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)