Transcript Introduction to Risk Sciences & Environmental Risk

Quantitative Risk Assessment of
Chemicals in Food and Beverages
Felicia Wu, PhD
John A. Hannah Distinguished Professor
Department of Food Science & Human Nutrition
Department of Agricultural, Food, & Resource Economics
Michigan State University
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Why quantitative
risk assessment?
• The public hears about risks in foods/beverages all the time,
some of which may truly cause fear:
– At work
– In the news
– From your family and friends
• We’ll be better off if we can assess:
– Whether this “agent” (GMOs, lead, arsenic) is really hazardous to
human health (Hazard Identification)
– How much of it causes a harmful effect, vs. how much is safe (DoseResponse Assessment)
– Whether we or others we care about are exposed to the agent in
amounts that could cause harm (Exposure Assessment)
– Whether this risk is, after all, worth our concern (Risk
Characterization)
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What is
risk assessment?
• “The process of quantifying the probability and magnitude of
a harmful effect to individuals or populations from certain
agents or activities.”
• Practically speaking, what does this mean?
– There are 2 main components to assessing risk:
• The magnitude of harm
• The probability of occurrence
– If you don’t have both of these, you don’t have a risk
– If you do have both of these, you can quantify the risk for policy
decision-making purposes
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Risk assessment: 4 steps
• Hazard identification
• Dose-response assessment
• Exposure assessment
• Risk characterization
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Hazard Identification
Determine whether agent of interest causes disease, based on
weight of evidence from studies.
Major sources of information
– Human (epidemiological) studies: cohort and case-control studies
most informative*
– Animal (toxicological) studies: basis of most dose-response
assessments
Supplemental sources of information
– Cell culture assays
– Structure-activity relationships
“Tox21”: reduce or
eliminate animal tests
through bioinformatics &
high-throughout screening
*Limited for many foodborne and waterborne toxins
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Guidelines for Judging Causality
(So: is it a hazard after all?)
When we finally evaluate all of the scientific studies for
our agent of concern in the Hazard ID process, we need
some set of criteria to determine if the sum total of the
studies establishing an association between exposure and
a health effect reach the level of establishing causation.
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Bradford-Hill criteria in summary
1. Exposure to agent precedes disease
2. “Strong” relationship between agent & disease
3. Dose-response relationship exists (higher doses  more
disease risk)
4. Findings can be replicated
5. Biological plausibility
6. Consideration of other explanations
7. Cessation of exposure leads to reduced disease
8. Specificity (1 agent  1 disease)
9. Findings are generalizable
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Dose Response Assessment
Purpose
The objective of Dose Response Assessment is to determine the
relationship between dose of a toxic agent and the occurrence
of health effects.
The information is often provided by the same animal and
human studies used for Hazard Identification.
Dose Response Assessment addresses non-carcinogenic and
carcinogenic effects separately and differently.
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Dose-response
assessment
Non-carcinogenic effects
Carcinogenic effects
• NOEL (no observed effect
level) or benchmark dose
found in animal study
• For genotoxic carcinogens, “no
safe level”
• Linearize dose-response curve
& drive through (0, 0)
• Extrapolate to safe dose for
humans: divide NOEL/BMDL
by uncertainty factors
– Usually 100 (10 for interspecies variability * 10 for
intra-species variability)
• This is reference dose (RfD) or
tolerable daily intake (TDI).
– Slope of line is slope factor, or
cancer potency factor
– For every unit increase in daily
dose of carcinogen, cancer risk
increases by the cancer potency
factor (e.g., aflatoxin)
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Exposure assessment
(dietary toxins)
Traditional
Human biomarkers of exposure
ADD = (Cave * IRave) / BW
where
ADD = Average daily dose,
Cave = concentration (average) of toxin per
unit food or drink,
IRave = intake rate (average) of the relevant
food or drink (usually determined by
dietary surveys),
BW = body weight
ADD units: mg/kg bw/day
• Substance measured in human
biospecimen (e.g., urine, blood,
hair)
– Indicates that person was exposed
to particular toxin
– May be used to estimate his/her
dietary intake of toxin
– Can indicate long-term or shortterm exposure to toxin
– Must be validated (i.e., shown to
increase or decrease with actual
increasing or decreasing dietary
intakes)
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Risk Characterization
Does the agent pose a significant human health risk? How much?
Non-carcinogenic risk: compare average daily dose (ADD) of toxin to its
reference dose (RfD) or tolerable daily intake (TDI).
Hazard Quotient = ADD / RfD
(HQ >>1 implies risk to health)
Carcinogenic risk: multiply lifetime average daily dose (LADD) of toxin by
its slope factor or “cancer potency factor” (from the dose-response
curve).
Risk = LADD * Slope Factor
Risk = a unitless proportion of the population developing cancer from
a particular substance
Aflatoxin &
Global Health Effects
• Aflatoxin produced by Aspergillus flavus, A. parasiticus
– Maize, peanuts, tree nuts, cottonseed, spices, copra
– Exposure highest in warm regions where maize & nuts are
dietary staples (Africa, Asia)
• Human health effects
– Hepatocellular carcinoma (HCC, liver cancer)
• Synergizes with chronic hepatitis B virus (HBV)
infection: much higher risk than either exposure
alone
– Childhood stunting
– Acute aflatoxicosis
– Immune system modulation
• What do risk assessments tell us about global impact
of aflatoxin?
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Quantitative cancer risk assessment: How
many HCC cases worldwide are caused by
aflatoxin? (Liu & Wu 2010)
• Dose-response assessment
– Slope of curve = cancer “potency”
• Aflatoxin  HCC: 0.01 cases /
100,000 per yr per ng/kg bw/day
• Aflatoxin+HBV  HCC: 0.30
cases / 100,000 per yr per ng/kg
bw/day (JECFA 1998)
• Exposure assessment
• Find, for each nation:
–
–
–
–
–
Daily consumption of maize / nuts
Aflatoxin levels in maize / nuts
HBV prevalence
Population size
Captured 5.96 billion people
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Risk characterization:
Simplified model
• Global population cancer risk =
Σ(all nations)
([PopulationHBV+ /100,000 * PotencyHBV+ * Average aflatoxin
intake] +
[PopulationHBV- /100,000 * PotencyHBV- * Average aflatoxin
intake])
– PotencyHBV+ = 0.30 cases per 100,000/yr per ng/kg bw/day
– PotencyHBV- = 0.01 cases per 100,000/yr per ng/kg bw/day
Data Sources:
• HBV prevalence: WHO, multiple peer-reviewed papers
• Aflatoxin exposure & food consumption: FAOSTAT, multiple peerreviewed papers
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Results: 25,200-155,000 global aflatoxininduced liver cancer cases/yr
~5-30% of all HCC cases
Where does aflatoxin-induced liver cancer occur?
Liu Y, Wu F. (2010). Global Burden of Aflatoxin-Induced Hepatocellular Carcinoma: A Risk Assessment.
Environ Health Perspect 118:818-824.
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““The science has to drive all the
regulatory decision making,” says
Shelly Burgess, an FDA
spokesperson.”
Influence diagram linking arsenic to human disease
Arsenic accumulates
in rice & grains
Arsenic and new rice.
Cotton pesticides still contaminate fields now used for food crops
Environmental Health Perspectives Volume 115, Number 6, June 2007
Rice Not So Nice for Babies?
Environmental Pollution volume 152, 2008
Inorganic and organo-arsenic
Inorganic As(III)
Inorganic As(V)
Low level
concentration in fin
fish, crabs, shrimps
and mollusks
Organic MMA (V)
Organic DMA(V)
Organic arsenobetaine
Organic arsenocholine
Organic arsenothiols
Organic arsenosugars
Organic arsenolipids
Seaweeds,
marine
mollusks
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Quantitative cancer risk assessment
Global estimate for cancer burden =  [Individual population
arsenic exposure * Cancer slope factor]
(i) Dose – response assessment:
Slope of curve = cancer potency
•Bladder and Lung Cancer  Morales et al. (2000)
•Skin cancer  EPA IRIS
•Conversion of water arsenic level (µg/L) to human dose (µg/day)
Cancer type
Slope factor
(increased cancer risk per µg iAs/kg bw/day)
Males
Females
Bladder
0.0000127
0.0000198
Lung
0.0000137
0.0000194
Skin
0.000025
0.000025
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Mean adjusted total arsenic content of foods used
in the EFSA (2009) dietary exposure estimates.
Food group
Total arsenic
lower bound
mean level (mg/kg)
Total arsenic
upper bound
mean level (mg/kg)
All cereal & cereal products
0.0671
0.0848
Sugar products and chocolate
0.0135
0.0320
Fats (vegetable and animal)
0.0063
0.0245
All vegetables, nuts, pulses
0.0121
0.0212
Fruits
0.0051
0.0155
Juices, soft drinks and bottled water
0.0030
0.0068
Coffee, tea, cocoa
0.0034
0.0051
Alcoholic beverages
0.0055
0.0151
All meat and meat products, offal
0.0044
0.0138
All fish and seafood
1.6136
1.6159
Eggs
0.0042
0.0117
Milk and milk-based products
0.0044
0.0139
Miscellaneous/special dietary
products
0.3993
0.4187
Source: Table 13, FAO/WHO JECFA Monographs 8, 2011.
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Reported conversion factors from total arsenic to inorganic
arsenic
Data Source
Food
Mean % inorganic Arsenic
EFSA (2009)
Fish
Cereal products and vegetables
Standard ratio
0.015 or 0.03 mg/kg
Standard ratio
0.05 or 0.10 mg/kg
50–60 (30–90 reported in
literature)
30–100
Tea
29–88
Edible algae
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Seafood products
Rice
Yost, Schoof & Aucoin Milk and dairy products
(1998)
Meat
Poultry
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100
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Source: Table15, FAO/WHO JECFA Monographs 8, 2011
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Global burden of cancers caused by foodborne arsenic
Cancer
Male
Female
Total (global) Total
estimated
incidence
of cancers
(global)
Bladder
4527 to
4,602 to
9,129 to
46,420
72,756
119,176
4,913 to
6,931 to
11,844 to
50,373
71,069
121,442
8,941 to
8,941 to
17,882 to
91,679
91,679
183,358
Lung
Skin
382,660 a
% of
global
cases due
to
foodborne
arsenic
2.39 to
31.15
1,608,055 a 0.74 to
7.55
2 to 3
millionb
0.72 to
7.34
a Data source: “GLOBOCAN 2008 v2.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 10
[Internet]”
b Data source: http://www.who.int/uv/faq/skincancer/en/index1.html
These numbers represent the expected number, globally, of additional cases of
bladder, lung, and skin cancer per year; due to inorganic arsenic through food in
different diets worldwide.
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Risk management
Your risk characterization tells you that 1 in a million Americans will develop
lung cancer as a result of being exposed to Chemical X. How will you manage
the risk, if at all?
Summary
– Risk assessment consists of 4 steps:
• Hazard ID
• Dose-response assessment
• Exposure assessment
• Risk characterization
– Can be applied to estimating burden of disease
caused by food and beverage contaminants
• Aflatoxin, arsenic
– Risk managers must decide how to use risk
assessment data
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The Business Case for
Food Protection: Food Safety,
Food Fraud, and Food Defense
John Spink, PhD
Director, Food Fraud Initiative
Michigan State University
www.foodfraud.msu.edu -- Twitter @FoodFraud and #FoodFraud
*
The FOOD RISK MATRIX
The Types of Food Protection Risks
The Cause leading to the Effect of Adulteration
Food
Quality
Food
Fraud(1)
Food
Safety
Food
Defense
Unintentional
Intentional
Motivation
Gain:
Economic
Harm:
Public Health,
Economic, or
Terror
Action
Source: Adapted from: Spink (2006), The Counterfeit Food and Beverage Threat, Association
of Food and Drug Officials (AFDO), Annual Meeting 2007; Spink, J. & Moyer, DC (2011)
Defining the Public Health Threat of Food Fraud, Journal of Food Science, November 2011
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Enterprise Risk Management
Continuum from Operational Risk
Operational Risk
Enterprise Risk
Tactical
Strategic
Quantitative
Qualitative
ROI
Vulnerability
Metal Shavings
Shoplifting
Counterfeiting
Source: Spink, SRA Conference, 2009, 5th Global Forum on Pharmaceutical Anti-Counterfeiting 2010
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ERM and CRO
• Enterprise Risk Management (ERM) and a Chief Risk
Officer (CRO) are becoming more common.
–
CFO/CRO expanding focus to all-hazards within their
structure…
•
•
•
–
–
Understand and speak the language of risk
Use a Risk Matrix and Risk Summing
Focus on strategic nature of risk: pro and con
Develop a Food Protection risk assessment consistant with
other corporate templates
Consider Food Protection with the context of all other
enterprise-wide risks
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Calibrating the Risk Assessment to the
Corporate Risk Appetitive
• Risk Analysis
– Risk Assessment
Hazard Identification
– Risk Management
– Risk Communication
• Risk Threshold
• Risk Mitigation
High
Medium
Low
Very
Low
Very
High
Severity
•
Very
High
Probability
High
Medium
Low
Very
Low
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Example
Very
Very
High
Probability
Very
High
Very
High
High
High
Probability
Medium
Medium
Very
Low Very
Low
Low
PC
Low
High
Severity
Severity
High
SL
High
$15M
$4M
Medium
Medium
Low
Low
Very
Very
Low
Low
MS
$1M
© 2013 John Spink
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Business Case to Respond to
HONEY SMUGGLING
• What: Honey is smuggled from high tariff countries
then transshipped through other countries and
illegally relabeled.
• Why Worry: Recalls or mislabeling due to incorrect
country of origin.
– Cost of a recall? Vulnerability?
• How Caught: Banned antibiotics, adulterated by
dilution
• Question: Before considering all costs, how could you
address it?
–
–
–
–
–
Review incidents in the marketplace, review similarities
Review suppliers and procurement process
Test for country of origin? Antibiotics and dilution
Communicate process to suppliers
Review program to test incoming goods, review market
for new incidents, review testing protocol
– Review costs and vulnerability vs. other enterprisewide risks
• Action: Mitigate, Transfer, or Retain – always monitor
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Laws
Regulations Requirements
Standards
for a Risk Assessment
Certifications
• Foundation: HACCP, GMP, GAP, Six Sigma
• Business Laws: Sarbanes-Oxley, Park Doctrine (Strict Liability), Enterprise
Risk Management
• Food Protection Laws-US: FDA Bioterrorism Act (Traceability), Food
Safety Modernization Act
– Science- and risk-based approach, written risk assessment
• Food Protection Laws: EP/EU Draft Resolution on Food Fraud (and others
on Medicines), Codex Alimentarious – TBD
– Harmonize terms and focus on prevention
• Certifications and Standards: GFSI and Third Party Standards, USP/ Food
Chemicals Codex, ISO Standards, Accounting Practices
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Thank You
John Spink, PhD
[email protected]
www.foodfraud.msu.edu
Twitter: @Food Fraud and #FoodFraud
517.381.4491
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