UNITED NATIONS ENVIRONMENT PROGRAMME
INTERNATIONAL LABOUR ORGANISATION
WORLD HEALTH ORGANIZATION
INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY
Environmental Health Criteria 214
HUMAN EXPOSURE ASSESSMENT
This report contains the collective views of an international group of
experts and does not necessarily represent the decisions or the stated
policy of the United Nations Environment Programme, the International
Labour Organization, or the World Health Organization.
First draft prepared by Dr D. L. MacIntosh, University of Georgia,
Athens, GA, USA and Professor J. D. Spengler, Harvard University,
Boston, MA, USA
Published under the joint sponsorship of the United Nations
Environment Programme, the International Labour Organization, and the
World Health Organization, and produced within the framework of the
Inter-Organization Programme for the Sound Management of Chemicals.
World Health Organization
Geneva, 2000
The International Programme on Chemical Safety (IPCS),
established in 1980, is a joint venture of the United Nations
Environment Programme (UNEP), the International Labour Organization
(ILO), and the World Health Organization (WHO). The overall
objectives of the IPCS are to establish the scientific basis for
assessment of the risk to human health and the environment from
exposure to chemicals, through international peer review processes, as
a prerequisite for the promotion of chemical safety, and to provide
technical assistance in strengthening national capacities for the
sound management of chemicals.
The Inter-Organization Programme for the Sound Management of
Chemicals (IOMC) was established in 1995 by UNEP, ILO, the Food and
Agriculture Organization of the United Nations, WHO, the United
Nations Industrial Development Organization, the United Nations
Institute for Training and Research, and the Organisation for Economic
Co-operation and Development (Participating Organizations), following
recommendations made by the 1992 UN Conference on Environment and
Development to strengthen cooperation and increase coordination in the
field of chemical safety. The purpose of the IOMC is to promote
coordination of the policies and activities pursued by the
Participating Organizations, jointly or separately, to achieve the
sound management of chemicals in relation to human health and the
environment.
WHO Library Cataloguing-in-Publication Data
Human exposure assessment.
(Environmental health criteria ; 214)
1.Environmental monitoring - methods 2.Environmental exposure
3.Models, theoretical 4.Data collection - methods
5.Toxicity tests
I.International Programme on Chemical Safety II.Series
ISBN 92 4 157214 0 (NLM Classification: QT 162)
ISSN 0250-863X
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CONTENTS
ENVIRONMENTAL HEALTH CRITERIA FOR HUMAN EXPOSURE ASSESSMENT
PREAMBLE
ABBREVIATIONS
FOREWORD
1. DEFINING EXPOSURE
1.1. Introduction
1.2. Defining exposure
1.2.1. Exposure and exposure concentration
1.2.2. Exposure estimation by integration and averaging
1.2.3. Exposure measurements and models
1.2.4. Exposure in the context of an environmental health
paradigm
1.3. Elements of exposure assessment
1.4. Approaches to quantitative exposure assessment
1.5. Linking exposure events and dose events
1.6. Summary
2. USES OF HUMAN EXPOSURE INFORMATION
2.1. Introduction
2.2. Human exposure information in environmental epidemiology
2.3. Human exposure information in risk assessment
2.3.1. Risk allocation for population subgroups or
activities
2.3.2. Population at higher or highest risk
2.4. Human exposure information in risk management
2.5. Human exposure information in status and trend analysis
2.6. Summary
3. STRATEGIES AND DESIGN FOR EXPOSURE STUDIES
3.1. Introduction
3.2. Study design
3.3. Sampling and generalization
3.4. Types of study design
3.4.1. Comprehensive samples
3.4.2. Probability samples
3.4.3. Other sample types
3.5. Exposure assessment approaches
3.5.1. Direct approaches to exposure assessment
3.5.1.1 Personal monitoring of inhalation exposures
3.5.1.2 Personal monitoring of dietary exposures
3.5.1.3 Personal monitoring of dermal absorption
exposures
3.5.2. Indirect approaches to exposure assessment
3.5.2.1 Environmental monitoring
3.5.2.2 Models as an indirect approach to assessing
exposure
3.5.2.3 Questionnaires as an indirect approach to
assessing exposure
3.6. Summary
4. STATISTICAL METHODS IN EXPOSURE ASSESSMENT
4.1. Introduction
4.2. Descriptive statistics
4.2.1. Numerical summaries
4.2.2. Graphical summaries
4.2.2.1 Histograms
4.2.2.2 Cumulative frequency diagrams
4.2.2.3 Box plots
4.2.2.4 Quantile-quantile plots
4.2.2.5 Scatter plots
4.3. Probability distributions
4.3.1. Normal distribution
4.3.2. Lognormal distribution
4.3.3. Binomial distribution
4.3.4. Poisson distribution
4.4. Parametric inferential statistics
4.4.1. Estimation
4.4.2. Measurement error and reliability
4.4.3. Hypothesis testing and two-sample problems
4.4.4. Statistical models
4.4.4.1 Analysis of variance and linear regression
4.4.4.2 Logistic regression
4.4.5. Sample size determination
4.5. Non-parametric inferential statistics
4.6. Other topics
4.7. Summary
5. HUMAN TIME-USE PATTERNS AND EXPOSURE ASSESSMENT
5.1. Introduction
5.2. Methods
5.2.1. Activity pattern concepts
5.2.1.1 Time allocation parameters
5.2.1.2 Microenvironment parameters
5.2.1.3 Intensity of contact
5.2.2. Surrogates of time-activity patterns
5.2.3. Data collection methods
5.3. Potential limitations
5.3.1. Activity representativeness
5.3.2. Validity and reliability
5.3.3. Inter- and intra-person variability
5.4. Summary
6. HUMAN EXPOSURE AND DOSE MODELLING
6.1. Introduction
6.2. General types of exposure model
6.3. Environmental media and exposure media
6.4. Single-medium models
6.4.1. Outdoor and indoor air
6.4.2. Potable water
6.4.3. Surface waters
6.4.4. Groundwater
6.4.5. Soil
6.5. Multiple-media modelling
6.5.1. Inter-media transfer factors
6.5.1.1 Diffusive partition coefficients
6.5.1.2 Advective partition coefficients
6.5.2. Exposure factors
6.5.3. Multiple-media/multiple-pathway models
6.6. Probabilistic exposure models
6.6.1. Variability
6.6.2. Uncertainty
6.6.3. Implementing probabilistic exposure models
6.7. A generalized dose model
6.8. Physiologically based pharmacokinetic models
6.9. Validation and generalization
6.10. Summary
7. MEASURING HUMAN EXPOSURES TO CHEMICALS IN AIR, WATER AND FOOD
7.1. Introduction
7.2. Air monitoring
7.2.1. Gases and vapours
7.2.1.1 Passive samplers
7.2.1.2 Active samplers
7.2.1.3 Direct-reading instruments
7.2.2. Aerosols
7.2.3. Semivolatile compounds
7.2.4. Reactive gas monitoring
7.3. Water
7.3.1. Factors influencing water quality
7.3.2. Water quality monitoring strategies
7.3.3. Sample collection
7.4. Assessing exposures through food
7.4.1. Duplicate diet surveys
7.4.2. Market basket or total diet surveys
7.4.3. Food consumption
7.4.3.1 Food diaries
7.4.3.2 24-h recall
7.4.3.3 Food frequency questionnaires
7.4.3.4 Meal-based diet history
7.4.3.5 Food habit questionnaires
7.4.4. Contaminants in food
7.5. Summary
8. MEASURING HUMAN EXPOSURE TO CHEMICAL CONTAMINANTS IN SOIL AND
SETTLED DUST
8.1. Introduction
8.2. Selected sampling methods
8.2.1. Soil
8.2.1.1 Surface soil collection
8.2.1.2 Soil contact and intake measurements
8.2.2. Settled dust
8.2.2.1 Wipe sampling methods
8.2.2.2 Vacuum methods
8.2.2.3 Sedimentation methods
8.3. Sampling design considerations
8.3.1. Concentration and loading
8.3.2. Collection efficiency
8.4. Sampling strategies
8.5. Summary
9. MEASURING BIOLOGICAL HUMAN EXPOSURE AGENTS IN AIR AND DUST
9.1. Introduction
9.2. House dust mites
9.2.1. Air sampling for house dust mites
9.2.2. Dust sampling for house dust mites
9.2.3. Available methods of analysis for house dust mites
9.2.3.1 Mite counts
9.2.3.2 Immunochemical assays of dust mite
allergens
9.2.3.3 Guanine determination
9.2.4. Mite allergens
9.3. Allergens from pets and cockroaches
9.3.1. Air sampling for allergens from pets and cockroaches
9.3.2. Dust sampling for allergens from pets and
cockroaches
9.3.3. Available methods of analysis
9.3.4. Typical allergen concentrations
9.4. Fungi
9.4.1. Air sampling for fungi
9.4.2. Settled dust for fungi
9.4.3. Available methods of analysis for fungi in air
9.4.3.1 Total counts of viable and non-viable
fungal particles
9.4.4. General considerations for fungi
9.5. Bacteria (including actinomycetes)
9.5.1. Air sampling for bacteria
9.5.2. Dust sampling for bacteria
9.5.3. Available methods of analysis for bacteria
9.5.3.1 Total count of viable and non-viable
bacteria
9.5.3.2 Viable bacteria
9.5.3.3 Endotoxins
9.6. Pollen
9.6.1. Air sampling for pollen
9.6.2. Dust sampling for pollen
9.6.3. Available methods of analysis for pollen in air
9.6.4. General considerations for pollen sampling
9.7. Summary
10. ASSESSING EXPOSURES WITH BIOLOGICAL MARKERS
10.1. Introduction
10.2. General characteristics
10.3. Considerations for use in environmental exposure assessment
10.3.1. Toxicokinetics and toxicodynamics
10.3.2. Biological variability
10.3.3. Validation of biological markers
10.3.4. Normative data
10.4. Advantages of biological markers for exposure assessment
10.4.1. Characterizing inter-individual variability
10.4.2. Efficacy of use
10.4.3. Internal exposure sources
10.5. Limitations of biological markers for exposure assessment
10.5.1. Source identification
10.5.2. Biological variability and altered exposure response
10.5.3. Participant burden
10.5.4. Biosafety
10.6. Media available for use
10.6.1. Blood
10.6.2. Urine
10.6.3. Exhaled breath
10.6.4. Saliva
10.6.5. Keratinized tissue (hair and nails)
10.6.6. Ossified tissue
10.6.6.1 Teeth
10.6.6.2 Bone
10.6.7. Breast milk
10.6.8. Adipose tissue
10.6.9. Faeces
10.6.10. Other media
10.7. Summary
11. QUALITY ASSURANCE IN EXPOSURE STUDIES
11.1. Introduction
11.2. Quality assurance and quality control
11.3. Elements of a quality assurance programme
11.4. Quality assurance programme
11.4.1. Organization and personnel
11.4.2. Record-keeping and data recording
11.4.3. Study plan and standard operating procedures
11.4.4. Collection of samples
11.4.5. Equipment maintenance and calibration
11.4.6. Internal audit and corrective action
11.5. Quality control/quality assurance for sample measurement
11.5.1. Method selection and validation
11.5.1.1 Accuracy
11.5.1.2 Precision
11.5.1.3 Sensitivity
11.5.1.4 Detection limits
11.5.2. Internal quality control
11.5.2.1 Control charts
11.5.3. External quality control
11.5.4. Reference materials
11.6. Quality assurance and control issues in population-based
studies
11.7. Summary
12. EXAMPLES AND CASE STUDIES OF EXPOSURE STUDIES
12.1. Introduction
12.2. Exposure studies
12.3. Air pollution exposure studies
12.3.1. Particle studies
12.3.2. Carbon monoxide
12.3.3. Nitrogen dioxide
12.3.4. Ozone
12.3.5. Combined exposure studies
12.3.6. Assessing ambient pollution impacts indoors
12.3.7. Volatile organic compounds
12.3.8. Commuter exposures
12.4. Exposures and biomarkers
12.4.1. Exposure to lead and cadmium
12.4.2. Exposure to furans, dioxins and polychlorinated
biphenyls
12.4.3. Exposure to volatile organic compounds and urinary
metabolites
12.5. Exposure to contaminants in drinking-water
12.6. Exposure to microbes
12.7. Exposure studies and risk assessment
12.7.1. The German Environmental Survey
12.7.2. The National Human Exposure Assessment Survey
12.7.3. Windsor, Canada exposure and risk study
12.7.4. Pesticide exposure study
12.7.5. Czech study of air pollution impact on human health
REFERENCES
RÉSUMÉ
RESUMEN
NOTE TO READERS OF THE CRITERIA MONOGRAPHS
Every effort has been made to present information in the criteria
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Criteria monographs, readers are requested to communicate any errors
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356, 1219 Châtelaine, Geneva, Switzerland (telephone no.
+ 41 22 - 9799111, fax no. + 41 22 - 7973460, E-mail irptc@unep.ch).
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This publication was made possible by grant number
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Sciences, National Institutes of Health, USA, and by financial support
from the European Commission.
Environmental Health Criteria
PREAMBLE
Objectives
In 1973 the WHO Environmental Health Criteria Programme was
initiated with the following objectives:
(i) to assess information on the relationship between exposure to
environmental pollutants and human health, and to provide
guidelines for setting exposure limits;
(ii) to identify new or potential pollutants;
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pollutants;
(iv) to promote the harmonization of toxicological and
epidemiological methods in order to have internationally
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The first Environmental Health Criteria (EHC) monograph, on
mercury, was published in 1976 and since that time an ever-increasing
number of assessments of chemicals and of physical effects have been
produced. In addition, many EHC monographs have been devoted to
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teratogenic and nephrotoxic effects. Other publications have been
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forth.
Since its inauguration the EHC Programme has widened its scope,
and the importance of environmental effects, in addition to health
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chemicals.
The original impetus for the Programme came from World Health
Assembly resolutions and the recommendations of the 1972 UN Conference
on the Human Environment. Subsequently the work became an integral
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monographs have become widely established, used and recognized
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The recommendations of the 1992 UN Conference on Environment and
Development and the subsequent establishment of the Intergovernmental
Forum on Chemical Safety with the priorities for action in the six
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the need for EHC assessments of the risks of chemicals.
Scope
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Content
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the chemical
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JMPR
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If an EHC monograph is proposed for a chemical not on the
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WHO TASK GROUP ON HUMAN EXPOSURE ASSESSMENT
Members
Dr J. Alexander, Department of Environmental Medicine, National
Institute of Public Health, Folkehelsa, Torshov, Oslo, Norway
Dr M. Berglund, Institute of Environmental Medicine, Division of
Metals and Health, Karolinska Institute, Stockholm, Sweden
Dr M. Dellarco, US Environmental Protection Agency,
Washington, DC, USA
Mrs B. Genthe, Environmentek, CSIR, Stellenbosch, South Africa
Dr L. Gil, Department of Biochemistry, University of Chile -
Faculty of Medicine, Casilla, Santiago, Chile
Dr S. Goto, Department of Community Environmental Sciences,
Institute of Public Health, Minato-ku, Tokyo, Japan
Professor M. Jantunen, Department of Environmental Hygiene and
Toxicology, National Public Health Institute, Kuopio, Finland
Dr N. Künzli, Department of Environment and Health, Institute of
Social and Preventive Medicine, University of Basel, Basel,
Switzerland
Dr D. MacIntosh, Environmental Health Science, University of
Georgia, Athens, GA, USA
Dr M. Morandi, Environmental Sciences, Houston School of Public
Health, Houston Health Science Center, University of Texas,
Houston, TX, USA
Dr S. Pavittranon, National Institute of Health, Department of
Medical Sciences, Bamrasnaradura Hospital, Nonthari, Thailand
Dr N. Rees, Risk Assessment, Management and International
Coordination Branch, Ministry of Agriculture, Fisheries and Food,
London, United Kingdom
Dr B. Schoket, Department of Biochemistry, National Institute of
Environmental Health, "Fodor József" National Public Health
Centre, Budapest, Hungary
Dr L. Sheldon, US Environmental Protection Agency, National
Research Laboratory, Research Triangle Park, NC, USA
Professor J. D. Spengler, School of Public Health, Harvard
University, Boston, MA, USA
Dr P. Straehl, Swiss Federal Agency for Environment, Forestry and
Landscape, Swiss Department of the Interior, Bern, Switzerland
Observers
Mrs S. Munn, European Commission, European Chemicals Bureau,
Environment Institute, Ispra (VA), Italy
Secretariat
Mr C. Corvalan, Office of Global and Integrated Environmental
Health, World Health Organization, Geneva, Switzerland
Dr K. Gutschmidt, International Programme on Chemical Safety,
World Health Organization, Geneva, Switzerland
Dr M. Krzyzanowski, European Centre for Environment and
Health, World Health Organization, Regional Office for Europe,
Bilthoven Division, De Bilt, Netherlands
Dr G. Moy, Food Safety, World Health Organization, Geneva,
Switzerland
Dr H. Tamashiro, Office of Global and Integrated Environmental
Health, World Health Organization, Geneva, Switzerland
Dr M. Younes, International Programme on Chemical Safety,
World Health Organization, Geneva, Switzerland
ENVIRONMENTAL HEALTH CRITERIA FOR HUMAN EXPOSURE ASSESSMENT
A Task Group on the Environmental Health Criteria for Human
Exposure Assessment met in Glion-sur-Montreux, Switzerland, from 16 to
20 February 1998. Dr M. Younes, IPCS, welcomed the participants on
behalf of the Manager, IPCS, and the three IPCS cooperating
organizations (UNEP/ILO/WHO). The Task Group reviewed and revised the
final draft of the monograph. In preparation for the final draft a
review meeting was held at the National Institute of Health Sciences
(NIHS), Tokyo, from 17 to 19 July 1996.
The first draft was prepared by Dr D. L. MacIntosh, University of
Georgia, USA and Professor J. D. Spengler, Harvard University, USA.
Dr K. Gutschmidt was responsible officer in IPCS for the overall
scientific content of the monograph and the organization for the
meetings, and Ms K. Lyle (Sheffield, United Kingdom) was responsible
for the technical editing of the monograph.
The efforts of all who helped in the preparation and finalization
of the monograph are gratefully acknowledged.
ABBREVIATIONS
ACGIH American Conference of Governmental Industrial Hygienists
ADD average daily dose
AI acceptance intervals
ALAD Delta-aminolaevulinic acid dehydratase
AMIS Air Monitoring Information System
ANOVA analysis of variance
AOAC Association of Official Analytical Chemists
ASTM American Society for Testing of Materials
CDF chlorinated dibenzofurans; cumulative distribution function
CFU colony-forming units
CI confidence interval
DG18 dichloran 18% diglycerol agar
DVM dust vacuum method
EDTA ethylenediamine tetra-acetic acid
ELISA enzyme-linked immunosorbent assays
EPS extracellular polysaccharides
ETS environmental tobacco smoke (exposure)
EU endotoxin unit
FDA US Food and Drug Administration
FFQ food frequency questionnaire
GEMS Global Environment Monitoring System
GerES German Environmental Survey
GM geometric mean
GSD geometric standard deviation
HEAL Human Exposure Assessment Location
HPLC high-pressure liquid chromatography
HUD US Department of Housing and Urban Development
IAEA International Atomic Energy Agency
IAQ internal air quality
ISEA International Society of Exposure Analysis
ISO International Organization for Standardization
LADD lifetime average daily dose
LAL Limulus amoebocyte lysate
LOD limit of detection
LOQ limit of quantification
LWW Lioy-Weisel-Wainman
MAD maximum allowable deviations
MCS multiple chemical sensitivity
MDL method detection limit
MEA malt extract agar
NAAQS National Ambient Air Quality Standard
NHEXAS National Human Exposure Assessment Survey
NIOSH National Institute for Occupational Safety and Health
NTA nitriloacetic acid
OR odds ratio
PAH polycyclic aromatic hydrocarbons
PBPK physiologically based pharmacokinetic (method)
PCB polychlorinated biphenyls
PCDD polychlorinated dibenzo- p-dioxin
PCP pentachlorophenol
PDF probability distribution function
PEM personal exposure monitor
PMn particulate matter with aerodynamic diameter < n µm
PTEAM particle total exposure assessment methodology
QA quality assurance
QC quality control
RAST radioallergosorbent tests
RIA radioimmunoassay
RSP respirable particulate matter
SAM stationary outdoor monitor
SBS sick building syndrome
SD standard deviation
SEM scanning electron microscope
SIM stationary indoor monitor
SOP standard operating procedure
SVOC semivolatile organic compound
TCCD 2,3,7,8-tetrachloro dibenzo- p-dioxin
TDS US FDA Total Diet Study
TEQ TCCD toxic equivalents
TSP total suspended particulates
TWI tolerable weekly intake
UNEP United Nations Environment Programme
VOC volatile organic compound
XRF X-ray fluorescence
FOREWORD
The International Programme on Chemical Safety (IPCS), launched
in 1980, is a joint collaborative programme of the International Labor
Organization (ILO), the United Nations Environment Programme (UNEP),
and the World Health Organization (WHO); WHO is the Administrating
Organization of the Programme. The two main roles of the IPCS are to
establish the scientific health and environmental risk assessment
basis for safe use of chemicals (normative function) and to
strengthen national capabilities for chemical safety (technical
cooperation). In the field of methodology, the work of the IPCS aims
at promoting the development, improvement, validation, harmonization
and use of generally acceptable, scientifically sound methodologies
for the evaluation of risks to human health and the environment from
exposure to chemicals. The work encompasses the development of
Environmental Health Criteria monographs on general principles of
various areas of risk assessment covering various aspects related to
risk assessment such as, in this publication, on exposure assessment.
The WHO and the World Meteorological Organization coordinate the
assessment of climate, urban air and water pollution, and health
status of populations. These measures provide the indicator of trends
and status.
Until 1995, the basic source for internationally comparable urban
air pollution data was the Global Environment Monitoring System
(GEMS/Air) of UNEP and WHO. Started in 1974, shortly after the
Stockholm Environment Conference, GEMS had built up a system that
collected comparable ambient air pollution data in about 50 cities of
35 countries, varied in geography and income (UNEP/WHO, 1988, 1992).
Typically, sulfur dioxide and total suspended particulates (TSP) had
been monitored in three stations of each city, one each in industrial,
commercial, and residential zones. Later, GEMS also collected
monitoring data for carbon monoxide, nitrogen dioxide, and lead, and
made emissions estimates for all five pollutants. The results were
published periodically by GEMS, and also often appeared in other
periodic international data sets, such as those of the World Bank
(World Bank, 1992), the World Resources Institute (World Resources
Institute, 1992), the United Nations (UN ESCAP, 1990) and UNEP itself
(UNEP, 1991).
More recently, WHO created with the Air Management Information
System (AMIS) the successor of GEMS/Air. Like GEMS/Air, AMIS provides
air quality data for major and megacities. Data on sulfur dioxide,
nitrogen dioxide, carbon monoxide, ozone, black smoke, suspended
particulate matter, PM10, lead and others are available. AMIS also
includes information on air quality management (WHO, 1997).
Much of what is known about contaminants in food, soils, water
and air has become available through WHO and UNEP publications. For
more than 20 years WHO/UNEP has been promoting an appreciation for
improved assessments of human exposures through training sessions,
workshops, demonstration projects, and published methodologies and
reports. Through a series of WHO-sponsored studies in every populated
continent, the principles of human exposure assessment have been
illustrated for indoor and outdoor air pollutants, food contamination
and water. In 1984, after some background reports (e.g., UNEP/WHO,
1982), WHO and UNEP conducted the Human Exposure Assessment Location
(HEAL) Project, which facilitates research and information sharing
among 10-15 institutions worldwide concerned with exposure assessment
for a limited number of pollutants (Ozolins, 1989). Unfortunately,
although providing important functions, the HEAL project has not had
the mandate or anything approaching the resources required to actually
make comparable international estimates of population exposures. HEAL
projects, for the most part, have investigated exposures to
conventional inorganic air pollutants such as carbon monoxide,
nitrogen dioxide and general undifferentiated particle mass where
inhalation is the primary route of exposures. However, the HEAL
programme does offer examples of lead, cadmium and pesticide studies
which illustrate multiple exposure pathways and demonstrate the
necessity of extensive analytical training and quality programmes. An
analytical quality control programme which involved all participating
laboratories enabled reliable international comparisons of exposure
despite differences in methodologies applied by the different
laboratories.
Preceding this criteria document the UNEP, FAO and WHO have been
actively advancing the concepts and methodologies for human exposures.
GEMS/Air, GEMS/Water and GEMS/Food are establishing the uniformity
among data collected worldwide to establish national and international
status and trends. These efforts, together with others, such as the
Codex Committee on Pesticide Residues, the several Joint FAO/WHO
Consultations on food consumption, pesticide residues, veterinary
drugs, additives and chemical contaminants, have been developing the
basis of quantitative assessment of human exposures and risk. Table 38
(pg. 279) provides a listing of pertinent publications related to
assessment of air, water and food contamination.
Scope
This current criteria document on human exposure assessment
presents in one publication the concepts, rationale, and statistical
and procedural methodologies for human exposure assessment. The
underpinnings of exposure assessment are the basic environmental and
biological measurements found in the more familiar specialties of air
and water pollution and food and soil sciences. Therefore, throughout
this document readers are referred to other publications for technical
details on instrumental and laboratory methods. This criteria document
is intended for the community of scientific investigators inquiring
about the human health consequences of contaminants in our
environment. As such, this text will be of interest to physical
scientists, engineers and epidemiologists. It is intended also for
those professions involved in devising, evaluating and implementing
policy with respect to managing the quality of environmental health,
inclusive of air, water, food and soil. By necessity environment is
defined broadly to include place, media, and activities where we
humans encounter contaminants.
Of primary concern in this document are those environmental
contaminants that exist in various media as a consequence of direct or
indirect human intention. We have included some biological agents that
are "natural" but, through actions of irritation and allergy, can
contribute to or cause morbidity and mortality as a result of
inadequate building design and maintenance. We recognize that viral,
bacterial and other biological agents in air, food, soil and water
contribute significantly to the burden of disease worldwide. However,
in the context of environmental exposure assessment the focus is on
chemical contaminants and a few specific allergens that might
contribute directly to disease or, in combination with biopathogens,
alter susceptibility and expression of disease.
To say that exposure assessment of environmental contaminants is
exclusive of any population or location is, in principle, a
contradiction. There are practical considerations, however, for
identifying the industrial workplace as a separate domain.
Administratively, many nations handle occupational health and safety
concerns separately from the environment. The management of workplace
hazards through well-established industrial hygiene practices of
source control, ventilation and worker protection are widely
recognized. This separation of workplace exposures from the general
environmental exposure focus in this document is not hard and fast.
Occupationally acquired contaminants can expose family members not
working in the specific industry. Industrial control strategies that
increase ventilation can adversely affect the neighbouring community.
In many societies, commercial and residential use of property are
integrated. Family operated business along congested streets means
that contaminants generated in outdoors, indoors and workplaces are
intermingled. Even where commercial and residential property are
distinct, chemical and biological contaminants can lead to non-worker
exposures.
Information on human exposures has a well-recognized role as a
corollary to epidemiology. But it is more than this, because
understanding human exposures to environmental contaminants is
fundamental to public policy. The adequacy of environmental mitigation
strategies is predicated on improving or safeguarding human and
ecological health. The public mandate for and acceptance of controls
on emissions is first based on sensory awareness of pollution.
Irritated airways, foul-smelling exhaust, obscuring plumes, oil slicks
on water, dirty and foul-tasting water, and medical waste and debris
on beaches are readily interpreted as transgressions against us and
threaten commonly shared natural resources. As we enter the
twenty-first century, we recognize that we, humans have had profound
but often subtle impacts on the chemistry of the biosphere and
lithosphere. Metals, organic compounds, particulate matter, and
photochemically produced gases are widely dispersed, recognizing no
geographic or political boundaries. Global markets, urbanization, and
increased mobility have environmental contamination as a consequence.
Assessing the quantities and distribution of potentially harmful
contaminant exposures to human populations is a critical component of
risk management. As long as disease prevention and health promotion
are the principal tenets of public health, then assessing the levels
of contaminant exposures in environmental and biological samples will
be necessary.
This book presents the methodologies for surveying exposures,
analysing data and integrating findings with the ongoing national and
global debate defining natural limits to human behaviour. It serves
the cross-disciplinary needs of environmental managers, risk assessors
and epidemiologists to learn something about the design, conduct,
interpretation and value of human exposure studies of multimedia
environmental contaminants. For investigators considering exposure
studies, this book guides them to contemporary information on
measurement of analysis methods and strategies.
In Chapter 1 of the document the basic terms and concepts used in
exposure assessment are defined. Similar understanding of terms used
commonly among health assessors working in the different fields of
air, water, soil and food sciences is a critical starting point in
defining the emerging specialist area of exposure assessment.
Application of exposure research and routine assessments to the
information needs of risk managers, policy-makers and epidemiologists
is established in Chapter 2. Discussion of these information needs is
developed in Chapter 3, which presents the objectives for various
study designs.
Chapter 4 covers basic statistical concepts used in exposure
assessment. The intent is to inform the reader of how statistical
analysis is vital to all components of an exposure assessment. By
examples and references the reader is directed to more substantial
texts on study design, data analysis, modelling and quality control.
Chapter 5 is devoted to a component of exposure assessment
related to the collection and interpretation of human activity
patterns. Information on how, where and when people contact
potentially contaminant media is useful for data interpretation,
establishing risk scenarios and identifying activities, locations and
populations at differential risk. The emphasis here is primarily
related to air pollution exposure studies. In the conduct of total
multimedia exposure investigations or modelling analogous information
is needed for the ingestion of water and food, as well as for dermal
contact.
Chapter 6 extends the concepts of the preceding chapters in
discussing models for human exposure assessment. The data requirements
for various pathways and various modelling approaches are presented.
Chapter 7 separates the conceptual first half of the text from
the pragmatic guidelines offered in the rest of the document. The
chapter contains a discussion of air monitoring, water monitoring and
food sampling. These particular fields are rather well developed
individually, if not well integrated into multimedia studies. The
reader is referred to many other resources that can guide the
investigator to details on instruments, sampling methods and
laboratory analysis.
In Chapter 8, proportionally more emphasis is placed on soil and
settled dust sampling. Again, the laboratory methods for metals,
organics and various chemical compounds are readily available in the
published literature. This chapter, then, focuses on relatively new
sampling techniques to quantify in a standardized way the contaminant
levels in soil and settled dust.
In Chapter 9, on microbiological agents, assessment techniques
for commonly encountered allergens, mycotoxins, fungal and pollen
spores, microbiological bacteria and endotoxins are presented. These
agents have been included because of their imputed contribution to
respiratory disease and potential interactions with chemical
pollutants. There is growing recognition that exposure to these agents
in schools, homes, hospitals and office buildings constitutes a
specific risk to atopic, asthmatic and compromised individuals.
The use of biomarkers for exposure assessments is presented in
Chapter 10. Biological samples derived from human tissue or fluids
have been used as markers of both effects as well as exposure (dose)
to a variety of occupational and environmental contaminants. The
chapter describes the applications of biomarkers in exposure studies.
The quality assurance (QA) activities that should be considered
in conducting and evaluating exposure studies are addressed in Chapter
11. Contributors to this document intended to impart their experiences
to improve future exposure study. It is emphasized that QA aspects
must be considered in all components of exposure studies, to enhance
comparability and interpretation.
Chapter 12 presents brief synopses of exposure studies.
Selections illustrate a variety of study designs with different
objectives and target pollutants and populations. Relatively more
emphasis has been given to particles and passive exposure to cigarette
smoke. The evidence is that cigarette consumption has increased almost
worldwide, suggesting that greater attention be given to
characterizing and reducing exposures to non-smokers, in particular,
infants and young children. Epidemiological studies conducted over the
last 15 years indicate that ambient particulate matter is adversely
affecting human health at levels well below many of the established
standards. Exposure assessment along with toxicology and epidemiology
will be needed to answer many of the remaining unresolved issues about
ambient and indoor suspended particles.
Other studies summarized show how exposure assessment is
supportive of epidemiology and risk management. The reader should
recognize that Chapter 12 is not comprehensive but is intended to help
educate the research community and others about the application, use
and limitations of exposure assessment methodologies.
1. DEFINING EXPOSURE
1.1 Introduction
People are exposed to a variety of potentially harmful agents in
the air they breathe, the liquids they drink, the food they eat, the
surfaces they touch and the products they use. An important aspect of
public health protection is the prevention or reduction of exposures
to environmental agents that contribute, either directly or
indirectly, to increased rates of premature death, disease, discomfort
or disability. It is usually not possible, however, to measure the
effectiveness of mitigation strategies directly in terms of prevented
disease, reduced premature death, or avoided dysfunction. Instead,
measurement or estimation of actual human exposure, coupled with
appropriate assumptions about associated health effects or safety
limits (e.g., acceptable daily intake, tolerable daily intake), is the
standard method used for determining whether intervention is necessary
to protect and promote public health, which forms of intervention will
be most effective in meeting public health goals, and whether past
intervention efforts have been successful (Ott & Roberts, 1998).
The purpose of this chapter is to define the concept of exposure,
and the direct and indirect method of exposure assessment. A brief
discussion of exposure in the environmental health paradigm and its
relationship to dose is presented.
1.2 Defining exposure
Exposure is defined as contact over time and space between a
person and one or more biological, chemical or physical agents (US
NRC, 1991a). Exposure assessment is to identify and define the
exposures that occur, or are anticipated to occur, in human
populations (IPCS, 1993). This can be a complex endeavour requiring
analysis of many different aspects of the contact between people and
hazardous substances (see Table 1). Although exposure is a
well-established concept familiar to all environmental health
scientists, its meaning often varies depending on the context of the
discussion. It is important however, that exposure and related terms
be defined precisely. In the following sections, we describe and
define important exposure-related terms used in this document. The
definitions are consistent with the US EPA's Exposure Assessment
Guidelines and related WHO publications (WHO, 1987, 1996a; US EPA,
1992a; IPCS, 1994). It is important to recognize, however, that
terminology and definitions vary among organizations and nations.
Thus, the reader is advised to concentrate on the concepts, rather
than the specific terms, as they represent the crux of exposure
assessment.
Table 1. Different aspects of the contact between people and pollution
that are potentially important in exposure analysis
(Sexton et al., 1995b)
Agent(s) biological, chemical, physical, single
agent, multiple agents, mixtures
Source(s) anthropogenic/non-anthropogenic, area/point,
stationary/mobile, indoor/outdoor
Transport/carrier medium air, water, soil, dust, food, product/item
Exposure pathways(s) eating contaminated food,
breathing contaminated workplace air
touching residential surface
Exposure concentration mg/kg (food), mg/litre (water), µg/m3 (air),
µg/cm2 contaminated surface), % by weight,
fibres/m3 (air)
Exposure route(s) inhalation, dermal contact, ingestion,
multiple routes
Exposure duration seconds, minutes, hours, days, weeks,
months, years, lifetime
Exposure frequency continuous, intermittent, cyclic, random,
rare
Exposure setting(s) occupational/non-occupational,
residential/non-residential, indoors/outdoors
Exposed population general population, population subgroups,
individuals
Geographic scope site/source specific, local, regional,
national, international, global
Time frame past, present, future, trends
1.2.1 Exposure and exposure concentration
Exposure, as defined earlier, is the contact of a biological,
chemical, or physical agent with the outer part of the human body,
such as the skin, mouth or nostrils. Although there are many instances
where contact occurs with an undiluted chemical (e.g., use of
degreasing chemicals for cleaning hands), contact more often occurs
with a carrier medium (air, water, food, dust or soil) that contains
dilute amounts of the agent. "Exposure concentration" (e.g., mg/litre,
mg/kg, µg/m3) is defined as the concentration of an environmental
agent in the carrier medium at the point of contact with the body.
1.2.2 Exposure estimation by integration and averaging
A minimal description of exposure for a particular route must
include exposure concentration and the duration of contact. If the
exposure concentration is integrated over the duration of contact
(Table 2), the area under the resulting curve is the magnitude of the
exposure in units of concentration multiplied by time (e.g.,
mg/litreÊday, mg/kgÊday, µg/m3Êh). This is the method of choice to
describe and estimate short-term doses, where integration times are of
the order of minutes, hours or days.
Over periods of months, years or decades, exposures to most
environmental agents occur intermittently rather than continuously.
Yet long-term health effects, such as cancer, are customarily
evaluated based on an average dose over the period of interest
(typically years), rather than as a series of intermittent exposures.
Consequently, long-term doses are usually estimated by summing doses
across discrete exposure episodes and then calculating an average dose
for the period of interest (e.g., year, lifetime). Although the
integration approach can also be used to estimate long-term exposures
or doses, its application to time periods longer than about a week is
usually difficult and inconvenient.
1.2.3 Exposure measurements and models
Direct measurements are the only way to establish unequivocally
whether and to what extent individuals are exposed to specific
environmental agents. But it is neither affordable nor technically
feasible to measure exposures for everyone in all populations of
interest. Models, which are mathematical abstractions of physical
reality, may obviate the need for such extensive monitoring programmes
by providing estimates of population exposures (and doses) that are
based on a smaller number of representative measurements (Fig. 1). The
challenge is to develop appropriate and robust models that allow for
extrapolation from relatively few measurements to estimates of
exposures and doses for a much larger population (US NRC, 1991b).
For relatively small groups, measurements or estimates can be
made for some or all of the individuals separately, and then combined
as necessary to estimate the exposure (or dose) distribution. For
larger groups, exposure models and statistics can sometimes be used to
derive an estimate of the distribution of population exposures,
depending on the quantity and quality of existing data. Monte Carlo
and other statistical techniques are increasingly being used to
generate and analyse exposure distributions for large groups (US EPA,
1992a).
1.2.4 Exposure in the context of an environmental health paradigm
The presence of hazardous substances in our environment does not
necessarily imply a risk to human health or to the ecosystem. Exposure
is an integral and necessary component in a sequence of events having
potential health consequences. An expanded and more detailed version
of the environmental health paradigm also showing the role of exposure
is depicted in Fig. 2. The role of exposure assessment in the risk
assessment framework applied by EU and US EPA is shown in Fig. 3.
The release of an agent into the environment, its ensuing
transport, transformation and fate in various environmental media, and
its ultimate contact with people are critical events in understanding
how and why exposures occur. Definitions for key events in the
continuum are summarized below. They were compiled from three sources:
Ott (1990); US EPA (1992a); Sexton et al. (1995a).
* Sources. The point or area of origin for an environmental agent
is known as a source. Agents are released into the environment from
a wide variety of sources, which are often categorized as
primary sources including point sources (e.g., incinerator)
versus area sources (e.g., urban runoff), stationary sources (e.g.,
refinery) versus mobile sources (e.g., automobile) and
anthropogenic sources (e.g., landfill) versus non-anthropogenic
sources (e.g., natural vegetation) and secondary sources
including condensation of vapours into particles and chemical
reactions of precursors producing new pollutants.
* Exposure pathway. An exposure pathway is the physical course
taken by an agent as it moves from a source to a point of contact
with a person. The substance present in the media is quantified as
its concentration.
* Exposure concentration. As discussed in 1.2.1, exposure is the
concentration of an agent in a carrier medium at the point of
contact with the outer boundary of the human body. The
concentration is the amount (mass) of a substance or contaminant
that is present in a medium such as air, water, food or soil
expressed per volume or mass. Assessments are often not at exposure
or exposure concentration, since that information alone is not very
useful unless it is converted to dose or risk. Assessments
therefore usually estimate how much of an agent is expected to
enter the body. This transfer of an environmental agent from the
exterior to the interior of the body can occur by either or both of
two basic processes: intake and uptake.
* Exposure route. Exposure route denotes the different ways the
substance may enter the body. The route may be dermal, ingestion or
inhalation.
* Intake. Intake is associated with ingestion and inhalation routes
of exposure. The agent, which is likely to be part of a carrier
medium (air, water, soil, dust, food), enters the body by bulk
transport, usually through the nose or mouth. The amount of the
agent that crosses the boundary per unit time can be referred to as
the "intake rate", which is the product of the exposure
concentration times the rate of either ingestion or inhalation. For
inhalation, intake may be calculated for any time period. For
ingestion, intake is usually expressed as the amount of food or
water consumed times the pollutant concentration in that medium
during a certain time period.
* Uptake. Uptake is associated with the dermal route of exposure,
as well as with ingestion and inhalation after intake has occurred.
The agent, as with intake, is likely to be part of a carrier medium
(e.g., water, soil, consumer product), but enters the body by
crossing an absorption barrier, such as the skin, respiratory tract
or gastrointestinal tract. The rates of bulk transport across the
absorption barriers are generally not the same for the agent and
the carrier medium. The amount of the agent that crosses the
barrier per unit time can be referred to as the uptake rate. This
rate is a function of the exposure concentration, as well as of the
permeability and surface area of the exposed barrier. The uptake
rate is also called a flux.
* Dose. Once the agent enters the body by either intake or uptake,
it is described as a dose. Several different types of dose are
relevant to exposure estimation. All these different dose measures
are approximations of the target or biological effective dose.
- Potential (administered) dose. Potential or administered dose
is the amount of the agent that is actually ingested, inhaled or
applied to the skin. The concept of potential dose is
straightforward for inhalation and ingestion, where it is
analogous to the dose administered in a dose-response
experiment. For the dermal route, however, it is important to
keep in mind that potential (or administered) dose refers to the
amount of the agent, whether in pure form or as part of a
carrier medium, that is applied to the surface of the skin. In
cases where the agent is in diluted form as part of a carrier
medium, not all of the potential dose will actually be touching
the skin.
- Applied dose. Applied dose is the amount of the agent directly
in contact with the body's absorption barriers, such as the
skin, respiratory tract and gastrointestinal tract, and
therefore available for absorption. Information is rarely
available on applied dose, so it is calculated from potential
dose based on factors such as bioavailability (Fig. 2).
- Internal (absorbed) dose. The amount of the agent absorbed,
and therefore available to undergo metabolism, transport,
storage or elimination, is referred to as the internal or
absorbed dose (Fig. 2). Bioavailability has been used to
describe absorbed dose.
- Delivered dose. The delivered dose is the portion of the
internal (absorbed) dose that reaches a tissue of interest.
- Biologically effective (target) dose. The biologically
effective dose is the portion of the delivered dose that reaches
the site or sites of toxic action.
The link, if any, between biologically effective (target) dose
and subsequent disease or illness depends on the relationship between
dose and response (e.g., shape of the dose-response curve), underlying
pharmacodynamic mechanisms (e.g., compensation, damage, repair), and
important susceptibility factors (e.g., health status, nutrition,
stress, genetic predisposition).
* Biological effect. A measurable response to dose in a molecule,
cell or tissue is termed a biological effect. The significance of a
biological effect, whether it is an indicator or a precursor for
subsequent adverse health effects, may not be known.
* Adverse effect. A biological effect that causes change in
morphology, physiology, growth, development or life span which
results in impairment of functional capacity to compensate for
additional stress or increase in susceptibility to the harmful
effects of other environmental influences (IPCS, 1994).
1.3 Elements of exposure assessment
Assessing human exposure to an environmental agent involves the
qualitative description and the quantitative estimation of the agent's
contact with (exposure) and entry into (dose) the body. Although no
two exposure assessments are exactly the same, all have several common
elements: the number of people exposed at specific concentrations for
the time period of interest; the resulting dose; and the contribution
of important sources, pathways and behavioural factors to exposure or
dose. A list of the types of estimates that might comprise a
comprehensive exposure assessment could include the following (as
described in part by Brown (1987) and Sexton et al. (1995a)):
* Exposure
- routes, pathways and frequencies
- duration of interest (short-term, long-term, intermittent or
peak exposures)
- distribution (e.g., mean, variance, 90th percentile) --
population, important subpopulations (e.g., more exposed, more
susceptible)
- individuals -- average, upper tail of distribution, most exposed
in population.
* Dose
- link with exposures
- distribution (e.g., mean, variance, 90th percentile) --
population important subpopulations (e.g., higher doses, more
susceptible)
- individuals -- average, upper tail of distribution, highest dose
in population.
* Causes
- relative contribution of important sources
- relative contribution of important environmental media
- contribution of important exposure pathways
- relative contribution of important routes of exposure.
* Variability
- within individuals (e.g., changes in exposure from day to day
for the same person)
- between individuals (e.g., differences in exposure on the same
day for two different people)
- between groups (e.g., different socio-economic classes or
residential locations)
- over time (e.g., changes in exposure from one season to another)
- across space (e.g., changes in exposure/dose from one region of
a city, country to another).
* Uncertainty
- lack of data (e.g., statistical error in measurements, model
parameters, etc.; misidentification of hazards and causal
pathways)
- lack of understanding (e.g., mistakes in functional form of
models, misuses of proxy data from analogous contexts).
Although comprehensive exposure assessments could be considered
the ideal, they are very costly; decisions therefore need to be made
on the most important elements for inclusion. For any study, the
purpose must first be defined. Possible purposes include environmental
epidemiology, risk assessment, risk management or status and trend
analysis (see Chapter 2). The data elements and measuring approaches
that are needed for this purpose are then determined. Table 3
summarizes the basic information that is required for each study. It
should be mentioned that different elements of the exposure assessment
framework might be selected to meet different study requirements.
Table 3. Basic information needed for exposure assessments in
different contexts
Information required
Risk assessment Point estimates or distributions of
exposure and dose
Duration of exposure and dose
Risk management Pollutant source contributing to
(conducted once hazard exposure and dose
is identified) Personal activities contributing
to exposure and dose
Effectiveness of intervention measures
Status and trend Change of exposure and dose of
populations over time
Epidemiology Individual and population exposures and
doses, exposure dose categories
1.4 Approaches to quantitative exposure assessment
Quantitative estimation of exposure is often the central feature
of assessment activities. The quantitative estimation of exposure can
be approached in two general ways: direct assessment, including
point-of-contact measurements and biological indicators of exposure;
and indirect assessment, including environmental monitoring,
modelling, questionnaires (US NRC, 1991b) (see Chapter 3.5). These two
generic approaches to quantitative estimation of exposure are
independent and complementary. Each relies on different kinds of data
and has different strengths and weaknesses. It is potentially useful,
therefore, to employ multiple approaches as a way of checking the
robustness of results. Among other factors, the choice of which method
to use will depend on the purpose of the assessment and the
availability of suitable methods, measurements and models.
Direct approaches for air, water and food include personal air
monitors, measurements of water at the point of use and measurement of
the food being consumed. Indirect approaches include
microenvironmental air monitoring and measurements of the water supply
and food supply (contents of a typical food basket, for instance).
Exposure models are constructed to assess or predict personal
exposures or population exposure distributions from indirect
measurements and other relevant information.
Measures of contaminants in biological material (biomarkers)
afford a direct measure of exposure modified by and integrated over
some time in the past which depends on physiological factors that
control metabolism and excretion. Such measures give no direct
information about the exposure pathways. Examples of the type of
biomarkers measured in human material that can be used for
reconstructing internal dose and their relevance to exposure
assessment are discussed in Chapter 10.
1.5 Linking exposure events and dose events
The schematic framework in Fig. 2 shows how the
interrelationships among significant exposure- and dose-related events
in the paradigm can be conceived.
It is important to keep in mind that, although events along the
continuum are correlated, the relative position of a particular
individual within a distribution may change dramatically from one
event to the next as the agent or its metabolite/derivative moves
through the various stages from exposure concentration to biologically
effective dose.
To make realistic estimates for a specific event (e.g., an
internal dose), it is necessary to have at least one of two types of
information: measurements of the event itself (e.g., internal dose),
or measurements of an earlier (e.g., potential dose) or later (e.g.,
delivered dose) event in the continuum. It is also necessary to
understand the critical intervening mechanisms and processes (e.g.,
pharmacokinetics) that govern the relationship between the event
measured and the event of interest (e.g., internal dose). Unless such
data are on hand, extrapolating from one event to another, moving
either from exposure to dose (downwards in Fig. 2) or from dose to
exposure (upwards in Fig. 2) is problematic.
Suitable data and adequate understanding are seldom, if ever,
available to describe and estimate all of the significant events for
the groups and individuals of interest. Generally speaking,
measurement of exposure concentration and delivered dose (body
burden) is in many cases relatively straightforward, whereas
measurement of potential (administered) dose and internal (absorbed)
dose is usually possible only with substantially greater effort.
Measurement of biologically effective (target) dose may also be
possible in some cases, although it is usually impossible to measure
the applied dose.
This situation presents us with a conundrum. We would like to
have realistic estimates of exposure concentrations of an agent for
all important pathways, and the resulting biologically effective dose.
Typically, however, if relevant data are available at all, they are
related to exposure concentrations for one pathway or route of
exposure. In the few cases where data on dose are also available,
these data usually reflect delivered dose (body burden) rather than
biologically effective dose. Even if suitable measurements of both
exposure concentration and delivered or target dose are on hand, the
absence of pharmacokinetic understanding to relate these measurements
to each other, as well as to other significant events along the
continuum, seriously impairs efforts to establish the link between
exposure and dose.
We are thus left with a situation in which we can measure
specific events on either side of the body's absorption boundaries,
but we can relate them to each other only by using a series of
unsubstantiated assumptions. Yet it is this relationship between
exposure and dose that is critical to, for example, establishing cause
and effect relationships between exposure and diseases.
1.6 Summary
Exposure requires the occurrence of the presence of an
environmental toxicant at a particular point in space and time; and
the presence of a person or persons at the same location and time. In
addition, the amount which comes in contact with the outer boundary of
the human body is required.
As the intrinsic value of exposure-related information has become
recognized, "exposure analysis" has emerged as an important field of
scientific investigation, complementing such traditional public health
disciplines as epidemiology and toxicology, and is an essential
component in informed environmental health decision-making (Goldman et
al., 1992; Sexton et al., 1992, 1994; Wagener et al., 1995).
2. USES OF HUMAN EXPOSURE INFORMATION
2.1 Introduction
Exposure assessments collect data on the route magnitude,
duration, frequency and distributions of exposures to hazardous agents
for individuals and populations. Human exposure data have been used
for the evaluation and protection of environmental health in four
interrelated disciplines: epidemiology, risk assessment, risk
management, and status and trends analysis. The fundamental goal of
exposure assessment studies is to reduce the uncertainty of the
exposure estimates that are used within each discipline to make public
policy decisions or reach research conclusions.
Epidemiology is the examination of the link between human
exposures and health outcomes (Sexton et al., 1992). Risk
assessment is the estimation of the likelihood, magnitude and
uncertainty of population health risks associated with exposures. In
contrast, risk management is the determination of the source and
level of health risks and which health risks are acceptable and what
to do about them. Status and trends analysis comprises the evaluation
of historical patterns, current status and possible future changes in
human exposures.
The purpose of this chapter is to describe the disciplines from
environmental epidemiology through risk assessment. It also describes
how human exposure assessment data are used in each of these
disciplines
2.2 Human exposure information in environmental epidemiology
Epidemiology is the study of the determinants and distribution of
health status (or health-related events) in human populations.
Environmental epidemiology searches for statistical associations
between environmental exposures and adverse health effects (presumed)
to be caused by such exposures. It is a scientific tool that can
sometimes detect environmentally induced health effects in
populations, and it may offer opportunities to link actual exposures
with adverse health outcomes (US NRC, 1991c, 1994; Matanoski et al.,
1992; Beaglehole et al., 1993).
Exposure assessment methods can be used for identifying and
defining the low or high exposure groups. They can also be used for
devising more accurate exposure data from measured environmental
contaminant levels and personal questionnaire or time-activity diary
data, or estimating population exposure differences between days of
high and low pollution, or between high and low pollution in
communities using measured environmental and population behavioural
data (see also Chapters 3 and 5).
In particular, to establish long-term health effects of "low
dose" environmental exposures, epidemiological methods are the
predominant, if not only, tools at hand for health-effect assessment.
However, the excess risk of most environmentally related health
effects is small, with relative risks and odds ratios usually being
less than 2 across the observed range of exposure experienced by
populations. Furthermore, there are usually no "non-exposed"
comparison groups, and the factors contributing to the development of
diseases are numerous. As a consequence, environmental epidemiology
faces considerable methodological challenges. Adequate exposure
assessment is one key issue, as well as the need for studies conducted
with large populations.
2.3 Human exposure information in risk assessment
Risk assessment is a formalized process for estimating the
magnitude, likelihood and uncertainty of environmentally induced
health effects in populations. Exposure assessment (e.g., exposure
concentrations and related dose for specific pathways) and effects
assessment (i.e., hazard identification, dose-response evaluation) are
integral parts of the risk assessment process. The goal is to use the
best available information and knowledge to estimate health risks for
the subject population, important subgroups within the population
(e.g., children, pregnant women and the elderly), and individuals in
the middle and at the "high end" of the exposure distribution (US NRC,
1983; Graham et al., 1992; Sexton et al., 1992).
Environmental health policy decisions should be based on
established links among emission sources, human exposures and adverse
health effects. The chain of events depicted in Fig. 4 is an
"environmental health paradigm": a simplified representation of the
key steps between emission of toxic agents into the environment and
the final outcome as potential disease or dysfunction in humans. This
sequential series of events serves as a useful framework for
understanding and evaluating environmental health risks (Sexton, 1992;
Sexton et al., 1992, 1993). It is directly related to the risk
assessment process.
* Exposure assessment in the risk assessment framework focuses on
the initial portion of the environmental health paradigm: from
sources, to environmental concentrations, to exposure, to dose. The
major goal of exposure assessment is to develop a qualitative and
quantitative description of the environmental agent's contact with
(exposure) and entry into (dose) the human body. Emphasis is placed
on estimating the magnitude, duration and frequency of exposures,
as well as estimating the number of people exposed to various
concentrations of the agent in question (US NRC, 1983, 1991a;
Callahan & Bryan, 1994).
* Effects assessment examines the latter portion of the events
continuum: from dose to adverse health effects (Fig. 4). The goals
are to determine the intrinsic hazards associated with the agent
(hazard identification) and to quantify the relationship between
dose to the target tissue and related harmful outcomes
(dose-response/effect assessment). The overlap between exposure
assessment and effects assessment reflects the importance of the
exposure-dose relationship to both activities (Sexton et al.,
1992).
* Risk characterization is the last phase of the risk assessment
process. The results of the actual exposure assessment and the
effects assessments are combined to estimate the human health risks
from the exposures.
Systemic (non-cancer) toxicants are usually assumed to have
thresholds below which no effects occur. For these toxicants, safety
assessments are performed with establishment of tolerable intakes
(IPCS, 1993) or reference concentrations/doses (USEPA). From these,
guidelines are derived and standards designed to protect public
health. Ambient concentration standards, and workplace personal
exposure limits, are often established at or below threshold levels
determined as part of the risk assessment process. Although these
standards are set with safety margins, exposures that exceed these
reference levels raise concerns about potentially elevated health
risks for the exposed population (Fig. 5a).
Quantitative risk assessment for carcinogens is a well
established, albeit controversial, procedure. As part of the
guidelines developed by the WHO, it is common practice to extrapolate
from high to low dose by assuming a linear, non-threshold model for
carcinogenicity. Under this assumption, cancer risk for individuals
can be estimated directly from the exposure or dose distribution, and
the number of excess cancer cases (i.e., the increase above background
rates) in the exposed population can usually be estimated by
multiplying the average dose by both the total number of people
exposed and the dose-response slope factor (Fig. 5b). Although
individual risk is assumed to increase with increasing exposure and
dose all along the distribution, exposures of concern are typically
defined to be those above some minimal level of risk (e.g., WHO
considers this to be a 1 in 105 or 106 excess lifetime risk of
developing cancer). Unit cancer risk numbers are given in inverse
concentration units for food, water and air as (ppm)-1, (ppb)-1 or
mg-1m-3). Expressed in inverse dose units (mg kg-1day-1), the cancer
slope risk factor is multiplied by ingestion or inhalation rates and
adjusted for body weight. Individual cancer risk is calculated by
assuming a lifetime of exposure at a given level of contamination.
When exposure data are available, it is then possible to approximate
the cancer risk of the typical or average person in the population or
one who might be at maximum risk due to a greater level of exposure.
In regulatory applications of risk assessments, exposure
estimates are often constructed using existing data or single point
measurements to estimate the risk of a facility, hazardous waste site
or chemical waste site, or even the use of a chemical product. This
approach can result in large errors in the exposure assessment and
hence the risk assessment. Exposure assessment studies are used to
obtain a more accurate determination of the exposure associated with a
health impact outcome of concern. Population-based risk assessments
benefit from the use of population-based measurements derived from
surveys or models (see Chapter 3) to estimate the distribution of
health effect outcomes in the total exposed population over a
specified time period.
2.3.1 Risk allocation for population subgroups or activities
Exposure studies may also be conducted to provide more realistic
and location-specific information for use in human health risk
assessments. Measurement data on pollutant concentrations and exposure
factors, such as contact rates, can be used instead of relying on
assumed "default" values for an "averaged" or representative
individual. An example of an exposure study designed to collect data
for the purpose of allocating risk to locations, sources and
activities is the Windsor Air Quality Study conducted in Windsor,
Ontario, Canada (Bell et al., 1994).
The Windsor Air Quality Study was designed to investigate the
Windsor airshed characteristics with respect to airborne toxic
compounds and to determine personal inhalation exposures to these
compounds. Data were then used as inputs for a multimedia assessment
of risk due to total pollutant exposure. The air quality study
examined just one aspect, the inhalation route. It was designed to
separately attribute risk to several airborne contaminants by indoor
and outdoor locations. Statistical analysis and inference were used to
impute source contributions to population risk (i.e., the waste
incinerator across the river in Detroit, Michigan, USA) for selected
volatile organic compounds (VOCs), carbonyls and trace metals (see
Table 4) based on microenvironmental and personal measurements and
time activity patterns. In general, air quality was determined to be
relatively poor in recreation halls, new office buildings, cars and
garages when compared to outdoor air quality standards and criteria.
Although high contaminant concentrations were detected in various
microenvironments, population exposures (defined as the product of
concentration and time) were relatively low because the study subjects
did not spend any appreciable time in those microenvironments. This
point is illustrated in Fig. 6. For all of the VOCs, the highest
concentrations were measured during the commuting periods, with
comparable concentrations being measured indoors at the office and
home and the lowest outdoors (Table 3). When time in each
microenvironment is considered, exposure in the home accounted for
over 70% of the total exposure profile for that individual.
Table 4. Target analytes in the Windsor air quality study
Volatile organic compounds
Propane, chloromethane, 2-methylpropane, chloroethene, 1,3-butadiene, butane,
2-methylbutane, pentane, isoprene, 1,1-dichloroethene, dichloromethane, allyl chloride,
hexane trichloromethane, 1,2-dichloroethane, 1,1,1-trichloroethane, benzene,
tetrachloromethane, xylenes, styrene, o-xylene, 1,1,2,2-tetrachloroethane, nonane,
1,3,5-trimethylbenzene, 1,2,4-trimethylbenzene, 1,4-dichlorobenzene; decane,
1,2-dichlorobenzene, undecane, 1,2,4-trichlorobenzene, dodecane, tridecane
Carbonyls
Formaldehyde, acetaldehyde, acrolein, acetone, propianaldehyde, crotonaldehyde, methyl
ethyl ketone, benzaldehyde, isovaleraldehyde, 2-pentanone, valeraldehyde, o-tolualdehyde,
m-tolualdehyde, p-tolualdehyde, methyl isobutyl ketone, hexanal, 2,5-dimethylbenzaldehyde
Trace metals
Beryllium, chromium, manganese, nickel, arsenic, selenium, cadmium, lead
Results of the study emphasize the importance of exposure
assessments for policy decisions. For this community, changes in
lifestyle, consumer product formulations, cleaning of indoor air and
increased ventilation would probably have more impact on reducing
health risks from exposures to VOCs than reliance on
government-mandated abatement strategies for ambient sources.
2.3.2 Population at higher or highest risk
Risk assessment may be used to identify and evaluate those
populations, subpopulations and individuals at potentially greater
risk so that, if warranted, appropriate mitigation actions can be
implemented. Individuals and groups are deemed to be at potentially
higher risk because they are exposed to high concentrations of
hazardous pollutants (Sexton et al., 1993). Individuals and groups can
also be at increased risk because they are more susceptible to the
adverse effects of a given exposure. Among the potential causes of
enhanced susceptibility are inherent genetic variability, age, gender,
pre-existing disease (e.g., diabetes, asthma), inadequate diet,
environmental or lifestyle factors (e.g., smoking), stress and
inadequate access to health care. As far as possible, it is important
to identify these susceptible individuals and groups so that we can
understand their exposures and take account of this information in
assessing and managing risks. Exposure and risk information for
susceptible populations is critical since health standards and
regulations are often developed with the intent of protecting these
individuals.
Exposure studies provide valuable information for the risk
assessment by quantifying the distribution of exposures in a
population and identifying those subpopulations or individuals who
have the highest exposures. Information is also gathered on
characteristics of the populations and factors that could contribute
to elevated exposures. In these studies, measures of central tendency,
such as the median and average, along with expressions of variability,
such as the standard deviation, are commonly used to describe the
distribution of exposures for a population (Fig. 7). Often, the
relative position of an individual or group in the exposure
distribution is of primary interest to the exposure assessor. Among
the most frequently used descriptors for individual and subgroup
exposures are values near the middle of the distribution, values above
the 90th percentile and values at the extreme upper end, such as for
the most exposed person in the population. Exposure studies that are
targeted on susceptible populations are used with the same type of
inputs in risk assessment for these groups.
2.4 Human exposure information in risk management
Risk management decisions carried out by policy-makers are of
four basic types: priority setting, selection of the most
cost-effective method to prevent or reduce unacceptable risks, setting
and evaluating compliance with standards or guidelines, and the
evaluation of the success of risk mitigation efforts. Exposure
information is crucial to these decisions. In addition to data on
exposures and related health effects, decision-makers also must
account for the economic, engineering, legal, social and political
aspects of the problem (Burke et al., 1992; Sexton et al., 1992).
Conceptually, as shown in Fig. 8, estimating and prioritizing
health risks are seemingly straightforward. Risk is a combination of
effects estimates, where "highest" priorities can be thought of as
those that entail both "high" toxicity for the agent of interest
(adverse effects are likely to occur in humans at relatively low
exposures or doses), and "high" exposures for the population,
subpopulation or individuals of interest (exposures or doses are above
a health-based standard). Conversely, "lowest" priority risks involve
"low" toxicity and "low" exposures. "Medium" priority risks are those
for which either toxicity or exposure is "low" while the other is
"high" (Sexton, 1993). The Windsor Air Quality Study, for example,
showed that incinerator emissions contributed little to total human
exposure for VOCs. Despite the fact that the pollutants were of high
toxicity, incinerator emissions were considered to be of relatively
low risk to the population. In contrast, studies show that second-hand
smoke has both high toxicity and high human exposures, and should
therefore be identified as a high priority risk.
Risk mitigation proceeds from first determining that an exposure
is a hazard (risk assessment) to identifying and quantifying the route
and the environmental pathways for a contaminant. Where a contaminant
has multiple sources or routes of exposure, relative contributions to
individual and population risk must be determined. Exposure
assessments are crucial for developing this information, and may rely
on both measurements and modelling. Once this information is obtained,
then effort can be directed toward the most effective mitigation
strategies.
In fact, intervention studies are implicitly or explicitly
predicated on the sequence of risk assessment and mitigation.
Intervention at the source, transmission or receptor (receiving
person) is intended to reduce the effect or risk of an effect.
Prohibiting smoking in public buildings or sections of restaurants is
designed to separate sources from receptors. Specific ventilation
requirements for operating theatres or isolation rooms of infectious
patients are designed to dilute potential contaminants and pathogens.
On a larger scale, substitution of cleaner fuels (e.g., reformulated
or unleaded gasoline, cleaner coal, low-sulfur oil, natural gas)
radiation of food or ozonation of drinking-water are examples of risk
mitigation interventions based on the assumption that contaminant
reductions experienced in the environmental media will result in a
corresponding reduction in actual exposures and hence risk. It is
essential, then, to understand the efficacy of mitigation strategies
with respect to their effect on human exposures.
The combined use of total exposure assessment for air,
receptor-source modelling and economic principles can assist
environmental policy and regulation in developing risk mitigation
strategies. The hybridization of these well-developed models can be
used to assist in the identification of priority sources to target
regulatory programmes, and in the development of cost-effective
strategies for air pollution control to bring about the greatest and
earliest reduction in pollutant exposures.
Epidemiological information about the health effects of
relatively low levels of air pollutants now raises controversial
policy issues for risk management. On the one hand, the economic
consequences of these health effects may be substantial; on the other
hand, for some pollutants, control measures may become very expensive.
For pollutants such as VOCs, for example, exposure monitoring rather
than ambient air monitoring may lead to more rapid and cost-effective
risk reduction policies.
Developed countries have experimented with regulatory reforms
that include emission trading. Basically, the concept calls for
emission reduction at one source to be credited to the emission levels
at another source. These trading schemes are based on the assumption
that equal mass emission reduction of a pollutant would result in
equal health or ecological benefits. Thinking in terms of total
exposure assessment reorients the relative importance of sources and
their impacts on different populations. Accordingly, control options
for reducing exposures can be broadened (Smith, 1995).
2.5 Human exposure information in status and trend analysis
Evaluating the current status of exposures and doses in the
context of historical trends is an important tool for both risk
assessment and risk management. In many cases it requires collecting
exposure data over a relatively long period of time (e.g., 5-20
years). This can only be done through an exposure assessment study and
often when the contaminant has a long residence time in the
environment or biological tissue. If concentrations of a contaminant
exhibit high variability in environmental media, the study may require
relatively large sample sizes, the use of probability samples and/or
extensive follow-up to observe trends. Data on status and trends can
be invaluable for identifying new or emerging problems, recognizing
the relative importance of emission sources and exposure pathways,
assessing the effectiveness of pollution controls, distinguishing
opportunities for epidemiological research and predicting future
changes in exposures and effects (Goldman et al., 1992; Sexton et al.,
1992).
Exposure studies may be conducted to document the status and
trends of human exposure (e.g., Kemper, 1993; Noren, 1993). A good
example of a study designed for this purpose is the German
Environmental Survey (GerES). The nationwide representative survey was
conducted for the first time in 1985-1986, on behalf of the Federal
Ministry for the Environment, Nature Conservation and Reactor Safety.
In 1990-1991 the survey was repeated in West Germany (the FRG before
reunification) and in 1991-1992 it was extended to East Germany
(former GDR) (Krause et al., 1992; Schulz et al., 1995).
The purpose of the survey was to establish a representative
database on the body burden of the general population. Biological
monitoring was used to characterize exposure to pollutants
(predominantly heavy metals). In addition, the occurrence of a number
of pollutants in the domestic area likely to contribute to total
exposure (house dust and drinking-water) was studied. The design of
the study is summarized as follows:
* Population samples. Cross-sectional samples using a stratified
two-step random sampling procedure according to the size of the
community, gender and age. The final set included 2731 West Germans
in 1985-1986 and 4287 adults from East and West Germany in
1990-1992 (aged 25-79 years). In addition about 700 children (aged
6-14 years) living in the same households were included in
1990-1992.
* Human biomonitoring. Analysis of blood (lead, cadmium, copper,
mercury), spot urine (arsenic, cadmium, copper, chromium, mercury)
and scalp hair (aluminium, barium, cadmium, chromium, copper,
magnesium, phosphorus, lead, strontium and zinc).
* Questionnaires. Questions about social factors, smoking habits,
potential sources of exposure in the domestic, working, and general
environment, and nutritional behaviour.
* Domestic environment. Concentration of trace elements in dust
deposit indoors, in vacuum cleaner bags (pentachlorophenol [PCP],
lindane and pyrethroids) and in household tap water; determination
of VOCs in homes of a subsample of 479 participants (passive
sampling) in 1985-1986.
* Personal sampling. Determination of VOCs by personal sampling
using a subsample of 113 people in 1991.
* Dietary intake. A 24-h duplicate study in 1990-1992 with a
subsample of 318 people.
Characteristics of the frequency distributions (percentiles) and
other statistical parameters of the concentration of elements and
pollutants in the different media were calculated. As an example, the
concentrations of elements and compounds in blood and urine of the
German adult population analysed in 1990-1992 are shown in Table 5.
The 1990-1991 and 1991-1992 surveys showed differences between East
and West Germany. The mercury concentrations in blood and urine as
well as the cadmium, chromium and copper concentrations in urine were
significantly higher ( p < 0.001) in East Germany than in West
Germany. The blood lead level was identical in both study populations
(geometric mean 45 µg/litre).
The comparison of the results for the biological, personal and
microenvironmental exposure measurements taken in East Germany in
1985-1986 and in 1990-1992 permits an analysis of trends over time.
The success of abatement measures could be shown in a number of cases:
the reduction of lead concentrations in petrol and of industrial
cadmium emissions resulted in decreased lead and cadmium
concentrations in the blood of the general population. The ban on PCP
led to a decrease of PCP in house dust. The results of the GerES have
provided a useful set of reference data to characterize and to assess
exposures of the general population. They have also been useful for a
number of risk assessments, for example the role of copper in
drinking-water and liver cirrhosis in early childhood, and presence of
mercury in amalgam fillings.
2.6 Summary
The specifics of any particular exposure analysis hinge on its
intended use or uses. For example, the pertinent aspects of exposure
to be considered, the nature of the information required and the
necessary quantity and quality of the data will depend on whether the
exposure assessment is being conducted in the context of an
epidemiological investigation (Matanoski et al., 1992), risk
assessment (Graham et al., 1992), risk management (Burke et al., 1992)
or status and trend analysis (Goldman et al., 1992) (see also Chapter
1, Table 1).
Table 5. Elements and compounds in blood and urine of the German population (aged 25-69 years, 1990-1992)
(Krause et al., 1992)
QL N <QL 10 50 90 95 98 MAX AM GM CI GM
Blood
Lead (µg/litre) 15 3966 61 24.0 45.3 86.8 105.6 134.2 708.0 52.4 45.3 44.5-46.0
Cadmium (µg/litre) 0.1 3965 231 0.1 0.3 1.9 2.6 3.6 11.3 0.7 0.4 0.4-0.4
Copper (mg/litre) 0.1 3968 0 0.8 0.9 1.2 1.3 1.5 2.5 1.0 0.9 0.9-1.0
Mercury (µg/litre) 0.2 3958 632 <0.2 0.6 1.6 2.1 3.0 12.2 0.8 0.5 0.5-0.5
Urine
Arsenic (µg/litre) 0.6 4001 210 1.8 7.1 19.8 29.9 56.7 205.5 10.5 6.3 6.1-6.5
Arsenic (µg/g creatinine) 4001 1.4 4.9 15.3 24.1 40.0 147.6 7.6 4.6 4.5-4.8
Cadmium (µg/litre) 0.1 4002 150 0.1 0.3 0.9 1.3 1.7 6.9 0.4 0.3 0.3-0.3
Cadmium (µg/g creatinine) 4002 0.1 0.2 0.7 0.9 1.3 6.1 0.3 0.2 0.2-0.2
Chromium (µg/litre) 0.2 4002 1716 0.15 0.2 0.4 0.6 1.0 21.2 0.3 0.2 0.2-0.2
Chromium (µg/g creatinine) 4002 0.0 0.1 0.3 0.5 0.9 10.6 0.2 0.1 0.1-0.1
Copper (µg/litre) 1.1 4002 20 4.5 9.7 18.7 22.9 28.7 444.2 11.6 9.5 9.3-9.7
Copper (µg/g creatinine) 4002 3.5 6.7 13.1 17.7 28.5 420.7 8.9 6.9 6.8-7.1
Mercury (µg/litre) 0.2 4002 785 <0.2 0.5 2.6 3.9 6.0 53.9 1.1 0.5 0.5-0.6
Mercury (µg/g creatinine) 4002 0.1 0.4 1.6 2.2 3.2 73.5 0.7 0.4 0.4-0.4
Nicotine (µg/litre) 5 3750 1566 <5 9.3 1438 2431 3567 10 984 422 24.9 23.0-27.1
Nicotine (µg/g creatinine) 3748 1.3 7.0 1003 1636 2431 10 478 292 18.4 17.0-20.0
Cotinine (µg/litre) 5 3800 1813 <5 5.6 2037 2681 3483 6573 537 26.6 24.3-29.1
Cotinine (µg/g creatinine) 3798 1.3 4.9 1396 1940 2788 8111 388 19.6 17.9-21.4
Creatinine (mg/100 ml) 0 4002 0.7 1.5 2.5 2.9 3.2 5.7 1.5 1.4 1.3-1.4
Annotations: QL = quantification limit, N = sample size, n < QL = number of values below QL, 10, 50, 90, 95, 98 = percentiles,
MAX = maximum value, AM = arithmetic mean, GM = geometric mean.
Source: UBA, WaBoLu, Environmental Survey 1990-1992, Federal Republic of Germany.
Knowledge of human exposures to environmental contaminants is an
important component of environmental epidemiology, risk assessment,
risk management and status and trends analysis. Exposure information
provides the critical link between sources of contaminants, their
presence in the environment and potential human health effects. This
information, if used in the context of environmental management
predicated on human risk reduction, will facilitate selection and
analysis of strategies other than the traditional "command and
control" approach. Most of the environmental management structures
around the world rely directly on the measured contaminants in various
media to judge quality, infer risk and interpret compliance. Even in
these cases, exposure information can evaluate the effectiveness of
protecting segments of population more susceptible or at higher risk.
It is this direct connection that makes exposure measures
invaluable for evaluation of environmental health impacts on a local,
regional and global scale.
3. STRATEGIES AND DESIGN FOR EXPOSURE STUDIES
3.1 Introduction
Accurate estimates of human exposure to environmental
contaminants are necessary for a realistic appraisal of the risks
these pollutants pose and for the design and implementation of
strategies to control and limit those risks. Three aspects of exposure
are important for determining related health consequences:
* Magnitude: What is the pollutant concentration?
* Duration: How long does the exposure last?
* Frequency: How often do exposures occur?
The design of an exposure study specifies the procedures that will be
used to answer these three questions.
In this chapter, strategies and designs for exposure studies are
discussed with emphasis on their relative advantages and
disadvantages. The brief discussion of study design presented in
Chapter 1 is expanded upon here in terms of fundamental types of
generic study designs and approaches to assessing human exposure to
chemicals in the environment. Statistical considerations for study
design are presented in Chapter 4. The reader is referred to
subsequent chapters for details on implementing exposure study designs
through modelling (Chapter 6), monitoring of environmental media
(Chapters 7, 8 and 9) and monitoring of biological tissue (Chapter
10).
3.2 Study design
A good study design is the most important element of any exposure
study. A flow chart that includes critical elements is shown in Fig.
9. First the purpose of the study is defined: epidemiology, risk
assessment, risk management or analyses of status and trends (see also
Chapter 2). Within this context, specific study objectives are
formulated. Often studies have several objectives, which must be
prioritized to ensure that the primary objective is fulfilled. Study
parameters must be selected that are consistent with the objective. A
study design is formulated which links objectives to measurement
parameters in a cost-effective manner. Two critical and often
overlooked elements of the study design are development of a
statistical analysis plan and quality assurance (QA) objectives. For
general population studies, methods for measurement and analysis of
contaminants in collected environmental or biological samples must be
sufficiently sensitive to determine their concentration at typical
ambient levels. For multimedia studies, method detection limits must
be consistent across media. The study design is not complete until a
pilot study has been conducted to evaluate sample and field study
procedures.
3.3 Sampling and generalization
Decisions on population sampling strategies involve consideration
both of the populations that are available and of the types of
measurements needed. Of prime consideration are the people, place and
time (i.e., individuals, locations, sampling period or conditions)
from which exposure samples are to be collected. Also, it is important
to determine if the estimates to be derived from the proposed sample
could be generalized to a wider population of interest. For example,
consider an exposure assessment study from a sample population of a
small town in southwestern Australia. The many potential populations
of interest which this sample might generalize include: all people
living in that town; people living in a small southwestern Australia
town; people living in southwestern Australia; people living in
Australia; people living in any small town; people in general. In this
case, the sample population is not likely to provide a representative
sample of the latter two populations.
The appropriateness of the generalization is determined by
considering if the sample is randomly selected in such a way as to be
representative of the larger population of interest (Whitmore, 1988).
This randomization is in terms of the distribution of the collected
data. For continuous outcomes, the percentages of key attributes, such
as demographic factors, should be similar between the sample and the
population. However, when this is not possible, owing to limited
funding for example, a descriptive study (described below) can provide
credible data, although the extent to which these can be generalized
is limited.
3.4 Types of study design
Once the population is defined, then the attention shifts to
sampling strategies; in particular, comprehensive samples, probability
samples, and other types of samples. A comprehensive sample includes
all members of the selected population. In a probability sample each
member has a known likelihood of being selected. Simple random
sampling is a special case where each member of the population has
an equal probability of being selected. Other types of study groups
are selected on the basis of other characteristics, such as
availability or convenience.