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TNO Triskelion BV

YOUR CONSULTING PARTNER IN

REGULATORY COMPLIANCE AND

PRODUCT DEVELOPMENT

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TNO

Triskelion bv

• 170 employees

• TNO Triskelion is independent since 1 January 2011

• TNO Triskelion is part of TNO Companies

• Located at TNO Zeist – ‘Innovation for life’

• Innovation by knowledge development by TNO

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3

Three markets:

• Chemistry

• Pharmaceuticals

• Food and Feed

Three technologies:

• Risk Assessment & Registration

• Experimental Toxicology

• Analytical Chemistry

Three core values:

• Quality

• Communication (personal touch)

• Innovation powered by TNO R&D

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Food contact materials at TNO Triskelion

• Food approval studies en advice

• Migration testing

• Screening methods

• Petitioning of new substances

• Fysical testing

• Issue management

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Adhesives

Wax

Silicones Printing inks

1935/2004 Framework Regulation

2006/2023 GMP Regulation

Glass Wood

Paper and board

Metals

Resins

Cork

Ceramics

Active and

Intelligent

Coatings

Textile

Silicones

Cellulose

Printing inks

Recycled

Plastics

BADGE

Rubber

Nitrosamines

450/2009 282/2008

2007/42 84/500

2005/31

93/11

Plastics

2011/10

2011/321

2011/1282

1895/2005

Wa x

fsives Adhe

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Framework Regulation (EC) No 1935/2004

Article 3: Materials and articles shall be manufactured in

compliance with good manufacturing practice so that, under

normal or foreseeable conditions of use, they do not transfer

their constituents to food in quantities which could:

– endanger human health;

– bring about an unacceptable change in the composition of the

food;

– bring about a deterioration in the organoleptic characteristics

thereof.

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Plastics Regulation (EU) No 10/2011

• This regulation applies to

– Plastic monomaterials (coated and non-coated)

– plastic multi-layers (coated and non-coated)

– multimaterial multi-layer of which at least one layer is a plastic

(coated and non-coated)

• If a substance used in the manufacture of a coating is listed

in (EU) No 10/2011, the final material has to comply with

the SML for this substance

– Only for plastic mono- or multilayers, does not apply to

multimaterial multilayers

• Substances used only in coatings are not covered by (EU)

No 10/2011 (refer to national legislation)

• Substances used in coatings which form gaskets in

closures are covered by (EU) No 10/2011

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Epoxy Regulation (EC) No 1895/2005

• Regulation applies to:

– materials and articles made of any type of plastics

– materials and articles covered by surface coatings

– Adhesives

• Regulation does not apply to:

– So called ‘Heavy duty coatings’ on containers and tanks with a

capacity greater than 10000 liter

• Sum of the migration of BADGE, BADGE.H2O and

BADGE.2H2O shall not exceed 9 mg/kg

• Sum of the migration of BADGE.HCl, BADGE.2HCl and

BADGE.H2O.HCl shall not exceed 1 mg/kg

• The use and/or presence of BFDGE and NOGE in the

manufacture of materials and articles are prohibited.

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Overall migration limit (OML)

Inertness test with OML of 10 mg/dm2 or 60 mg/kg

food in special cases (Containers <0.5 l or >10 l)

(for infant foods always mg/kg)

• Only in food simulants A-D (not in food)

• Total amount of non-volatile substances

• Does not cover volatile substances

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Specific migration limits (SML)

• Safety limit: restriction based on toxicological data. Varies

from 0.01 – 60 mg/kg food or mg/6 dm2

• For young children always expressed in mg/kg

• SML restrictions set out in Annex 1 of Regulation (EU) No

10/2011, (positive list)

• If no SML is specified in Annex 1, then 60 mg/kg (OML)

• Limits given in Union list.

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EU migration assumptions

• A person consumes one kg of packed food per

day.

• The food is packed in 6 dm2 of packaging

material.

• A person weighs 60 kg.

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Migration testing: simulants

Food Type

- Water

- Acid

- Alcoholic

- Fatty

- Dry

- Dairy

Simulant

- 10% ethanol

- 3% acetic acid

- 20-50% ethanol

- Vegetable oil

- MPPO (Tenax)

- 50% ethanol

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Migration testing

Contact conditions Testing conditions

For example:

- 2 hours at 121°C

- 10 days at 40°C

- 10 days at 20°C

For example:

- Sterilisation

- Room temperature

- Chilled / Frozen

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Migration modeling

• Use generally recognised diffusion models based on scientific

evidence

• Overestimation of migration

• Needed information:

– Residual content of substances in packaging material

– Partition coefficients of substances over packaging/food/simulant

– Diffusion coefficients of substances through plastic

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Modelling of migration (10 days at 40°C)

Layer (100 µm) Simulant

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Route for testing a food contact material

material

safety evaluation

functional barrier

Petition / FCN Safety statement

(Framework 1935/2004)

no

Collect full composition information

components on positive list yes

calculate 100% migration

overall

migration

specific migration

residual content

math. modelling

Compliance

statement

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(EU) National coating legislations exist in:

• The Netherlands

• Germany

• France

• Spain

• Italy

• Greece

• Czech republic

• Slovenia

• Slovakia

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Dutch Warenwet: Packaging and Food

Utensils Regulation (VGB)

- I Plastics (Incl. Regulation 10/2011)

- II Paper and Board

- III Rubber

- IV Metals

- V Glass and glass ceramics

- VI Ceramics (Incl. EU Directive)

- VII Regenerated cellulose (Incl. EU Dir.)

- VIII Textile

- IX Wood and Cork

- X Coatings

- Warenwet chapters are legally binding

- Packaging and Utensils regulation is under revision

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Chapter IV: Metals

• Chapter 4 is under revision

• VGB Chapter IV metals, specifies

– Basic materials: aluminium (+alloys), copper, steel (+alloys)

– Solderings: copper, tin, silver, zinc, lead (lead not in direct food

contact)

– Metallic coatings: aluminium, chrome, nickel, copper, tin (+alloys)

– Organic coatings (also cross-referencing to chapter I)

– Metal packaging processing aids (lubricants, rolling oils)

– can-end sealants and sealing tape

• Contains a positive list of monomers and additives

• Substances used should be of good technical quality and not

be used more than strictly needed.

• Colorants and pigments (according to VGB Chapter I.4).

• Solvents (according to Article 3 of (EC) No 1935/2004)

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VGB Chapter X: Coatings

• Chapter X is under revision

• Applicable to coatings on all substrates, except RCF

(Chapter VII)

• Contains a positive list of monomers and additives

• Substances used should be of good technical quality and

not be used more than strictly needed.

• Colorants and pigments (according to VGB Chapter I.4).

• Solvents (according to Article 3 of (EC) No 1935/2004)

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Sections in Chapter X

• Chapter X is under revision

• Dispersion of

– macromolecular substances in water (X.3)

– paraffines and waxes in water (X.4)

– macromolecular substances in organic liquids (X.5)

• Solution in

– water (X.6)

– organic liquids (X.7)

• Solvent free material as

– waxes and wax-like products (X.8)

– other solvent-free materials (X.9)

• Directly as metallic layer

– By evaporation of metal (according to Chapter IV)

• PTFE based non-stick/high temperature coatings for cooking

utensils (X.11)

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Requirements of the end-product (X.12)

• Chapter X is under revision

• Total migration < 60 mg/kg.

– Coatings in Section 8: waxes/wax-like products are exempted

• Contains a list of specific migration requirements

• The presence of a coating does not exempt the substrate

from the rules (SML’s) applicable to the substrate (X.12.7)

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France

• Brochure 1227

– Circulaire 159 of 23 June 1950 related to lacquers and

coatings

– Circulaires of 22 February 1966 and 2 April 1969 which

complete the lists of substances that may be used.

• Applies to coatings for direct food contact with

– metal cans

– packaging films

– paper and board.

• Use of Bisphenol A in food contact materials to be banned

per

– 2013 for packaging for food for children < 3 years

– 2015 for all other food contact materials, including coatings

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Bisphenol A bans in European countries

Infant food

(0-36 months)

Adult

food

France Since

1-1-2013

Per

1-1-2015

Belgium Since

1-1-2013

Denmark Since

1-6-2011

Sweden Per

1-7-2013

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United States of America

• Chapter 21 Code of Federal Regulation

• Food packaging: 21 CFR Parts 174-179

• Constituents of food contact materials are referred to

as indirect food additives

• Part 174 specifies usage under conditions of GMP – Do not exceed prescribed limitations

– where no limits are specified, use minimal amounts required to

accomplish the intended physical or technical effect

– Substances should not be intended to accomplish any physical or

technical effect in the food itself

– Substances of a purity suitable for its intended use

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Substances that may be used

• Substances permitted for use by parts 174-179

– 174 Indirect food additives: General

– 175 Adhesives and components of Coatings

– 176 Paper and paperboard components

– 177 Polymers

– 178 Adjuvants, production aids and sanitizers

– 179 Irradiation in the production, processing and handling of food

• Substances generally recognized as safe (GRAS) in or on food

or in food packaging

• Substances used in accordance with prior sanction or approval

• Substances used in accordance with an effective pre-market

notification (FCN)

• Substances exempted from FCN/FAP because they are

(expected to) migrate at negligible amounts (threshold of

regulation (ToR); <0.5 ppb in food) and are not carcinogenic

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Part 175 – Indirect food additives:

adhesives and components of coatings

• 175.210 Acrylate ester copolymer coating.

• 175.230 Hot-melt strippable food coatings.

• 175.250 Paraffin (synthetic).

• 175.260 Partial phosphoric acid esters of polyester resins.

• 175.270 Poly(vinyl fluoride) resins.

• 175.300 Resinous and polymeric coatings.

• 175.320 Resinous and polymeric coatings for polyolefin films.

• 175.350 Vinyl acetate/crotonic acid copolymer.

• 175.360 Vinylidene chloride copolymer coatings for nylon film.

• 175.365 Vinylidene chloride copolymer coatings for polycarbonate film.

• 175.380 Xylene-formaldehyde resins condensed with 4,4′-

isopropylidenediphenolepichlorohydrin epoxy resins.

• 175.390 Zinc-silicon dioxide matrix coatings

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21 CFR 175.300 Resinous and polymeric

coatings

• For application on metals and other suitable (repeated use)

substrates (i.e. heavy use coatings)

• 37 sub-headings covering different types of coatings and

additives (i.e. epoxy resins, phenolic resins, styrene polymers,

polyethylene polymers, acrylics, can end cements) including

restrictions

• Includes test procedures for determining amount of extractives

using specific solvents and time-temperature conditions for

specific food contact uses (Table 2)

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Council of Europe

• Framework resolution ResAP (2004) 1 on coatings intended

to come into contact with foodstuffs (Version 3 - 12.02.2009

– Coatings for metal packaging

– Flexible packaging coatings

– Heavy duty coatings

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CoE resolution requires coatings to:

• Not endanger human health, change composition or

organoleptic properties of the food

• Be manufactured in accordance with GMP

• Be made using substances of

– Substances of “Technical document No. 1”

– aids to polymerisation as set out in Resolution AP (92)

– substances of relevant national regulations

• Meet OML of 10 mg/dm2 or 60 mg/kg of foodstuff

• Not release not-listed substances with molecular weight below

1000 Da in quantities which could endanger human health.

– Use appropriate risk assessment

– Dietary exposure

– Toxicological information

– Structure activity relationship (SAR)

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Council of Europe resolution Technical document No. 1

monomers Additives

EFSA/SCF list 1-4 List A List C

FDA / EU memberstate List B List D

• SML of all substances in List C and D: to be fixed

• No further guidance how to deal with these.

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Code of Practice for Coated articles where

the food contact layer is a coating

• Written by organisations from across the supply chain

• Currently 4th version of 2 February 2009

• Code of Practice is voluntary

• Applies to:

– Coated light metal packaging up to a volume of 10 litres

– Coated metal pails and drums with volumes ranging from 10 to

250 litres

– Coated articles with volumes 250 to 10,000 litres

– Heavy duty coated articles having a volume >10,000 litres

– Coated flexible aluminium packaging

– Printing inks and coatings in direct food contact

• Is based on CoE Res AP(2004)1, technical document no1.

• But the Code of Practice suggests a way how to

demonstrate compliance to the framework regulation.

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Code of Practice’s Lists of substances

• B and D substances may be used, provided that they are

subjected to additional toxicological information dependent on

the migration level or exposure…

Monomers Additives

EFSA/SCF list 1-4 List A List C

FDA / EU memberstate List B List D

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List B and D substances

Migration Requirements

< 10 ppb no further testing provided that SAR does

not indicate mutagenicity, in which case

mutagenicity data required.

10-50 ppb substances should have mutagenicity

data according to REACH timetable (or

use exposure assessment)

>50 ppb submit EFSA dossier with industry group

(or use exposure assessment)

Migration >10 ppb

and exposure

<10 µg/person/day

no further testing required

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Not intentionally added substances (NIAS)

• Impurities, breakdown products and reaction

products

• EU/10/2011: Any potential health risk in the final material

or article arising from reaction and degradation products

should be assessed by the manufacturer in accordance with

internationally recognised scientific principles on risk

assessment.

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Forest of Peaks (FoP) screening

Focus on what comes out, instead of what goes in.

1. Extraction: worst-case simulant

2. Detection: HS/GC/MS, GC/MS, LC/MS

3. Identification: through commercial and in-house

libraries

4. Quantification: via internal standards

5. Toxicological evaluation

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Threshold of toxicological concern (TTC)

• TTC is method to estimate

toxicity of unknown substances,

using existing tox info

• New approach currently under

development at TNO, combining:

– TTC

– Forest of peaks screening

– In-vitro genotox tests for complex

mixtures (blue screen)

• Will be a powerful way to proof

food safety and to address NIAS.

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Thank you for your attention!

Koen Weel PhD

TNO Triskelion BV

Koen.Weel@TNO.Triskelion.nl