Dr Malcolm Driffieldmalcolm.driffield@fera.gsi.gov.uk

The identification and implicationsof reaction and breakdown products

from starting substances usedto produce food contact plastics

Presentation overview

• Fera at a glance• Introduction to food contact materials• Introduction to NIAS• Project – Reaction and breakdown products

from starting substances used to produce food contact plastics

• Summary

The Food and Environment Research Agency

www.defra.gov.uk/fera

• An executive agency of the parent Government department - Department of Environment Food and Rural Affairs (Defra)

• Agency – a not-for-profitorganisation that nevertheless covers its full economic costs

Our role

• Regulation– Policy and inspectorate functions for plant health, bee

health and plant varieties and seeds

• Research– Robust scientific research, analysis and evidence for

government and commercial customers worldwide

• Response– Advice, guidance and support as part of the UK’s

capability to respond and recover in emergency situations

A very wide range of work areas including......

• Food and environmental safety• Crop and food security• Land use and sustainability• Wildlife management• Plant pests and diseases• National Bee Unit• FAPAS etc.• Government Decontamination Service.............

Food and Environmental Safety Programme

• Environmental contaminants e.g. dioxins, PCBs, metals

• Natural toxicants e.g. mycotoxins

• Pesticides• Veterinary drugs• Processing contaminants• Additives and colours• Authenticity and profiling• Deliberate adulteration• Packaging migration

Food packaging

• Packaging is beneficial– Protects foodstuff from spoilage

• However the transfer of chemicals from packaging to food (migration) may have a negative impact on the quality and safety of the food– No food contact material is completely

inert– Need to ensure the safety of these

materials – Controls in place to ensure consumer

safety

What is migration?

• The mass transfer from an external source into food by sub-microscopic processes

• May impact food in two ways– Food safety – migration of harmful substances– Food quality – migration of substances which impart taint or

odour

• Migration occurs from:– Food packaging– Materials and articles used in food manufacture, transport

and storage– Materials and articles used in food preparation and

consumption

Factors effecting migration

• Migration is a diffusion process

• It is dependent on:– The nature of the food contact material

– The nature of the foodstuff

– The nature of the migrating substance

– The nature, the extent and the type of contact between thefood contact material/article and the foodstuff

– The duration of the contact

– The temperature of the contact

What migrates?

• Known ingredients needed to make the food contact material– Monomers and starting substances, catalysts, solvents and

suspension media, additives etc….

• Known or unknown isomers, impurities, reaction products and breakdown products of these ingredients

• Possible contaminants– Recycled materials– Contamination from indirect food contact sources;

inks, coatings, adhesives, secondary packaging

The problem being addressed (1)

• Article 3 of the EU Framework Regulation– Chemical migration from food packaging materials should

not endanger human health

• Recital 13 of Directive 2007/19/EC– A general requirement to assess the safety of ALL potential

migrants, including impurities, reaction and breakdown products and the onus is on the business operator to do so

• Neither the EU commission, Member States, or industry, really know what is reasonably achievable in the assessment of NIAS – Hundreds of plastic formulations and manufacturing

conditions

The problem being addressed (2)

• US FDA

• Information on new substances/oligomerswith MW<1000 Da

• Levels as low as 10 ppb

6x10

0

0

0

0

0

0

0

1

1

1

1

1

1

1

1

1

1

2

2

2

2

+ TIC Scan 151210_029.d

Counts vs. Acquisition Time (min)

1.5 2 2.5 3 3.5 4 4.5 5 5.5 6 6.5 7 7.5 8 8.5 9 9.5 10 10.5 11 11.5 12 12.5 13 13.5 14

8x10

0

0

0

0

1

1

1

1

1

2

2

2

2

2

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3

3

3

+ TIC Scan 180111_002.d

1 1

Counts vs. Acquisition Time (min)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34

FSA funded research

• UK Food Standards Agency

• Joint project with TNO (Netherlands)

• An investigation into the reaction and breakdown products from starting substances used to produce food contact plastics (A03054)

• Aim– To identify and catalogue the reaction and breakdown

products formed from starting substances used to make six major food contact polymers

Project approach

• Selection of polymers and associated additivesfollowed by manufacture

• Prediction of impurities/reaction products/breakdown products

• Extraction and analysis of test plastics and controls

• Confirmation of identities of predicted substances

• Examination and interpretation of the data for anynon-predicted substances

Polymers selected

• Polyethylene (HDPE)• Polypropylene (PP)• Polystyrene (PS) The 5 volume polymers• Polyvinyl chloride (PVC)• Polyethylene terephthalate (PET)

• Polyamide (PA)– Finds use in demanding applications - good barrier

properties, high temperature resistance– High content of nitrogen which might make the reaction

chemistry different

• HDPE will be used as an example here

Plastics additives

Use Level (wt%)

HDPE Base polymer 92.35

Tetrakis(2,4-di-tert-butylphenyl)[1,1-biphenyl]-4,4’-diylphosphonite Antioxidant 0.1

Octadecyl 3,5-di-t-butyl-4-hydroxyhydrocinnamate Antioxidant 0.1

Oleamide Slip agent 0.1

Titanium dioxide Inorganic colourant 5.0

N,N-Bis-(2-hydroxyethyl)alkyl(C13-C15)amine Antistatic agent 0.25

Glycerol monooleate Lubricant 1.0

Sodium (C10-C18) alkyl sulfonate Lubricant 1.0

2,5-Bis(5'-tert-butylbenzoxazol-2-yl)thiophene Optical brightener 0.1

Risk assessment

Three components:

(a) the identification of the substances present in the material or article

(b) an estimation of their migration level leading to an estimate of possible consumer exposure

(c) a risk assessment which considers the potential exposure in context with any hazard (nature and potency) posed by the substance

Risk assessment

Three components: (a) the identification of the substances present in the

material or article- Predicted substances- Extraction and analysis of test polymers and

controls

(b) an estimation of their migration level leading to an estimate of possible consumer exposure

(c) a risk assessment which considers the potential exposure in context with any hazard (nature and potency) posed by the substance

Database of predicted substances prepared

• Scientific literature examined for known reactions• Knowledge of the chemistry of the additives used to

predict reaction products

• HDPE – 8 additives– 85 predicted substances and classes of substances– e.g. octadecyl-3,5-di-t-butyl-4-hydroxyhydrocinnamate

• oxidation• dealkylation

Oxidation reaction

Octadecyl-3,5-di-t-butyl-4-hydroxyhydrocinnamate

Quinone methide Cinnamate

R = C18H37

OH

CH3

CH3CH3

CH3

CH3

CH3

O OR

O

CH3

CH3CH3

CH3

CH3

CH3

O OR

OH

CH3

CH3CH3

CH3

CH3

CH3

O OR

Dimers Dimers

Dealkylation reaction

R = C18H37

OH

CH3

CH3CH3

CH3

CH3

CH3

O OR

Thermal degradationCH3

CH3CH3

OH

O OR

CH3

CH2

CH3

+

Octadecyl-3,5-di-t-butyl-4-hydroxyhydrocinnamate

Extraction and analysis

• Carried out for– Additives only– Control polymer samples with no additives– Polymer with additives included

• HDPE– Direct analysis by thermodesorption (TD) GC-MS– Solvent extraction followed by liquid injection GC-MS– Solvent extraction followed by LC-TOF-MS– (NMR)

TD-GC-MS - HDPE

HDPE

HDPE + additives

5.00 10.00 15.00 20.00 25.00 30.00

5000000

1e+07

1.5e+07

2e+07

2.5e+07

3e+07

3.5e+07

4e+07

4.5e+07

5e+07

5.5e+07

Time-->

Abundance

TIC: rxn_230107_008.D

5.00 10.00 15.00 20.00 25.00 30.00

2000000

4000000

6000000

8000000

1e+07

1.2e+07

1.4e+07

1.6e+07

1.8e+07

2e+07

2.2e+07

2.4e+07

2.6e+07

2.8e+07

3e+07

3.2e+07

3.4e+07

3.6e+07

3.8e+07

4e+07

4.2e+07

4.4e+07

4.6e+07

4.8e+07

5e+07

5.2e+07

5.4e+07

Time-->

Abundance

TIC: rxn_230107_010.D

50 100 150 200 250 300 350 400 4500

1000

2000

3000

4000

5000

6000

7000

8000

9000

m/z-->

Abundance

Average of 11.490 to 11.519 min.: rxn_230107_010.D (-)43

74281

133 429169 239207112 342188 311 39994 361258

50 100 150 200 250 300 350 400 4500

1000

2000

3000

4000

5000

6000

7000

8000

9000

m/z-->

Abundance

#799: 2-Propanone, 1-hydroxy-43

7415

0 50 100 150 200 250 300 350 4000

1000

2000

3000

4000

5000

6000

7000

8000

9000

m/z-->

Abundance

Average of 12.871 to 12.910 min.: rxn_230107_010.D (-)45

76 281 344165 207 237133 325189104 429402299 383255 364

0 50 100 150 200 250 300 350 4000

1000

2000

3000

4000

5000

6000

7000

8000

9000

m/z-->

Abundance

#918: Propylene Glycol45

2776

propylene glycol

(144 µg/dm2)

1-hydroxy-propanone(4 µg/dm2)

Peaks in both attributedto internal standard and short chained alkanes

2 new peaks detected

Neither compound in predicted database

Solvent extraction followed by GC-MS - HDPE

• Additives, polymer controls and polymers + additives all extracted into ethanol and isooctane

• Impurities found in some additives – e.g. Oleamide (slip agent) also included

other fatty acid amides and esters– These were added to the database

GC-MS chromatogramse.g. isooctane extract

HDPE

HDPE + additives4.006.008.0010.0012.0014.0016.0018.0020.0022.0024.0026.0028.0030.00

1000000

2000000

3000000

4000000

5000000

6000000

7000000

8000000

Time-->

Abundance

TIC: RXN_LSCREEN_060207_014.D

4.006.008.0010.0012.0014.0016.0018.0020.0022.0024.0026.0028.0030.00

1000000

2000000

3000000

4000000

5000000

6000000

7000000

8000000

Time-->

Abundance

TIC: RXN_LSCREEN_060207_017.D

HDPE GC-MS results

• Mainly PE oligomers

• 87 new substances detected in HDPE + additives only extracts– 25 substances in EtOH

• 15 attributed to additives and impurities

– 81 substances in isooctane (some the same as in EtOH)

• 31 attributed to additives and impurities

– Estimated concentration range 1 – 720 µg/dm2

Non-volatile and polar compounds by LC-TOF-MS

• Instrument on loan as a part of Agilent/Fera collaboration

• Mass accuracy, fragmentation and isotope patterns used to aid identification

• Excel database searched

LC-TOF-MS - HDPE

• Isooctane and ethanol extracts evaporated and residue re-dissolved in acetonitrile

HDPE(EtOH, ESI+)

HDPE + additives(EtOH, ESI+)

LC-TOF-MS – HDPE results

• 26 new substances detected in HDPE + additives only extracts

• 4 attributed to additives• 6 attributed to additive impurities

– Identity proposed for 4• 16 reaction and breakdown products

– Identity proposed for 14

• Estimated concentration range 20 – 2600 µg/dm2

Stacked 1H 1D NMR plot - HDPE

Overview of substances detected - HDPE

TD-GC-MS 0 additives 0 impurities

2 substances detected 2 reaction/breakdown products- identities proposed for 2- 0 predicted

Solvent extraction GC-MS 4 additives 29 impurities

87 substances detected - identities proposed for 10- 3 predicted 54 reaction/breakdown products- identities proposed for 21- 12 predicted

LC-TOF-MS 4 additives 6 impurities

26 substances detected - identities proposed for 4- 0 predicted 16 reaction/breakdown products- identities proposed for 14- 2 predicted

Risk assessment

Three components (a) the identification of the substances present in the

material or article

(b) an estimation of their migration level leading to an estimate of possible consumer exposure

(c) a risk assessment which considers the potential exposure in context with any hazard (nature and potency) posed by the chemical

Migration modelling

• Worst case migration calculated– applies the convention that 1 kg of food is packaged in 6

dm2 of plastic and that all substances present in the plastic transfers to the foodstuff

– Over-estimation for some plastic/substance combinations

• Migration from FCMs can be regarded as an elementary physical process– Predicted by mathematical calculations and models– Diffusion theory (Dp)– Partitioning effects (kp,f)

Estimation of migration levels

• Assessment of significance of the levels detected in the polymers carried out by migration modelling– commercially available software package Migratest© Lite

(kindly provided by FABES)

• Migration potentials estimated and modellingperformed– Defined as mono-layer plastics– 10 days at 40oC

Consequences

• HDPE (PP and PVC)– contained the most NIAS– relatively high diffusivity polymers– as identity of some substances unknown,

migration potentials of NIAS>10 µg/kg identified– Substances present with the potential to migrate

at concentrations >10 µg/kg

[10 µg/kg generally defined as the concentration in the food at which a non-permitted ingredient should be not detectable, this is used for non-CMR substances (carcinogens, mutagens and reprotoxins) and does not imply a threshold of concern]

Risk assessment

Three components (a) the identification of the substances present in the

material or article

(b) an estimation of their migration level leading to an estimate of possible consumer exposure

(c) a risk assessment which considers the potential exposure in context with any hazard (nature and potency) posed by the chemical

Potential exposure and associated hazards

• A number of substances that would previously have been reported as NIAS have been identified– Migration potential/exposure potential can be linked with

consideration of the hazard associated with the substance

• A large number of substances remain either unidentified or with an ambiguous identification only– Migration potential/exposure potential can NOT be linked

with consideration of the hazard associated with the substance

Summary of project A03054

• Six polymers were prepared containing additives chosen to be representative of those typically used in plastic materials and articles intended for contact with food

• Theoretical list of possible impurities/degradation products/reaction products was prepared for each of the plastic/additive combinations

• A suite of analytical methods were applied to the plastics themselves and to extracts of the materials

• Migration modelling to determine the significance of the levels of the substances estimated in the plastics

Additive purity and the impact on NIAS• Many unexpected impurities in the additives

• Illustrates the demands placed when considering migration potential at the low ppb levels

• These impurities have the potential to persist in the finished plastic food contact material and may migrate

• They may decompose under the process and fabrication conditions, or they may interact with each other to form other substances, all with the potential to migrate

Limitations of analytical methods to identify and measure NIAS

• This project represented the state-of-the-art with two highly experienced and well equipped institutes

• Many substances identified and concentrations estimated

• A number of substances that would previously have been ‘unknown’ have been identified

• A large number of substances remain either unidentified or with an ambiguous identification

Implications for other food contact materials and articles

• The same approach has been applied elsewhere– Defra Link Project – can coatings – Working closely with

Industry– Irradiated FCM plastics– Bio-based FCMs

• Advanced chromatographic and spectrophotometricmethods are also applicable to extracts of other materials

• Expect the same findings

What else is required?

• This analytical approach would provide a useful demonstration of due diligence

• It may need to be considered along with other complementary approaches– toxicological evaluation of the whole migrate and/or – threshold concepts such as threshold of regulation or

thresholds of toxicological concern

Acknowledgements

• Fera– E. Bradley, D. Speck, N. Harmer, S. Jones, M. Scotter and L.

Castle

• TNO– L. Coulier, R. Bas, S. Steegman, M. Tienstra and B. Muilwijk

• Food Standards Agency– Report A03054 – http://www.foodbase.org.uk//admintools/reportdocuments/518-1-

911_A03054_reaction_and_breakdown_products_final_report.pdf

• Agilent– J. Zweigenbaum