Composition-based risk (and benefit) assessment

Transcription

1 SESSION: Risk and benefit assessment Composition-based risk (and benefit) assessment Antonella Guzzon, Hylobates

2 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.

3 Outline of the second presentation 1. Application of the methodology to case studies in the Opasnet platform. Cinnamomum verum, dried bark, essential oil Foeniculum vulgare, dried seeds and essential oil Ginkgo biloba, dried leaves

4 Risk and benefit assessment of plant food supplements Food supplements are concentrated sources of nutrients or other substances with a nutritional or physiological effect whose purpose is to supplement 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 considered by European consumers as an additional source for deriving health benefits in their diet.

5 Risk and benefit assessment of plant food supplements Plant extracts used in food supplements may raise safety concerns due to particular substances contained in their concentrated form. Various approaches to risk-benefits assessment have been proposed for foods and food supplements but such approaches have not been yet adapted to PFS. An appropriate methodology for risk and benefit assessment of PFSs was developed, to promote the safe use of PFS by increasing science-based decision-making.

6 Development of the model for the risk-benefit assessment of PFSs Existing methodologies for RBA in the food sector EFSA RBA Guidance on human health risk-benefit assessment of foods. EFSA Journal, 2010, 8(7), BRAFO Hoekstra et al. 2010: BRAFO tiered methodology for benefit-risk assessment of foods. Food and Chemical Toxicology, doi: /j.fct Step 1: initial assessment Step 2: refined assessment Step 3: assessment using a composite metric 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 In both approaches, when evaluating the evidence for adverse and beneficial health effects, priority is given to data from human studies.

7 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),

8 EFSA approach to RBA Purpose of RBA: To allow risk-benefit manager to weigh the probability of a 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 concern as well as the characteristics of the specific target system [the human body] References EFSA. Guidance on human health risk-benefit assessment of foods. The EFSA Journal, 2010, 8(7),

9 EFSA approach to RBA Situations requiring RBA - A single compound or food constituent has both positive and negative effects in the same population (zinc, vitamin A, etc.) or in different populations (folic acid fortified food) - Positive and negative health effects result from different components in the same food (e.g. fatty fish with positive effects from n3 fatty acids and negative effects of dioxins) Current approaches to food restrict RBA to net health effects without taking into consideration social, economic or legal factors

10 EFSA approach to RBA 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 population by a particular diet or food? what would be the net health impact of a specified change in the diet (e.g. new product)?

11 EFSA approach to RBA Step 1: Risks and benefits are evaluated separately and their health effects are compared qualitatively Risk assessment Benefit assessment Hazard identification Hazard characterization (dose-response) Exposure assessment Risk characterization (probability to occur) Positive health effect identification Positive health effect characterization (dose-response) Exposure assessment Benefit characterization (probability to occur)

12 EFSA approach to RBA Step 1 Problem formulation Initial assessment Risks >> Benefits Assessment stops Risks and Benefits do not clearly outweigh each other Risks << Benefits Assessment stops Step 2

13 Refined assessment Risks >> Benefits Assessment stops Risks and Benefits do not clearly outweigh each other Comparing risks and benefits using a composite metric Risks << Benefits 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 composite metrics (QALYs, DALYs). The outcome is a single net impact value.

14 BRAFO approach to RBA Development of a framework for RBA applied on natural foods 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 References Hoekstra et al. 2010: BRAFO tiered methodology for benefit-risk assessment of foods. Food and Chemical Toxicology, doi: /j.fct

15 BRAFO approach to RBA Tier 1: Risks and benefits assessments are performed separately and their health effects are compared No clear dominance of risks or benefits the assessment proceeds to Tier 2 Problem formulation Tier 1 Individual assessment of risks and benefits No risk Assessment stops Both risks and benefits Tier 2 No benefit Assessment stops

16 BRAFO approach to RBA 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 >> Benefits Assessment stops Tier 2 Qualitative integration of risks and benefits Risks and Benefits do not clearly outweigh each other Risks << Benefits Assessment stops Tier 3 Deterministic computation of common health metric (QALYs, DALYs) Tier 4 Probabilistic determination

17 BRAFO APPROACH TO RBA Example: CONSUMPTION OF SALMON Scenario: low intake weighed against scenario: intake of 200 g/week Positive health effects: Fatty acids, selenium, iodine and vitamin D Negative health effects: methyl mercury, PCB, dioxins Tier 1 no clear dominance of risks or benefits Tier 2 comparison of intake and reference doses for risks and benefits in the two scenarios addressed: Increased fish consumption would reduce the incidence of cardiovascular diseases References Bernhard et al. 2011: Application of the BRAFO tiered approach for benefitrisk assessment of to case studies on natural foods. Food and Chemical Toxicology, doi: /j.fct

18 Development of the model for the risk-benefit assessment of PFSs Existing methodologies for RBA in the food sector EFSA RBA Guidance on human health risk-benefit assessment of foods. EFSA Journal, 2010, 8(7), BRAFO Hoekstra et al. 2010: BRAFO tiered methodology for benefit-risk assessment of foods. Food and Chemical Toxicology, doi: /j.fct Step 1: initial assessment Step 2: refined assessment Step 3: assessment using a composite metric 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 In both approaches, when evaluating the evidence for adverse and beneficial health effects, priority is given to data from human studies.

19 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 Cinnamomum verum J.Priesl (ceylon cinnamon) Chemical composition: main bioactive compounds are cinnamaldehyde (55-76% of the oil), eugenol (1-18%), safrole ( 2%)

20 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 required before RBA

21 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 effect 2. Characterization of the adverse effect 3. Estimate of product intake 4. Evaluation of the quality of scientific evidence Benefit assessment: 1. Identification of the beneficial effect 2. Characterization of the positive effect 3. Estimate of product intake 4. Evaluation of the quality of scientific evidence Comparison between risks and benefits and evaluation of their health impact

22 Scientific approach for evaluating risks and benefits of PFSs Step of the assessment 1. Identification of adverse effects 2. Characterization of the adverse effects 3. Estimate of product intake 4. Evaluation of the evidence Example for cinnamon essential oil 1. & 2. Lesions to oral mucosa from case-reports, glutatione-depleting action (in-vitro), chronic toxicity (animal studies) 3. Recommended dose: mg/day of 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

23 Scientific approach for evaluating risks and benefits of PFSs Step of the assessment 1. Identification of positive effect 2. Characterization of the positive effect 3. Estimate of product intake 4. Evaluation of the evidence Example for cinnamon essential oil 1. & 2. Maintenance of normal blood glucose concentration (tradition of-use, animal studies on cinnamaldehyde and on the preparation. 3. Recommended dose: mg/day of essential oil 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

24 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

25 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 effect Probabile fairly consistent association between exposure and effect Possibile uncertain association between exposure and effect Insufficient lack of or scarce data from poor quality studies that do not allow establishing an association between exposure and effect MORE DATA NEEDED

26 What is the result of risk-benefit assessment of PFS Description of risks and benefits following consumption 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 botanical preparations to promote safe-use The result of the evaluation is useful for authorities and industries