Anne Theobald - FoodDrinkEurope

EFSA’s guidance in the field of
nanotechnologies
4 th Nanotechnology Stakeholder Dialogue Day
`Potential food applications of nanotechnologies`
Brussels, 5 October 2011
Anne Theobald – Senior Scientific Officer
Scientific Panel on food contact materials, flavourings,
enzymes and processing aids (CEF) Unit

EFSA‘s opinions on
Nanotechnologies
Two mandates from the European Commission:
• In 2007 a request was received and an opinion adopted
by the Scientific Committee in 2009
• In 2009, a follow-up request was received and a
guidance opinion adopted by the Scientific Committee in
April 2011
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1. Opinion – Terms of Reference
• to produce a scientific opinion on the need for specific
risk assessment approaches for
technologies/processes and applications of nanoscience
and nanotechnologies in the food and feed area.
• to identify the nature of the possible hazards
associated with actual and foreseen applications in the
food and feed area
• to provide general guidance on data needed for the
risk assessment of such technologies and applications.
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1. Opinion – Conclusions
• The opinion is generic in nature and is not in itself a risk
assessment of nanotechnologies as such or of tentative
applications or possible uses thereof or of specific
products.
• It considers Engineered Nanomaterials (ENM) and.
• It provides generic guidance for risk assessment.
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1. Opinion – Conclusions
• The current risk assessment paradigm is applicable
for ENM.
• The nanospecific properties and characteristics of ENM
are likely to affect their toxicokinetic behaviour and
toxicity profile.
• Uncertanties e.g. measurement , exposure and
toxicological data.
• The risk assessment of ENM has to be performed on a
case-by-case basis.
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http://www.efsa.europa.eu/fr/scdocs/doc/sc_op_ej958_nano_en, 0.pdf
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2. Opinion: Terms of Reference
(1) EFSA is requested to prepare a guidance document
… (including food additives, enzymes, flavourings, food
contact materials, novel foods, food supplements, feed
additives and pesticides).
(2) This document should provide practical
recommendations for the risk assessment of food
related applications of nanotechnology to the extent
possible with current knowledge.
In the cases where knowledge is insufficient, it should
indicate the endpoints and/or parameters that would
have to be known in order to carry out a risk
assessment.
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2. Opinion: Terms of reference
(cont’d)
(2) Consultation with stakeholders: The proposed guidance
document should be subject to public consultation
and if deemed appropriate discussed with stakeholders
in a dedicated meeting prior to its adoption.
(3) Follow-up: Subsequent to these opinions, the
Commission invites EFSA to monitor scientific
advances and keep the Commission informed on
relevant developments and, when appropriate, to revise
the draft document.
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http://www.efsa.europa.eu/en/efsajournal/doc/2140.pdf
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General considerations
• Risk assessment paradigm is applicable
• Reference to existing guidelines in various food and feed
areas for the non-nano form
• Provide guidance on nano specific considerations that
need to be assessed in addition to conventional aspects
(e.g. additional information on physico-chemical
properties)
• In principle also applicable for contaminants
• Uncertainty analysis
• Acknowledges fast scientific development and the need
for update of the guidance document
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Characterisation at several steps
• As manufactured (pristine state)
• Prior to use in food/feed (as delivered to producer)
• As used in food/feed
• As used for toxicological testing
• In biological fluids and tissues
– Lays down parameters for characterisation and
identification
– Methods used need to be carefully selected and
described and demonstrated to be fit for purpose
– Acknowledged that characterisation can be difficult in
certain matrixes
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Exposure scenarios
• Outline anticipated exposure scenarios as this will
influence the extent of the hazard characterisation.
– Direct or indirect addition to food/feed
– Certain applications may give rise to a very limited
exposure
– Where ENM exposure is not detected by appropriate
methods, conventional risk assessment should be
considered for any non-nanoform fraction
(degradation)
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Toxicity Testing Outline
1. No persistence of ENM in preparations (as marketed)
2. No migration from food contact materials
3. Transformation in the food/feed matrix before digestion
4. Transformation during digestion
– In vitro studies
5. Information on non-nanoform available (if present in food/GI)
– Compare genotox, ADME and repeat dose 90-day study
6. No information on non-nanoform available (if present in
food/GI)
– Provide full data according to relevant EFSA guidance for
intended use, with modifications to tests as proposed
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No
Consider need for further testing
E.g.
No migration from FCM
•Follow EFSA FCM Guidance
Transformed to non-nanoform in
food/feed matrix before ingestion
•Follow relevant EFSA Guidance for nonnanoform
Yes
Assess local GIT effects and possible ENM
absorption before transformation
Test according to relevant EFSA Guidance for nonnanoform
or refer to existing data*
ENM Present in Food/feed?
Yes
ENM absorbed from the GIT?
(e.g. from assessment of stability in GI fluids
or ADME data)
No
ENM is completely
transformed into nonnanoform
in the GIT?
No
Yes
ENM is not (or only partially) transformed into
non-nanoform
In vitro tests:
Genotoxicity
•Gene mutations in mammalian cells test
•In vitro micronucleus test
In vivo tests**:
ADME
Repeated-dose 90-day oral toxicity
In vivo genotoxicity (if positive in vitro or not testable in
vitro)
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Exposure assessment
• Determination of the amount present in food/feed
• Estimate worst case exposure unless information
suggest otherwise.
– Assume that all added ENM is present, ingested and
adsorbed in the nanoform.
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GUIDANCE????
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Guidance documents for RA
Specific guidance documents are already in place for the
RA in the following areas:
• Food additives
• Food supplements
• Food contact materials
• Active and Intelligent Packaging
• Flavouring substances
• Pesticides
• GMOs and GMMs
• Feed
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Guidance documents for RA
Relate to preparation and submission of a dossier for
safety evaluation of substances by a producer
- before it can be placed
on the market
- for re-evaluation
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Data requirements in Guidance
documents
Some elements are common:
• Identification of substance
• Manufacturing process
• Dietary exposure
• Toxicological studies
Some information is specific:
• Environmental fate (pesticides, feed additives)
• Occupational health (pesticides, feed additives)
• Migration data into food (food contact materials)
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EFSA risk assessment of ENM
So far only two assessments have been provided by
EFSA on risks of specific nanomaterials in food and
feed:
o ANS Panel: Submitted data were insufficient to
adequately characterise silver hydrosol and the
Panel could not provide an opinion.
o CEF Panel: No safety concern for titanium nitride for
use as food contact material on the basis of absence of
migration into food simulant.
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EFSA Re-evaluation of food
additive by the ANS Panel.
Calcium carbonate (E170)
– Total number of particles with diameter less than 100
nm less than 1 %.
– A range of toxicological studies have been performed
with calcium carbonate described as nanoform
– none of these provided comprehensive data on
characterisation of the nano material
– nor do these studies provide a full toxicological
database in line with the guidance provided by EFSA
Scientific Committee Opinion
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Thank you for your interest!
anne.theobald@efsa.europa.eu
http://www.efsa.europa.eu/
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