake by which an agent crosses the boundary from outside to inside the body (Hoppin et al., 2006). An agent uptake rate is the amount of the agent absorbed per unit time (Lioy PJ, 1990; Wallance LA, 1995). In this process, mass transfer occurs by diffusion, so uptake can depend on the concentrations gradient across the boundary, permeability of the barrier, and other factors (EPA, 1992). Agent uptake rates can be expressed as a function of the exposure concentration, permeability coefficient, and surface area exposed, or as a flux (Lioy, 1990). Table 1-1 summarizes concepts and dose terms for dermal, inhalation, and ingestion exposures (EPA, 1992).

Table 1-1: Summary of concepts and dose terms for dermal, inhalation, and ingestion exposures

Variables	Definitions	Typical units
Exposure	Contact with a chemical, biological, physical agent at the boundary of the human body over a specified time period	Dermal: water = (mg/L)·(hrs of contact) or Soil = (mg/kg)·(hrs of contact) Inhalation: Air = (ppm) ·(hrs of contact) or (µg/m3)·(days of contact) Ingestion: Water = (mg/L)·(min of contact), or (mg/kg)·(min of contact)
Potential dose	Amount of an agent deposited on a surface such as food ingested, air breathed, or soil applied to the skin	Dermal: Soil = (mg/kg)· (kg on skin) = mg in soil applied to skin Inhalation: Air = (µg/m3)·(m3 breathed/min) x (min exposed) = µg agent in air breathed Ingestion: Water = (mg/L)·(L consumed/day) x days exposed = mg ingested in water (also dose rate: mg/day)
Applied dose	Amount of an agent that is available to be absorbed in the absorption boundaries (e.g., skin, lungs gastrointestinal tract)	Dermal: Soil = (mg/kg)·(kg directly touching skin) x (% of agent in soil actually touching skin) = mg actually touching skin Inhalation: Air = (µg/m3) ·(m3 directly touching lung) x (% of agent actually touching lung) = mg actually touching lung barrier Ingestion: Food = (mg/kg)·(kg consumed/day) x (% of agent touching digestion tract) = mg actually touching digestion tract absorption barrier
Internal dose	The amount of an agent across body boundary through either physical or biological process	Dermal: Soil = mg absorbed through skin Inhalation: Air = mg absorbed through lung Ingestion: Food = mg absorbed through ingestion tract Dose rate = mg absorbed/day or mg/kg day)
Biologically effective dose	Amount of agent reaching tissue, organ, or cell	mg available to an organ or a cell Dose rate = mg/day
Note: ppm = parts per million Data source: Data source: U.S. EPA, 1992. Guidelines for Exposure Assessment.

Examples of Dose Calculation

Potential dose for intake processes

The general equation for potential dose for intake processes, e.g., inhalation and ingestion is the integration of the agent intake rate (concentration of the agent in the medium (C) times the intake rate of the medium IR) over time (WHO, 2000):

(Equation 1-1)

Internal dose for uptake processes

For absorption processes, there is a method generally in use for calculating internal dose. This method is commonly used for dermal absorption from a liquid where at least partial immersion occurs (WHO, 2000; EPA, 1992).

(Equation 1-2)

Where D_int is an internal dose, C(t) is the agent concentration, K_p is the permeability coefficient, and SA is the surface area exposed. The equation is similar to Equation 1-1 except that the agent uptake rate (C · K_p · SA) replaces the agent intake rate (C · IR).

Methods of Exposure Quantification

There are three approaches of estimating exposure quantitatively. These three approaches are illustrated below (WHO, 2000; EPA, 1992):

• Point-of-contact measurement
• Scenario evaluation
• Reconstruction

Point-of-Contact Measurement

The exposure is measured at the outer boundary of the human body (point of contact) while it is taking place (Baldauf, et al., 2006). This approach measures both the time of contact and exposure concentration and integrating them.

A typical example of the point-of-contact measurement is the radiation dosimeter (EPA, 1992). The small badge-like device measures exposure to radiation as the exposure occurs. The device provides an integrated estimate of exposure for the period of time over which the measurement has been taken (WHO, 2000). Another example is the carbon monoxide (CO) point-of-contact measurement studies where subjects carry a small CO monitor for several days (EPA, 1992). The other examples are dermal patch studies and duplicate meal studies (Hoppin et al., 2006). Table 1-2 below shows examples of estimating exposure using the point-of-contact approach.

Table 1-2. Examples of Exposure Using the Point-of-Contact Approach

Type of measurement	Characterization	Needed information	Examples
Air pump/vapors and particles	Exposure via air medium	Duration of sample, representativeness of the sampled population	Baldauf, et al., 2006
Passive samplers for vapors	Same as above	Same as above	Lebret et al., 2000
Split food/water samples	Exposure via ingested media	Amount of media ingested, and representativeness of the population	Kathryn et al., 2006
Skin patch samples	Exposure via dermal contact	Duration of sample, skin penetration, and the population representativeness	Hoppin et al., 2006

The above table was developed based on EPA Guidelines for Exposure Assessment (EPA, 1992).

The key point in all of the above examples is that the measurements are taken at the interface between the person and environment while exposure is occurring (WHO, 2000). The advantage of this approach is that it measures exposure directly and is likely to give the most accurate exposure value for the period of time over which the measurement was taken (Lioy PJ, 1990; Wallance LA, 1995). The limitation is that it is often expensive and monitors and techniques do not currently exist for many of agents (EPA, 1992). In addition, this approach may require assumptions to be made concerning the relationship between short-term sampling and long-term exposures (EPA, 1992).

Scenario Evaluation

The scenario evaluation determines the exposure concentration of an agent in a medium or location and links this data with the time (exposure duration) that individual or population contact (Laden et al., 2006; Lebret et al., 2000). The exposure scenario is defined as the set of assumptions about how this contact takes place (EPA, 1992). In evaluating exposure scenarios, the investigator usually characterizes the agent concentration and the time of contact separately (Morgan et al., 2005; Backer et al., 2005).  

To characterize an agent concentration is to develop estimates of exposure concentration (Lebret et al., 2000). The estimate is typically done indirectly by measuring, modeling, or using existing data on the agent concentration in the bulk media (e.g., water, air, and soil), rather than at the point of contact (Laden et al., 2006). The assumption that the concentration in the bulk medium is the same as the exposure concentration at the point of contact is a clear source of potential error in the exposure estimate and must be explored and discussed in the uncertainty analysis (Laden et al., 2006; EPA, 1992; WHO, 2000). Generally, the closer the medium can be measured to the point of contact in both space and time, the less uncertainty there is in the characterization of exposure concentration (EPA, 1992).

To characterize time of contact for an individual or populations is to develop estimates of the frequency and duration of exposure (WHO, 2000). Like an agent concentration characterization, the estimates are usually obtained indirectly by use of activity diaries data, demographic data, questionnaire survey data, behavior observation data (Morgan et al., 2005; Backer et al., 2005). In the absence of the above-mentioned data, the investigator has to make assumption about behavior of an individual or population under study (Laden et al., 2006).

After obtaining both exposure duration and exposure time data, the investigator ultimately combines them in an exposure scenario under some assumptions (Morgan et al., 2005; Backer et al., 2005). The advantage of this approach is that it is an inexpensive method (Laden et al., 2006). Also, it is particularly suited to analysis of the heath effects of proposed action. It is both strength and a weakness of scenario development that evaluation can be performed with little or no data; it is a technique that is best used when some knowledge exists about the soundness, validity, and uncertainty of the underlying assumptions (EPA, 1992). Table 1-3 below shows examples of estimating exposure using the scenario evaluation approach.

Table 1-3: Examples of Exposure Using the Scenario Evaluation Approach

Type of measurement	Characterization	Needed information	Examples
Fixed location monitoring	Media of air, water, soil, samples used to characterize trend and status	Human activity pattern, relationship between the monitoring location and population	Laden et al., 2006
Source monitoring	Release rates in the environment	Exposure pathway information, human activity, temporal release	Stack sampling, pollution control sampling
Food samples	Concentration distribution in food supply	Dietary habits of study populations, relationships between concentration in uncooked versus prepared food	Cooked-food diet sample such as a hamburg
Drinking water samples	Concentration distribution in drinking water	Fate and distribution of an agent from point of sample to point of consumption, people  consumption rate, human activity pattern	Tap water
Microenvironmental samples	Ambient concentration in a defined location	Human activity pattern and the population representativeness	Morgan et al., 2005
Breathing zone samples	Air concentration where people breath	Human activity pattern and the population representativeness	Backer et al., 2005

The above table was developed based on EPA Guidelines for Exposure Assessment (EPA, 1992).

Reconstruction

The exposure is estimated from a dose, which in turn can be reconstructed through internal indicators (biomarkers, body burden, excretion levels, etc.) after the exposure has taken place (EPA, 1992; WHO, 2000). Table 1-4 below shows examples of estimating exposure using the reconstruction approach.

The advantage of this approach is that it generates a good estimate of past exposure (Gosselin et al., 2006; Gordon et al., 2006). If a total dose is known and information about intake and uptake rates is available, an investigator can estimate an average past exposure (Xu and Weisel, 2005). The limitation is that the methodology is not available for every agent due to interferences or the reactive nature of the agent (Mucha et al., 2006; Aronson et al., 2000).

Table 1-4. Examples of Exposure Using the Reconstruction Approach

Type of measurement	Characterization	Needed information	Examples
Blood	Internal dose of an agent or amount of metabolites	Pharmacokinetics, variability in population, storage in body, relationship to body burden, time frame since exposure	Gosselin, et al., 2006
Breath	Internal dose of vapors and amount of metabolites	Pharmacokinetics, variability in population, storage in body, relationship to blood, time frame since exposure	Gordon et al., 2006; Xu and Weisel, 2005
Urine	Internal dose or amount of metabolized	Same as breath	Mucha et al., 2006
Adipose tissues	Internal dose of long-lived and storage in human body	Same as breath	Aronson et al., 2000

The above table was developed based on EPA Guidelines for Exposure Assessment (EPA, 1992).

Summary

Each of the above approaches is independent since the three approaches use different data to quantify exposure exposure (EPA, 1992; WHO, 2000). The independence of these three approaches is important concept in verifying or validating results. Each of the three has strengths and weaknesses; using them in combination can considerably strengthen the credibility of an exposure assessment (EPA, 1992).

The Exposure Concept: Activities

Lesson Review Worksheet

Complete The Exposure Concept: Lesson Review Worksheet to check your knowledge of the material in this lesson.

Misconceptions around Human Exposure

Based on the first of this lesson's two assigned readings, write a 300-word summary of the key misconceptions around human exposure. Submit your summary to the Misconceptions around Human Exposure Drop Box.

9-11 Lessons Learned

Lessons learned from Ground Zero have been intensively discussed since the 9-11 World Trade Center attacks. For this exercise, work as a team using your team discussion area to generate a list of lessons learned based on the second of this lesson's two assigned readings (200 words). Your list should target each of the following four parts in terms of exposure:

• Outdoor exposure monitoring

• Emergency response standards

• Indoor cleanup

• Respiratory protection

Submit your team list to the 9-11 Lessons Learned Drop Box.

Works Cited

Armstrong B. K., White E., and Saracci R. Principles of exposure measurement in epidemiology, pp. 1-291. Oxford University Press, Walton Street, Oxford, 1991.

Aronson K. J., Miller A. B., Woolcott C. G., et al. Breast Adipose Tissue Concentrations of Polychlorinated Biphenyls and Other Organochlorines and Breast Cancer Risk. Cancer Epidemiology Biomarkers & Prevention 9:55-63, 2000.

Backer L. C., Kirkpatrick B., Fleming L. E. Occupational Exposure to Aerosolized Brevetoxins during Florida Red Tide Events: Effects on a Healthy Worker Population. Environ Health Perspect 113:644–649, 2005.

Baldauf R., Fortune C., Weinstein J., et al. Air contaminant exposures during the operation of lawn and garden. J Expo Anal Environ Epidemiol 16:362-370, 2006.

Bouvier G., Blanchard O., Momas I., et al. Environmental and biological monitoring of exposure to organophosphorus pesticides: application to occupationally and non-occupationally exposed adult populations. J Expo Anal Environ Epidemiol 16:417-426, 2006.

Gosselin N., Brunet R. C., Carrier G., et al. Reconstruction of methylmercury intakes in indigenous populations from biomarker data. J Expo Anal Environ Epidemiol 16:19-29, 2006.

Gordon S. M., Brinkman M. C., Ashley D. L., et al. Changes in breath Trihalomethane levels resulting from household water-use activities. Environ Health Perspect 114:514-521, 2006.

Hoppin J. A., Adgate J. L., Eberhart M. et al. Environmental Exposure Assessment of Pesticides in Farmworker Homes. Environ Health Perspect 114:929–935, 2006.

Kathryn C. L., Toepel K., Irish R., et al. Organic diets significantly lower children’s dietary exposure to organophosphorus pesticides. Environ Health Perspect 114:260-263, 2006.

Laden F., Schwartz J., Speizer F. E. et al. Reduction in Fine Particulate Air Pollution and Mortality, Extended Follow-up of the Harvard Six Cities Study Am J Respir Crit Care Med 173:667-672, 2006.

Lebret E., Briggs D., van Reeuwijk H., et al. Small area variations in ambient NO2 concentrations in four European areas. Atmos Environ 34, 2000.

Lioy P. J. Assessing total human exposure to contaminants. Environ Sci Technol; 24(7):938-945, 1990.

Lioy P. J., et al. Defining Exposure Science. J Expo Anal Environ Epidemiol 15, 2005.

Lioy P. J. and Gochfeld M. Lessons learned on environmental, occupational, and residential exposures from the attack on the World Trade Center. American Journal of Industrial Medicine 42:560-565, 2002.

Morgan M. K., Sheldon L. S., Croghan C. W., et al. Exposure of preschool to chlorpyrifos and its degradation product 3,5,6-trichloro-2-pyridinol in their everyday environment. J Expo Anal Environ Epidemiol 15:297-309, 2005.

Mucha A. P., Hryhorczuk D., Serdyuk A., et al. Urinary 1-hydroxypyrene as a biomarker of PAH exposure in 3-year-old Ukrainian children. Environ Health Perspect 114:603-609, 2006.

U.S. Environmental Protection Agency. Guidelines for Exposure Assessment. Federal Register 57(104):22888-22938, 1992.

Wallace L. A. Human exposure to environmental pollutants: a decade of experience. Clinical and Experimental Allergy; 25:4-9, 1995.

World Health Organization. Human exposure assessment. Geneva, Switzerland, 2000.

Xu X. and Weisel C. P. Dermal uptake of chloroform and haloketones during bathing. J Expo Anal Environ Epidemiol 15:289-296, 2005.