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TRANSCRIPT
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National Health Research Institutes
Yi-Jun Lin Postdoctoral Fellow
2015.10.07
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1. What is Risk Characterization () ?
2. What are the differences between
Qualitative () and Quantitative ()? How to Quantify the Risk?
3. What is Uncertainty ()? Sources of Uncertainty
How to proceed the Uncertainty Analysis?
4. What is Sensitivity Analysis ()?
5. Case study
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Risk Assessment of Food
Hazard
Identification
Hazard
Characterization
Exposure
Assessment
Risk
Characterization
(Codex Alimentarius Commission, Working Principles for Risk Analysis for
Food Safety for Application by Governments, CAC/GL 62-2007)
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What is Risk Characterization?
(Qualitative Risk Assessment)
(Quantitative Risk Assessment)
(Uncertainty Analysis)
(Sensitivity Analysis)
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What are the differences between
Qualitative and Quantitative?
Example:
Quantitative cancer
risk of a chemical
1 10-6
Qualitative description
(Average exposed person)
=
(Maximally exposed person)
= 1 10-6
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How to Quantify the Risk?
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Hazard Quotient (HQ)
C: Contaminant concentration in food (g/g)
IR: Ingestion rate (g/day)
EF: Exposure frequency (day/year)
ED: Exposure duration (year)
RfD: Reference dose (mg/kg-day)
BW: Body weight (kg)
ATnc: Averaging time for noncarcinogens (year)
10-3: Unit conversion factor
HQ
>1
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Target Cancer Risk (TR)
TR =BW ATc
C CSF IR EF ED 10-3
C: Contaminant concentration in food (g/g)
CSF: Carcinogen slope factor (mg/kg-day)-1
IR: Ingestion rate (g/day)
EF: Exposure frequency (day/year)
ED: Exposure duration (year)
BW: Body weight (kg)
ATc: Averaging time for carcinogens (year)
10-3: Unit conversion factor
TR
Unacceptablecancer risk
Acceptablecancer risk
>110-6
1cancer
cases
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What is Uncertainty?
Uncertainty stems from lack of knowledge,
incomplete information, or incorrect
information, either qualitative or quantitative.
Types of uncertainty
Ambiguity, Measurement, Sampling,
Assumption, Extrapolation, Distribution,
Others
(NRC, Advancing Risk Assessment, 2009)
(European Food Safety Authority (EFSA), Public consultation
on Draft Guidance document on Uncertainty in Scientific
Assessment in 2015)
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Example: in exposure assessment
491109()
95
(EFSA, Public consultation on Draft Guidance document on Uncertainty in Scientific Assessment in 2015)
Types and Sources of Uncertainty
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How to proceed the Uncertainty
Analysis?
Quantitative Uncertainty Analysis
A probabilistic analysis techniques:
Monte Carlo (MC) simulation
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Monte Carlo (MC) simulation
(
)
(Metropolis, 1987. The beginning of the Monte Carlo method.
Los Alamos Science, special issue.)
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Risk model
= f(X, Y, Z)
1. Selecting uncertain
model parameters
3. A value is randomly sampling
from each distribution
by MC simulation
2. Determine an appropriate
probabilistic distributionPro
bab
ility
X Y Z
6.Uncertainty in model outcomesRisk
Pro
bab
ilit
y
Run 1: Risk = 0.5
Run 2: Risk = 0.1
Run N: Risk = 0.8
4. Running the model and
calculating output values
5. Enough simulations to
obtain stable solution
X:
Y:
Z:
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What is Sensitivity Analysis?
To understand how the parameters of model influence the predicted outcomes (e.g., risk estimates)
To identify the most significant parameters
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Contribution (%)0 20 40 60 80
Human Body weight
Tilapia ingestion rates
As in tilapia muscle
Human Body weight
Tilapia ingestion rates
As in tilapia muscle
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Example for Sensitivity Analysis
HQ and TR for consumption of As-contaminated tilapia Reference: Lin MP, et al., 2005. A PBTK/TD Modeling-based approach can assess arsenic
bioaccumulation in farmed tilapia (Oreochromis Mossambicus) and human health risks.
Integrated Environmental Assessment and Management 1: 40 54.
74.5%
73.9%Target Cancer Risk (TR)
Hazard Quotient (HQ)
26.1%
25.3%
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Case Study
Assessing human exposure risk to Zn and Cu through milkfish consumptionReference:Lin MC, 2009. Risk assessment on mixture toxicity of
arsenic, zinc and copper intake from consumption of
milkfish, Chanos chanos (forsskal), cultured using contaminated groundwater in southwest Taiwan.
Bulletin of Environmental Contamination and Toxicology 83: 125 129.
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Hazard Quotient (HQ)
HQ = (C IR EF ED 10-3) / (RfD BW ATnc)
Parameters Symbol Estimated value
Zn concentration in milkfish CZn (g/g) N(37.98, 6.49)
Cu concentration in milkfish CCu (g/g) N(2.09, 0.40)
Milkfish ingestion rate IR (g/day) N(374.07, 134.22)
Exposure frequency EF (day/year) 350
Exposure duration ED (year) 30
Body weight for Taiwanese adult BW (Kg) N(60.55, 4.67)
Averaging time for noncarcinogens ATnc (day) 10950
Reference dose for Zn RfDZn (mg/kg-day) 0.3
Reference dose for Cu RfDCu (mg/kg-day) 0.04
N(a, b) denotes the normal distribution with mean a and SD b
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To implement MC simulation
by Crystal Ball software
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Download Crystal Ball
Free for 30 Days
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Installing Crystal Ball
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Open Crystal Ball in Excel
/
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Sampling method
Monte Carlo (MC)
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Calculating Food Safety Risk by HQ
Hazard index (HI) = Total HQ = (HQZn + HQCu)
HQ = (C IR EF ED 10-3) / (RfD BW ATnc)
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: Zn conc. in milkfish
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: Ingestion rate
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HQ Forecasts and Simulations
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HQ Forecasts and Simulations
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Create Reports
Statistics Figures (probabilistic distribution) Percentile
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HQZn
HIZn+Cu
HQCu
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Extra Data
95%
HQ
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Sensitivity Analysis
Ingestion rate
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Thank you
for your attention