Modeling the migration of chemicals from food contact materials to food: The MERLIN-expo/VERMEER toolbox.

Evaluating the migration of chemicals from food contact materials (FCM) into food is a key step in the safety assessment of such materials. In this paper, a simple mechanistic model describing the migration of chemicals from FCM to food was combined with quantitative property-property relationships (QPPRs) for the prediction of diffusion coefficients and FCM-Food partition coefficients. The aim of the present study was to evaluate the performance of these operational models in the prediction of a chemical's concentration in food in contact with a plastic monolayer FCM. A comparison to experimental migration values reported in literature was conducted. Deterministic simulations showed a good match between predicted and experimental values. The tested models can be used to provide insights in the amount and the type of toxicological data that are needed for the safety evaluation of the FCM substance. Uncertainty in QPPRs used for describing the processes of both diffusion in FCM and partition at the FCM-Food interface was included in the analysis. Combining uncertainty in QPPR predictions, it was shown that the third quartile (75th percentile) derived from probabilistic calculations can be used as a conservative value in the prediction of chemical concentration in food, with reasonable safety factors.

Occurrence of (suspected) genotoxic flavoring substances in Belgian alcohol-free beers.

The regulatory landscape of flavorings is evolving, thereby putting pressure on control laboratories to develop analytical methods for a wide range of compounds in various types of food and drinks. In order to improve the monitoring of flavoring substances, a versatile and accurate analytical method using the solvent-assisted flavor evaporation (SAFE) technique coupled to GC-MS(SIM) was developed and validated. Focus was put on authorized flavoring substances requiring specific attention due to a genotoxic concern based on information from European risks assessment reports. Thirty-seven (suspected) genotoxic flavoring substances were analyzed in a selection of ten alcohol-free beers. Five suspected genotoxic compounds (i.e. 1-(2-furyl)-2-propanone, 2-acetylfuran, 2-acetyl-5-methylfuran, 2-acetyl-3,5-dimethylfuran, hex-2-eno-1,4-lactone) as well as two confirmed genotoxic flavoring substances (p-mentha-1,8-dien-7-al, 2,4-pentanedione) were identified and quantified among the selected samples. Low concentrations and natural occurrences of the identified compounds suggested that these were not added as such but rather originated from heat-treatments or from plant-based extracts.

Assessing the receptor-mediated activity of PAHs using AhR-, ERα- and PPARγ- CALUX bioassays.

Polycyclic aromatic hydrocarbons (PAH) are a complex group of organic compounds, consisting of at least three fused aromatic rings, which are formed during combustion of organic matter. While some PAHs have been reported to have carcinogenic and/or mutagenic properties, another possible negative health impact is their endocrine disrupting potential. Therefore, the aim of this study was to determine both the agonistic and antagonistic endocrine activity of 9 environmentally relevant PAHs using three different CALUX bioassays: The AhR-CALUX, The ERα-CALUX and PPARγ-CALUX. For the PPARγ-CALUX anthracene, fluoranthene, pyrene and fluorene showed weak agonistic activity, whilst benzo(a)pyrene (B(a)P) was the only one exhibiting weak antagonistic activity. For the AhR-CALUX, chrysene was the only PAH that showed relatively strong agonist activity (except for B(a)P which was used as a standard). Pyrene, anthracene and fluoranthene showed weak AhR agonist activity. In the ERα-CALUX bioassay, fluoranthene had agonistic activity whilst B(a)P exhibited both agonistic and antagonistic activity (lowering E2 activity by 30%). Phenanthrene and anthracene had weak ERα agonist activities. These results indicate that certain PAHs have multiple modes of action and can activate/inhibit multiple receptor signaling pathways known to play critical roles in mediating endocrine disruption.

Assessment of estrogenic compounds in paperboard for dry food packaging with the ERE-CALUX bioassay.

Paperboard used as packaging, a non-inert material, can transfer chemicals into food. Over the years, endocrine disrupting compounds (EDCs), such as NonylPhenols (NPs), BisPhenol A (BPA) and phthalates have been shown to migrate from packaging materials into food. Due to chronic exposure and mixture effects of these EDCs, they could cause health effects even at very low doses. Many EDCs are still unknown and many more are still unregulated. The ERE-CALUX bioassay was used as a bioanalytical tool to investigate estrogenic activities of paperboard food packaging and its characteristics, including recycling rate and printing ink. A "worst case" scenario with full extraction is compared to a dry food migration experiment. By measuring an overall estrogenic activity, known and unknown estrogenic chemicals and mixture effects are taken into account and the data are compared to molecule specific analysis. Estrogenic activities ranged from 682 ±â€¯66 pg E2 eq./dm2 to 3250 ±â€¯400 pg E2 eq./dm2 for "worst case" extraction and from 347 ±â€¯30 pg E2 eq./dm2 to 1350 ±â€¯70 pg E2 eq./dm2 for migration experiments. A two-factor ANOVA revealed a relationship between estrogenic activity and the recycling rate of the paperboard, but no significant difference with printing ink was observed for these paperboard samples. Bis(2-ethylhexyl)phthalate (DEHP), dibutyl phthalate (DBP), butyl benzyl phthalate (BBP) and 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH) were determined in all extraction and migrations experiment samples. A Spearman rank correlation analysis showed a relationship between the estrogenic activity and the total phthalates as well as with each compound individually.

Coatings in food contact materials: Potential source of genotoxic contaminants?

Up till now, no harmonized EU regulation exists on chemicals used in coatings for food contact materials (FCM). Therefore, these substances need to comply with the general provisions of EU Regulation 1935/2004 and, if present, with national legislation. Different 'inventory lists' of compounds that might be present in coatings are available, but for hundreds of these substances, the potential human health impact of their use in FCM coatings has not (recently) been evaluated. Since detailed evaluation of all compounds is not feasible, a pragmatic approach was developed to identify substances with a potential concern for human health. First, an inventory was assembled containing all substances potentially used in coatings. Afterwards, the genotoxic potential of the non-evaluated substances was predicted in silico using two structure-activity relationship (SAR) software programs. For substances yielding structural alerts in both models, genotoxicity data were collected from previous European evaluations in a non-FCM context and from the European CHemicals Agency (ECHA) website. In total, 53 substances were identified as genotoxic in both in silico models, of which ten were considered to be of high concern. For most of the substances, additional toxicological information is needed.

Use of Tenax® films to demonstrate the migration of chemical contaminants from cardboard into dry food.

Contaminants in food packaging are a challenge of our time since the packaging material itself has been found to represent a source of food contamination through the migration of substances from it. Before first use, packaging materials destined for the packaging of dry foods can be evaluated by performing migration experiments with the simulant for dry foods, Tenax®. This simulant is commercially available as a powder that is more difficult to handle during the migration experiments. This paper reports the development of a Tenax film. The film can be applied to the cardboard surface to conduct the migration test. After the migration is completed, the film can be easily extracted to determine the concentration of the contaminants in the film. Finally, the performance of the Tenax film was compared with the conventional Tenax powder for the evaluation of 15 model migrants.

Clustering and diagnostic modelling of slimming aids based on chromatographic and mass spectrometric fingerprints.

Herbal medicines and food supplements intended as slimming aids are increasingly gaining popularity worldwide, especially for treating obesity. In this study, an ultra-performance liquid chromatography coupled to photodiode array detection (UPLC-PDA) and an ultra-performance liquid chromatography mass spectrometry (UPLC-MS) method were developed to analyze 92 slimming aids (confiscated by customs), aimed at acquiring highly informative fingerprints. Three types of fingerprints were acquired (PDA, Total Ion Chromatograms (TIC), and MS fingerprints) which were used in the chemometric data analysis. Both unsupervised (i.e., Hierarchical Cluster Analysis (HCA)) and supervised techniques (i.e., Classification and Regression Tree (CART) and Partial Least Squares - Discriminant Analysis (PLS-DA)) were applied. The aim was to perform an in-depth study of the samples, thereby exploring potential patterns present in the data. HCA was able to generate a clustering which was mainly defined by chemical compounds detected in the samples, i.e., sibutramine, phenolphthalein and amfepramone. PLS-DA generated the best diagnostic models for both PDA and TIC fingerprints, characterized by correct classification rates of external validation of 85% and 80%, respectively. For the MS fingerprints, the best model was obtained by CART (65% correct classification rate of external validation). Despite a lower correct classification rate, exploration of the concerned misclassifications revealed that the MS fingerprints proved to be superior since even very low concentrations of sibutramine could be detected. This study shows that reliable chemometric models can be obtained, based on the presence of prohibited chemical substances, which allow high-throughput data analysis of such samples. Moreover, they generate a prime notion of potential threat to a patient's health posed by these kinds of slimming aids. Copyright © 2016 John Wiley & Sons, Ltd.

Evaluation of the migration of 15 photo-initiators from cardboard packaging into Tenax(®) using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).

Photo-initiators are widely used to cure ink on packaging materials used in food applications such as plastic films or cartonboards. In migration studies, food simulants are very often used to simulate food, like Tenax(®), which is the simulant for dry foodstuffs. In this paper a fast and reliable confirmation method for the determination of the following photo-initiators in Tenax(®) is described: benzophenone (BP), 4,4'-bis(diethylamino)benzophenone (DEAB), 2-chloro-9H-thioxanthen-9-one (CTX), 1-chloro-4-propoxy-9H-thioxanthen-9-one (CPTX), 2,4-diethyl-9H-thioxanthen-9-one (DETX), 2,2-dimethoxy-2-phenyl acetophenone (DMPA), 4-(dimethylamino)benzophenone (DMBP), 2-ethylanthraquinone (EA), ethyl-4-dimethylaminobenzoate (EDMAB), 1-hydroxylcyclohexyl phenyl ketone (HCPK), 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone (HMMP), 2-isopropyl-9H-thioxanthen-9-one (ITX), 4-methylbenzophenone (MBP), Michler's ketone (MK), and 4-phenylbenzophenone (PBZ). After the migration study was completed, the simulant Tenax(®) was extracted using acetonitrile, followed by analysis on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Quantification was carried out using benzophenone-d10 (BP-d10) as internal standard. The presented method is validated in terms of matrix effect, specificity, linearity, recovery, precision and sensitivity, showing the method can detect all photo-initiators at very low concentrations (LOD < 0.125 µg g(-1) for all substances). Finally, the procedure was applied to real samples, proving the capabilities of the presented method.

Characterization of suspected illegal skin whitening cosmetics.

An important group of suspected illegal cosmetics consists of skin bleaching products, which are usually applied to the skin of the face, hands and décolleté for local depigmentation of hyper pigmented regions or more importantly, for a generalized reduction of the skin tone. These cosmetic products are suspected to contain illegal active substances that may provoke as well local as systemic toxic effects, being the reason for their banning from the EU market. In that respect, illegal and restricted substances in cosmetics, known to have bleaching properties, are in particular hydroquinone, tretinoin and corticosteroids. From a legislative point of view, all cosmetic products containing a prohibited whitening agent are illegal and must be taken off the EU market. A newly developed screening method using ultra high performance liquid chromatography-time off flight-mass spectrometry allows routine analysis of suspected products. 163 suspected skin whitening cosmetics, collected by Belgian inspectors at high risk sites such as airports and so-called ethnic cosmetic shops, were analyzed and 59% were classified as illegal. The whitening agents mostly detected were clobetasol propionate and hydroquinone, which represent a serious health risk when repeatedly and abundantly applied to the skin.

Analysis of benzophenone and 4-methylbenzophenone in breakfast cereals using ultrasonic extraction in combination with gas chromatography-tandem mass spectrometry (GC-MS(n)).

Benzophenone (BP) and 4-methylbenzophenone (4MBP) are photo-initiators that are generally used to cure ink on carton boards. In this contribution, a fast and reliable method for the determination of BP and 4MBP in breakfast cereals is described. The sample was extracted ultrasonically using a mixture of dichloromethane and acetonitrile (1:1), followed by a clean-up of the extract using solid phase extraction with a silica cartridge. Finally, the extract was analysed by GC-MS(n). Benzophenone-d(10) was used as internal standard. The presented method is validated in terms of linearity, recovery, repeatability and intra-laboratory reproducibility, specificity, limit of detection and limit of quantification. In conclusion, this method is able to detect both BP and 4MBP at very low concentrations (LOD=2microg kg(-1)) in breakfast cereals.