Components of Risk Assessment

1
Components of Risk Assessment

• Hazard Identification
• Dose-Response Assessment
• Exposure Assessment
• Risk Characterization

2
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).

3
Illustration of Exposure Pathways
From Paustenbach, DJ. (2000) The practice of
exposure assessment a state-of-the-art review. J
Toxicol Env Health, 3179-291
4
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.

5
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.

6
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

7
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.

8
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

9
Why assess exposure?(Isnt 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

10
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

11
Exposure Elements
12
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.

13
Exposure Assessment

• Chemical and physical properties of hazardous
  agent/action/event
• Environmental fate
• Determining environmental concentration
• Determining human intake of environmental media
• Factors affecting exposure conditions
• Estimating dose LADD and ADD
• Characterization of exposed populations and
  individuals

14
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

15
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

16
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

17
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

18
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

19
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

20
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?

21
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?

22
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 assessors 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.

23
Direct Measurement of Exposure

• Sampling of one individuals 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).

24
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.

25
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.

26
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.

27
Direct Environmental and Human Monitoring

• Measurements are made of the actual pollutant
  concentrations contacting a persons 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.

28
Each assessment strategy presents different
issues of relevance

• Data
• Sample type personal/area
• Chem. Specific
• Time specific
• Location specific
• Activity specific

29
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

30
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

31
Another example of Direct Measurement of Pollutant

• In the Team Studies, a small pump with a
  collector and absorbent is attached to a persons
  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

32
Indirect Monitoring

• Site selection influences results (e.g. spacial
  and temporal variation)
• Must incorporate pattern analysis for exposure
  estimates job classification
• Human activity patterns

33
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

34
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

35
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.

36
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)

37
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

38
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

39
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/depos
  ition
• 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

40
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

41
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 subjects pregnancy.

42
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.

43
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).

44
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.

45
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 doesnt
• Reconstruction based on questionnaire
• Questions asked concerning activities or
  locations that may result in exposure

46
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.

47
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)

48
Integrated Exposure

• Area under the curve or AUC
• Exposure profile

49
Issues in Dose and Response
Blood lead levels
Time (Days)
50
Time-Weighted Average

• TWA
• Total dose divided by time period of dosing
• This is what we used for toxicology assumption

51
One needs to answer key questions in every
exposure assessment

• Who?
• How?
• Where?
• When?
• How much?

52
Who could be exposed?

• Potentially Exposed Human Populations
• Residents
• Workers
• Sensitive Subpopulations (school children and the
  elderly)
• Visitors
• Future Population Groups

53
Wildlife that could be exposed?

• Cattle
• Birds
• Fish
• Deer
• Rabbits
• Domestic animals

54
Environmental Media

• Soil
• Air
• Sediment
• Foods
• Water

55
Routes of Exposure

• Ingestion
• Inhalation
• Dermal contact

56
Mobility

• Water Solubility
• Soil Binding
• Octanol Water Partioning
• Vapor Pressure

57
Other fate/ Transport Factors

• Persistence
• Microorganisms
• Light
• Moisture
• pH
• Temperature
• Half-life

58
How are people exposed?

• Airborne Dust
• Mothers milk
• Fish
• Meat
• Dairy Products
• Vapors
• Soil
• Vegetables
• Water
• House Dusts

59
A complete exposure pathway is needed

• Source and mechanism for release
• Transport mechanism
• Potential contact with the contaminant
• Absorption into blood

60
Other Routes of Exposure

• Acetone Inhalation Ingestion (drinking water)
• TCE Inhalation Ingestion (drinking water)
• DDT Dermal (soil and sediment) Ingestion
  (dust/food)

61
Five Case Studies Typical Exposure Scenarios

• Case I Airborne dust/vapor
• Case II Soil
• Case III Groundwater
• Case IV Sediment
• Case V Foods

62
Case I (Who)

• Location of Exposed Persons
• On-site
• Off-site
• Air Concentration
• Peak concentration (1 and 24 hours)
• Annual average concentration

63
Air Contaminants (When?)

• Exposure Duration
• Constant exposure
• Routine (but non-continuous)
• Sporadic

64
Air Contaminants (How much?)

• Determine
• Concentration at point of exposure
• Breathing rate per body weight
• Absorbed dose (uptake)

65
Air Contaminants (How much?)

• Estimating Concentration
• Direct measurements
• Indirect measurements
• Published emission rates
• Mathematical models for emissions
• Dispersion models

66
Air Contaminants from Soil (How Much?)

• Mathematical Models
• Farmers Model
• Jurys Behavior Assessment Model (BAM)
• Fugitive dust model
• Particulate emission models

67
Air Contaminants from soil

• Factors Affecting Vapor Flux
• Physical properties of chemical
• Vapor pressure
• Solubility
• Saturation Vapor Density
• Adsorption Tendencies
• Molecular Weight

68
Other Factors

• Properties of Soil Matrix
• Bulk Density
• Porosity
• Moisture Content
• Organic Carbon Fraction

69
Other Factors (Vapor from Soil)

• Environmental Factors
• Humidity
• Temperature
• Barometric Pressure
• Precipitation
• Wind Speed

70
Air Contaminants (How much?)

• Dispersion Models
• Box Model
• PTPLU
• ISCST
• Complex I
• Inpuff
• Complex II
• FDM

71
Air Contaminants (How much?)

• Other Factors
• Fine particle enrichment
• Particle size distribution
• Vapor flux

72
Air Contaminants (How much?)

• Dose Concentration (mg/m3) Ventilation
  (m3/hr) bioavailability ()

73
Case IIContaminated Soil

• Residential (children/adults)
• Industrial (adults)
• Parks/Recreation (children/adults)
• Sediments due to Runoff (fishermen/fish)
• Wildlife (grazing animals)

74
Contaminated Soil (How?)

• Residential (children eat soil or dust)
• Industrial (dermal contact)
• Agricultural (food)
• Parks/recreation (ingestion/dermal contact)
• Wildlife (soil ingestion/forage)

75
Contaminated Soil (When and How much?)

• Frequency (Every day that it does not rain)
• Dose (Eat 10mg/day or 50 mg/day)

76
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

77
Contaminated Soil (How much?)

• Bioavailability
• Important when estimating dose
• Often mistakenly assumed to equal 100

78
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.

79
Case III Contaminated Ground Water

• Who?
• How?
• When?
• How much?

80
Contaminated Ground Water (Who?)

• Those who use it in the home
• Wildlife

81
Contaminated Water (How?)

• Ingestion of water
• Showering
• Bathing
• Dishwater
• Uptake from garden vegetables
• Swimming

82
Contaminated Ground Water

• One time
• Weekly
• Lifetime

83
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

84
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)

85
Case VI Contaminated Sediment

• Who?
• How?
• When?
• How much?

86
Contaminated Sediment (Who?)

• Sediment organisms.
• Fishes
• Mullusks
• Birds
• Muskrat and minks
• Higher food chain
• Humans (indirectly)
• Humans sub-population (indirectly)

87
Contaminated Sediment (How?)

• Organisms pass sediment through system
• Fish eat benthos
• Birds eat fish
• People eat fish/mollusks

88
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)

89
Contaminated Sediment (Tricky Issues)

• Determining sediment concentration
• Determining bioavailability
• Determining sediment toxicity
• Allocating chemical-specific contributions to
  toxicity

90
Case V Trace Contaminants in Pharmaceuticals

• Who?
• How?
• When?
• How much?

91
Trace Contaminants in Drugs (Who, How, When?)

• Average American (e.g. vitamins)
• Chronic use (e.g. decongestants)
• Infrequent use (e.g. antibiotics)
• The unborn

92
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

93
Trace Contaminants in Drug

• Pharmacokinetics
• Biologic half-life
• Peak body burden
• Peak target tissue burden

94
Trace Contaminants in Drugs (How much ?)

• Dose to the fetus
• Dose to sensitive populations (elderly, sick,
  etc.)

95
Warning Do not forget dosimetrics

• Consider peak daily dose
• Consider non-chronic effects
• Consider chronic effects

96
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

97
Lifetime Average Daily Dose

• 72 year old person
• Has eaten lettuce since age 4 (14,000 kg)

• Bioavailability
• 4 mg Aldrin per kg lettuce

98
Empirical Data

• Direct measurement
• Usually measures applied dose
• A variety of methods and equipment have been
  developed

99
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 chemicals metabolites
• Biological response chemicals
• Chemical or metabolites bound to target molecules

100
Modeling Exposure

• Exposure Scenarios
• Recreating past doses
• Predicting future doses
• Two major components
• Chemical concentrations (including time trends)
• Population characterizations

101
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?

102
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?

103
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 assessors 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.

104
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

105
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

106
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

107
Exposure Factors Handbook

• Drinking water consumption rates
• Breast milk consumption rates
• Consumption rates of foods
• Soil ingestion rates
• Breathing rates

• Body surface areas
• Body weights
• Shower times, intensities, temperatures
• Animal exposures
• Domestic
• Wildlife

108
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

109
Dermal exposure

• Cutaneous permeability
• Dermal bioavailability
• Skin surface area
• Soil loading on the skin

110
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)

111
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?

112
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

113
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

114
Monte Carlo Uptake?