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SESSION: Risk and benefit assessment
“Composition -based risk (and benefit) assessment”
BRAMA training for technicians & authorities – Modul e III, Cairo (19-21 October 2015)
Antonella Guzzon, Hylobates
Outline of the first presentation
1. Risk and benefit assessment (RBA ) of plant food supplements (PFSs): the background.
2. Development of the model for the risk-benefit assessment of plant food supplements:• existing methodologies in the food sector,• key features of the proposed model.
BRAMA training for technicians & authorities – Modul e III, Cairo (19-21 October 2015)
Outline of the second presentation
1. Application of the methodology to case studies in the Opasnet platform.
Cinnamomum verum, dried bark, essential oilFoeniculum vulgare, dried seeds and essential oilGinkgo biloba, dried leaves
BRAMA training for technicians & authorities – Modul e III, Cairo (19-21 October 2015)
Risk and benefit assessment of plant foodsupplements
�Food supplements are concentrated sources ofnutrients or other substances with a nutritional orphysiological effect whose purpose is tosupplement the normal diet.
�They are marketed 'in dose' form i.e. as pills,tablets, capsules, liquids in measured doses,etc.
�Plant food supplements (PFS) are consideredby European consumers as an additional sourcefor deriving health benefits in their diet.
BRAMA training for technicians & authorities – Modul e III, Cairo (19-21 October 2015)
Risk and benefit assessment of plant foodsupplements
�Plant extracts used in food supplements may raisesafety concerns due to particular substancescontained in their concentrated form.
�Various approaches to risk-benefits assessmenthave been proposed for foods and food supplementsbut such approaches have not been yet adapted toPFS.
� An appropriate methodology for risk and benefitassessment of PFSs was developed, to promotethe safe use of PFS by increasing science-baseddecision-making.BRAMA training for technicians & authorities – Modul e III, Cairo (19-21 October 2015)
Development of the model for the risk-benefit assessment of PFSs
� Existing methodologies for RBA in the food sector
BRAFOHoekstra et al. 2010: BRAFO tiered methodology for benefit-risk assessment of foods. Food and Chemical Toxicology, doi:10.1016/j.fct.2010.02.049
EFSA RBAGuidance on human health risk-benefit assessment of foods. EFSA Journal, 2010, 8(7), 1673-1714
Tier 1: individual assessment of risks andbenefitsTier 2: qualitative integration of risks and benefitsTier 3: deterministic computation of commonhealth metricsTier 4: probabilistic computation
Step 1: initial assessmentStep 2: refined assessmentStep 3: assessment using a composite metric
In both approaches, when evaluating the evidence fo r adverse and beneficial health effects, priority is given to data from huma n studies.
BRAMA training for technicians & authorities – Modul e III, Cairo (19-21 October 2015)
Risk-benefit assessment: the general concept
The risk-benefit paradigm according to EFSA (2010).Reference
EFSA. Guidance on human health risk-benefit assessment of foods. The EFSA Journal, 2010, 8(7), 1673-1714
BRAMA training for technicians & authorities – Modul e III, Cairo (19-21 October 2015)
EFSA approach to RBA
ReferencesEFSA. Guidance on human health risk-benefit assessment of foods. The EFSA Journal, 2010, 8(7), 1673-1714
� Purpose of RBA:
To allow risk-benefit manager to weigh the probability ofa health risk against the probability of an health benefit,by a qualitative and/or quantitative approach
� EFSA definition of RBA
A process intended to calculate or estimate the risk to a given(sub)population, including the identification of attendant uncertainties,relating to exposure to a particular agent [a food or a food constituent],taking into account the inherent characteristics of the agent of concernas well as the characteristics of the specific target system [the humanbody]
BRAMA training for technicians & authorities – Modul e III, Cairo (19-21 October 2015)
� Situations requiring RBA
- A single compound or food constituent has both positive andnegative effects in the same population (zinc, vitamin A, etc.) orin different populations (folic acid fortified food)
- Positive and negative health effects result from differentcomponents in the same food (e.g. fatty fish with positiveeffects from n3 fatty acids and negative effects of dioxins)
Current approaches to food restrict RBA to net health effectswithout taking into consideration social, economic or legalfactors
EFSA approach to RBA
BRAMA training for technicians & authorities – Modul e III, Cairo (19-21 October 2015)
� Structure of RBA assessment
Step 1: initial assessment
Step 2: refined assessment
Step 3: assessment using a composite metric
Problem formulation:what is the balance of risks and benefits caused in a populationby a particular diet or food?
what would be the net health impact of a specified change in thediet (e.g. new product)?
EFSA approach to RBA
BRAMA training for technicians & authorities – Modul e III, Cairo (19-21 October 2015)
Step 1: Risks and benefits are evaluated separately and their healtheffects are compared qualitatively
Risk assessment Benefit assessment
• Hazard identification• Hazard characterization(dose-response)• Exposure assessment• Risk characterization(probability to occur)
• Positive health effectidentification• Positive health effectcharacterization (dose-response)• Exposure assessment• Benefit characterization(probability to occur)
EFSA approach to RBA
BRAMA training for technicians & authorities – Modul e III, Cairo (19-21 October 2015)
Step 1
Risks >> Benefits
Problem formulation
Assessment stops
Initial assessment
Risks << BenefitsRisks and Benefits do not clearly outweigh each other
Assessment stops
Step 2
EFSA approach to RBA
BRAMA training for technicians & authorities – Modul e III, Cairo (19-21 October 2015)
Refined assessment
Risks >> Benefits Risks << BenefitsRisks and Benefits do not clearly outweigh each other
Comparing risks and benefits using a composite metric
Assessment stops Assessment stops
Step 2: Problem is reformulated and risks and benefits are estimated.No clear dominance � the assessment proceeds to Step 3
Step 3: Comparison or risks and benefits using single compositemetrics (QALYs, DALYs).The outcome is a single net impact value.
BRAMA training for technicians & authorities – Modul e III, Cairo (19-21 October 2015)
� Stepwise process
Tier 1: individual assessment of risks and benefits
Tier 2: qualitative integration of risks and benefits
Tier 3: deterministic computation of common health metrics
Tier 4: probabilistic computation
BRAFO approach to RBA
References
Hoekstra et al. 2010: BRAFO tiered methodology for benefit-risk assessment of
foods. Food and Chemical Toxicology, doi:10.1016/j.fct.2010.02.049
Development of a framework for RBA applied on natural fo ods
BRAMA training for technicians & authorities – Modul e III, Cairo (19-21 October 2015)
Tier 1: Risks and benefits assessments are performed separately and theirhealth effects are compared
No clear dominance of risks or benefits � the assessment proceeds to Tier 2
No risk
Tier 1Individual assessment of risks
and benefits
Problem formulation
Assessment stops
No benefit
Assessment stops
Both risks and benefits
Tier 2
BRAFO approach to RBA
BRAMA training for technicians & authorities – Modul e III, Cairo (19-21 October 2015)
BRAMA training for technicians & authorities – Modul e III, Cairo (19-21 October 2015)
Tier 2: qualitative comparison of risks and benefits on the basis of
positive health and hazard identification done in Tier 1
Tier 3 & 4: quantitative comparison
BRAFO approach to RBA
Risks and Benefits do not
clearly outweigh each
other
Tier 2
Qualitative integration of
risks and benefits
Risks >> Benefits Risks << Benefits
Assessment stops Assessment stops
Tier 3
Deterministic computation of common health metric (QALYs, DALYs)
Tier 4
Probabilistic determination
BRAMA training for technicians & authorities – Modul e III, Cairo (19-21 October 2015)
Example: CONSUMPTION OF SALMON
Scenario: low intake weighed against scenario: intake of 20 0 g/week
Positive health effects: Negative health effects:Fatty acids, selenium, iodine and vitamin D methyl mercury, PCB, dioxins
Tier 1 ���� no clear dominance of risks or benefits
Tier 2 ���� comparison of intake and reference doses for risks and benef its in thetwo scenarios addressed:
Increased fish consumption would reduce the incidence ofcardiovascular diseases
References
Bernhard et al. 2011: Application of the BRAFO tiered approach for benefit-
risk assessment of to case studies on natural foods. Food and Chemical
Toxicology, doi:10.1016/j.fct.2011.02.010
BRAFO APPROACH TO RBA
Development of the model for the risk-benefit assessment of PFSs
� Existing methodologies for RBA in the food sector
BRAFOHoekstra et al. 2010: BRAFO tiered methodology for benefit-risk assessment of foods. Food and Chemical Toxicology, doi:10.1016/j.fct.2010.02.049
EFSA RBAGuidance on human health risk-benefit assessment of foods. EFSA Journal, 2010, 8(7), 1673-1714
Tier 1: individual assessment of risks andbenefitsTier 2: qualitative integration of risks and benefitsTier 3: deterministic computation of commonhealth metricsTier 4: probabilistic computation
Step 1: initial assessmentStep 2: refined assessmentStep 3: assessment using a composite metric
In both approaches, when evaluating the evidence fo r adverse and beneficial health effects, priority is given to data from huma n studies.
BRAMA training for technicians & authorities – Modul e III, Cairo (19-21 October 2015)
Scientific approach for evaluating risks and benefits of PFSs
The subject of the assessment is the botanical preparation,contained in the supplement, and its bioactive compounds.
1 . Identification and chemical characterization of the botanical preparation of interest
Example: essential oil extracted from the dried bark of Cinnamomumverum J.Priesl (ceylon cinnamon)
Chemical composition: main bioactive compounds are cinnamaldehyde
(55-76% of the oil), eugenol (1-18%), safrole (≤2%)
BRAMA training for technicians & authorities – Modul e III, Cairo (19-21 October 2015)
Scientific approach for evaluating risks and benefits of PFSs
Critical step: identification and characterization of the
botanical preparation
A certain botanical preparation might have variation in composition among different marketed supplements (e.g. due to different extraction methods)
Systematic analysis of all the possible variations in composition of the botanical preparation is require d before RBA
BRAMA training for technicians & authorities – Modul e III, Cairo (19-21 October 2015)
Scientific approach for evaluating risks and benefits of PFSs
2. Parallel evaluation of adverse and positive effects for the botanical preparation and single compounds
Risk assessment:1. Identification of adverse effect2. Characterization of the adverse
effect3. Estimate of product intake4. Evaluation of the quality of
scientific evidence
Benefit assessment:1. Identification of the beneficial
effect2. Characterization of the positive
effect3. Estimate of product intake4. Evaluation of the quality of
scientific evidence
Comparison between risks and benefits and evaluation of their health impact
BRAMA training for technicians & authorities – Modul e III, Cairo (19-21 October 2015)
Scientific approach for evaluating risks and benefits of PFSs
1. Identification of adverse effects
2. Characterization of the adverse effects
Example for cinnamon essential oil
Evidence Health outcome Weight
History of use No severe, non reversible adverse effects Probable
History of use Rare allergic or irritant distal skin reactions Convincing
In vitro Paracetamol or alcohol interaction Possible
Animal No chronic toxicity Possible
Human No unknown adverse events from chronic consumption Insufficient
3. Estimate of product intake
Step of the assessment
1. & 2. Lesions to oral mucosa fromcase-reports, glutatione-depletingaction (in-vitro), chronic toxicity(animal studies)
3. Recommended dose: 50-200 mg/dayof essential oil
4. Evaluation of the evidence
BRAMA training for technicians & authorities – Modul e III, Cairo (19-21 October 2015)
Scientific approach for evaluating risks and benefits of PFSs
1. Identification of positive effect
2. Characterization of the positive effect
Example for cinnamon essential oil
3. Estimate of product intake
Step of the assessment
1. & 2. Maintenance of normal bloodglucose concentration (tradition of-use,animal studies on cinnamaldehyde andon the preparation.
3. Recommended dose: 50-200 mg/dayof essential oil4. Evaluation of the evidence
Evidence Health outcome Weight
Tradition Maintenance of normal blood glucose concentration Probable
In vitro Maintenance of normal blood glucose concentration Insufficient
Animal Maintenance of normal blood glucose concentration Possible
Human Maintenance of normal blood glucose concentration Insufficient
BRAMA training for technicians & authorities – Modul e III, Cairo (19-21 October 2015)
Data used in the assessment are…
� Literature data from in vitro, in vivo studies
� Data from human clinical trials
� Case reports of adverse effects
� Tradition of use
ALL the available evidence is analysed and used in the assessment model
BRAMA training for technicians & authorities – Modul e III, Cairo (19-21 October 2015)
Evaluation of scientific evidence
� A quality judgement is assigned to each type of evidence (in vitro studies, in vivo studies, human studies, tradition of use) based on study quality and data strength :
Convincing – consistent association between exposure and effectProbabile – fairly consistent association between exposure and
effectPossibile – uncertain association between exposure and effectInsufficient – lack of or scarce data from poor quality
studies that do not allow establishing an association between exposure and effect
MORE DATA NEEDED
BRAMA training for technicians & authorities – Modul e III, Cairo (19-21 October 2015)
What is the result of risk-benefit assessment of PFS…� Description of risks and benefits following consump tion of
the botanical preparation accompanied by evaluation of scientific data quality
� Possible direct comparison between risks and
benefits, if adequate data are available
� Risk-benefit assessment is necessary for all botani cal preparations to promote safe-use
The result of the evaluation is useful for authorit ies and industries
BRAMA training for technicians & authorities – Modul e III, Cairo (19-21 October 2015)