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Quantitative Risk Assessment of Chemicals in Food and BeveragesFelicia Wu, PhDJohn A. Hannah Distinguished ProfessorDepartment of Food Science & Human NutritionDepartment of Agricultural, Food, & Resource EconomicsMichigan 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 (Dose-

Response 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

“Tox21”: reduce oreliminate animal teststhrough bioinformatics &high-throughout screening

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Guidelines for Judging Causality(So: is it a hazard after all?)

When we finally evaluate all of the scientific studies forour agent of concern in the Hazard ID process, we need some set of criteria to determine if the sum total of thestudies establishing an association between exposure anda health effect reach the level of establishing causation.

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Bradford-Hill criteria in summary

1. Exposure to agent precedes disease2. “Strong” relationship between agent & disease3. Dose-response relationship exists (higher doses more

disease risk)4. Findings can be replicated5. Biological plausibility6. Consideration of other explanations7. Cessation of exposure leads to reduced disease8. Specificity (1 agent 1 disease)9. Findings are generalizable

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Dose Response AssessmentPurpose

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 andcarcinogenic effects separately and differently.

Dose-response assessment

Non-carcinogenic effects Carcinogenic effects• For genotoxic carcinogens,

“no safe level”• Linearize dose-response curve

& drive through (0, 0)– 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

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

Human biomarkers of exposure• 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 short-term 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 CharacterizationDoes 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 FactorRisk = a unitless proportion of the population developing cancer from a particular substance

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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?

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 peer-

reviewed papers

Results: 25,200-155,000 global aflatoxin-induced liver cancer cases/yr

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~5-30% of all HCC casesWhere 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.

““The science has to drive all the regulatory decision making,” says Shelly Burgess, an FDA spokesperson.”

Influence diagram linking arsenic to human disease

Arsenic and new rice. Cotton pesticides still contaminate fields now used for food cropsEnvironmental Health Perspectives Volume 115, Number 6, June 2007

Arsenic accumulates in rice & grains

Rice Not So Nice for Babies? Environmental Pollution volume 152, 2008

Inorganic and organo-arsenic

Inorganic As(III) Inorganic As(V)

Organic MMA (V)Organic DMA(V)Organic arsenobetaineOrganic arsenocholineOrganic arsenothiolsOrganic arsenosugarsOrganic arsenolipids

Low level concentration in fin fish, crabs,

shrimps and mollusks

Low level concentration in fin fish, crabs,

shrimps and mollusks

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Seaweeds, marine

mollusks

Seaweeds, marine

mollusks

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 0.00002520

Mean adjusted total arsenic content of foods usedin the EFSA (2009) dietary exposure estimates.

Food groupTotal 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 arsenicData Source Food Mean % inorganic Arsenic

EFSA (2009) Fish

Standard ratio0.015 or 0.03 mg/kg

Seafood products

Standard ratio0.05 or 0.10 mg/kg

Rice 50–60 (30–90 reported inliterature)

Cereal products and vegetables 30–100

Tea 29–88

Edible algae 60

Yost, Schoof & Aucoin (1998)

Milk and dairy products

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Meat 100

Poultry 41

Source: Table15, FAO/WHO JECFA Monographs 8, 201122

Global burden of cancers caused by foodborne arsenicCancer Male Female Total (global)

Total estimated incidence of cancers (global)

% of global cases due to foodborne arsenic

Bladder 4527 to

46,420

4,602 to

72,756

9,129 to

119,176

382,660 a 2.39 to 31.15

Lung 4,913 to

50,373

6,931 to

71,069

11,844 to

121,442

1,608,055 a 0.74 to 7.55

Skin 8,941 to

91,679

8,941 to

91,679

17,882 to

183,358

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 managementYour risk characterization tells you that 1 in a million Americans will developlung cancer as a result of being exposed to Chemical X. How will you managethe 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, PhDDirector, Food Fraud InitiativeMichigan State University

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www.foodfraud.msu.edu -- Twitter @FoodFraud and #FoodFraud

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The FOOD RISK MATRIXThe Types of Food Protection Risks

Action

IntentionalUnintentional

Harm: Public Health, Economic, or

Terror

Food Defense

Food Safety

Motivation

Gain: Economic

Food Fraud(1)

Food Quality

The Cause leading to the Effect of Adulteration

Source: Adapted from: Spink (2006), The Counterfeit Food and Beverage Threat, Associationof 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 ManagementContinuum from Operational Risk

Operational Risk Enterprise Risk

Metal Shavings

Source: Spink, SRA Conference, 2009, 5th Global Forum on Pharmaceutical Anti-Counterfeiting 2010

Tactical

Quantitative

ROI

Strategic

Qualitative

Vulnerability

Shoplifting Counterfeiting

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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

Very High High Medium Low

Very Low

Very High

High

Medium

LowVery Low

Probability

Sev

erity

31© 2013 John Spink

Example

Very High High Medium Low

Very Low

Very High

High

Medium

LowVery Low

ProbabilitySev

erity

MS$1M

SL

$4M

PC

$15M

Very High High Medium Low

Very Low

Very High

High

Medium

LowVery Low

ProbabilitySev

erity

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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 enterprise-wide risks

• Action: Mitigate, Transfer, or Retain – always monitor

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Laws Regulations StandardsCertifications

• 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

Requirements for a Risk Assessment

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Thank You

John Spink, PhD

SpinkJ@msu.eduwww.foodfraud.msu.eduTwitter: @Food Fraud and #FoodFraud517.381.4491