CONFERENCE ON “ FOOD ADDITIVES : SAFETY IN USE AND CONSUMER CONCERNS“
JOMO KENYATTA UNIVERSITY OF AGRICULTURE AND TECHNOLOGY
NAIROBI , 24 JUNE 2014
HAZARD
is the potencial capacity of producing harm.
is proportional to both the
and the
.
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
 Hazard identification
 Inherent biological activity
 Hazard assessment
 Assessment of relevance for humans
 Dose-response analysis
EXPOSURE ASSESSMENT
 Active principle
 Dose of food additives
 Dose in individuals
 Dose in special population groups
 Max/min chronically/occasionally
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

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
Reference points (RPs) in toxicology studies used to calculate
a safe level for human intake:
 Benchmark Dose (BMD).
Toxicant and/or NON Genotoxic Carcinogen
Toxicants
Dietary supplements
Botanicals – Herbs
Contaminants
•
ADI
(Acceptable Daily Intake)
•
ARfD
(Acute Reference Dose)
•
TMDI
(Tolerable Maximum daily Intake)
•
XYZ
……………………………………………………… etc. etc
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.
ALLOCATION
ADI – ARfD -TMDI– xxz…..
TOXICOLOGICAL PROTOCOL
 Absorption
 LD50 oral
 Mutagenesis
 Distribution
 LD50 dermal
 Clastogenesis
 Metabolism
 LC50 inhalation
 Aneuploidy
 Excretion
 Skin irritation
 Eye irritation
 Skin sensitization
 Teratogenicity tests (Rat-Rabbit)
 Two generation reproductive toxicity
 Mouse
90 day toxicity
 Rat
90 day toxicity
 Dog
90 day toxicity
 Dog
1 year toxicity
 Mouse 18 months
 Rat 104 weeks
• 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
HUMANS
sensitive subjects
HUMANS
population average
ARfD
AOEL
1
10
dose mg/kg bw
100
ADI =
NOAEL
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)
Differences
10
Interindividual Differences
10
Interspecies
-∞
Log Concentration
+∞
 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
•
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?
:

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

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.
• Methodologies to integrate food consumption, fate and
chemical concentration to make the best estimate of exposure.
Concentration
of chemical in
diet
Weight of
diet consumed
daily
Body weight
(60 kg )
Exposure = mg/kg body weight/day

Sampling and Analysis

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
Consumer Loyalty
Quantity of
food
consumed
Distribution of
concentrations
Usage level of
the Additive
in food
Presence
probability
Occurrence of
the Additive
in food
INTAKE
Specific
Codification
System
ILSI EUROPE
http://www.ilsi-guidea.org/index.php?title=Main_Page
PERCEIVED RISKS (media)
REAL RISK (WHO)
Nutritional Deficiencies
Food Additives
Bacterial Intoxications
Nutritional Deficiencies
Biological Toxins
Bacterial Intoxications
Biological Toxins
Food Additives
 ABSORPTION
 GENOTOXICITY
In vitro testing
 TOXICITY (28-day/90-day study)
TRIGGERS FOR CONSIDERING TIER 2


Toxicity in the 28/90-day study

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
Systemic availability
Genotoxicity in vitro
 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)
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

ADME

Repeated doses
CARCINOGENICITY

Mode of action
REPRODUCTIVE & DEVELOPMENTAL TOXICITY

Endocrine Disruptor?
SPECIALIZED STUDIE
Immunotoxicity
Neurotoxicity
Endocrine activity
Mode of Action
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