Presented by Dr. Ray Matulka at IFT15 on Sunday, July 12 at 1:15 PM. The basic principles of safety can apply to all constituents in foods and beverages whether they are present purposefully or not. However, numerous factors can influence the approaches utilized for hazard characterization and risk assessment for various food and beverage constituents. These factors can include; the regulatory and legal framework being followed, what is and what is not known scientifically about the safety of a constituent, what the substance is and its function in a food or beverage, and consumer perception of the substance in the food or beverage. Simply segregating the safety assessment of compounds found in foods and beverages based how they came to be present in foods and beverages can be problematic for all stakeholders charged with ensuring the safety of foods and beverages. Additionally, food safety organizations around the world have adopted a variety of different approaches for addressing the safety of constituents in foods and beverages, which complicates, rather than simplifies the risk assessment process. The ability to adopt and adapt various scientifically valid approaches for evaluating safety becomes important for ensuring the safety and continuity of supply of foods and beverages. Another important factor that must be considered while evaluating the safety of constituents in food and beverages is communication with the consumer and crafting appropriate messaging demonstrating the rigor of the evaluation with a goal of preserving and promoting trust in the safety of the food and beverage supply.

1. Ray A. Matulka, Ph.D.
Director of Toxicology
Burdock Group
© 2015 Institute of Food Technologists
Harmonization of Approaches for Food Ingredients
and Constituents: Is It Possible?

2. Thank you for the privilege of speaking today.
► This presentation was given at the Institute of Food
Technologist’s IFT15 conference in the McCormick
Convention Center in Chicago, IL on Sunday, July 12th.
► If you would like to receive additional information regarding
Burdock Group’s capabilities in cosmetics, personal care, food
& feed ingredients and dietary supplement safety or
regulations, please contact Amanda Roche
(aroche@burdockgroup.com).
► Please not that this material is protected by copyright.
► Disclaimer: Concepts and examples discussed in this lecture
are for illustrative purposes only and do not constitute safety
or regulatory advice. The example provided herein may not
apply to your specific situation. Please contact us for an
analysis of your particular circumstance to determine the best
pathway for your product and team.
© 2015 Institute of Food Technologists2

3. Risk vs. Hazard
►Risk:
– A measure of the probability and consequence of uncertain future
events
– Quantification or qualification of the chance of an undesirable
outcome.
Risk = Probability X Consequence
“Zero Risk” is NOT an option
►Hazard:
– The action or situation that causes the potential for an adverse
consequence
© 2015 Institute of Food Technologists3

4. Risk Analysis
►Three components:
►Risk Assessment
– Systematic process for describing the nature, likelihood, and
magnitude of risk associated with some substance, situation,
action or event
►Risk Management
– Process of problem identification, requesting information,
evaluating risks, and initiating action to identify, evaluate, select,
implement, monitor and modify actions to reach acceptable risk
levels
►Risk Communication
– Open, two-way exchange of information and opinion about risks,
to result in better risk management decisions.
© 2015 Institute of Food Technologists4

5. Risk Analysis
© 2015 Institute of Food Technologists5
Risk Management Risk Assessment
• Policy,
preferences and
values
• Science and
evidence
Risk Communication
• Interactive exchange of
information, opinions, and
preferences concerning risks
Yoe, C., 2012

6. Risk Management
© 2015 Institute of Food Technologists6
Problem
Identification
Risk
Estimation
Risk
Evaluation
Risk
Monitoring
Risk
Control
Yoe, C., 2012

7. External Risk Communication
Internal Risk Communication
Risk Communication
© 2015 Institute of Food Technologists7
Coordination between
assessors and managers
Risk Communication
process
Document the
process
Risk Communication
Crisis Communication
Public Involvement
Conflict Resolution
Yoe, C., 2012

8. Scientific Food Safety Risk Assessment
© 2015 Institute of Food Technologists8
1. Hazard Identification
2. Hazard
Characterization 3. Exposure
Assessment
4. Risk Characterization
Food and Agriculture Organization of the United Nations
(FAO)

9. Scientific Food Safety Risk Assessment
© 2015 Institute of Food Technologists9
1. Hazard Identification
2. Hazard
Characterization 3. Exposure
Assessment
4. Risk Characterization
Food and Agriculture Organization of the United Nations
(FAO)
Hazard Identification: What is the agent
capable of causing adverse health
effects? (i.e., Food Ingredient)

10. Scientific Food Safety Risk Assessment
© 2015 Institute of Food Technologists10
1. Hazard Identification
2. Hazard
Characterization 3. Exposure
Assessment
4. Risk Characterization
Food and Agriculture Organization of the United Nations
(FAO)
Hazard Characterization:
Qualitative or quantitative
evaluation of the adverse health
effect.
What kind and how much harm?

11. Scientific Food Safety Risk Assessment
© 2015 Institute of Food Technologists11
1. Hazard Identification
2. Hazard
Characterization 3. Exposure
Assessment
4. Risk Characterization
Food and Agriculture Organization of the United Nations
(FAO)
Exposure Assessment: Qualitative or
quantitative evaluation of likely
intake.
How much will a certain population
be exposed to it?

12. Scientific Food Safety Risk Assessment
© 2015 Institute of Food Technologists12
1. Hazard Identification
2. Hazard
Characterization 3. Exposure
Assessment
4. Risk Characterization
Food and Agriculture Organization of the United Nations
(FAO)
Risk Characterization: Qualitative or
quantitative estimation of the probability of
occurrence and severity of potential adverse
effect.
What will be the harm to a certain
population?

13. Evaluation of Food Safety: Harmonization?
►Definition of “safe” for food ingredients
(European Commission, FSANZ, US FDA):
►Safe: reasonable certainty of no harm resulting from
consumption of the proposed food additive
– Ingredient characterization, exposure assessment and
toxicological testing REQUIRED for adequate risk assessment
– Threshold of Toxicological Concern (TTC) approach:
Qualitatively assess the risk of low-level substances in the diet
© 2015 Institute of Food Technologists13

14. Core Data Utilized for Risk Assessment of
Food Additives
 Hazard Identification:
– Identity of substance
– Specifications
– Manufacturing process
– Methods of analysis
– Reaction and fate in foods
– Proposed use and use levels in foods
© 2015 Institute of Food Technologists14
EFSA Journal 2012; 10(7):2760
FDA Guidance for Industry, 2014
FDA iRISK: https://risk.foodrisk.org

15. Core Data Utilized for Risk Assessment of
Food Additives
 Biological and Toxicological Data
– Absorption, Metabolism, Distribution and Excretion (ADME)
– Genotoxicity studies (in vitro and in vivo)
– Subchronic studies
– Chronic toxicity and carcinogenicity studies
– Reproductive and developmental studies
– Other studies determined on case-by-case basis
Toxicological endpoints evaluated:
© 2015 Institute of Food Technologists15
Hepatotoxicity
Renal/nephrotoxicity
Reproductive
Developmental
Neurotoxicity
Immunotoxicity
Respiratory toxicity
Ocular toxicity
OECD toxicity guidelines: Harmonization between EFSA, FDA, EPA

16. Risk Assessment
 Establish a human Acceptable Daily Intake (ADI) level
for the food additive
 “An estimate of the amount of food additive, expressed
on a body weight basis, that can be ingested daily over
a lifetime without appreciable health risk” EFSA, 2012
 ADI = Determined by applying an uncertainty factor (UF)
to the dose of the additive found in the toxicological
studies to produce no adverse health effect in animals
(NOAEL)
ADI = NOAEL / UF
The Benchmark Dose Lower Bound (BMDL) approach
may also be used.
© 2015 Institute of Food Technologists16

17. Uncertainty Factors
 FDA: 21 CFR §170.22
– Except where evidence is submitted which justifies use of a different
safety factor, a safety factor in applying animal experimentation
data to man of 100 to 1, will be used; that is, a food additive for use by
man will not be granted a tolerance that will exceed 1/100th of the
maximum amount demonstrated to be without harm to experimental
animals.
 EFSA (2012)
– In the absence of chemical-specific data on kinetics and/or dynamics,
the Scientific Committee recommends using the overall default
uncertainty factor of 100 (10 for inter-species variability x 10 for intra-
human variability).
– If available and relevant:
– for inter-species variability in toxicokinetics: 4.0
– for inter-species variability in toxicodynamics: 2.5
– for intra-human variability in toxicokinetics: 3.16
– for intra-human variability in toxicodynamics: 3.16
© 2015 Institute of Food Technologists17

18. World Health Organization – Int’l Program on Chemical
Safety (IPCS) Harmonization Project Strategic Plan
►Improve chemical risk assessment globally
– Common principles and approaches
– Develop and use new and harmonized methods for risk
assessment
►Harmonize global approach to chemical risk assessment
►Develop international guidance documents on specific
issues
– To be adopted and used in countries and agencies worldwide
– Developed in stepwise approach
• Share information on different (and similar) methods/practices
• Identify areas for converging methods
• Develop guidance for implementation of harmonized approaches
• International peer review of methods = scientific integrity
►Result: internationally accepted scientific studies
© 2015 Institute of Food Technologists18

19. Key Takeaways
 Effective Risk Assessment increases Risk Management
which Improves Risk Communication
 The core elements of the Risk Assessment process are
the same for all scientific food regulatory agencies
 The Int’l Programme on Chemical Safety (IPCS) has
initiated Harmonization of methods for use for all
countries and agencies
 Harmonization is achievable with communication and
partnership between scientific agencies
© 2015 Institute of Food Technologists19

20. Ray Matulka, Ph.D.
Burdock Group
Orlando, FL
rmatulka@burdockgroup.com
© 2015 Institute of Food Technologists
Questions?