Madrid, 30 June 2016

Nanomaterials in agri/food/feed: update from EFSA

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OUTLINE

Short Introduction to EFSA

Risk assessment process

Current applications

Current guidance for risk assessment

What to expect

Future guidance development

Introduction to EFSA and who is assessing nanomaterials

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EFSA IS…

Set up in 2002 as an independent source of scientific advice

Located in Parma since 2005

Having 450 Staff, 60% engaged in science

Delivering scientific outputs

Providing independent, timely risk communication

Promoting scientific cooperation

PROVIDING SCIENTIFIC ADVICE FROM FARM TO FORK

Plant Health

Animal health

and welfare Biological

hazards

Chemical

contaminants Nutrition

Plant

Protection Genetically modified

organisms

Animal feed

Food

additives

Food

packaging

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Cross-cutting science

OTHER EFSA UNITS INVOLVED

Scientific Committee and Emerging Risks for guidance development

ApDesk for registration of applications

EFSA’s scientists evaluate, assess, advise

…BUT NOT TO

develop food safety policies and legislation

adopt regulations, authorise marketing of new products

enforce food safety legislation

take charge of food safety/ quality controls, labelling or other such issues, like inspections and traceability

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Alignment and

cooperation

Applicants <> EC + MS <> EFSA

EFSA RISK ASSESSMENT PROCESS

Nano = Key enabling technology

producers

Legislation in place for safe governance

Risk Analysis (RA, RM, RC)

Definition in progress to enhance clarity

Food inspection

Labelling in progress to enhance transparency

Consumers, NGO, media

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2 3

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Current applications received at EFSA: http://registerofquestions.efsa.europa.eu/roqFrontend/login?2

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No applications yet

NOVEL FOODS

Legal framework being implemented

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Passed and ongoing applications

FOOD CONTACT MATERIALS

Dossiers submitted on explicitly engineered nanomaterial

Exposure scenario: no migration into the food

No food flavouring nano-applications

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FOOD CONTACT MATERIALS

EFSA-Q-2014-00529 Additional data request Request for the evaluation of Zinc oxide nano particles

EFSA-Q-2014-00308 Finished Request for safety evaluation of zinc oxide, nano particles for use as an additive in plastics

EFSA-Q-2013-00641 Additional data request Request for safety evaluation of Nano-Hexadecyltrimethylammonium Bromide modified Montmorillonite Organoclay for use as additive in plastics

EFSA-Q-2013-00100 Finished Request for the evaluation of additive : coplymer in Nanoform of methacrylic acid, ethyl acrylate, n-butyl acrylate, methyl acrylate, butadiene

EFSA-Q-2012-00706 Finished

Request for the evalutation of Additive : Copolymer in nanoform of ethyl acrylate, methyl methacrylate, butadiene, styrene and either not crosslinked or crosslined with divinyl benzene or 1,3-butanediol dimethacryalte

EFSA-Q-2011-01079 Finished Titanium nitride, nanoparticles

EFSA-Q-2006-323 Finished Titanium nitride, nanoparticles

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Re-evaluation programme (Reg (EU) n. 257/2010)

FOOD ADDITIVES

All FAs permitted before January 2009, All on bulk materials

Re-evaluations of food colours to be finalised by 2015.

No dossier, no applicant.

Data gathered following EFSA public calls for data (by interested parties), or public domain.

Silver (E174), gold (E175), iron oxides (E172) and titanium dioxide (E171).

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FOOD ADDITIVES RE-EVALUATION PROGRAMME

No limit for nanofraction according to EC specifications of FA (Reg (EU) n. 231/2012)

According to the information provided by interested parties, bulk materials may comprise a small nanofraction, which can be considered as unintentionally present or formed

Facts

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FOOD ADDITIVES RE-EVALUATION PROGRAMME

Nanofraction not sufficiently characterized in biological studies (e.g. % of substance in nanoform; methodology used)

Difficult to know how much nanofraction is present in the FA on the market:

- Silver: mass conc 20% of the mean total

silver conc in pearls (Verleysen, 2015)

- TiO2: limited % of particle size (by

weight) < 100 nm in different batches

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Elementary gold may include NP

EFSA OPINION ON E175 (GOLD) JAN 2016

Lots of studies cited and discussed

In vivo, in vitro

Studies on pristine gold nanoparticles

Capped or coated particles not useful for RA (appendix)

http://www.efsa.europa.eu/sites/default/files/scientific_output/files/main_documents/4362.pdf

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EFSA OPINION ON E175 (GOLD) JAN 2016

Conclusions:

Despite the absence of toxicity data, but taking into account the low solubility of elemental gold, systemic availability and thus systemic effects of elemental gold would not be expected.

Recommendations:

specifications for E 175 should include particle size distribution (± SD), the percentage (in number) of nanoparticles, using electron microscopy

Biological relevance

Future directions

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Iron Oxides and hydroxides (E172): insufficient data for RA

http://www.efsa.europa.eu/sites/default/files/scientific_output/files/main_documents/4317.pdf

Silver (E174): insufficient data for RA

http://www.efsa.europa.eu/sites/default/files/scientific_output/files/main_documents/4364.pdf

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Nutrient sources One application in the past – lack of data

comparing toxicity and bioavailability of nano- and bulk- forms

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Ongoing re-evaluation of bulk materials

FEED ADDITIVES

Dossier submitted on the bulk

Presence of NP

Cooperation with Food additive evaluation

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EFSA assesses only active ingredient

PESTICIDES

Formulations are assessed by Member States

Member States ask EFSA for harmonised guidance on nano-formulated pesticides

Nanopesticides/formulatons will be included in guidance update 2016-2019

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Current mandate

CONTAM

Microplastics in food

Current EFSA Guidance document for risk assessment of nanomaterials: (EFSA

Journal (2011) 9(5):2140 http://www.efsa.europa.eu/en/efsajournal/doc/2140.pdf)

04

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In spite of many practical limitations, chemico-physical characterization of ENMs should be considered in five stages

NM TEND TO INTERACT

(i) as manufactured (pristine state);

(ii) as delivered in food/feed products , taking into account also storage effects;

(iii) as present in the food/feed matrix;

(iv) as present in toxicity testing medium; and

(v) as present in biological tissues in

the human or animal body

nano activities at EFSA

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Assessing the extent of exposure is fundamental as it heavily determines the safety testing strategy

NM TEND TO INTERACT

Exposure meaning to the specific ENM and/or, if any, to a new ENM structure or degradation/dissolution products formed within the food /feed matrix and/or in the gastrointestinal tract

6 exposure scenarios provide indications on how to carry out toxicity tests such as in vitro and in vivo genotoxicity tests, ADME and subchronic toxicity to take into account structural peculiarities of ENMs.

nano activities at EFSA

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FOLLOW ONE OF THE 6 EXPOSURE SCENARIOS

nano activities at EFSA

1: No persistence of ENM in preparations/formulations as marketed (only exposure to the non-nanoform): the relevant toxicity testing outline should apply in relation to the intended use unless data are already available

2: No migration from food contact materials: (no exposure: no toxicity testing);

3: Complete ENM transformation into a non-nanoform in the food/feed matrix before ingestion (only exposure to the non-nanoform): the relevant toxicity testing outline in relation to the intended use should apply unless data are already available

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FOLLOW ONE OF THE 6 EXPOSURE SCENARIOS

nano activities at EFSA

4: Complete transformation into a non-nanoform in the gastro-intestinal tract ( as shown through studies in gastro-intestinal fluids and/or ADME) and possibility of excluding absorption of the nanoform before digestion: limited testing is required mainly consisting of in vitro genotoxicity and some in vivo local effects.

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FOLLOW ONE OF THE 6 EXPOSURE SCENARIOS

nano activities at EFSA

5: Total or partial persistence of the ENMs in the food/feed matrix and in the gastro-intestinal fluid and toxicity data on the non-nanoform available: ADME, 90 day-toxicity in rodents and genotoxicity to be tested. Resulting data are to be compared with those of the non-nanoform (if available) and:

If the difference observed indicates an increased hazard, the more toxicity testing will be required on the ENM;

If the differences observed indicate less hazard, requests to waive further testing could be scientifically justified.

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FOLLOW ONE OF THE 6 EXPOSURE SCENARIOS

nano activities at EFSA

6: Total or partial persistence of the ENM in the food/feed matrix and in the gastro-intestinal fluid and toxicity data on the non-nanoform not available:

full testing required as foreseen by the relevant testing outline in relation to the intended use, taking also into account the presence of nano-particles.

What is in the pipeline 05

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Systematic Literature Survey 2014

NANOMATERIALS IN AGRI/FOOD/FEED

http://www.efsa.europa.eu/en/supporting/pub/621e

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Systematic Literature Survey 2014

NANOMATERIALS IN AGRI/FOOD/FEED

Peters et al, 2016 (submitted)

Case-by-case safety studies +

RA

Future EFSA guidance for risk assessment 06

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DATA

EFSA RISK ASSESSMENT REQUIREMENTS

In dossiers prepared by applicants

Need more guidance

Aligned with ECHA

From call for data

Interested parties

Scientific Publications

Robustness, reporting and consistency

To be generated

case by case

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TEST METHODS

EFSA RISK ASSESSMENT REQUIREMENTS

From OECD

Work in progress

Standards and reference materials

For complex matrices like food/beverages

From FP7 projects

Coming through

From REACH

…

As standard as possible

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Human and animal health

MORE GUIDANCE FOR MORE CLARITY

Input from NanoReg, NanoDefine, +…

Incl. ADME, in vitro digestion, allergenicity, soft/hard NM, read across, solubility, aggregation/agglomeration, p-chem, dispersion

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Environment

MORE GUIDANCE FOR MORE CLARITY

Input from NanoFate, + …

Exposure throgh manure, sludge, pesticides/formulations

Incl. Environmental fate, biodegradation/accumulation/ biomagnification, non-target organisms selection, protection goals,

Possible life cycle (for FCM)

News from the EFSA NanoNetwork 07

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ToR of the NanoNetwork

since 2010, to exchange information with Member States on best practice and needs for risk assessment. http://www.efsa.europa.eu/en/scer/scernetworks

Outputs: Yearly meetings + Annual reports: http://www.efsa.europa.eu/en/publications/advanced-search/?sub_subject=63551

Contributors: 19 EU Member States, JRC, EU research (NanoDefine, NanoFate), DG SANTE, ECHA, EMA

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Possible future update of the SC guidance:

Pesticides formulation and implementation of the Novel food legislation (central applications for EFSA)

Address the issues of solubility and of soft nanomaterials (enhancing bioavailability)

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THANKS FOR YOUR ATTENTION

Acknowledgement

Maria Vittoria Vettori (feed)

Paolo Colombo, Ana Rincon (food)

Frederica Lodi, Anne Theobald (FCM)

Wolfgang Gelbmann (NDA)

Andrea Terron (PPR)

Tom Meyvis (ApDesk)

Ruud Peters (RIKILT) & Karin Aschberger, Hubert Rauscher (JRC)

Reinhilde.Schoonjans@efsa.europa.eu