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Components of Risk Assessment
• Hazard Identification
• Dose-Response Assessment
• Exposure Assessment
• Risk Characterization
Uses of Exposure Assessment in
Risk Assessment
Hazard Identification
Dose-response assessment
Exposure Assessment
Risk Characterization
Risk Communication
• Used to estimate internal dose which, with dose response data
(usually in animals), is used to estimate risk.
• For risk-based regulations, provides the link to emissions (point
source, consumer products, area sources).
• Evaluation of efficacy of cleanup (risk to most exposed
subgroup).
Illustration of Exposure
Pathways
From:
Paustenbach, DJ.
(2000) The practice of
exposure assessment:
a state-of-the-art
review. J Toxicol Env
Health, 3:179-291
Exposure Assessment
• Once a dose-response relationship is
established, and often this is done in a
controlled situation such as a laboratory, one
can make certain statements.
• If the dose is “x”, then the response should be
“y.”
• A major problem confronting risk assessors
when trying to apply the dose-response
relationship to an actual “real-world” problem is
the question of what dose to use as
representative of the actual situation.
Definitions
• Exposure
– The contact with a chemical, biological, or physical
agent at the boundary of the body over a specified
time.
• Exposure Route
– How a substance contacts the body and results in an
internal dose (inhalation, ingestion, dermal
penetration).
• Boundaries of the body
– By Exposure Route: For inhalation, could be the
tissue in the lung separating air from blood. For
ingestion, the layer of cells, lining the gastrointestinal
tract.
Definitions II
• Exposure Pathway
– How a substance moves from the source to the
receptor (in this case, people).
• Intake
– Amount of substance that is inhaled or consumed
• Uptake
– Amount or fraction of intake that passes through a
boundary of the body
Definitions III
• Dose
– Applied Dose: amount available at a boundary
– Potential Dose: amount ingested or inhaled
– Internal Dose: the amount of a substance
crossing one of the route barriers into the
body
– Biologically-effective dose: the amount of a
substance reaching a target organ.
Definitions IV
• Bioavailability
– Most research is on ORAL, but also some on
dermal and inhalation
– Fraction of the administered dose that
reaches the central (blood) compartment
– Relative bioavailability compares different
FORMS or MEDIA
Why assess exposure?
(Isn’t it EASY?!)
• Determine factors that put segments of the
population at higher risk to chemical
toxicity
• Help establish dose-response
relationships in the “real world”
• Hazard = Toxicity x Exposure
Three elements of exposure
assessment
• Transportation, transformation and fate
processes
– Before it meets up with people
• Exposures
– As it meets up with people
• Physiologically based pharmacokinetics
(PBPK)
– What goes on In people
Exposure Elements
Transport, Transformation,
and Fate Process Models
SOURCE/STRESSOR EFFECT
FORMATION
Chemical Acute
Exposure Chronic
Microbial
Models
TRANSPORT/ DOSE
TRANSFORMATION
Dispersion Target
Kinetics PBPK Absorbed
Thermodynamics Models Applied
Spatial variability ENVIRONMENTAL
Distribution CHARACTERIZATION
Meteorology
Air
Water
Diet
Soil and dust EXPOSURE
Groundwater
Pathway • Individual
Duration • Community
ACTIVITY Frequency • Population
PATTTERN Magnitude
Statistical profile
Reference population
Susceptible individual
Susceptible subpopulations
Population distributions
Exposure Assessmet_EPA
• The process of measuring or estimating the intensity, frequency, and
duration of human contact with agents currently present in the
environment or the hypothetical contact that might arise from their
release in the environment.
• The EPA Guidelines for Estimating Exposure (U.S. EPA, 1986a)
defines exposure as the contact with a chemical or physical agent.
• --The magnitude of this contact is determined by measuring or
estimating the amount of an agent available at the exchange
boundaries during some specified time.
• --Once the agent is absorbed through these boundaries, the amount
crossing the boundary becomes the absorbed dose.
• The primary purpose of an exposure assessment is usually to
estimate the real-world dose (exposure) value to use in a dose-
response relationship.
Exposure Assessment
1. Chemical and physical properties of hazardous
agent/action/event
2. Environmental fate
3. Determining environmental concentration
4. Determining human intake of environmental
media
5. Factors affecting exposure conditions
6. Estimating dose: LADD and ADD
7. Characterization of exposed populations and
individuals
Methods of exposure assessment
vary with needs
• A highly sophisticated exposure assessment may be
needed if the objective is to ensure that no individual is
overexposed to a dangerous substance
• Only screening exposure assessment may be needed as
an approximate estimate of exposure for priority setting
• Exposure should be assessed so that it can be related to
dose (and possible health effect) with sufficient accuracy
and precision to meet research, regulatory, or exposure
control objectives
Exposure Assessment Continuum
• Presence of the chemical in a medium
to…
• Evaluation of the concentration of the
chemical in the medium interfacing with
the population/ individual of interest over
some averaging period to…
• Modeling of uptake and distribution of a
chemical within a person
EPA exposure assessment
categories
• Direct: direct monitoring of exposure (personal
sampling or media sampling) combined with
statistical models (assuming population
homogeneity) and time-activity models
• Reconstructive: uses qualitative or quantitative
data to establish past exposure levels among
populations
• Predictive: combination of deterministic models
and time activity models to estimate exposures
Exposure Assessment
Strategies
• Determination of Presence
• 1. Least sophisticated exposure
assessment
• 2. Simple attribution of exposure by a
person being in a location
• 3. Prospective and retrospective
epidemiologic studies
Exposure Assessment Strategies
Continued
• Direct Medium Concentration Monitoring
• 1. Personal/Area monitoring food, water,
and inhaled air
• 2. Represents the amount of toxicant at
the interface of the human physiology but
not the delivered dose
Exposure Assessment Strategies
Continued
• Biological Monitoring
• 1. Measure of the absorbed dose
• 2. Development and use requires an
understanding of the pharmacodynamics and
pharmacokinetic of the agent
• Modeling
• 1. Use of a mathematical construction to
estimate exposure
• 2. Several tiers of model sophistication
Defining Objectives
• Why is the study being conducted? What
questions does the study intend to address and
to what uses will the results be put?
• Where does the study area begin and where
does it end? Is the intent of the study to make
inferences on a national, regional, or local
scale?
• Who is to be monitored? Will the study involve
human and/or nonhuman populations? How are
they to be identified, characterized, and
stratified?
Defining Objectives (Continued)
• What substances and what media will be
measured? What is known about the
environmental fate as well as the fate of the
substance within the receptor organism?
• What are the important exposure pathways?
• What is known about expected concentration
levels, analytical methods, and detection limits?
• How will the samples be collected? How
frequently will the sampling be conducted? Is the
intent to characterize exposure as a function of
specified variables?
Use of Measurement Data in
Making Inferences for Exposure
Assessments
• The primary purpose for making measurements
and using data related to exposure assessments
is to make inferences from the measurements to
the whole.
• The exposure assessor must have a clear
picture between the sample and whole.
• It is the exposure assessor’s primary
responsibility to understand, explain, and justify
the relationship between the sample data and
the inferences or conclusions being drawn from
the data in the assessment.
Direct Measurement of Exposure
• Sampling of one individual’s exposure
must be related to the exposures of a
collection of individuals (the whole).
• This relationship may also include
inferences about different times and
locations form those in the sample (e.g.,
different cities, winter vs. summer, present
vs. past).
Reconstructive Exposure
Assessment
• The whole is usually the total absorbed
dose over some period of the past, which
is reconstructed from samples of various
tissues, fluids, or other biomarkers;
• Individual absorbed doses might then be
used to make inferences about collections
of individuals.
Predictive Exposure Assessments
• The whole is usually a medium of interest
such as outdoor air, drinking water, a
consumer product, etc.
• Once characterization of the medium has
been made (and this may include changes
over time), a matched link to individuals or
populations being assessed must be
made, usually via use of exposure
scenarios.
Developing a Sampling Strategy
• Make decisions regarding the types of
measurements to be undertaken.
• Frequency considerations might depend
on whether the effects studies have
examined average concentrates of the
chemical of interest of the effect of peak
exposure.
Direct Environmental and Human
Monitoring
• Measurements are made of the actual pollutant
concentrations contacting a person’s body by essentially
using split samples of the air breathed, the food eaten,
and the water consumed, and by using patch or other
techniques to estimate dermal exposure.
• Existing methodology developed for occupational
exposure or environmental monitoring may not be
adequate to meet the special demands of direct
measurement of exposure.
• Assess individual exposures, groups of individuals, or
segment the population.
Each assessment strategy
presents different issues of
relevance
• Data
• Sample type personal/area
• Chem. Specific
• Time specific
• Location specific
• Activity specific
Data must match objective of the
assessment
• E.g. 8 hr TWA available and objective is to assess the exposure
over 10 years.
• What must be known to use the data?
• Exposure do not change significantly day-to-day/ year-to-year
• Data collected that day are representative or typical
• Individual data to estimate exposure
• Measure the appropriate agent
• Represent exposure
• Not possible to sample the entire population
• Statistical sample evaluated to obtain estimate for population
• Inference to population (subgroups)
• Statistically base sampling strategy
• Sampled population representative of target
Examples of direct monitoring
• The best-known example of the direct
measurement of exposure is the radiation
dosimeter
• CO Assessment by EPA
• Individuals randomly selected; Interviewed by
telephone and screened to obtain smaller
stratified population
• Stratified by CO Exposure Risk Factors:
Smoking, commute time, other
• Personal CO Monitor used for several days
• Urban CO Exposure profile established
Another example of Direct
Measurement of Pollutant
• In the Team Studies, a small pump with a
collector and absorbent is attached to a
person’s clothing and measures the
exposures to airborne solvents or other
pollutants while the exposure takes place.
• The absorbent cartridges are then
analyzed for a variety of chemicals
Indirect Monitoring
• Site selection influences results (e.g.
spacial and temporal variation)
• Must incorporate pattern analysis for
exposure estimates job classification
• Human activity patterns
databases
• Plumbs from power plants to determine nature of
transport and transformation processes from a single-
point source of emission
• Non-point source air pollution evaluation
• PCBs and DDT in Western Lake Superior
• Dispersion of sewage sludge discharged from vessels off
the coast of NYC
• National Emissions Data Systems: TSP, Sox, Nox, HCs
& CO.
• Hazardous and Trace Emission System: Pollutants not
regulated by primary ambient air quality standards
Spacial Variation
• Random Sampling: Monitor locations
selected in a random manner so that it is
not possible to predict location of any
sampling point based on the location of
others
• Systematic Sampling; laying out a grid
• Initial point selected randomly
• Assures uniform sampling across areas
• More complex statistically
Temporal Variation
• Sequential measurements at one site
• Temporal correlations must be accounted
for; if ignored, mean and confidence
interval underestimated
• E.g. concentration of a contaminant in an
aquifer measured at a given well on one
day depends on the concentration on the
previous day.
Models for Exposure Assessment
• A model is a mathematical expression
representing a simplified version of exposure
processes.
• Provides a means by which diverse data on
relevant factors can be combined to predict
levels of human or environmental exposure
• Modeling is an iterative process of input and
refinement
• Large range of models of different complexity,
from back of the envelope to complex computer
simulations (EPA-Air Pollution Models)
Pollution Fate and Transport
Models
• Objective- determine the average
concentration of a pollutant in time for a
population by one or more exposure
pathways
• Pollutant may be a chemical or biological
agent
• Time may range from seconds to years
• Exposure pathways-standard
Variables in different pollutant
transport and fate models
• Environmental transport media (air, surface or ground
water, biota)
• Geographic scale (global, national, regional, local)
• Pollutant source characteristics (continuous or
instantaneous release, industrial, residential or
commercial, and point or area sources
• Risk agents (e.g., a specific compound or class of
related subjects)
• Receptor populations (normal
humans/animals/plants/MO, highly exposed, susceptible)
• Exposure routes (typical or unusual e.g. breast milk)
• Time Frame
Atmospheric Models
• Focus on pollution transport, diffusion, and deposition
• Transport- movement of suspended of pollutant through the
atmosphere
• Diffusion- microspread and dilution of individual particles and
molecules
• Deposition- transfer to ground/water or vegetation (wet or dry)
• Many variables influence transport/diffusion/deposition
• Atmospheric stability (resist or enhance vertical motion of the air)
• Temperature inversion
• Industrial emissions dispersion a function of: stack velocity,
temperature not atmospheric stability, and stack height
• Model Outputs
• Atmospheric concentrations
• Wet and dry deposition rates
Types of Models
• Gaussian Plume Model- plume from an
emission source spreads laterally and
vertically, ascending to a Gaussian
distribution
• Trajectory Models-compute the trajectory
that a pollutant might follow.
• Puff Transport Models- rapid, short-
duration emissions
• Compartmental Models
Other Factors in Exposure
Assessment
• Duration and frequency of exposure must be considered in an
exposure assessment. In terms of duration, exposures may be acute
(one-time), chronic (repeated, for a substantial fraction of the
lifespan (example: 10%) of a lifetime). Except for acute exposures,
there are no standardized quantitative definitions of these terms.
Frequency of exposure is also important-exposure may be
continuous (daily) or intermittent (less than daily, with no
standardized, quantitative definition).
• Finally, it is important to know, for exposures of limited duration, the
time in life during which exposure took place. For a teratogenic
agent, for example, it is essential to know whether exposure took
place or could take place during the subject’s pregnancy.
The Importance of an Accurate
Exposure Assessment
• Estimated risks are based on the results.
• Over-estimation of risks can lead to
unnecessarily costly cleanup.
• Under-estimation can result in health risk
on ecosystem degradation.
Use Exposure Assessment for
Status and Trends
• Determine exposure at a particular place
and time as well as trends over time.
• Provide a profile of a population or a
population segment.
• Establish effectiveness of risk mitigation
strategy (regulations).
Exposure Assessment in
Epidemiology
• A goal of epidemiology is to establish a
dose-response relationship to a
contaminant and to identify an exposed
population.
• Improve the chances of identifying a valid
dose-response relationship.
• Reduces misclassification in
epidemiological studies.
Use of Exposure Assessment in
Epidemiology
• Case-Control studies: relates disease
incidence to exposure by comparing
health outcomes in a group that has
exposure and one that doesn’t
• Reconstruction based on questionnaire
– Questions asked concerning activities or
locations that may result in exposure
Population based studies
• Exposure reconstruction or assignment of
exposure classification (i.e., high, medium, low)
• Personal monitoring
– I.e. collect water at home along with water use
information
– Time period? Latency?
• Exposure modeling
– Assess individual exposure OR generate a population
base distribution for boundaries on risk assessment.
Aggregate Exposure
• Sum total of exposure to a chemical via
ALL routes of exposure and in all media
• Concentration times duration
• DDT:
– 6 to 10 sources (fruits and veggies)
– Three routes (air, food, water)
Integrated Exposure
• “Area under the curve” or AUC
• Exposure profile
Issues in Dose and Response
Blood lead levels
Time (Days)
Time-Weighted Average
• TWA
• Total dose divided by time period of
dosing
• This is what we used for toxicology
assumption
One needs to answer key
questions in every exposure
assessment
• Who?
• How?
• Where?
• When?
• How much?
Who could be exposed?
• Potentially Exposed Human Populations:
• Residents
• Workers
• Sensitive Subpopulations (school children
and the elderly)
• Visitors
• Future Population Groups
Wildlife that could be exposed?
• Cattle
• Birds
• Fish
• Deer
• Rabbits
• Domestic animals
Environmental Media
• Soil
• Air
• Sediment
• Foods
• Water
Routes of Exposure
• Ingestion
• Inhalation
• Dermal contact
Mobility
• Water Solubility
• Soil Binding
• Octanol: Water Partioning
• Vapor Pressure
Other fate/ Transport Factors
• Persistence
• Microorganisms
• Light
• Moisture
• pH
• Temperature
• Half-life
How are people exposed?
• Airborne Dust
• Mother’s milk
• Fish
• Meat
• Dairy Products
• Vapors
• Soil
• Vegetables
• Water
• House Dusts
A complete exposure pathway is
needed
• Source and mechanism for release
• Transport mechanism
• Potential contact with the contaminant
• Absorption into blood
Other Routes of Exposure
• Acetone: Inhalation Ingestion (drinking
water)
• TCE: Inhalation Ingestion (drinking water)
• DDT: Dermal (soil and sediment) Ingestion
(dust/food)
Five Case Studies: Typical
Exposure Scenarios
• Case I: Airborne dust/vapor
• Case II: Soil
• Case III: Groundwater
• Case IV: Sediment
• Case V: Foods
Case I (Who)
• Location of Exposed Persons
• On-site
• Off-site
• Air Concentration
• Peak concentration (1 and 24 hours)
• Annual average concentration
Air Contaminants (When?)
• Exposure Duration
• Constant exposure
• Routine (but non-continuous)
• Sporadic
Air Contaminants (How much?)
• Determine
• Concentration at point of exposure
• Breathing rate per body weight
• Absorbed dose (uptake)
Air Contaminants (How much?)
• Estimating Concentration
• Direct measurements
• Indirect measurements
• Published emission rates
• Mathematical models for emissions
• Dispersion models
Air Contaminants from Soil
(How Much?)
• Mathematical Models
• Farmer’s Model
• Jury’s Behavior Assessment Model (BAM)
• Fugitive dust model
• Particulate emission models
Air Contaminants from soil
• Factors Affecting Vapor Flux
• Physical properties of chemical
• Vapor pressure
• Solubility
• Saturation Vapor Density
• Adsorption Tendencies
• Molecular Weight
Other Factors
• Properties of Soil Matrix
• Bulk Density
• Porosity
• Moisture Content
• Organic Carbon Fraction
Other Factors (Vapor from Soil)
• Environmental Factors
• Humidity
• Temperature
• Barometric Pressure
• Precipitation
• Wind Speed
Air Contaminants (How much?)
• Dispersion Models
• Box Model
• PTPLU
• ISCST
• Complex I
• Inpuff
• Complex II
• FDM
Air Contaminants (How much?)
• Other Factors
• Fine particle enrichment
• Particle size distribution
• Vapor flux
Air Contaminants (How much?)
• Dose= Concentration (mg/m^3) *
Ventilation (m^3/hr) * bioavailability (%)
Case II:Contaminated Soil
• Residential (children/adults)
• Industrial (adults)
• Parks/Recreation (children/adults)
• Sediments due to Runoff (fishermen/fish)
• Wildlife (grazing animals)
Contaminated Soil (How?)
• Residential (children eat soil or dust)
• Industrial (dermal contact)
• Agricultural (food)
• Parks/recreation (ingestion/dermal
contact)
• Wildlife (soil ingestion/forage)
Contaminated Soil (When and How
much?)
• Frequency (Every day that it does not rain)
• Dose (Eat 10mg/day or 50 mg/day)
Dermal Exposure Parameters
• Concentration in soil, dust, or water
• Soil/dust deposition rate from the air
• Direct soil contact
• Skin permeability rate
• Area of exposed skin
• Body weight
Contaminated Soil (How much?)
• Bioavailability
• Important when estimating dose
• Often mistakenly assumed to equal 100%
Contaminated Soil (How much?)
• Environmental Degradation
• Account for surface soil losses due to
photolysis and vaporization.
• Account for movement to lower depths
over time due to water solubility.
• Account for biodegradation.
Case III: Contaminated Ground
Water
• Who?
• How?
• When?
• How much?
Contaminated Ground Water
(Who?)
• Those who use it in the home
• Wildlife
Contaminated Water (How?)
• Ingestion of water
• Showering
• Bathing
• Dishwater
• Uptake from garden vegetables
• Swimming
Contaminated Ground Water
• One time
• Weekly
• Lifetime
Contaminated Ground Water
(How much?)
• Ingestion (water)
• Adults: 0 to 2 liters/day
• Children: 0 to 1 liter/day
• Ingestion (due to vegetables)
• Usually insignificant
• Swimming
• Usually very low or insignificant
Contaminated Ground Water
(How much?)
• Inhalation (for volatiles)
• Showering 950% of daily dose)
• Bathing (10% of daily dose)
• Vapor from dishwater (5% of daily dose)
Case VI: Contaminated Sediment
• Who?
• How?
• When?
• How much?
Contaminated Sediment (Who?)
• Sediment organisms.
• Fishes
• Mullusks
• Birds
• Muskrat and minks
• Higher food chain
• Humans (indirectly)
• Humans sub-population (indirectly)
Contaminated Sediment (How?)
• Organisms pass sediment through system
• Fish eat benthos
• Birds eat fish
• People eat fish/mollusks
Contaminated Sediment
(When and how much?)
• Mollusks (everyday; process gallons
water)
• Fish (everyday; eat their body weight per
week)
• Humans (some eat game fish 2 to 5
times/month)
Contaminated Sediment (Tricky
Issues)
• Determining sediment concentration
• Determining bioavailability
• Determining sediment toxicity
• Allocating chemical-specific contributions
to toxicity
Case V: Trace Contaminants in
Pharmaceuticals
• Who?
• How?
• When?
• How much?
Trace Contaminants in Drugs
(Who, How, When?)
• Average American (e.g. vitamins)
• Chronic use (e.g. decongestants)
• Infrequent use (e.g. antibiotics)
• The unborn
Trace Contaminants in Drugs
(How much?)
• Average Contaminant Concentration in
Drug
• Average daily dose of drug
• Maximum daily dose
• Average/peak 90 day dose
• Lifetime average daily dose
Trace Contaminants in Drug
• Pharmacokinetics
• Biologic half-life
• Peak body burden
• Peak target tissue burden
Trace Contaminants in Drugs
(How much ?)
• Dose to the fetus
• Dose to sensitive populations (elderly,
sick, etc.)
Warning: Do not forget dosimetrics*
• Consider peak daily dose
• Consider non-chronic effects
• Consider chronic effects
State-of-the-Art Issues
• Consider using site/sub-population
exposure parameters
• Soil ingestion
• Water ingestion
• Bioavailability
• Greater use of Monte Carlo analysis
• Better presentation of uncertainty
Lifetime Average Daily Dose
• 72 year old person • Bioavailability
• Has eaten lettuce • 4 mg Aldrin per kg
since age 4 (14,000 lettuce
kg)
C IR D B
LADD
BW LT
Empirical Data
• Direct measurement
• Usually measures applied dose
• A variety of methods and equipment have
been developed
Biological Monitoring
• Body burden levels or biomarkers
• Concentration of chemical in tissues or
sera
– Usually not the tissue of concern
– Need to understand internal dose relationship
• Concentration of the chemical’s
metabolites
• Biological response chemicals
• Chemical or metabolites bound to target
molecules
Modeling Exposure
• “Exposure Scenarios”
• Recreating past doses
• Predicting future doses
• Two major components
– Chemical concentrations (including time
trends)
– Population characterizations
Defining Objectives
• Why is the study being conducted? What
questions does the study intend to address and
to what uses will the results be put?
• Where does the study area begin and where
does it end? Is the intent of the study to make
inferences on a national, regional, or local
scale?
• Who is to be monitored? Will the study involve
human and/or nonhuman populations? How are
they to be identified, characterized, and
stratified?
Defining Objectives (Continued)
• What substances and what media will be
measured? What is known about the
environmental fate as well as the fate of the
substance within the receptor organism?
• What are the important exposure pathways?
• What is known about expected concentration
levels, analytical methods, and detection limits?
• How will the samples be collected? How
frequently will the sampling be conducted? Is the
intent to characterize exposure as a function of
specified variables?
Use of Measurement Data in
Making Inferences for Exposure
Assessments
• The primary purpose for making measurements
and using data related to exposure assessments
is to make inferences from the measurements to
the whole.
• The exposure assessor must have a clear
picture between the sample and whole.
• It is the exposure assessor’s primary
responsibility to understand, explain, and justify
the relationship between the sample data and
the inferences or conclusions being drawn from
the data in the assessment.
Important goals for the
Improvement of Exposure
Information
• Collect data over time (Establish a “baseline”, and follow
trends)
• Establish standard methods and protocols (Use standard
methods and protocols, and apply consistent
requirements for quality control/quality assurance)
• Develop statistically representative sampling data (Allow
extrapolation beyond the individual study)
• Collect more measurements of exposure
• (For developing, validating, and refining human exposure
models)
• Support epidemiologic studies
Important goals for the
Improvement of Exposure
Information
• Collect data over appropriate time frames
(Support epidemiologic studies, allow evaluation
or prediction of acute and subchronic, as well as
chronic effects
• Characterize total human exposures (Allow
evaluation of total exposures to individual,
multiple polluntants)
• Allow source apportionment or identification of
key sources of exposure
Important goals for the
Improvement of Exposure
Information
• Characterize exposures to pollutant mixtures (For
individual routes of exposure)
• Identify high-risk groups (Identify biologically susceptible
subpopulations and subgroups receiving exposures at
upper tail of exposure distribution, or “high-end”
exposures
• Address environmental inequities
• Identify regional, ethnic, or socioeconomic
subpopulations likely to receive “high-end” exposures
• Develop distributions of exposure (Allow characterization
of variability and uncertainty in exposure parameters,
estimates, and measurements
Exposure Factors Handbook
• Drinking water • Body surface areas
consumption rates • Body weights
• Breast milk • Shower times,
consumption rates intensities,
• Consumption rates of temperatures
foods • Animal exposures
• Soil ingestion rates – Domestic
• Breathing rates – Wildlife
Standard Regulatory Defaults
• Point estimates
– 2 L water / day, RME adult
– 1.4 L water / day, Avg. adult
– 1.0 L water / day, avg child
• Variability?
– Geographic
– Cultural
• Variability versus central tendencies
Dermal exposure
• Cutaneous permeability
• Dermal bioavailability
• Skin surface area
• Soil loading on the skin
Skin uptake of a chemical in soil
• Uptake = C × A × r × B
• C in mg material per kg soil
• A in cm2
• r in mg / cm2
• B is unitless (bioavailability)
Monte Carlo Analysis
• Uptake = C × A × r × B
• What if we know distributions of C, A, and
r, and uncertainty surrounding B!
• MEI (maximally exposed individual)
• 95% worst case for each?
• 1 - (1-0.95)4 = 99.9994 case?
Monte Carlo Analysis
• A taste:
• C = lognormal (12 mg / kg, 3 mg / kg)
• A = 500 cm2
• r = uniform (0.015 kg / cm2,0.025 kg / cm2)
• B = lognormal (0.75, 0.02)
• Mean Uptake = 70 mg
• Upper 95%? = 180 mg / kg
Monte Carlo Analysis
• 95% upper CI?
• C = lognormal (12 mg / kg, 3)
• A = 500 cm2
• r = uniform (0.015 kg / cm2,0.025 kg / cm2)
• B = lognormal (0.75, 0.02)
• Uptake = 70 mg
Monte Carlo Uptake?
Forecast: Uptake
10,000 Trials Frequency Chart 9,828 Display ed
.025 252
.019 189
.013 126
.006 63
.000 0
26.86 59.54 92.22 124.90 157.58
Certainty i s 95.00% from 49.19 to 151.37 mg
