RBA presentation

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Risk-Benefit Assessment of Food The Approach
taken by EFSA Dr David Carlander Scientific
Officer Scientific Committee and Advisory Forum
The 7th Valamo Conference on Environmental and
Health Approaches to Benefit-Risk Analysis 3-5
December 2007
www.efsa.europa.eu
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Outline

• EFSA
• EFSA 2006 Colloquium on Risk-Benefit
• EFSA WG on RBA
• Nitrate in Vegetables
• Food Fortification
• GMO and Environment

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Creation of EFSA
EFSA has three main goals
Improving EU food safety
Make a significant contribution to
Re-building consumer confidence in EU food safety
Re-building confidence of trading partners in the
EU food supply
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EFSA structure
Management Board
Advisory Forum
EFSA Directorate and Staff 300
Scientific Committee and Panels More than 400
Scientists
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EFSA Directorat Organigram
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• When a food or food substance is associated
  with both potential health risks and benefits,
  and particularly when the levels of intake
  associated with risk and benefit are close, there
  is a need to define an intake range within which
  the balance of risk and benefit is acceptable for
  risk management purposes.
• EFSA Scientific Colloquium Summary Report 6
  Risk-Benefit Analysis of Foods Methods and
  Approaches, 2006

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Possible risks with food

• Related to
• Diets Composition, inadequacy - relationship to
  disease
• Foods Content of nutrients, other natural
  constituents, allergens, contaminants, residues,
  microbes toxicology
• Nutrients (indispensable) Insufficiency or
  excess

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Food Hazard

• Harm through inadequacy/insufficiency is not due
  to an inherent property of the nutrient, but to
  its absence
• Harm through excessive intake is due to an
  inherent property of the nutrient

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Risk-Benefit Analysis

• Risk Assessment
• Hazard Identification
• Hazard Characterisation
• Exposure Assessment
• Risk Characterisation

• Benefit Assessment
• Benefit Identification
• Benefit Characterisation
• Exposure Assessment
• (Probability for)
• Benefit Characterisation

Risk-Benefit Assessment Risk-Benefit
Comparison (Also Risk-Benefit Management and
Risk-Benefit Communication)
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When RBA

• The same substance has the potential for both
  harm and benefit in the same subject
• Example selenium
• The same substance has the potential for harm in
  one population group and for benefit in another
  population group
• Examples folic acid
• The same food contains substances which can
  cause harm and substances which can provide
  benefit in the same population group
• Example human milk with environmental
  pollutants
• The same food contains substances which can
  cause harm in one population group and provide
  benefit to another population group
• Example fish

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EFSA Colloquium

• http//www.efsa.europa.eu/EFSA/Scientific_Document
  /comm_colloque_6_en.pdf

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Objectives of Colloquium

• To have an open debate on scientific approaches
  and methods available and tools and data needed
  for conducting a risks-benefit analysis of foods
  and food components
• To explore opportunities and limitations for
  defining a common scale of measurement (common
  currency) to quantitatively compare health risks
  and benefits
• To define further research needs

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Participants

• About 100 participants with expertise in
  toxicology, microbiology, exposure, epidemiology,
  nutrition
• From the private, academic and regulatory sector
• From 26 European Countries, Australia, Canada and
  USA

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Discussion groups

• 1. Nutrient content of food versus toxic
  contaminants
• and constituents
• 2. Risk and benefit assessment of food
  fortification and functional foods
• 3. Food preservation versus microbial hazards

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Questions addressed at the Colloquium

• What human health risks and benefits should be
  considered and which one can be quantified?
• What tools/data do we currently have and what
  tools and data would be needed?
• When should a risk-benefit analysis be carried
  out?
• What type of risk-benefit analysis is needed?
• Do we need a risk-benefit analysis for different
  population groups?
• What could be a common scale of measurement?
• Where is the borderline to risk management?

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Effects to be considered

• That can be clearly identified
• For which causality with food or food components
  exist
• For which good quality exposure and dose-response
  data exist
• For which a clear problem formulation exist

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Tools and data

• Incidence of outbreaks and quantification of
  impact of the disease (burden of disease)
• Nutritional status in population can be
  quantified
• ADI or RDA useful for identifying whether or not
  we need risk-benefit assessment, but not
  appropriate for quantitative considerations
• Human dose-response curves or data are mostly not
  available for foods and scarce for single
  nutrients
• Probabilistic exposure and effect modelling
• Interspecies scaling (e.g. using physiologically
  based pharmacokinetic modelling (PBPK))

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When and why risk benefit?

• Risk-benefit analysis is not a routine procedure,
  only to be used when impact on public health is
  expected (e.g. when margin between beneficial and
  detrimental intake levels is small)
• A clear problem formulation is needed
• Tiered approach (qualitative, semi-quantitative,
  quantitative) should be considered
• What is feasible depends on the availability of
  data
• Assumptions and uncertainties should be clearly
  addressed

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Different population groups

• Its essential to evaluate risks and benefits in
  the appropriate population groups
• Different life stages for the manifestation of
  risks and benefits should be considered
• Weighing of one population group against another
  should be avoided

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Common scale of measurement

• The following measures were mentioned
• Mortality and morbidity
• Days of work lost
• Disability adjusted life years (DALYs)
• Quality adjusted life years (QALYs)
• Cost of illness/willingness to pay
• ? Common scale not always needed
• ? No generally applicable measure
• ? DALY/QALY for complex, societal-wide situations

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Disability Adjusted Life Years
In complex situations the DALY can be chosen as
an integrated measure of health impact. DALY
(Disability Adjusted Life Years) YLL
YLD YLL number of life years lost (deaths)
YLD number of years with illness or
disability, corrected for the seriousness of the
effect with a weighing factor varying between 0
(totally healthy) and 1 (as serious as death)
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Borderline with risk management

• Borderline between risk-benefit assessment and
• management is not fixed and may shift with the
• nature of the outcome
• Scientific tools are becoming available to allow
  the assessor to quantify risk and benefits,
  moving the task of risk-benefit comparison from
  risk management into risk assessment
• Continuous iterative interaction between
  assessors and managers with possible input from
  stakeholders is essential throughout the process

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Recommendations from the Colloquium

• Guidance document to be developed by EFSA
• to address
• Problem formulation
• Definitions and language to be used
• Conversion of animal data to human situation
• Methods and approaches
• Potential pitfalls

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EFSA Working Group on RBA

• The Scientific Committee established spring 2007
  a
• Working Group on Human Health Risk-Benefit
  Assessment of Foods
• (WG RBA)
• 3rd meeting held on 12 October, 2007

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WG RBA

• The Working Group is composed of 12 Experts
• Ada Knaap (Chair) Ivar Vågsholm
• Alan Boobis Ivonne Rietjens
• Diane Benford Josef Schlatter
• Helmut Heseker Hildegard Przyrembel
• Howard Davies Rolaf Van Leeuwen
• Harry Kuiper Lie Øyevind
• Also observers from European Commission
• http//www.efsa.europa.eu/EFSA/efsa_locale-1178620
  753812_1178621709323.htm

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Terms of Reference

• The WG on RBA is
• To prepare a guidance document for performing
  risk-benefit assessments of food related to human
  health risks and human health benefits
• Guidance to be ready by 2009

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Terms of Reference (2)

• Scope and objective, common languageIdentificatio
  n of situations
• Guidance on problem formulation
• Consideration of methods and approaches needed to
  assess risks and benefits and how to compare them
  (common scale of measurement)
• Consideration of how animal and other data can be
  extrapolated
• Identification of potential limitations of any
  RBA
• Review of ongoing activities
• Recommendations of future initiatives

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Current status of the WG RBA

• The WG on RBA is currently discussing the various
  sections indicated in the Terms of Reference
• Draft definition of Benefit (Improvement of
  Health)
• A reduction in probability and/or severity of
  an adverse health effect and/or an increase in
  the probability and/or magnitude of a positive
  health effect in a group of individuals under
  defined conditions of exposure

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RBA of Nitrate in Vegetables

• EFSA CONTAM Panel working on an opinion
• ToR ...to provide a scientific risk
  assessmentfor managing the risk from nitrates in
  vegetables
• The assessment should take into account any
  relevant information on the risks and benefits,
  for example of the possible negative impact of
  nitrate versus the positive effects of eating
  vegetables

NB Opinion expected beginning next year
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Vegetables

• Provide
• Nutrients, micronutrients, vitamins and minerals
  and
• Nitrate (NO3)
• Nitrite (NO2)
• Nitric oxide (NO) amino substrates
• N-nitroso compounds
• Adverse health outcomes, mainly from Nitrite
• Gastric Carcinoma, Blue Baby Syndrome
• ADI 3.7mg/kg/day (adult of 60kg)
• Equates to acceptable exposure of 222 mg/adult

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EC 1881/2006 Maximum Levels
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Nitrate in Leafy Vegetables (examples)
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Benefits and Risks of Vegetables

• 400 g/day fruit and vegetables WHO recommendation
• Prevention of non-communicable diseases e.g.
• Cardiovascular
• Cancer
• Obesity
• Type 2 diabetes
• Risks related to
• Antinutrients, allergens, mycotoxins,
  contaminants, pesticide residues

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Risks and benefits
Exposure to Nitrate
Eating Vegetables
Risk
Benefit
Risk
Benefit
Antinutrients Allergens Mycotoxins Contaminants Pe
sticide residues
Health Macro/micro nutrients Lifestyle
MetHb Cancer
Host defence Nitric oxide
Opinion to be published by beginning 2008
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Food Fortification Risks and Benefits

• Some examples Micronutrients and Vitamins

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Micronutrients
Source Renwick, 2004
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Nutrition and Food Fortification

• Requirements vary at different life stages and in
  different persons
• Potentially harmful micronutrient intakes vary at
  different life stages and in different persons
• Intakes that are beneficial for some may be
  harmful for others
• Detailed information on dose-response
  relationship is generally lacking
• Benefits of fortification are likely to be
  greatest for those with otherwise low intake
• Risk of fortification are likely to be greatest
  for those with otherwise high intake
• RBA needs to take into account the dietary habits
  of relevant subgroups

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GMO and Risk Benefit Analysis

• Briefly discussed at EFSA Colloquium -
  Environmental Risk Assessment of Genetically
  Modified Plants - Challenges and Approaches, 20
  -21 June 2007
• A benefit assessment could be conducted as a
  part of the Environmental Risk Assessment,
  particularly if adverse effects are identified.
• However, the regulatory status of RBA in GMO is
  unclear.

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EFSA Participation

• EFSA also involved in the following projects
• QALIBRA (http//qalibra.eu/)
• BENERIS (http//www.beneris.eu/)
• BRAFO (http//europe.ilsi.org/activities/ecproject
  s/BRAFO/default.htm)

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Grazie! Healthy food Safe
food Hildegard Przyrembel Rolaf Van
Leeuwen Diane Benford Andrew Cockburn Juliane
Kleiner