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

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

Thank you

for your attention