“composition-basedrisk (and benefit) assessment” · outline of the first presentation 1. risk...

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.


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


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.


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.


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


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]


� 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



� 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)?



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)



Step 1

Risks >> Benefits

Problem formulation

Assessment stops

Initial assessment

Risks << BenefitsRisks and Benefits do not clearly outweigh each other

Assessment stops

Step 2



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.


� 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


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




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


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


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.


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%)



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



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



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



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


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


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


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


“composition-basedrisk (and benefit) assessment” · outline of the first presentation 1. risk...

Documents