Harnessing the Power of CCS for Routine

Screening Applications on the UNIFI Informatics Platform

Cristina Nerín I3A, Dept. Anal. Chem. University of Zaragoza

(Spain) cnerin@unizar.es

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Outline

• Introduction: Food Packaging Materials – Migration – IAS and NIAS – Analytical protocols

• Case Study 1: PSA • Case study 2: NIAS and set-off migration (1) • Case study 3: NIAS and set-off migration (2) • Risk assessment

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FOOD PACKAGING MATERIALS

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Cardboard packaging

Material A + Printing Inks + Lacquer/varnish Material A + Adhesive + material B + Printing inks + Lacquer/varnish Adhesives directly applied on food: PSA

High Barrier Materials (multilayers)

Monomaterial/monolayer Multilayer&multimaterial

food

MIGRATION FROM PACKAGING TO FOOD

TOXIC EFFECTS IN FOOD CONSUMERS

CHANGES IN FOOD SENSORY PROPERTIES

PHYSICO-CHEMICAL CHANGES ON PACKAGING

adhesive printing ink

food

K,D

Multilayer packaging Monolayer packaging

SET OFF (ink transference)

Direct contact Pressure

From manufacturing processes

NIAS NON INTENTIONALLY ADDED SUBSTANCES

Degradation processes: • Polymer degradation • Additives degradation

Impurities of raw materials

Reaction Products

Contaminants

IAS INTENTIONALLY

ADDED SUBSTANCES

Polymer additives: antioxidants, flame retardants, UV absorbers, …

Additives from adhesives, varnishes, printing inks

Residual monomers, catalysts

MIGRANTS ORIGIN

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Well known NIAS

2,4-DTBP

ADDITIVES DEGRADATION Irgafos 168 (antioxidant)

Formaldehyde and acetaldehyde

(off-flavours)

P O O

O

P O

O

P O

+

+

[ H 2 O ]

O OOP

OO O

OP[O]

POLYMER DEGRADATION PET bottles

[Dabrowska et al. Food Addit. Contam. 20 (2003) 1170] [Bach et al. Water Res. 46 (2012) 571]

[Burman et al. J. Chromatogr. A 1080 (2005) 107] [Alin et al. J. Agric. Food Chem. 59 (2011) 5418] [Bertoldo et al. Polymer 45 (2004) 8751]

Factors that can affect: temperature oxygen irradiation

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NIAS

NEOFORMED COMPOUNDS

Epoxy phenolic coatings: BADGE

BADGE-H2O BADGE-2H2O BADGE-HCl

+H2O, +HCl

BY-PRODUCTS

Polyurethane adhesives

Isocyanates Polyols +

+H2O

Primary aromatic amines

[Aznar et al. J. Chromatogr. A 1216 (2009) 5176]

[Sendon Garcia et al. J. Chromatogr. A 1032 (2004) 37] [Perez-Lamela, et al. Int. J. Environ. Anal. Chem. 82 (2002) 123]

PU ADHESIVES LACTONES

lactones

Migration test

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C. Nerin et al. Scientific reports (NATURE) http://www.nature.com/srep/2014/140509/srep04913/full/srep04913.html F. Isella, E. Canellas, O. Bosetti, C. Nerin, Journal of Mass Spectrometry, 48, 4, 430–437, April 2013 - 10.1002/jms.3165, 2013 Juliana S. Félix, Francesca Isella, Osvaldo Bosetti, Cristina Nerín Analytical and Bioanalytical Chemistry, Volume 403, Number 10 (2012), 2869-2882

Analytical Challenges

• Sample treatment developments

• Decision about the analytical procedure: Usually working with “blind samples” (no information about the composition or the likely migrants). What is the target?

• Identification of unknowns

• Origin of the migrants: responsibility!!

• Low concentration of many migrants

• Complex analysis of food

• Analytical artifacts

POLYMER

DirectAnalysis Migration Test

Tenax Liquid FoodSimulants

SPME LLE LLMEHSThermal

DesorptionSolid / Liquid

extraction

HS SPMEPurge

&Trap

HS: Headspace SPME: Solid Phase Microextraction LLE: Liquid – Liquid extraction LLME: Liquid – Liquid microextraction

General scheme for sample treatment MIGRATION CELL

10

Polymer Food simulant

EU/10/2011

Decision tree for the analytical procedure in NIAS identification

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L C - M S (Q T OF ) GC - M S

-

C on f i r mat i on b y St a nd a r d

Y es

GC - M S ( Q T O F )

No

Y es

No

Q u a n t i f i c a t i o n

C on f i r mat i on b y f r a g m e n t a t i o n

C on f i r mat i on b y Sta nd a r d

Y es No

Y es

S e l e c t i o n o f c a nd i d a te s t r u c t u r e

• C h e m i c al d a t ab a s e s • Sa m ple in f or m a t i o n • Bibli o gra p hi c s e ar c h • C a ndid a t e prop e r t i e s

S e l e ct i on o f p a r e n t i on e m p i r i c a l f o r m u l a

• Ele m e n t s s ele c t i o n • M a s s t olera n c e • I s o t o pi c f it

I d e n t i f i c a t i on b y :

• N I S T libr a ry • Ko v a t s in d ex

ANA L Y SIS

No

Volatiles Non

volatiles

C. Nerin*, P. Alfaro, M. Aznar, C. Domeño Anal. Chim. Acta. Volume 775, 2 May 2013, Pages 14–24 DOI:10.1016/j.aca.2013.02.028. 2013

Examples

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Reprotoxic compounds identified in plastic bags for semen dosis

By-products resulting from interaction between ingredients in common adhesives

NIAS from adhesives in high barrier materials

Contamination of food from Set-off of printing inks

Oligomers and NIAS in Polymers

NIAS from active packaging materials

Degradation compounds from gamma irradiation on packaging materials

Degradation compounds from interaction with the packaged product

Migrants from the packaging in food

Identification of volatiles by GC-MS (EI)

Identification of volatiles by APGC-MS (TOF)

1

2

3 Comparison of both techniques

APGC-MS-QTOF versus GC-MS-Q

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Migration of Volatile compounds from PSA adhesives

Case study 1

4 Specific migration analysis and Risk Asssessment

Case study 1

Migration from Pressure Sensitive Adhesive

GC-MS

APGC-MS-QTOF

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Function 1 cone voltage 30 V

Function 2 High energy30 v in cone

voltage and a collision ramp energy in the collision cell

from 20 to 40 v

Migration from Pressure Sensitive adhesive

Case study 1

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Migration from Pressure Sensitive adhesive

Case study 1

Phosphorous was confirmed by ICP-MS

Migration from Pressure Sensitive adhesive

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Case study 1

Migration through pork intestine to isoctane

adhesive Smoking thin paper

tenax

Migration from Pressure Sensitive adhesive

Case study 1

Canellas,E., Vera, P, Nerín. C. J. Mass Spectrometry, 2014, 49. 1181

Migration of PSA adhesives in meat(longaniza) and simulants

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Case study 1

Dicyclohexylphosphino isomer3(III)

Set D

PET: polyethylene terephtalate OPP: Oriented Polypropylene Al: aluminum PE: polyethylene

Case study 2

1 2 3 4

Migration tests with food Simulants

Set D / EtOH 95% Material 2

Set D / Tenax® Material 2

Case study 2

PET

AL PE

1A

Food

SCR1

INK PET AL

PE

Food

Case study 2

INK PET AL PE

SCR1

Food

PET INK

AL PE

4A

LAQUER MATT

Food

Case study 2

Ink migrants (ID_code) M.2 Molecular

formula Candidates Mat. 3 Mat. 4

3.90_217.1080 2 C10H16O5 Cyclic polyester ↓↓ ↓↓ 4.62_285.1315 1 C12H22O6 Adipate structure ↓↓ ↓↓ 5.35_251.1260 2 C12H20O4 Cyclic polyester ↓(IM3=40%IM2) ↓↓ 5.44_453.1770 2 C22H28O10 Cyclic polyester ↓↓ ↓↓ 5.50_473.1448 1 C24H24O10 Cyclic polyester ↓↓ ↓↓ 5.71_337.1627 1 C16H26O6 Di(tetrahydrofurfuryl)adipate ↑(IM3=150%IM2) ↓↓ 6.50_273.2067 3 C15H28O4 Dibutyl pimelate ↓↓ ↓↓ 6.50_259.1911 3 C14H26O4 Diethyl sebacate ↓↓ ↓↓ 6.82_389.1118 <1 C14H20N4O7S n.i. ↓↓ ↓↓ 6.97_403.2334 3 C20H34O8 ATBC ↓↓ ↓↓ 7.05_287.2230 3 C16H30O4 Dipropyl sebacate ↓↓ ↓↓ 7.19_297.2412 1 C16H34O3 n.i. ↓↓ ↓↓

7.22_341.2655 1 C18H38O4 Triethylene glycol

monododecyl ether ↓↓ ↓↓

7.23_385.2928 1 C20H42O5 Tetraethylene glycol monododecyl ether

↓↓ ↓↓

7.36_315.2549 3 C18H34O4 Dibutyl sebacate = = 7.62_343.2855 3 C20H38O4 Glycol ricinolate = ↓(IM4=20%IM2) 7.80_371.3174 2 C22H42O4 Di-hexyl sebacate ↑(IM3=200%IM2) ↓(IM4=15%IM2)

Set D / Tenax®

Mat

. 1

Mat

. 2

Mat

. 3

Mat

. 4

Table 1: Migrants coming from ink due to set-off (material 2), I (1: low intensity, 2: medium intensity, 3: high intensity), molecular formula, candidates and relative changes of intensity in migration from materials 3 and 4 (↓↓ total decrease, ↓partial decrease, = same intensity)

Case study 2

PCA of migration data

-100

-80

-60

-40

-20

0

20

40

60

80

100

0010001-

t[2]

t[1]

Scores Comp[1] vs. Comp[2] colored by Sample Group

1A1A1A1A1A1A1A1A1A

2A

2A2A

2A

2A

2A2A

2A

2A

2A

2A

2A

3A3A3A3A3A3A

3A3A3A

4A

4A4A

4A4A4A

4A

4A

4A

4A4A4A

SCR1SCR1SCR1

SCR1SCR1SCR1SCR1SCR1

SCR1SCR1SCR1

PET AL

PE

1A

Food

INK PET AL

PE

SCR1

Food

INK PET

AL PE

3A

LAQUER MATT

Food

PET INK

AL PE

4A

LAQUER MATT

Food

INK PET

AL PE

2A

LAQUER GLOSS

Food

Case study 2

Case study 2

Identification by RT and MS fragments

Identification by IM (CCS)

Candidates

CCS

Pure standards

Case study 2

OPP OPP INK

Migrats from ink Elemental composition Molecular formula Candidates CCS

4.93_299.1108 C12H20O7Na C12H20O7 Citric acid triethyl ester 103.03

5.63_285.2909 C17H37N2O C17H36N2O Schercodine L

(lauramidopropyl-dimethylamine) 120.19

5.92_271.1885 C13H28O4Na C13H28O4 Tripropyleneglycol monobutyl

ether 99.69

5.96_299.1835 C14H28O5Na C14H28O5 Triethylene glycol caprylate No standard

6.09_313.3217 C19H41N2O C19H4ON2O Schercodine M

(Myristamidopropyl-dimethylamine)

No standard

6.39_343.2965 C19H39N2O3 C19H38N2O3 Lauraimidopropyl betaine No standard

6.98_425.2151 C20H34O8Na C20H34O8 Acetyltributylcitrate (ATBC) 137.45

Food simulant Food simulant

Case study 3

DIRECT ANALYSIS OF SAMPLE 1

DESI-TOF

ATBC

m/z 285.29

Schercodine L

Case study 3

m/z 285.3

m/z 425.2 m/z 149.1

Sample 2

Schercodine L

DESI-TOF Case study 3

Phthalate?

ATBC

TOXICITY REPORTS

EUROPEAN LEGISLATION (EU/10/2011)

What to do after identification?

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NO TOXICITY DATA

Threshold of Toxicological Concern (TTC) approach (not suitable for carcinogenic, mutagenic or teratogenic compounds)

CRAMER RULES

RISK ASSESSMENT OF NIAS

NATIONAL LEGISLATION

Threshold of Toxicological Concern (TTC)

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TOXICITY CLASIFICATION-Cramer rules (Toxtree v1.51)

Class I (Low) <1.8 mg/person/day Class II (Medium) <0.54 mg/person/day Class III (High) 0.09 mg/person/day

BHT

EDI (Estimated Dayly Intake) (mg/person/day)= Mig (mg/Kg) x 3 Kg /day/person x CF

Migration estimation

Where • Estimated Daily Intake is the Cramer value • Mig: Migration limit (proposal) • 3Kg/1Kg is the daily food intake (including beverage) • CF is the fraction of the daily diet expected to be in contact

with a specific packaging material (e.g.for adhesives this is 0.14).

EDI (mg/person/day)= Mig (mg/Kg) x 3 Kg* /day/person x CF

Consumption factors exist in FDA but not in Europe

35 GUIA GROUP, UNIVERSITY OF ZARAGOZA, SPAIN

Acknowledgements

Research Projects:

• SAFEMTECH (IAPP-Marie Curie) • SAENMA (AGL-2012) • MAGAPOR • MIGREFILMS • MIGRESIVES (EU) • NANOFLEXIPACK • R&D&i with several companies • ……… • Collaboration with Waters

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Thank you very much for your attention!

cnerin@unizar.es