Title: Components of Risk Assessment
1Components of Risk Assessment
- Hazard Identification
- Dose-Response Assessment
- Exposure Assessment
- Risk Characterization
2Uses 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).
3Illustration of Exposure Pathways
From Paustenbach, DJ. (2000) The practice of
exposure assessment a state-of-the-art review. J
Toxicol Env Health, 3179-291
4Exposure 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.
5Definitions
- 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.
6Definitions 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
7Definitions 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.
8Definitions 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
9Why 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
10Three 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
11Exposure Elements
12Exposure 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.
13Exposure 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
14Methods 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
15Exposure 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
16EPA 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
17Exposure 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
18Exposure 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
19Exposure 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
20Defining 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?
21Defining 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?
22Use 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.
23Direct 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).
24Reconstructive 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.
25Predictive 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.
26Developing 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.
27Direct 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.
28Each assessment strategy presents different
issues of relevance
- Data
- Sample type personal/area
- Chem. Specific
- Time specific
- Location specific
- Activity specific
29Data 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
30Examples 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
31Another 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
32Indirect Monitoring
- Site selection influences results (e.g. spacial
and temporal variation) - Must incorporate pattern analysis for exposure
estimates job classification - Human activity patterns
33databases
- 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
34Spacial 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
35Temporal 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.
36Models 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)
37Pollution 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
38Variables 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
39Atmospheric 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
40Types 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
41Other 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.
42The 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.
43Use 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).
44Exposure 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.
45Use 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
46Population 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.
47Aggregate 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)
48Integrated Exposure
- Area under the curve or AUC
- Exposure profile
49Issues in Dose and Response
Blood lead levels
Time (Days)
50Time-Weighted Average
- TWA
- Total dose divided by time period of dosing
- This is what we used for toxicology assumption
51One needs to answer key questions in every
exposure assessment
- Who?
- How?
- Where?
- When?
- How much?
52Who could be exposed?
- Potentially Exposed Human Populations
- Residents
- Workers
- Sensitive Subpopulations (school children and the
elderly) - Visitors
- Future Population Groups
53Wildlife that could be exposed?
- Cattle
- Birds
- Fish
- Deer
- Rabbits
- Domestic animals
54Environmental Media
- Soil
- Air
- Sediment
- Foods
- Water
55Routes of Exposure
- Ingestion
- Inhalation
- Dermal contact
56Mobility
- Water Solubility
- Soil Binding
- Octanol Water Partioning
- Vapor Pressure
57Other fate/ Transport Factors
- Persistence
- Microorganisms
- Light
- Moisture
- pH
- Temperature
- Half-life
58How are people exposed?
- Airborne Dust
- Mothers milk
- Fish
- Meat
- Dairy Products
- Vapors
- Soil
- Vegetables
- Water
- House Dusts
59A complete exposure pathway is needed
- Source and mechanism for release
- Transport mechanism
- Potential contact with the contaminant
- Absorption into blood
60Other Routes of Exposure
- Acetone Inhalation Ingestion (drinking water)
- TCE Inhalation Ingestion (drinking water)
- DDT Dermal (soil and sediment) Ingestion
(dust/food)
61Five Case Studies Typical Exposure Scenarios
- Case I Airborne dust/vapor
- Case II Soil
- Case III Groundwater
- Case IV Sediment
- Case V Foods
62Case I (Who)
- Location of Exposed Persons
- On-site
- Off-site
- Air Concentration
- Peak concentration (1 and 24 hours)
- Annual average concentration
63Air Contaminants (When?)
- Exposure Duration
- Constant exposure
- Routine (but non-continuous)
- Sporadic
64Air Contaminants (How much?)
- Determine
- Concentration at point of exposure
- Breathing rate per body weight
- Absorbed dose (uptake)
65Air Contaminants (How much?)
- Estimating Concentration
- Direct measurements
- Indirect measurements
- Published emission rates
- Mathematical models for emissions
- Dispersion models
66Air Contaminants from Soil (How Much?)
- Mathematical Models
- Farmers Model
- Jurys Behavior Assessment Model (BAM)
- Fugitive dust model
- Particulate emission models
67Air Contaminants from soil
- Factors Affecting Vapor Flux
- Physical properties of chemical
- Vapor pressure
- Solubility
- Saturation Vapor Density
- Adsorption Tendencies
- Molecular Weight
68Other Factors
- Properties of Soil Matrix
- Bulk Density
- Porosity
- Moisture Content
- Organic Carbon Fraction
69Other Factors (Vapor from Soil)
- Environmental Factors
- Humidity
- Temperature
- Barometric Pressure
- Precipitation
- Wind Speed
70Air Contaminants (How much?)
- Dispersion Models
- Box Model
- PTPLU
- ISCST
- Complex I
- Inpuff
- Complex II
- FDM
71Air Contaminants (How much?)
- Other Factors
- Fine particle enrichment
- Particle size distribution
- Vapor flux
72Air Contaminants (How much?)
- Dose Concentration (mg/m3) Ventilation
(m3/hr) bioavailability ()
73Case IIContaminated Soil
- Residential (children/adults)
- Industrial (adults)
- Parks/Recreation (children/adults)
- Sediments due to Runoff (fishermen/fish)
- Wildlife (grazing animals)
74Contaminated Soil (How?)
- Residential (children eat soil or dust)
- Industrial (dermal contact)
- Agricultural (food)
- Parks/recreation (ingestion/dermal contact)
- Wildlife (soil ingestion/forage)
75Contaminated Soil (When and How much?)
- Frequency (Every day that it does not rain)
- Dose (Eat 10mg/day or 50 mg/day)
76Dermal 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
77Contaminated Soil (How much?)
- Bioavailability
- Important when estimating dose
- Often mistakenly assumed to equal 100
78Contaminated 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.
79Case III Contaminated Ground Water
- Who?
- How?
- When?
- How much?
80Contaminated Ground Water (Who?)
- Those who use it in the home
- Wildlife
81Contaminated Water (How?)
- Ingestion of water
- Showering
- Bathing
- Dishwater
- Uptake from garden vegetables
- Swimming
82Contaminated Ground Water
83Contaminated 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
84Contaminated Ground Water (How much?)
- Inhalation (for volatiles)
- Showering 950 of daily dose)
- Bathing (10 of daily dose)
- Vapor from dishwater (5 of daily dose)
85Case VI Contaminated Sediment
- Who?
- How?
- When?
- How much?
86Contaminated Sediment (Who?)
- Sediment organisms.
- Fishes
- Mullusks
- Birds
- Muskrat and minks
- Higher food chain
- Humans (indirectly)
- Humans sub-population (indirectly)
87Contaminated Sediment (How?)
- Organisms pass sediment through system
- Fish eat benthos
- Birds eat fish
- People eat fish/mollusks
88Contaminated 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)
89Contaminated Sediment (Tricky Issues)
- Determining sediment concentration
- Determining bioavailability
- Determining sediment toxicity
- Allocating chemical-specific contributions to
toxicity
90Case V Trace Contaminants in Pharmaceuticals
- Who?
- How?
- When?
- How much?
91Trace Contaminants in Drugs (Who, How, When?)
- Average American (e.g. vitamins)
- Chronic use (e.g. decongestants)
- Infrequent use (e.g. antibiotics)
- The unborn
92Trace 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
93Trace Contaminants in Drug
- Pharmacokinetics
- Biologic half-life
- Peak body burden
- Peak target tissue burden
94Trace Contaminants in Drugs (How much ?)
- Dose to the fetus
- Dose to sensitive populations (elderly, sick,
etc.)
95Warning Do not forget dosimetrics
- Consider peak daily dose
- Consider non-chronic effects
- Consider chronic effects
96State-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
97Lifetime Average Daily Dose
- 72 year old person
- Has eaten lettuce since age 4 (14,000 kg)
- Bioavailability
- 4 mg Aldrin per kg lettuce
98Empirical Data
- Direct measurement
- Usually measures applied dose
- A variety of methods and equipment have been
developed
99Biological 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
100Modeling Exposure
- Exposure Scenarios
- Recreating past doses
- Predicting future doses
- Two major components
- Chemical concentrations (including time trends)
- Population characterizations
101Defining 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?
102Defining 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?
103Use 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.
104Important 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
105Important 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
106Important 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
107Exposure 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
108Standard 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
109Dermal exposure
- Cutaneous permeability
- Dermal bioavailability
- Skin surface area
- Soil loading on the skin
110Skin 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)
111Monte 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?
112Monte 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
113Monte 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
114Monte Carlo Uptake?