Food Chemistry 295 (2019) 274–288

Contents lists available at ScienceDirect

Food Chemistry
journal homepage: www.elsevier.com/locate/foodchem

Identification of unexpected chemical contaminants in baby food coming T

from plastic packaging migration by high resolution accurate mass
spectrometry
Anna Bauera, Florencia Jesúsb, María José Gómez Ramosa, Ana Lozanoa,
⁎
Amadeo Rodríguez Fernández-Albaa,
a
Chemistry and Physics Department, University of Almeria, Agrifood Campus of International Excellence (ceiA3), 04120 Almería, Spain
b
Grupo de Análisis de Compuestos Traza, Polo de Desarrollo Universitario “Abordaje holístico”, CENUR Litoral Norte Sede Paysandú, Universidad de la República, Ruta 3
km 363, 60000 Paysandú, Uruguay

A R T I C LE I N FO A B S T R A C T

Keywords: Plastic multilayers are widely used for baby food packaging. However, it is important to consider that migration
Baby food squeezes of food contact materials (FCM) into the baby food can occur. The comprehensive identification of potential
Multilayer packaging migrants, including intentionally added substances (IAS) and non-intentionally added substances (NIAS), is
LC-QTOF MS required to assess the safety of these packaging materials. In this study, high resolution accurate mass spec-
SWATH
trometry (HRAMS) with a data-independent acquisition method of sequential mass windows enables the de-
Migrants
tection of substances with corresponding deconvoluted fragment mass spectra. The identification of unexpected
Polyester oligomers
migrants present in the food simulants and in real baby food was facilitated by filtering strategies and by an in-
house library. This approach has allowed the identification of 42 migrants, including eight NIAS detected for the
first time. Two oligomers were quantified by means of reference standard materials at concentration levels above
0.010 mg/kg, exceeding the maximum residue levels for baby food.

1. Introduction 2012). Frequently a multilayer film, instead of single-film of plastic, is

used to combine different materials to extend the capacity. Such la-
Packaging made of plastics commonly protects food from the en- minate structure is widely used to improve the preservation barrier and
vironment and improves its shelf life. Additionally, plastics are light, printing properties. Polyester urethane-based adhesives are commonly
flexible and amenable to modifications to achieve properties such as used for bonding the plastic layers to simplify technical applications as
stability and permeability. Thus, over a third of packaging material on well as chemical and temperature resistance (Zhang, Kenion,
the market is being made of plastic (Athenstädt, Fünfrocken, & Schmidt, Bankmann, Mezouari, & Hartman, 2018).

Abbreviations: PET, polyethylene terephthalate; 2AA-2DEG, 1,4,7,14,17,20-hexaoxacyclohexacosane-8,13,21,26-tetraone; 2AA-2DEG (linear), 1-hydroxy-7,12,20-

trioxo-3,6,13,16,19-pentaoxapentacosan-25-oic acid; 2NPG-2AA, 3,3,14,14-tetramethyl-1,5,12,16-tetraoxacyclodocosane-6,11,17,22-tetraone; 2NPG-2AA (linear),
6-(3-((6-(3-hydroxy-2,2-dimethylpropoxy)-6-oxohexanoyl)oxy)-2,2-dimethylpropoxy)-6-oxohexanoic acid; 3NPG-3AA, 3,3,14,14,25,25-hexamethyl-
1,5,12,16,23,27-hexaoxacyclotritriacontane-6,11,17,22,28,33-hexaone; AA, adipic acid; AA-DEG, 1,4,7-Trioxacyclotridecane-8,13-dione; AA-DEG-DEG (linear), bis
(2-(2-hydroxyethoxy)ethyl) adipate; AA-HD, 1,8-dioxacyclotetradecane-2,7-dione; Al, aluminium; BHET, Bis(2-hydroxyethyl) phthalate; DEG, diethylene glycol; EG,
ethylene glycol; FCM, food contact materials; HDPE, high-density polyethylene; IAS, intentionally added substances; ISTD, Internal standard; LC-HRAMS, Liquid
chromatography coupled to high resolution accurate mass spectrometry; NIAS, non-intentionally added substances; NPG, neopentyl glycol; NPG+PG+PA+SA, 4,4-
dimethyl-4,5,8,9,10,11,12,13,14,15,19,20-dodecahydro-3H,18H-benzo[g][1,5,10,14]tetraoxacyclotetracosine-1,7,16,22-tetraone; NPG-AA, 3,3-Dimethyl-1,5-diox-
acycloundecane-6,11-dione; NPG-AA (linear), 6-(3-hydroxy-2,2-dimethylpropoxy)-6-oxohexanoic acid; NPG-AA-HD-AA, 3,3-dimethyl-1,5,12,19-tetra-
oxacyclopentacosane-6,11,20,25-tetraone; NPG-SA, 3,3-dimethyl-1,5-dioxacyclopentadecane-6,15-dione; NPG-SuA, 3,3-dimethyl-1,5-dioxacyclotridecane-6,13-
dione; PA, phthalic acid; PE, polyethylene; PET dimer, Ethylene terephthalate cyclic dimer; PTFE, Polytetrafluoroethylene; PU, polyurethane; SA, sebacic acid; SMLs,
specific migration limits; SuA, suberic acid; SWATH, sequential windowed acquisition of all theoretical mass spectrometry; TBoAC, Tributyl citrate acetate; TTC,
Threshold of Toxicological Concern
⁎
Corresponding author.
E-mail addresses: anabauer@ual.es (A. Bauer), fjesus@fq.edu.uy (F. Jesús), mjramos@ual.es (M.J. Gómez Ramos), analozano@ual.es (A. Lozano),
amadeo@ual.es (A.R. Fernández-Alba).

https://doi.org/10.1016/j.foodchem.2019.05.105
Received 13 December 2018; Received in revised form 23 April 2019; Accepted 14 May 2019
Available online 17 May 2019
0308-8146/ © 2019 Elsevier Ltd. All rights reserved.
A. Bauer, et al. Food Chemistry 295 (2019) 274–288

In the last decade, flexible baby food pouches, made of plastic Chen, & Subramanian, 2014). Consequently, SWATH data acquisition
multilayers have become popular for baby food like fruit purées due to enables the recording of all detectable peaks in a sample with high
their practical handling properties for food packers and customers. The quality deconvoluted fragment mass spectra. Additionally, using mass
analysts forecast that the global flexible packaging market for baby windows in combination with data deconvolution we can achieve high
food will have an annual growth rate of almost 9% during the period sensitivity specific MS/MS spectra. Parrilla Vázquez, Lozano, Ferrer,
2018–2022 (Packaging Report, 2017). Such squeezes are classically Martínez Bueno, & Fernández-Alba, 2018 studied the benefits of this
made of a three-layer lamination consisting of an outer layer typically approach and optimized the number of mass windows resulting in the
of PET followed by a functional barrier of PET/Al/PE equipped with a number of 10 mass windows to achieve the best results in sensitivity
cap of HDPE. The outer layer, typically PET, is reverse printed in eight and ion ratio deviation.
to ten colours and heat-sealed to the film. As a functional barrier be- There are no actual studies available about the migration of IAS or
tween colours and food, an aluminum foil is used. However, since NIAS from commercial multilayer packaging into baby food or food
aluminum is acid and salt soluble, squeezes are coated inside with PE simulants recommended by regulatory agencies. In general, a few ex-
(food contact side) to avoid the migration of aluminum ions to the fruit amples exist regarding FCM screening approaches, but there is still a
purée (Reynolds, 2010; Fruchtbar, 2018). lack of knowledge of nature and availability of analytical reference
There is an increasing concern over the safety assessment of food standards of potential migrants occurring in baby food.
packaging. To prevent contamination of food and hazards to human Poor or no toxicity data of most of the FCM migrants is available
health the migration of hazardous chemicals from FCM are regulated by emphasizing the need for the assessment of potential risks arising from
European Regulation (EU) No 10/2011 in conjunction with Regulation these compounds. The theoretical toxicity of the compounds, that is
(EC) No 1935/2004. In this regulation, a positive list of authorized based on scientific risk assessment principles, was estimated by ap-
compounds for use in plastic packaging has been established providing plying the TTC using the Cramer rules, as EFSA recommended when
SMLs in food simulants depending on food classification (European hazard data are incomplete (EFSA Scientific Committee, 2018). Hence,
Commission, 2011). In general, according to the actual legislation, the theoretical toxicity of compounds is assessed via their molecular
SMLs are specified for IAS. The release of NIAS, which are not permitted structure and categorized in three classes of toxicity: low (class I),
substances, is limited to a maximal concentration of 0.010 mg/kg moderate (class II) and high (class III). Following the Cramer rules the
(European Commission, 2011). NIAS may be formed during manu- recommended maximal daily intake for compounds from each toxicity
facture and use or as a result of the reaction and degradation processes group for class I, II and III should not exceed the amount of 30, 9 and
or may constitute impurities of raw materials. Typically, degradation 1.5 µg/kg body weight/day (Cramer et al., 1976; Kalkhof, Herzler,
occurs due to thermal processes or irradiation of the packages of ad- Stahlmann, & Gundert-Remy, 2012; Gómez Ramos et al., 2018).
ditives like antioxidants exposed to UV radiation. Further, compounds Thus, the aim of this work was to develop and apply a non-targeted
like primary aromatic amines are released from PU or azo dyes (Nerin, and suspect screening methodology for the identification and quanti-
Alfaro, Aznar, & Domeño, 2013; Biedermann-Brem, Kasprick, Simat, & fication of unknown compounds in food simulants and baby food ori-
Grob, 2012). Diverse plastic polymers and adhesives were identified as ginating from multilayer baby food pouches. Simultaneously in simu-
a source of unintended by-products or polyester oligomers. Onghena lants and fruit purée, both screening approaches were applied to
et al. (2015) detected phthalates and different NIAS of stearate and commercial samples using SWATH by HRAMS.
laurolactam structures originating from polypropylene and polyamide
baby bottles. Different studies of Omer et al. (2018), Athenstädt et al. 2. Material and methods
(2012) and Zhang et al. (2018) described cyclic polyester oligomers
based on diols like DEG, EG or NPG and aliphatic and aromatic di- 2.1. Reagents and chemicals
carboxylic acids like AA or PA originating from PU adhesives. Paseiro-
Cerrato, MacMahon, Ridge, Noonan, and Begley (2016) detected sev- Reference standards for migrants from food contact materials
eral linear oligomers during the analysis of coatings of polyester cans. comprising ε-Caprolactam (purity 99%), TBoAC (purity 97.7%), BHET
Félix, Isella, Bosetti, and Nerín (2012) identified 63 potential migrants (purity 99.7%) were purchased from Sigma-Aldrich GmbH
coming from PU adhesives in multilayer packaging. In a previous study, (Taufkirchen, Germany). AA-DEG (purity 98%), NPG-AA (purity 98%)
Gómez Ramos, Lozano, and Fernández-Alba (2018) described a non- and PET dimer (purity 98%) were purchased from LGC Limited
targeted screening approach for the analysis of multilayer materials, (Teddington, United Kingdom). Polyamid 6 oligomer standard (capro-
resulting in the identification of 26 potential migrants. Most of them lactam cyclic oligomers, n = 2–9) (purity according to provided spe-
were classified in the higher toxicity classes II and III according to cification) was purchased from Technische Universität Dresden
Cramer rules (Cramer, Ford, & Hall, 1976). Generally, small molecules (Dresden, Germany). Dimethoate-d6 (purity 98.5%) was purchased
(< 1000 Da) will be of interest as the toxicologically relevant fraction from CDN Isotopes Inc. (Quebec, Canada). Malathion-d10 (purity
(Hoppe, Voogt & Franz, 2016). The toxicity and pharmacokinetic 92.5%) and Carbendazim-d3 (purity 98.5%) were purchased from Dr.
properties of potential migrants have not been published yet (Zhang Ehrenstorfer GmbH (Augsburg, Germany). Stock solutions at
et al., 2018). (10 mg L−1) were prepared in acetonitrile, except AA-DEG, NPG-AA
Hence, multilayers manufactured by a combination of different and PET dimers that were prepared in methanol and stored at −20 °C.
polymers and a multitude of adhesive compounds may release a di- Standard working solutions for the purpose of compound identification
versity and a high quantity of food contaminants (Grob, 2014). Analysis and quantification were prepared by dilution of the stock solution with
of potential migrants is complex and challenging, as many different acetonitrile (LC-MS grade) and methanol (LC-MS grade). LC-MS grade
steps are involved in the manufacture of multilayer packaging from raw methanol was obtained Riedel-de Haën (Selze, Germany) and gradient
material to multilayer films. LC-HRAMS is one of the most suitable HPLC-grade acetonitrile from Merck (Darmstadt, Germany). LC-MS
techniques in the detection and identification of non-volatile IAS and Optima grade water from Fisher Scientific (Fair Lawn, NJ, USA) was
NIAS (Hoppe, Voogt & Franz, 2016; Nerin et al., 2013). Non-target data used. Sodium citrate tribasic dihydrate, sodium chloride, sodium hy-
independent acquisition method with the sequential windowed acqui- drogencitrate sesquihydrate, anhydrous magnesium sulphate and am-
sition of SWATH improves and facilitates the comprehensive identifi- monium formate were purchased from Sigma-Aldrich (Steinheim,
cation of unknown compounds (Gómez Ramos et al., 2018). Applying Germany). Formic acid (98% purity) was bought from Fluka (Buchs,
this technique, the full m/z range of precursor ions is continuously Switzerland). Absolute ethanol was supplied by Panreac Química SLU
stepped along average mass windows of 20–85 Da. Using this method, (Barcelona, Spain) and acetic acid was obtained from J.T Baker (Fair
MS2 data of much narrower precursor ion ranges are obtained (Zhu, Lawn, NJ, USA).

275
A. Bauer, et al. Food Chemistry 295 (2019) 274–288

Fig. 1. HRAMS spectra of 2NPG + 2AA oligomer in simulant B of a squeezy sample. full scan XIC of NH4+ adduct at 446.2749 m/z (A) with MS spectra and isotope
profile of [C22H36O8 + NH4]+ (B). Fragment 1 XIC (in blue) overlay with the precursor (in pink) (C) with MS/MS spectra (D) and molecular structure of
2NPG + 2AA (E). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

2.2. Samples and sample treatment incubator (CIR 260C; Ing. Climas, Barcelona, Spain), to ensure the ac-
curate thermostatic conditions throughout the migration test time.
Fifteen commercially-available baby food squeezes were purchased Baby food jars were treated following the same protocol and employed
from local retailers in Spain (9 from 4 brands), Australia (2 from 2 as plastic blanks for comparison. An aliquot of 500 μL of the simulants
brands) and Germany (4 from 4 brands). Most baby food samples were samples was centrifuged (Sigma 1–14 from Sartorius AG, Göttingen,
based on a mixture of fruit purées (apple, banana, pear), except for one Germany) for 5 min at 14800 rpm and finally transferred to a glass vial
product based on fruit jelly (Hero, Spain) and another based on cho- suitable for LC-MS analysis and 10 μL of a solution of dimethoate-d6
colate custard (Rafferty’s Garden, Australia). The multilayer materials were added to each vial as injection control standards.
used as packaging were expected to comprise PET/Al/PE (Fruchtbar,
2018). A baby food glass jar was used as a blank sample.
Baby food samples were squeezed out of the plastic packages into a 2.4. Instrumentation and conditions
glass flask and the pH was measured (Crison GLP 21, Hach Lange,
Barcelona, Spain). The pH range of the samples was 4–4.5. 2.4.1. Uhplc-ESI-QTOF MS
Extraction of baby food was performed according to citrate-buffered An UHPLC system (ExionLC; Sciex, Framingham, MA, USA) coupled
QuEChERS method (Anastassiades, Tasdelen, Scherbaum, & Stajnbaher, to a quadrupole time-of-flight mass spectrometer (QTOF X500R; Sciex,
2007). 10 g of sample was weighed into a 50 mL PTFE centrifuge tube, Framingham, MA, USA) equipped with a Turbo V™ Source with a
which was previously rinsed with 10 mL acetonitrile and allowed to dry TwinSprayer probe (Sciex, Framingham, MA, USA) was used for sample
at room temperature. Then, 10 mL acetonitrile was added and 10 μL of a measurement and data acquisition.
solution of ISTDs (Malathion-d10 and Carbendazim-d3) at 10 mg L−1 Sample separation was performed on a Zorbax Eclipse Plus C8
were added for extraction quality control purpose. Afterwards, the column (2.1 mm × 100 mm, 1.8 μm particle size) from Agilent
samples were shaken in an automatic axial shaker (AGYTAX®; Cirta Lab Technologies (Santa Clara, CA, USA). The column temperature was set
S.L., Madrid, Spain) for 4 min. Thereafter, a mixture consisting of 4 g at 35 °C. The analytes were separated using ultra-pure water: methanol
anhydrous magnesium sulphate, 1 g sodium chloride, 1 g sodium citrate (98:2, v/v) as solvent A whereas solvent B was methanol: ultra-pure
tribasic dihydrate and 0.5 g sodium hydrogen citrate sesquihydrate was water (98:2, v/v); both mobile phases contained 5 mM ammonium
added. The tubes were shaken again and centrifuged afterwards (Consul formate and 0.1% (v/v) formic acid. The optimized gradient program
21; Ortoalresa, Madrid, Spain) at 3700 rpm for 5 min. Finally, 100 μL of was as follows: 80% solvent A maintained for 2 min; from 2 to 15 min
the extract were transferred to a vial and diluted 5 times with LC-MS the amount of solvent B was increased linearly to 100% and this pro-
grade water. Afterwards 10 μL of a solution of Dimethoate-d6 at portion was maintained for another 2 min. Following this, the mobile
2.5 mg L−1 were added to each vial as the injection control standard. phase was changed to 80% A and kept over 3 min for re-equilibration,
The final extract corresponded to 0.2 g of sample per mL of extract. resulting in a total run time of 20 min. The gradient was run at a con-
stant flow rate of 300 μL min−1 and the injection volume was 5 μL. The
autosampler temperature was set at 10 °C.
2.3. Migration test The electrospray ionization (ESI) interface was operated in positive
ionization mode. The source parameters were as follows: ion source gas
The inner plastic layer of the packages was rinsed twice with ap- 1: 40 psi; Ion source gas 2: 50 psi; Curtain gas: 25 psi; CAD gas: 7;
proximately 2 × 2 mL LC-MS grade water for cleansing. Migration Temperature: 450 °C; Spray voltage: 5500 V. Resolution power of the
started in the food, so the pouches can be partially depleted. Migration TOF system was 32,000 FWHM (for m/z 200). SWATH®, a data in-
tests with packaging material were carried out according to Regulation dependent non-targeted acquisition mode was used. The MS analysis
(EU) No 10/2011. Dedicated for food contact with processed fruit purée was carried out simultaneously in both MS and MS/MS mode.
simulant B (acetic acid 3% (w/v)) and simulant C (ethanol 20% (v/v)) Parameters used in full scan mode were: accumulation time: 0.2 s;
are specified to be used for evaluating the legal compliance (European Declustering potential: 80 V; TOF start mass: 100; TOF stop mass: 950.
Commission, 2011). For long term food storage at room temperature, as For the MS/MS mode, the parameters were: accumulation time: 0.05 s;
in the case of baby food, a temperature of 40 °C for 10 days is suggested. TOF start mass: 50; TOF stop mass: 950. A generic collision energy of
Baby food packages were filled with equal net weight (90–100 g) as 35 ± 15 V was used in all windows. The number of isolation mass
baby food simulants B and C and kept during 10 days at 40 °C using an windows in Q1 was set as 10 divided as follows: m/z 100–185,

276
 Table 1
Migrants of plastic material in simulant B and C and baby food samples. The screening was performed with mass filter error of ± 5 ppm, retention time error of ± 0.1 min, two diagnostic ions (precursor and fragments),
isotope confidence < 20%.
A. Bauer, et al.

Plastic migrants1 Structure and Formula Precursor mass Adducts Rt (min) Fragments (ion ratio) Confirmation Classification Sample containing Country Cramer class
(Da) migrants

ε-Caprolactam 114.0913 [M+H]+ 3.01 79.0542 (0.033) 96.0808 Confirmed IAS simulant B, C baby Spain I
(0.021) food Germany
Australia

C6H11NO
2-Allyl-2,6-dimethoxyphenol 195.1016 [M+H]+ 10.11 154.0617 (0.118) 139.0386 Tentative NIAS simulant B, C baby Spain I
(Methoxyeugenol) (0.122) food Germany
Australia

C11H14O3
PA-PG** 207.0652 [M+H]+ 9.51 192.0421 (0.0566) 149.0233 Tentative NIAS simulant B, C baby Germany III
(0.0576) food

C11H10O4
NPG-AA 215.1278 [M+H]+ 9.78 129.0547 (0.046) 111.0441 Confirmed NIAS simulant B, C baby Australia I
(0.073) food Spain

277
C11H18O4
AA-DEG 217.1071 [M+H]+ 5.93 173.0807 (0.102) 155.0703 Confirmed NIAS simulant B, C baby Australia III
(0.079) food Germany
Spain

C10H16O5
Caprolactam Dimer 227.1754 [M+H]+ 2.55 114.0916 (0.072) 96.0814 Tentative NIAS simulant B, C baby Germany III
(0.033) food Australia
Spain

C12H22N2O2
AA-HD 229.1434 [M+H]+ 10.60 111.0441 (0.053) 55.0546 Tentative NIAS simulant B baby Australia I
(0.192) food

C12H20O4
NPG-AA (linear)** 233.1384 [M+H]+ 8.29 129.0547 (0.199) 55.0534 Tentative NIAS simulant B baby Spain I
(0.273) food

C11H20O5
(continued on next page)
Food Chemistry 295 (2019) 274–288
 Table 1 (continued)

Plastic migrants1 Structure and Formula Precursor mass Adducts Rt (min) Fragments (ion ratio) Confirmation Classification Sample containing Country Cramer class
(Da) migrants
A. Bauer, et al.

PA-DEG 237.0757 [M+H]+ 8.03 149.0233 (0.347) 89.0632 Confirmed NIAS simulant B, C baby Australia III
(0.074) food Germany
Spain

C12H12O5
NPG-SuA 243.1591 [M+H]+ 11.80 185.1176 (0.024) 139.1124 Tentative NIAS simulant B, C baby Germany I
(0.040) food Spain

C13H22O4
Bis(2-hydroxyethyl) terephthalate (BHET) 255.0863 [M+H]+ 6.77 103.0540 (0.845) 179.1077 Confirmed NIAS simulant B, C baby Australia I
(0.605) food

C12H14O6
AA-DEG (linear) 257.0996 [M+Na]+ 4.62 173.0804 (0.085) 155.0703 Tentative NIAS simulant B baby Germany III
(0.068) food Spain

278
C10H18O6
NPG-SA 271.1904 [M+H]+ 13.15 185.1172 (0.054) 139.1118 Tentative NIAS simulant B, C baby Germany I
(0.058) food Spain

C15H26O4
Cyasorb UV 12 275.0914 [M+H]+ 7.78 107.0491 (0.052) 169.0495 Tentative IAS simulant B, C baby Australia III
(0.342) food Germany
Spain

C15H14O5
AA-DEG-DEG (linear)** 323.17 [M+H]+ 6.00 217.1066 (0.213) 155.0706 Tentative NIAS simulant B baby Germany III
(0.176) food Spain

C14H26O8
(continued on next page)
Food Chemistry 295 (2019) 274–288
 Table 1 (continued)

Plastic migrants1 Structure and Formula Precursor mass Adducts Rt (min) Fragments (ion ratio) Confirmation Classification Sample containing Country Cramer class
(Da) migrants
A. Bauer, et al.

Caprolactam Cyclic Trimer 340.2595 [M+H]+ 5.18 322.2485 (0.050) 209.1647 Tentative NIAS simulant B, C baby Germany III
(0.084) food Spain

C18H33N3O3
Bis(2-methoxyethyl) sebacate 341.1935 [M+Na]+ 10.80 215.1280129.0546 Tentative NIAS simulant B Spain I

C16H30O6
AA-MEG-AA-MEG 345.1544 [M+H]+ 9.40 155.0703 (0.364) 173.0808 Tentative NIAS simulant B, C baby Australia I
(0.311) food Germany
Spain

279
C16H24O8
AA-MEG-AA-DEG 367.1363 [M+Na]+ 9.50 345.1533 (0.100) 155.0705 Tentative NIAS simulant B, C baby Germany III
(0.643) food Spain

C18H28O9
Tributyl citrate acetate (TBoAC) 403.2326 [M+H]+ 14.58 129.0182 (0.3161) 185.0808 Confirmed IAS simulant C baby Germany I
(0.2225) food Spain

C20H34O8
(continued on next page)
Food Chemistry 295 (2019) 274–288
 Table 1 (continued)

Plastic migrants1 Structure and Formula Precursor mass Adducts Rt (min) Fragments (ion ratio) Confirmation Classification Sample containing Country Cramer class
(Da) migrants
A. Bauer, et al.

C19H33NO8AA-DEG-NPG-Caprolactam** 404.2279 [M+H]+ 11.63 173.0709 (0.224) 155.0703 Tentative NIAS simulant B baby Australia III
(0.138) food

C19H33NO8
MEG-AA-NPG-PA 407.17 [M+H]+ 12.60 149.0233 (0.149) 155.0703 Tentative NIAS simulant B baby Australia III
(0.067) food

C21H26O8
C21H29NO8PA-DEG-NPG-Caprolactam** 424.1966 [M+H]+ 12.60 193.0495 (0.426) 279.1226 Tentative NIAS simulant B baby Australia III
(0.103) food

C21H29NO8
PA-MEG-AA-DEG 426.1759 [M+NH4]+ 10.58 281.1016 (0.129) 155.0703 Tentative NIAS simulant B, C baby Spain III
(0.214) food

280
C20H24O9
PA-DEG-AA-BD 437.1806 [M+H]+ 11.60 173.0809 (0.821) 155.0705 Tentative NIAS simulant B baby Spain III
(0.578) food

C22H28O9
NPG—PA-PG-PA 441.1544 [M+H]+ 12.45 355.0811 (0.193) 149.0233 Tentative NIAS simulant B, C baby Germany III
(0.507) food Spain

C24H24O8
(continued on next page)
Food Chemistry 295 (2019) 274–288
 Table 1 (continued)

Plastic migrants1 Structure and Formula Precursor mass Adducts Rt (min) Fragments (ion ratio) Confirmation Classification Sample containing Country Cramer class
(Da) migrants
A. Bauer, et al.

NPG-AA-HD-AA 443.2639 [M+H]+ 13.50 69.0701 (0.205) 111.0441 Tentative NIAS baby food Australia I
(0.201)

C23H38O8
AA-NPG-AA-NPG 446.2748 [M+NH4]+ 13.16 283.1912 (0.022) 215.1269 Tentative NIAS simulant B, C baby Spain I
(0.148) food

C22H36O8
AA-NPG-AA-NPG (linear)** 447.2589 [M+H]+ 11.94 215.1272 (0.563) 429.1185 Tentative NIAS simulant B baby Spain I
(0.118) food

281
C22H38O9
AA-DEG-AA-DEG 450.2334 [M+NH4]+ 9.55 155.0703 (0.211) 217.1070 Tentative NIAS simulant B, Cbaby Germany III
(0.068) food Spain

C20H32O10
Caprolactam Cyclic Tetramer 453.3435 [M+H]+ 6.89 435.3319 (0.176) 322.2484 Tentative NIAS simulant B, C Germany III
(0.081) Spain

C24H44N4O4
NPG-AA-NPG-PA 466.2435 [M+NH4]+ 13.77 235.0965 (0.294) 149.0233 Tentative NIAS simulant B, C baby Australia III
(0.113) food Spain

C24H32O8
(continued on next page)
Food Chemistry 295 (2019) 274–288
 Table 1 (continued)

Plastic migrants1 Structure and Formula Precursor mass Adducts Rt (min) Fragments (ion ratio) Confirmation Classification Sample containing Country Cramer class
(Da) migrants
A. Bauer, et al.

AA-DEG-AA-DEG (linear)** 468.2439 [M+NH4]+ 8.60 217.1070 (0.312) 173.0809 Tentative NIAS simulant B baby Germany III
(0.419) food Spain

AA-DEG-PA-DEG 470.2021 [M+NH4]+ 10.3 409.1494 (0.222) 193.0493 Tentative NIAS simulant B, C baby Germany III
(0.192) food Spain

C22H28O10
AA-DEG-PA-DEG (linear) 471.1861 [M+H]+ 9.57 173.0808 (0.087) 155.0695 Tentative NIAS simulant B baby Spain I
(0.780) food

C22H30O11
PA-DEG-PA-DEG 473.1442 [M+H]+ 10.43 429.1178 (0.145) 385.0906 Tentative NIAS simulant B, C baby Germany III

282
(0.232) food Spain

C24H24O10
NPG-PA-NPG-PA 486.2122 [M+NH4]+ 13.44 383.1130 (0.271) 149.0233 Tentative NIAS simulant B, C baby Germany III
(0.213) food Australia
Spain

C26H28O8
diethyl 5-(2-((2,4,5-trimethoxybenzoyl)oxy) 490.1708 [M+H]+ 10.44 149.0233 (0.347) 429.1190 Tentative NIAS simulant B, C baby Germany I
acetamido)isophthalate (0.180) food Spain

C24H27NO10
(continued on next page)
Food Chemistry 295 (2019) 274–288
 Table 1 (continued)

Plastic migrants1 Structure and Formula Precursor mass Adducts Rt (min) Fragments (ion ratio) Confirmation Classification Sample containing Country Cramer class
(Da) migrants
A. Bauer, et al.

NPG-PG-PA-SA** 494.2748 [M+NH4]+ 14.30 235.0965 (0.058) 149.0233 Tentative NIAS simulant B, C baby Germany III
(0.112) food Spain

C26H36O8
NPG-PA-NPG-SA 505.2796 [M+H]+ 14.95 149.0233 (0.458) 235.0967 Tentative NIAS simulant C baby Germany III
(0.350) food Spain

C28H40O8
NPG-SA-NPG-SA 541.3735 [M+H]+ 15.72 455.3004 (0.662) 69.0701 Tentative NIAS simulant C baby Germany I
(0.218) food Spain

283
C30H52O8
NPG-AA-NPG-AA-NPG-AA 643.3688 [M+H]+ 14.59 69.0701 (0.477) 111.0441 Tentative NIAS simulant C baby Spain I
(0.214) food

C33H54O12

AA- adipic acid; MEG- monoethylene glycol; DEG- diethylene glycol; PA- phthalic acid; NPG- neopentyl glycol; SA- sebacic acid; BD- butandiole; SuA- suberic acid; HD- hexandiole; PG- propandiole.
1
References compound names according to (Athenstädt et al., 2012; Gómez Ramos et al., 2018; Omer et al., 2018; Onghena et al., 2015; Ubeda, Aznar, & Nerín, 2018; Úbeda et al., 2017; Zhang et al., 2018)
** Detected by non-targeted approach.
Food Chemistry 295 (2019) 274–288
A. Bauer, et al. Food Chemistry 295 (2019) 274–288

Fig. 2. Full scan XIC of the migration study with the most abundant peaks in simulant C of squeezy package (A) and corresponding baby food sample (B). Migration
chromatogram of simulant C blank (C) and blank baby food sample (jar) (D).

184–270, 269–355, 354–440, 439–525, 524–610, 609–695, 694–780, (Athenstädt et al., 2012; Hoppe, Voogt & Franz, 2016; Bradley et al.,
779–865 and 864–950. A total cycle time of 0.78 s was obtained. An 2009; Eckardt & Simat, 2016; Omer et al., 2018; Onghena et al., 2015).
external TOF mass axis calibration was carried out daily. For the full- An entry is containing information about monoisotopic exact mass,
scan TOF-MS calibration, a mixture containing 10 reference compounds molecular structure and two fragments, observed retention time and
(CsI, amino-dPEG 4-acid, amino-dPEG 6-acid, amino-dPEG 8-acid, re- adducts.
serpine, ALILTLVS, ALILTLVS + CS, Heptakis(2,3,6-tri-O-methyl)-β- The identification criteria were adopted from the SANTE 11813/
cyclodextrin + NH3, Heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin + Cs 2017 document (Commision, 2018). These were as follows: a mass
and Triacetyl-β-cyclodextrin + NH3) with masses in the range of accuracy ± 5 ppm for each diagnostic ion (if m/z < 200, then the mass
132.9049–2034.6255 m/z was used. For calibration in MS/MS mode it accuracy of 1 ± mDa) was applied, retention time shift ± 0.1 min, two
was used reserpine at m/z 609.28066 (C33H40N2O9). The character- diagnostic ions (precursor and fragment ion), and as recommended an
istic masses used were: C11H12NO (174.09134), C10H11O4 ion ratio of ± 30%. Additionally, isotope confidence of < 20% differ-
(195.06519), C23H29N2O4 (397.21218) and C23H30NO8 ence from the theoretical isotope match (isotope distribution and ratio)
(448.19659). Also, this mixture was automatically injected throughout was used.
the batch every 5 samples to maintain the mass accuracy below 5 ppm. Confirmation and semi-quantification were performed via com-
mercially-available reference standards by matrix-matched calibration.
Blank sample extracts (baby food – equal mixture of apple, banana,
2.4.2. Data analysis pear) were spiked with available standards at four different levels
SciexOS software v. 1.4.0.18067 (Sciex, Framingham, MA, USA) corresponding to 0.010, 0.100, 1.00 and 5.00 mg/kg for quantification
was used for qualitative and quantitative analyses. In-silico fragmen- purpose. Additional analytical data is described in Table S-1 and cali-
tation was additionally performed by populate compound library soft- bration curves are presented in Fig. S-1.
ware v 1.0.0.0 (Sciex, Framingham, MA, USA).
Post-acquisition data processing was carried out for the identifica-
tion and structural characterization of the potential migrants. A non- 3. Results and discussion
targeted approach by SWATH is analyzing the full scan mass range
acquiring all fragment ions for all precursor ions throughout the entire 3.1. Non-targeted and suspect screening approaches
chromatographic run. After extraction of product ion spectra of the
corresponding precursor ion range, all chromatogram peaks are The analysis was performed with commercially-available baby food
grouped and statistically assessed by mathematical deconvolution, re- squeeze packaging. Data sets were subjected to both a non-targeted and
ceiving high quality non-interfered fragment spectra. The compound suspect screening approach for identification of unknown compounds
peaks were automatically identified and grouped by adducts, eluci- and tentative plastic migrant’s identification using a customized sci-
dating the molecular mass and identified with formula finder tool, entific library, enabling a fast screening of FCMs.
considering carbon, hydrogen, nitrogen, oxygen, chlorine, bromine, In a non-targeted approach, the most abundant unique components
phosphorus and sulphur atoms for an elemental composition assign- coming from the plastic material were identified in the samples. For this
ment with a mass tolerance < 5 ppm. Area thresholds of tenfold (non- workflow, a control sample (blank) was used to trace peaks associated
targeted screening) and fivefold (suspect screening) were set for the with the plastic packaging (only in the samples or area ratio
acquired data of test samples over control samples to enable the dis- threshold > 10 in comparison to blank sample), followed by data re-
covery of compounds associated with the plastic packaging materials. duction steps, resulting in the selection of the most abundant peaks
For a suspect screening approach, data was processed using a sci- Baby food containing the same ingredients and mixture of a baby food
entific library created in-house comprising a suspect database of 237 commercialised in a glass jar were used as a blank sample. The tested
compounds (103 NIAS entities). NIAS were included to in-house library simulants B and C were compared with simulants obtained from mi-
from a previous study (Gómez Ramos et al., 2018) and literature gration experiments using the jar.

284
A. Bauer, et al. Food Chemistry 295 (2019) 274–288

Fig. 3. Pathway of of linear and cyclic polyester oligomers based on monomers of neopentyl glycol and adipic acid in baby food packaging.

For a suspect screening approach, the database containing 237 IAS baby food package.
and NIAS mentioned above was applied in order to detect and identify Using sequential SWATH via precursor ion acquisition in multiple
potential migrants. Additionally, the workflow was set up with a re- specific mass windows combined with the deconvolution of MS/MS
ference sample (blank) with an area ratio > 5. spectra comprise an additional advantage, decreasing the number of
There is still a limited number of commercial or public FCM spectral interferences and avoiding false positive and negative detections
databases. So elucidation of potential structures was achieved by i) (Parrilla Vázquez et al., 2018). Especially, at low compound levels the
comparison of full scan MS and MS/MS data with literature if available reason for non-detects in accordance to the SANTE AQC document may
and ii) competitive fragmentation modelling for metabolite identifica- result from the inability of the detection of fragment ions (Bauer,
tion (CFM-ID, http://cfmid.wishartlab.com) by using SMILE strings to Kuballa, Rohn, Jantzen, & Luetjohann, 2018).
predict fragmentation by known structure. For unknown compounds a Further confirmation by available reference standards was per-
tentative identification was enabled by the grouping of a spectrum of formed for the identified compounds ε-Caprolactam and oligomers,
adducts receiving the neutral exact mass and elemental composition NPG-AA, AA-DEG, BHET and TBoAC. As reference standards for most
finally resulting in a candidate structure. This process was followed by NIAS were not commercially-available, identification was performed to
fragment spectra interpretation to elucidate the structure via char- meet the criteria described in Section 2.4.2.
acteristic fragments of an integral part of the molecule. An example is
showed in Fig. 1 HRAMS data of SWATH data acquisition of the
2NPG + 2AA oligomer is presented for identification in simulant B of a

285
A. Bauer, et al. Food Chemistry 295 (2019) 274–288

3.2. Identification of intentionally and non-intentionally added substances oligomer families were observed to appear in a similar relation based
in baby food and packaging on AA-DEG oligomers and ε-caprolactam up to cyclic tetramer.

The baby food and the packages were analyzed to identify potential 3.2.1. Comparison of samples from different countries
migrants. Table 1 summarizes the results obtained in the current study. A high homology of the detected compounds in samples from
In total 42 compounds were detected during the study. Three sub- Germany and Spain were recognized (Table 1), potentially due to the
stances were identified as IAS: Cyasorb UV2908 (light stabilizers), fact of similar manufacturing ways of multilayer packages. Only in
TBoAC (plastizer) and ε-Caprolactam (additive). The rest of the mi- Australia, on the other hand, heterogenic oligomers with ε-caprolactam
grants detected were NIAS, whereby 35 of the compounds were were detected. ε-Caprolactam has been found in the 15 samples ana-
polyester oligomers, 29 cyclic and six linear oligomers. Further, four lysed, derived from all three countries. Additionally, AA-HD oligomer,
NIAS were detected as BHET and diethyl 5-(2-((2,4,5-trimethox- HD was found in NPG-AA-HD-AA oligomer only in Australian baby food
ybenzoyl)oxy)acetamido)isophthalate, methoxyeugenol and Bis(2- samples. Exclusively in German samples a PA-PG 2-unit oligomer was
methoxyethyl) sebacate. found in all simulant studies and baby food. Bis(2-methoxyethyl) se-
For the first time ε-caprolactam was tentatively identify as a het- bacate was detected only in Spanish samples exclusively in experiments
erogenic polyester oligomer in combination with AA, DEG, PA and NPG using simulant B. ε-Caprolactam cyclic tetramer was detected in
in food and food simulant samples. Therefore ε-caprolactam must have German and Spanish samples in migration studies with both simulants,
been hydrolysed formerly, which seems logical as it was detected only showed in Table 1.
in acidic simulant B and baby food samples. This elemental formula was Similar FCM migrants presumably coming from the adhesive in-
previously identified in multilayer plastic materials samples in the gredients were detected both in migration studies and baby food sam-
study of Gómez Ramos et al. (2018). ples.
Furthermore, by using the non-targeted approach, PA-PG and Anyway, it should be considered that a more exhaustive study, using
NPG + PG + PA + SA (cyclic oligomers), 2AA-2DEG (linear), AA-DEG- a greater number of samples per country, would be necessary to draw
DEG (linear), NPG-AA (linear) and 2NPG-2AA (linear) were detected more clear conclusions derived from the geographical origin of the
for the first time in baby food. In general, linear oligomers were only samples.
observed in food simulant B samples containing acetic acid and in baby
food samples with pH ∼ 4. Simulant B mimics the migration from food 3.3. Confirmation and quantitation of FCM migrants
contact materials in a realistic way due to acidic conditions, possibly
leading to a hydrolysis of cyclic oligomers. According to literature, only ε-Caprolactam and cyclic oligomers (n = 2,3,4), NPG-AA, DEG-AA,
cyclic oligomers as inert and non-bonded polymerization ingredients BHET and TBoAC were verified via individual analytical reference
were described to be capable to migrate through the layer (Schaefer, standards. These compounds were quantified using matrix-matched
Ohm, & Simat, 2004; Bradley et al., 2009; Omer et al., 2018). calibration curves for simulants and separately for baby food
In Fig. 2 an overview of identified compounds is presented con- (Supplementary data Table S-1). For the most abundant oligomers NPG-
cerning the study applying simulant C (sample and blank) as well as SA, NPG-SuA and 2NPG-2AA no standards were commercially avail-
baby food sample and blank sample from a glass jar. As it is shown, the able. These two oligomers were semi-quantified via NPG-AA as a
detections are similar between the experiments using food simulants structure analogue. For 2AA-2DEG a semi-quantitation was calculated
and baby food study. ε-Caprolactam monomer, dimer, trimer and tet- via AA-DEG. All quantitation results are summarized in Supplementary
ramer were detected in both food simulants and baby food. The con- data Table S-2.
centrations of AA-DEG and 2-Allyl-2,6-dimethoxyphenol (1 and 3 in ε-Caprolactam was detected in 67% of the baby food samples in a
Fig. 2, respectively) were even higher in baby food in comparison to the range of 0.01–7.50 mg/kg complying with the SML of 15 mg/kg. In
food simulant samples. AA is used as an ingredient of polyurethane simulant B, ε-caprolactam was detected only in 36% of the samples
adhesives as well as plasticizer, while DEG is a common solvent and an between 0.06 and 0.99 mg/kg and in simulant C in 25% of the samples
impurity in plastic production (Castellan, Bart, & Cavallaro, 1991; in a range of 0.08–1.34 mg/kg. TBoAC was detected in 67% of the
Hoppe, Voogt & Franz, 2016). Traces of these compounds were also samples; in baby food at 0.07–1.97 mg/kg and only in simulant C at
detected in the blank sample (glass jar), potentially resulting from a 0.01–0.13 mg/kg. As TBoAC and ε-caprolactam are to be considered as
contamination of the cap and were considered for concentration cal- IAS the concentration is expected to be below the SML, due the fact the
culations. Most frequently and at highest intensity oligomers containing samples were commercial ones which have to comply with the EU-
NPG, a diglycol used for production of polyurethane adhesives were legislations.
detected in the study (Zhang et al., 2018). In combination with different Also, in 10% of the investigated baby food samples the cyclic ε-
dicarboxylic acids like SA and SuA or AA in constellation of 2, 4, 6 units caprolactam oligomer dimer was quantified via a reference standard
oligomers were observed to be the most abundant NIAS in both food compound in a range of 0.01–0.02 mg/kg. In 4 of the samples the
simulant and real food, which are typically used to generate pre- maximum residue level of 0.010 mg/kg for NIAS for all three countries
polymers in polyurethane production (Shrikhande, 2012). was exceeded. In one Spanish sample 0.01 mg/kg of ε-caprolactam
A possible formation mechanism of the most common linear and cyclic tetramer was quantified. Similar results were observed during the
cyclic polyesters based on NPG and AA is presented in Fig. 3. During the migration study applying simulant B, while in migration experiments
study, NPG-AA, a 2-unit oligomer, 2NPG-2AA, a 4-unit oligomer and a using simulant C of Spanish and German samples ε-caprolactam cyclic
6-unit oligomer 3NPG-3AA were detected in migration study and fruit dimer was quantified at 0.02–0.03 mg/kg.
purées. Cyclic oligomers are generated during manufacturing of ad- Further, a NIAS phthalate BHET was identified just in 20% of baby
hesives as by-products. In consequence of esterification process difficult food samples at levels between 0.03 and 0.18 mg/kg. No BHET was
to control cyclic polyesters are formed instead of intended long chain observed in simulant studies leading to the conclusion that it has had to
linear polyester (Zhang et al., 2018). Moreover, under acidic conditions be completely adsorbed by food or is a contamination during the pro-
these compounds are hydrolysed and were consequently detected in duction of baby food before filling in pouches.
simulant B and baby food with acidic medium. Oligomers were ob- Cyclic polyester oligomer NPG-AA was detected in 60% of the baby
served in different homogenic or heterogonic combinations with dif- food samples, mainly derived from Spain and Australia. Examples of
ferent aliphatic and aromatic dicarboxylic acids like SA, SuA and PA, as verification and quantification chromatograms are presented in Fig. S-
displayed in Table 1. Thus, indirect propositions can be made about 1. The determined concentration range in baby food was 0.01–1.06 mg/
which kind of ingredients were used for the adhesive PU layer. Further kg, while concentrations in 4 samples would exceed the limit of

286
A. Bauer, et al. Food Chemistry 295 (2019) 274–288

0.010 mg/kg allowed for NIAS. In comparison to baby food, in food Declaration of Competing Interest
simulants amounts in a range between 0.01 and 0.05 mg/kg were de-
termined in simulant B and 0.06–0.08 mg/kg in simulant C. There is no conflict of interest. The manuscript was approved for
In over 40% of the tested food samples AA-DEG was quantified publication by all authors.
between 1.42 and 5.86 mg/kg. In the studies applying simulants B and
C the range was between 0.18 and 0.25 mg/kg. In all three cases the Acknowledgements
concentration limit of 0.010 mg/kg for NIAS was exceeded.
One of the most abundant compounds NPG-SA was semi-quantified Dr. María José Gómez Ramos acknowledges funding obtained from
in a range between 0.05 and 1.36 mg/kg in over 65% of the baby food the Spanish Government for a Ramón y Cajal Research Fellowship
samples and was detected in both simulants. This polyester oligomer (RYC-2015-17959).
was predominantly detected in European pouches during the study.
Another main oligomer NPG-SuA was semi-quantified at an average Appendix A. Supplementary data
amount of 0.42 mg/kg in German and Spanish samples only. Similar to
the other results, the concentration was lower than in food with Supplementary data to this article can be found online at https://
0.04–0.09 mg/kg. doi.org/10.1016/j.foodchem.2019.05.105.
Moreover, the concentration of oligomers, of four units 2NPG-2AA
was estimated in food at an upper limit of 2.00–4.00 mg/kg in Spanish References
and German samples by semi-quantitation via NPG-AA. 2AA-2DEG in
baby food was semi-quantified via DEG-AA in a range of 0.03–1.10 mg/ Anastassiades, M., Tasdelen, B., Scherbaum, E., & Stajnbaher, D. (2007). Recent
kg. Both oligomers have been detected at higher concentration in baby Developments in QuEChERS Methodology for Pesticide Multiresidue Analysis. Weinheim:
Wiley-VCH.
food than in simulants studies. However, it has to be taken into account Athenstädt, B., Fünfrocken, M., & Schmidt, T. C. (2012). Migrating components in a
that in this study the food was emptied from the packaging and after- polyurethane laminating adhesive identified using gas chromatography/mass spec-
wards the migration studies had been performed, so the pouches could trometry. Rapid Communications in Mass Spectrometry, 26, 1810–1816.
Bauer, A., Kuballa, J., Rohn, S., Jantzen, E., & Luetjohann, J. (2018). Evaluation and
be partially depleted. validation of an ion mobility quadrupole time-of-flight mass spectrometry pesticide
One aspect to consider of the migrant compounds in food is its screening approach. Journal of Separation Science, 41, 2178–2187.
possible toxicity, especially when it comes to infant foods. According to Biedermann-Brem, S., Kasprick, N., Simat, T., & Grob, K. (2012). Migration of polyolefin
oligomeric saturated hydrocarbons (POSH) into food. Food Additives & Contaminants:
Eckardt and Simat (2016) and Gómez Ramos et al. (2018) cyclic com- Part A, 29, 449–460.
pounds can be mostly classified as Level III and linear oligomers as Bradley, E. L., Driffield, M., Guthrie, J., Harmer, N., Thomas Oldring, P. K., & Castle, L.
Level II group of Cramer rules. As this model is based on molecular (2009). Analytical approaches to identify potential migrants in polyester-poly-
urethane can coatings. Food Additives & Contaminants Part A, Chemistry, Analysis,
structure toxicity, an example based on DEG-AA (free software Toxtree
Control, Exposure & Risk Assessment, 26, 1602–1610.
v2.6.13 to estimate the toxicity of compounds, http://toxtree. Castellan, A., Bart, J. C. J., & Cavallaro, S. (1991). Industrial production and use of adipic
sourceforge.net/) can be classified in Level III category, thus a daily acid. Catalysis Today, 9, 237–254.
intake of 0.0015 mg/kg body weight/day is allowed. Level classifica- Commision, E. (2018). Guidance Document on Analytical Quality Control and Method
Validation Procedures for Pesticide Residues and Analysis in Food and Feed. SANTE/
tion of the detected compounds according to Cramer rules are sum- 11813/2017.
marized in Table 1. An average body weight of an infant of 10 kg is to Cramer, G. M., Ford, R. A., & Hall, R. L. (1976). Estimation of toxic hazard-A decision tree
be assumed, so a total intake of 0.015 mg would be allowed. As an approach. Food and Cosmetics Toxicology, 16, 255–276.
Eckardt, M. & Simat, T. J. (2016). Migration of linear and cyclic polyester oligomers from
example, calculation on AA-DEG (showed in Supplementary data) for polyester-phenolcoatings into food and food simulants: Unpublished.
an infant consuming one baby food pouch resulted in a daily intake EFSA Scientific Committee (2018). Guidance on the use of the Threshold of Toxicological
of > 30 times higher than the TTC value. 2 Concern approach in food safety assessment. EFSA J..
European Commission (2011). Commission Regulation (EU) No 10/2011 of 14 January
2011 on plastic materials and articles intended to come into contact with food Text
4. Conclusions with EEA relevance: Regulation (EU) No 10/2011.
Félix, J. S., Isella, F., Bosetti, O., & Nerín, C. (2012). Analytical tools for identification of
non-intentionally added substances (NIAS) coming from polyurethane adhesives in
In this study, a high potential non-targeted and suspect screening
multilayer packaging materials and their migration into food simulants. Analytical
approach using LC-HRAMS was presented. The SWATH acquisition fa- and Bioanalytical Chemistry, 403, 2869–2882.
cilitates the identification of unexpected IAS and NIAS in migration Fruchtbar (2018). Aus welchen Materialien besteht die Quetschie-Verpackung? https://
www.fruchtbarewelt.de/aus-welchen-materialien-besteht-die-quetschie-
studies and baby food samples. The approach used with an in-house
verpackung/. Accessed 18.07.18.
library can be applied to routinely screen samples in a fast and easy Gómez Ramos, M. J., Lozano, A., & Fernández-Alba, A. R. (2018). High-resolution mass
way. spectrometry with data independent acquisition for the comprehensive non-targeted
The FCM migrants detected in this study mainly originate from the analysis of migrating chemicals coming from multilayer plastic packaging materials
used for fruit purée 4 and juice. Talanta in press.
PU layer of the plastic multilayer packaging. A total of 42 migrants Grob, K. (2014). Work plans to get out of the deadlock for the safety assurance of mi-
were detected in migration studies and baby food samples. The che- gration from food contact materials? A proposal. Food Control, 46, 312–318.
micals detected were similar in both food simulants and baby food, Hoppe, M., de Voogt, P., & Franz, R. (2016). Identification and quantification of oligo-
mers as potential migrants in plastics food contact materials with a focus in poly-
showing the effectivity of food simulants recreating FCM migration into condensates-A review. Trends in Food Science & Technology, 50, 118–130.
real food. Kalkhof, H., Herzler, M., Stahlmann, R., & Gundert-Remy, U. (2012). Threshold of tox-
Twentynine of the detected oligomers were cyclic, that according to icological concern values for non-genotoxic effects in industrial chemicals: Re-eva-
luation of the Cramer classification. Archives of Toxicology, 86, 17–25.
Cramer rules are classified in the higher toxicity class. This study re- Nerin, C., Alfaro, P., Aznar, M., & Domeño, C. (2013). The challenge of identifying non-
veals the importance of evaluating NIAS in FCM to ensure food safety, intentionally added substances from food packaging materials: a review. Analytica
as they could be a very important part of the migration from food Chimica Acta, 775, 14–24.
Omer, E., Cariou, R., Remaud, G., Guitton, Y., Germon, H., Hill, P., ... Le Bizec, B. (2018).
packaging into food and could have a high toxicity.
Elucidation of non-intentionally added substances migrating from polyester-poly-
There is still a lack of databases and analytical reference standards urethane lacquers using automated LC-HRMS data processing. Analytical and
for the identification, confirmation and quantification of the FCM Bioanalytical Chemistry, 1–13.
Onghena, M., van Hoeck, E., van Loco, J., Ibáñez, M., Cherta, L., Portolés, T., ... Covaci, A.
found.
(2015). Identification of substances migrating from plastic baby bottles using a
Comparing the origin of countries and brands of the 15 samples combination of low-resolution and high-resolution mass spectrometric analysers
analysed, similar migrant profiles are identified, especially in samples coupled to gas and liquid chromatography. Journal of Mass Spectrometry, 50,
originating from the European countries Spain and Germany, poten- 1234–1244.
Packaging Report (2017). Global Flexible Packaging Market for Baby Food 2018-2022.
tially resulting from the same manufacturing process.

287
A. Bauer, et al. Food Chemistry 295 (2019) 274–288

Available at: https://www.technavio.com/report/global-flexible-packaging-market- Supplied.

for-baby-food-analysis-share-2018. Ubeda, S., Aznar, M., & Nerín, C. (2018). Determination of oligomers in virgin and re-
Parrilla Vázquez, P., Lozano, A., Ferrer, C., Martínez Bueno, M. J., & Fernández-Alba, A. cycled polyethylene terephthalate (PET) samples by UPLC-MS-QTOF. Analytical and
R. (2018). Improvements in identification and quantitation of pesticide residues in Bioanalytical Chemistry, 410, 2377–2384.
food by LC-QTOF using sequential mass window acquisition (SWATH®). Analytical Úbeda, S., Azanar, M., Vera, P., Nerin, C., Henriquez, L., Taborda, C., & Restrepo, C.
Methods, 10, 2821–2833. (2017). Overall and specific migration from multilayer high barrier food contact
Paseiro-Cerrato, R., MacMahon, S., Ridge, C. D., Noonan, G. O., & Begley, T. H. (2016). materials–kinetic study of cyclic polyester oligomers migration. Food Additives &
Identification of unknown compounds from polyester cans coatings that may po- Contaminants: Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment, 34,
tentially migrate into food or food simulants. Journal of Chromatography A, 1444, 1784–1794.
106–113. Zhang, N., Kenion, G., Bankmann, D., Mezouari, S., & Hartman, T. G. (2018). Migration
Reynolds, P. (2010). Pouch format is 'baby food 2.0. https://www.packworld.com/ studies and chemical characterization of low molecular weight cyclic polyester oli-
article/food/frozen/pouch-format-baby-food-20. Accessed 18.07.18. gomers from food packaging lamination adhesives. Packaging Technology and Science,
Schaefer, A., Ohm, V. A., & Simat, T. J. (2004). Migration from can coatings: Part 2. 31, 197–211.
Identification and quantification of migrating cyclic oligoesters below 1000 Da. Food Zhu, X., Chen, Y., & Subramanian, R. (2014). Comparison of information-dependent ac-
Additives and Contaminants, 21, 377–389. quisition, SWATH, and MSAll techniques in metabolite identification study em-
Shrikhande, A. (2012). Migration Studies and Chemical Characterization of Short Chain ploying ultrahigh-performance liquid chromatography-quadrupole time-of-flight
Cyclic Polyester Oligomers from Food Packaging Laminate Adhesives. No Publisher mass spectrometry. Analytical Chemistry, 86, 1202–1209.

288