Introduction to

Exposure Assessment
Marina E. Eremeeva
meremeeva@georgiasouthern.edu
September 1, 2011
9/1/2011

Introduction
Exposure

a substance or factor affecting human

health

Assessment

a study of distribution and determinants

of exposure
design
data collection
data interpretation and analysis

Components

Focus

chemical
physical
biological

Risks

significant
small

9/1/2011

What Types of Exposures?

Characteristic

Occupational exposure

Environmental exposure

Exposure level

High

Low

Duration of exposure

Short

Extended

Temporal/spatial distribution Defined

Sporadic

Population affected

Healthy adults

All age groups and

susceptible individuals

Activity

Similar

Variable

9/1/2011

Epidemiological Study Design

Major Aim
To determine if there is an association of a
particular substance and morbidity and/or
mortality to humans

Types of Studies
1. Cohort study (relative risk or incidence rate ratio)
2. Cross-sectional study (prevalence ratio)
3. Case-control study (odds-ratio)
4. Time series study (exposure variability)
9/1/2011

Exposure Estimates (Indices)

Required by all studies
Variable depending on the study design
Must be
accurate
o precise
o biologically relevant
o cover entire range of exposure levels

Must consider confounder assessment

9/1/2011

Example 1: Relative Risks* of Oral Cancer According to

Level of Exposure to Alcohol and Smoking
Alcohol
consumption
(oz/day)

Cigarette equivalents per day

0

< 20

20-39

> 40

1.00

1.52

1.43

2.43

<0.4

1.40

1.67

3.18

3.25

0.4-1.5

1.60

4.36

4.46

8.21

>1.5

2.33

4.13

9.59

15.50

*Risks are expressed relative to a risk of 1.00 for persons who neither smoked not drunk

Source: Rothman K. & Keller A. 1972. The effect of joint exposure to alcohol and tobacco on risk of
cancer of the mouth and pharynx. J. Chron. Dis. 25: 711-716.
9/1/2011

Example 2: Summary of Epidemiological Studies on

Childhood Cancer
Study

Case selection

Control
selection

Exposure
markers

Cofounders
analyzed

Additional
notes

Wertheimer
& Leeper
(1979)

Cancer mortality records

(1950-73) of persons under
19 yr old, born in CO and
resided in Denver; largest
number of cases used in
the analysis 328.

Denver area birth

certificates.
Controls enrolled:
344

2-level wire code

(HCC vs. LCC),
non-blinded wire
code assessment

Cancer onset age

Urban/suburban
Socioeconomic
Birth order
Maternal age
Traffic congestion
Gender

Crude relative risk

estimates cited.
Potential
confounders were
analyzed
individually.

Saviz et al.
(1988)

All cancer incidence cases

reported in Denver, CO
during1979-83 of persons
under 15 yr old. 356 cases
were identified
320 cases had 5-level wire
code assessed
252 cases were
interviewed
128 cases had magnetic
field measurement data

Controls selected
via random digit
phone dialing
methods.
Matched to cases
by age, gender, &
phone exchange
area.
278 controls,
259 had 5-level
wire codes
assessed
222 interviewed
207 measurement
data.

5-level wire code

In home electric
and magnetic
field spot
measurements
under low and
high power use
conditions

Gender, age
Housing, income
Socio-economic
Smoking, drug,
pregnancy
Traffic delay
Parental age
Race, education
Family cancer
In vivo alcohol exposure
X-ray, influenza,
medication
Birth defects, order,
weight
Illness
Residential stability
Medical X-ray

Control selection
procedures
resulted in the
controls being
more residentially
stable than the
cases.
Matched analysis
not performed.
Adjusted relative
risks estimates
were described
but not presented
in the table and
did not change the
results.

9/1/2011

Source: Wertheimer N. & Leeper E. 1979. Electrical wiring configurations and childhood cancer. Am J Epidemiol. 109:273-84. 7
Savitz D.A., et al. 1988. Case-control study of childhood cancer and exposure to 60-Hz magnetic fields. Am J Epidemiol. 128:21-38.

Source-Receptor Models:
exposure route and pathways
Exposure Pathway - physical course a
pollutant takes from the source to a subject
Exposure Route the way a pollutant enters
the body
Source-Receptor Model includes the routes
and pathways of exposure and aids to
understand how exposure occurs
9/1/2011

Major Exposure Routes

Respiratory inhalation
Gastrointestinal ingestion
Skin absorption

9/1/2011

Source-Receptor Model for Air Pollutants

Source

Environment

Car Emission Gas

Emissions/dispersion
Environmental concentrations
Micro-environmental concentrations

Exposure

Biologically relevant dose

Human

Whole-body uptake

Health impact
9/1/2011

10

Source: Nieuwenhuijsen M.J.

Distribution of Inhaled Particles

Inhalation particles : 100 mM
Thoracic particles : 40 mM
Respirable Particles :
PM2.5 Particles

4 mM

: 2.5 mM

Example 3. Exposure pathways, routes

and biomarkers for thrihalomethanes
Exposure pathways
Drinking tap water/
Tap water based drinks
Showering
Bathing
Swimming
Dishwashing
Toilet

9/1/2011

Source: Nieuwenhuijsen M.J.

Exposure routes

Biomarker

Ingestion
Serum
Skin absorption

Exhaled breath
Inhalation

12

What Happen in a Human Body?

ADME absorption, distribution, metabolism
and excretion
PBPK physiologically based pharmacokinetics

9/1/2011

13

Physiologically Based Pharmacokinetics

(PBPK)
Inhalation of volatile organic chemical
Inhaled
chemical

Alveolar space

Exhaled
chemical

Pulmonary blood
Fat tissues
Venous blood flow

Moderately perfused tissues

(muscle, skin, bone, cartilage)

Arterial blood flow

Richly perfused tissues

(viscera, kidney, brain)

Liver
Metabolism
9/1/2011

Source: Nieuwenhuijsen M.J.

14

http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=202847
15

Exposure Parameters (Dimensions)

Duration (hours, days, years)
Concentration (mg/m3, mg/l)
Frequency (times per week)

Used to calculate
Exposure Index

Exposure Index may differ for different studies

Acute exposure:
short-term concentration
Chronic exposure: cumulative exposure

9/1/2011

16

Example 4. The relationship between various silica exposure

indices and silicosis in nine North American industrial sand plants
Employment duration (yr)

Exposure concentration
(mgm-3)

Cumulative exposures
(mgm-3 x yr)

Index

Odds ratio

Index

Odds ratio

Index

Odds ratio

< 16

1.0

< 100

1.0

< 700

1.0

16-22

1.0

> 100

2.4

700 to < 1800

2.5

22-27

0.7

>1800-5100

4.6

> 27

2.6

>5100

5.2

9/1/2011

Source: Nieuwenhuijsen M.J.

17

Exposure Level and Variability

Exposure concentration varies depending on
Time
Space
Exposure varies
Daily for any given individual (within)
Between different individuals or subjects
(between)

9/1/2011

18

Example 5. Variation in Fine Particulate Levels in the

Kitchen and Living Room over a Day (smocking household)

9/1/2011

Source: Wigzell et al. 2000. J. Exp. Anal. Env. Epid. 10:307-314// Classroom exercise

19

Example 6. Variation in Fine Particulate Levels in the Kitchen

and Living Room over a Day (non-smoking household)

9/1/2011

Source: Wigzell et al. 2000. J. Exp. Anal. Env. Epid. 10:307-314// Classroom exercise

20

Distribution of Exposure to Different Size

Particles

2004 by Oxford University Press

BROUWER D H et al. Ann Occup Hyg 2004;48:439-453

Quantitation of Exposure
Often has lognornal distribution
Best characterized by Geometric Mean (GM) and
Geometric Standard Deviation (GSD)
=

ln

GM= exp
Arithmetic Mean =

2=

lnln
1

GSD=exp

(average of exposure)

Range, Minimum, Maximum or 95% confidence

interval
9/1/2011

22

Ecological vs. Individual Exposure Estimates

Main Approaches
Individual estimates
Exposure grouping
population is split into smaller
subpopulations or exposure groups
based on specific determinants

9/1/2011

23

How to Define Exposure Groups?

Environmental Epidemiological Studies
presence of absence of an exposure source
distance from an exposure source
activity
Occupational Epidemiological Studies
similar work environment
similar professional duties
exposure to the same substances
9/1/2011

24

Exposure Classification,
Measurement, or Modeling
Main Aim to obtain accurate, precise and biologically
relevant exposure estimates using the most efficient and
cost effective tools
Tools for exposure estimates and analyses
o questionnaires
o air pollution monitors
o statistical techniques
Methods
o direct
o indirect
9/1/2011

25

Point of Decision Making

Increase in
accuracy and
precision
9/1/2011

Increase in
cost of
assessment
26

Exposure Assessment Approaches

Direct methods

Biological
monitoring

Personal
monitoring

Indirect methods

Environmental
monitoring/
modeling

Questionnaires
/diaries

PBPK modeling

Dose models

9/1/2011

Source: Nieuwenhuijsen M.J.

Exposure models

27

Exposure Classification
Occurrence of exposure
o
o

yes /no
no/low/medium/high

Recording exposure (who makes decision?)

o

9/1/2011

expert assessment
self-assessment

28

Exposure Measurement
Subjective methods (cheapest)
o expert assessment
o self-assessment
Objective methods (measurement of concentration)
o stationary ambient air models
o personal exposure monitors
o water and soil contamination
o biological monitoring

9/1/2011

29

Exposure Modeling
Typically can be carried out in conjunction with
exposure measurements to aid model building or
model validation
Types of modeling
o

9/1/2011

Deterministic (physical) modeling to describe the

relationship between variables mathematically on the
basis of knowledge of the physical, chemical and/or
biological mechanisms defining these relationship
Stochastic (statistical) modeling to establish statistical
relationships between variables

30

Example 7. Hierarchy of Exposure Data and

Surrogates for Fixed-Source Contaminants
N

Type of data

Quantified personal measurements

Quantified area measurements in the vicinity of the

residence or sites of activity

Quantified surrogates of exposure (e.g. estimates of

drinking water use)

Distance from the site and duration of exposure

Distance or duration of residence

Residence or employment in the geographical area in

reasonable proximity to the site where exposure can
be assumed

Residence or employment in a defined geographical

area (e.g. county) of the site

9/1/2011

Source: Nieuwenhuijsen M.J. adapted from NRC (1991)

Approximation to
actual exposure
Best

Worst

31

Validation Studies
In epidemiological studies, it is not feasible to
obtain detailed exposure information on each
subject of the study so validation on a
representative subset of a larger population is
ideal

What does this mean?

9/1/2011

32

Retrospective Exposure Assessment

In epidemiological studies for diseases of long
latency (cancer), current exposures are not
the concern, but that of the past.
A reconstruction of historical exposure is often
referred to as retrospective exposure
assessment and has gained an important role
in occupational epidemiology.
Many obstacles: changes in technology, job
titles and associated tasks (and exposures).
9/1/2011

33

Quality Control Issues

9/1/2011

Well-designed strategy
Well-trained and knowledgeable personnel
Estimated cost
Feasibility and pilot studies
Bias
Clear protocols

34

Terminology
to know, to use and to remember

Accuracy
Bias
Limit of detection (LOD)
Precision
Power
Reliability

9/1/2011

Reproducibility
Robustness
Sensitivity
Specificity
Validity

35

Additional Materials Used

1. Nuclear Medicine Technologists :
http://www.youtube.com/watch?v=wge1McxCkOU&feature=related
2. Canada nuclear plant accident turns drinking water radioactive :
http://www.youtube.com/watch?v=P1s2TpM7EEU
3. Silica exposure:
http://www2.worksafebc.com/Publications/Multimedia/Videos.asp?ReportID
=36018

9/1/2011

36