RISK ASSESSMENT OF FOOD ADDITIVES

1. RISK ASSESSMENT OF FOOD ADDITIVES CORRADO LODOVICO GALLI CONFERENCE ON “ FOOD ADDITIVES : SAFETY IN USE AND CONSUMER CONCERNS“ JOMO KENYATTA UNIVERSITY OF AGRICULTURE AND TECHNOLOGY NAIROBI , 24 JUNE 2014

2. Structure of Risk Analysis • RiskAssessment • Risk Management • RiskCommunication

3. Structure of Risk Analysis • HazardAssessment • Risk Management • RiskCommunication

4. HAZARD Hazard is the potencial capacity of producing harm.

5. RISK Riskis proportional to both the hazardand the extent of exposure.

6. Structure of Risk Analysis • HazardAssessment • Risk Management • RiskCommunication

7. Structure of Risk Analysis • RiskAssessment • Expert Judgement • Risk Management • Weight of Evidence • RiskCommunication

8. Ensuring the safety of food additives RISK ANALYSIS • Food additives are highly regulated at global level. (i.e. EFSA, FAs etc. etc.) • No food additive can be used without safety assessment and approval • Safety assessment is undertaken PRIOR to approval • The applicant (industry) provides the safety data, which have to be performed to defined quality standards (GLP, QA, OECD, UE guidelines……) • The assessment Panels – which include scientists and regulators with a wide range of expertise – are responsible for safety assessments RISK ANALYSIS RISK ANALYSIS RISK ANALYSIS RISK ANALYSIS

9. HAZARD IDENTIFICATION • Identification of adversehealtheffects • In silicomethodologies • In vitrotoxicology data • Animal-basedtoxicologicalstudies • Human observation HAZARD ASSESSMENT • Quantification of adversehealtheffects • Kineticvariability • Dynamicvariability • Mode/mechanism of action • Selection of criticaldata • Dose-response for criticaleffect RISK assessment • Hazard identification • Inherent biological activity • Hazard assessment • Assessment of relevance for humans • Dose-response analysis EXPOSURE ASSESSMENT • Active principle • Dose of foodadditives • Dose in individuals • Dose in special populationgroups • Max/minchronically/occasionally RISK CHARACTERISATION

10. Principle 1 Risk management should follow a structured approach Principle 2 Protection of human health should be the primary consideration in risk management decisions Principle 3 Risk management decisions and practices should be transparent Principle 4 Determination of risk assessment policy should be included as a specific component of risk management Principle 5 Risk management should ensure the scientific integrity of the risk assessment process by maintaining the functional separation or risk assessment and risk management Principle 6 Risk management decisions should include clear, interactive communication with consumers and other interested parties in all aspects of the process Principle 7 Risk management should be a continuing process that takes into account all newly generated data in the evaluation and review of risk management decisions Risk Management: General Principles of Food Safety

11. HEALTH BASED GUIDANCES • Reference points(RPs) in toxicologystudiesusedto calculatea safe level for human intake: • No-Observed-Adverse-Effect-Level (NOAEL); • Benchmark Dose (BMD).

12. HEALTH BASED GUIDANCES • Toxicant and/or NON Genotoxic Carcinogen • Toxicants • Dietary supplements • Botanicals – Herbs • Contaminants

13. HEALTH BASED GUIDANCES • ADI(Acceptable Daily Intake) • ARfD(Acute Reference Dose) • TMDI (Tolerable Maximum daily Intake) • XYZ ……………………………………………………… etc. etc

14. ADIrepresents the amount of afood additive, a pesticide or a veterinary drug residue, expressed on a body weight basis, that can be ingested daily over a lifetimewithout appreciable health risk. ARfDrepresents the amount ofa pesticide, expressed on a body weight basis, that can be ingested over a short period of time (one day)without appreciable health risk ADI - ARfd– T(M)DI(health based guidances) T(M)DIrepresents permissible human daily exposure to those contaminants, expressed on a body weight basis, unavoidably associated with the consumption of nutritious foods.

15. HEALTH BASED GUIDANCES ALLOCATION ADI – ARfD-TMDI– xxz….. TOXICOLOGICAL PROTOCOL

16. NOAEL ANIMAL-BASED TOXICOLOGICAL STUDIES • TOXICOKINETIC • Absorption • Distribution • Metabolism • Excretion • ACUTE TOXICITY • LD50 oral • LD50 dermal • LC50 inhalation • Skin irritation • Eye irritation • Skin sensitization • GENOTOXICITY • Mutagenesis • Clastogenesis • Aneuploidy • SHORT-TERM TOXICITY • Mouse 90 day toxicity • Rat 90 day toxicity • Dog 90 day toxicity • Dog 1 yeartoxicity • DEVELOPMENTAL TOXICITY • Teratogenicity tests (Rat-Rabbit) • REPRODUCTIVE TOXICITY • Two generation reproductive toxicity • LONG-TERM TOXICITY • and/or CARCINOGENICITY • Mouse 18 months • Rat 104 weeks

17. No-ADVERSE-Observed-Effect-Level (NOAEL) • The greatest concentration or amount of an agent, found by study or observation that causes detectable, usually adverse (or toxic?) alteration of morphology, functional capacity, growth, development or lifespan of the target

18. HUMANS populationaverage HUMANS sensitive subjects ANIMALS response Speciesdifferences Human variability 10 100 1 dose mg/kg bw ANIMAL-BASED TOXICOLOGICAL STUDIES(NOAEL and ADI) :10 :10 NOAEL ADI ARfD AOEL

19. ADMISSIBILE DAILY INTAKE NOAEL ADI = SF ADI=Admissible Daily Intake mg/kg b.w. NOAEL = No Observed Adverse Effect Level(mg/kg b.w.) SF= Safety Factor (10, 100, n)

20. 10 Interspecies Differences Interindividual Differences 10 SAFETY FACTOR

21. InterindividualDifferences INDIVIDUAL SUSCEPTIBILITY - GENETIC POLYMORPHISM Frequency of the phenomenon -∞ +∞ Log Concentration

22. Exposure Assessment • Exposure assessment is • a key element of risk assessment and • a tool for risk management • It’s theoretically simple but practically complex due to data deficiencies • Examples of exposure models: ILSI Europe’s ‘ GUIDEA ‘ and FACET

23. THREE MAIN QUESTIONS FOR Exposure Assessment • Which substances are present in what amounts in a given food/diet: • including information concerning factors influencing their levels and qualities such as bioavailability • How much of the foods containing these substances are consumed • and what is the consumption of potentially relevant risk groups, including high users? • What are the conditions and the probabilities of consuming occasionally or regularly • high amounts of such foods which at the same time contain high levels of the substance(s) in question?

24. DATA REQUIREMENTS for exposure assessment • Concentration: • Regulated Maximum Levels (MLs) in the EUfor: mycotoxins (aflatoxins, ochratoxin A, patulin, deoxynivalenol, zearalenone, fumonisins, T2 and HT-2-toxin) metals (cadmium, lead, mercury and inorganic tin) dioxins and dioxin-like PCBs, 3-MCPD, polycyclic aromatic hydrocarbons (benz(o)pyrene). • Manufacturer’s Use Levels • Consumption Patterns and General Population/Sub-Groups • Total Diet Survey( TDS ) determines levels of various contaminants and nutrients in foods. • Duplicate DietsTest persons consume their ordinary diet, but for subsequent analysis, they also prepare a duplicate portion of all food products as prepared, served and consumed. • Individual Food Diary Recordsinterviews. • Household Budget Surveys( HBS ) national surveys mainly focusing on consumption expenditure.

25. EXPOSURE ASSESSMENT CONCERNS • ANALYSIS • FATE • CONSUMPTION • Methodologies to integrate food consumption, fate and chemical concentration to make the best estimate of exposure.

26. Acute and Chronic Dietary Exposure

27. DATA UNCERTAINTIES in exposure assessment Concentration • Sampling and Analysis Consumption Surveys • Temporal- extrapolation to lifetime exposure • Under/Over reporting • Representativeness of population sample • Other sources of exposure eg. supplements , medicines • Coding system not specific enough • Portion size • Processed food

28. ADDITIVES EXPOSURE ASSESSMENT – FACET(Flavours, additives and food contact material exposure task) Consumer Loyalty INTAKE

29. Practical ILSI EUROPE guide for conducting intake and exposure assessments to encourage harmonisation leading to better health recommendations. ILSI EUROPE ‘ GUIDEA ‘ http://www.ilsi-guidea.org/index.php?title=Main_Page

30. RISK communication

31. FA-TOXICITY TESTING STRATEGIES • ABSORPTION • GENOTOXICITY • In vitro testing • TOXICITY (28-day/90-day study) TIER 1 • TRIGGERS FOR CONSIDERING TIER 2 • Systemic availability • Toxicity in the 28/90-day study • Genotoxicityin vitro Guidance for submission for food additive evaluations EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS) - EFSA Journal 2012;10(7):2760

32. FA-TOXICITY TESTING STRATEGIES • ADME • Single dose • GENOTOXICITY • In vivo testing • TOXICITY (stand alone or combined) • Chronic toxicity • Carcinogenicity • REPRODUCTIVE & DEVELOPMENTAL TOXICITY • Extended One–Generation Reproduction Toxicity Study • PRENATAL DEVELOPMENTAL TOXICITY (Teratogenicity) TIER 2 • TRIGGERS FOR CONSIDERING TIER 3 • Bioaccumulation • Positive in vivo genotoxicity • Chronic toxicity/Carcinogenicity • Reproductive & developmental toxicity Guidance for submission for food additive evaluations EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS) - EFSA Journal 2012;10(7):2760

33. FA-TOXICITY TESTING STRATEGIES • ADME • Repeated doses • CARCINOGENICITY • Mode of action • REPRODUCTIVE & DEVELOPMENTAL TOXICITY • Endocrine Disruptor? • SPECIALIZED STUDIE • Immunotoxicity • Neurotoxicity • Endocrine activity • Mode of Action TIER3 Guidance for submission for food additive evaluations EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS) - EFSA Journal 2012;10(7):2760

34. shukrani kwa ajili ya KUNISIKILIZA (google translator)