RISK ASSESSMENT OF FOOD ADDITIVES
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Transcript of RISK ASSESSMENT OF FOOD ADDITIVES
RISK ASSESSMENT OF FOOD ADDITIVES
CONFERENCE ON “ FOOD ADDITIVES : SAFETY IN USE AND CONSUMER CONCERNS“
JOMO KENYATTA UNIVERSITY OF AGRICULTURE AND TECHNOLOGY
NAIROBI , 24 JUNE 2014
CORRADO LODOVICO GALLI
STRUCTURE OF RISK ANALYSIS
Risk Communicat
ion
Risk Managemen
t
Risk Assessment
STRUCTURE OF RISK ANALYSIS
Risk Communicat
ion
Risk Managemen
t
Hazard Assessment
HAZARD
Hazard is the potencial capacity of producing harm.
RISK
Risk is proportional to both the hazard and the extent of exposure.
STRUCTURE OF RISK ANALYSIS
Risk Communicat
ion
Risk Managemen
t
Hazard Assessment
STRUCTURE OF RISK ANALYSIS
Risk Communicat
ion
Risk Managemen
t
Risk Assessment
Weight of
Evidence
Expert Judgement
• 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
ENSURING THE SAFETY OF FOOD ADDITIVES
RISK ANALYSIS
Hazard identification Inherent biological activity
Hazard assessment Assessment of relevance for
humans
Dose-response analysis
HAZARD IDENTIFICATION Identification of adverse health effects
In silico methodologies In vitro toxicology data Animal-based toxicological studies Human observation
HAZARD ASSESSMENT Quantification of adverse health effects
Kinetic variability Dynamic variability Mode/mechanism of action Selection of critical data Dose-response for critical effect
RISK CHARACTERISATION
EXPOSURE ASSESSMENT
Active principle Dose of food additives Dose in individuals Dose in special population groups Max/min chronically/occasionally
RISK ASSESSMENT
RISK MANAGEMENT: GENERAL PRINCIPLES OF FOOD SAFETY
Principle 1Risk management should follow a structured approach
Principle 2Protection of human health should be the primary consideration in risk management decisions
Principle 3Risk management decisions and practices should be transparent
Principle 4Determination of risk assessment policy should be included as a specific component of risk
management
Principle 5Risk 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 7Risk management should be a continuing process that takes into account all newly generated
data in the evaluation and review of risk management decisions
HEALTH BASED GUIDANCES
Reference points (RPs) in toxicology studies used to
calculate a safe level for human intake:
NO-OBSERVED-ADVERSE-EFFECT-LEVEL (NOAEL);
Benchmark Dose (BMD).
Toxicant and/or NON Genotoxic Carcinogen
Toxicants
Dietary supplements
Botanicals – Herbs
Contaminants
HEALTH BASED GUIDANCES
• ADI (Acceptable Daily Intake)
• ARfD (Acute Reference Dose)
• TMDI (Tolerable Maximum daily Intake)
• XYZ ……………………………………………………… etc. etc
HEALTH BASED GUIDANCES
ADI - ARfD – T(M)DI(HEALTH BASED GUIDANCES)
ADI represents the
amount of a food additive, a pesticide or a veterinary drug residue, expressed on a body weight basis, that can be ingested daily over a lifetime without appreciable health risk.
ARfD represents the
amount of a pesticide, expressed on a body weight basis, that can be ingested over a short period of time (one day) without appreciable health risk
T(M)DI represents
permissible human daily exposure to those contaminants, expressed on a body weight basis, unavoidably associated with the consumption of nutritious foods.
TOXICOLOGICAL PROTOCOL
ADI – ARfD -TMDI– xxz…..
ALLOCATION
HEALTH BASED GUIDANCES
TOXICOKINETIC Absorption Distribution Metabolism Excretion
GENOTOXICITY Mutagenesis Clastogenesis Aneuploidy
ACUTE TOXICITY LD50 oral
LD50 dermal
LC50 inhalation
Skin irritation Eye irritation Skin sensitization
SHORT-TERM TOXICITY
Mouse 90 day toxicity Rat 90 day toxicity Dog 90 day toxicity Dog 1 year toxicity
DEVELOPMENTAL TOXICITY Teratogenicity tests (Rat-Rabbit)
REPRODUCTIVE TOXICITY Two generation reproductive toxicity
LONG-TERM TOXICITY
AND/OR CARCINOGENICITY
Mouse 18 months Rat 104 weeks
ANIMAL-BASED TOXICOLOGICAL STUDIES
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
res p
onse
dose mg/kg bw100101
NOAEL
ADI ARfDAOEL
HUMANSsensitive subjects
HUMANSpopulation average
ANIMALS
ANIMAL-BASED TOXICOLOGICAL STUDIES(NOAEL AND ADI)
:10SPECIES DIFFERENCES
:10HUMAN VARIABILITY
ADMISSIBILE DAILY INTAKE
NOAEL = No Observed Adverse Effect Level (mg/kg b.w.)
SF = Safety Factor (10, 100, n)
NOAEL
SFADI =
ADI = Admissible Daily Intake mg/kg b.w.
SAFETY FACTOR
Interindividual Differences 10
Interspecies Differences 10
Log Concentration-∞ +∞Frequency
of
the p
henom
enon
INTERINDIVIDUAL DIFFERENCESINDIVIDUAL SUSCEPTIBILITY - GENETIC POLYMORPHISM
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
EXPOSURE ASSESSMENT
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?
DATA REQUIREMENTS FOR EXPOSURE ASSESSMENT
CONCENTRATION:
Regulated Maximum Levels (MLs) in the EU for: 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 Diets Test 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 Records interviews.
Household Budget Surveys ( HBS ) national surveys mainly focusing on consumption
expenditure.
EXPOSURE ASSESSMENT CONCERNS
• ANALYSIS
• FATE
• CONSUMPTION
• Methodologies to integrate food consumption, fate and
chemical concentration to make the best estimate of
exposure.
ACUTE AND CHRONIC DIETARY EXPOSURE
Exposure = mg/kg body weight/day
Body weig
ht (60 kg )
Concentration of
chemical in
diet
Weight of diet consumed daily
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
ADDITIVES EXPOSURE ASSESSMENT – FACET(FLAVOURS, ADDITIVES AND FOOD CONTACT MATERIAL EXPOSURE TASK)
Specific Codification
SystemQuantity of food
consumed
Distribution of concentrations
Usage level of the Additive in food
Presence probability Occurrence of the Additive in food
INTA
KE
Con
su
mer
Loyalt
y
http://www.ilsi-guidea.org/index.php?title=Main_Page
ILSI EUROPE ‘ GUIDEA ‘
PRACTICAL ILSI EUROPE GUIDE FOR CONDUCTING INTAKE AND EXPOSURE ASSESSMENTS
TO ENCOURAGE HARMONISATION LEADING TO BETTER HEALTH RECOMMENDATIONS.
RISK COMMUNICATION
REAL RISK (WHO)
Nutritional Deficiencies
Bacterial Intoxications
Biological Toxins
PESTICIDES RESIDUES
Food Additives
PERCEIVED RISKS (media)
PESTICIDES RESIDUES
Food Additives
Nutritional Deficiencies
Bacterial Intoxications
Biological Toxins
FA-TOXICITY TESTING STRATEGIES
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
TRIGGERS FOR CONSIDERING TIER 2
Systemic availability
Toxicity in the 28/90-day study
Genotoxicity in vitro
ABSORPTION
GENOTOXICITY
In vitro testing
TOXICITY (28-day/90-day study)
TIER 1
FA-TOXICITY TESTING STRATEGIES
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
ADMESingle dose
GENOTOXICITYIn vivo testing
TOXICITY (stand alone or combined)Chronic toxicityCarcinogenicity
REPRODUCTIVE & DEVELOPMENTAL TOXICITYExtended One–Generation Reproduction Toxicity
Study PRENATAL DEVELOPMENTAL TOXICITY (Teratogenicity)
TRIGGERS FOR CONSIDERING TIER 3
Bioaccumulation
Positive in vivo genotoxicity
Chronic toxicity/Carcinogenicity
Reproductive & developmental
toxicity
TIER 2
FA-TOXICITY TESTING STRATEGIES
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
ADMERepeated doses
CARCINOGENICITYMode of action
REPRODUCTIVE & DEVELOPMENTAL TOXICITYEndocrine Disruptor?
SPECIALIZED STUDIE Immunotoxicity
NeurotoxicityEndocrine activityMode of Action
TIER 3
SHUKRANI KWA AJILI YA KUNISIKILIZA(GOOGLE TRANSLATOR)