Article
To read the full-text of this research, you can request a copy directly from the authors.

Abstract and Figures

Linear and cyclic oligomers are unavoidable non-intentionally added substances (NIAS) present in food contact materials made from common polyesters such as polyethylene terephthalate (PET), polybutylene terephthalate (PBT) and polyester coatings. Although polyester oligomers can migrate into fats in significant amounts in high-temperature processes such as baking or frying, little is known about their toxicological properties and their behaviour in the human gastrointestinal tract. In the present study, first indications of a possible digestibility of polyester oligomers formed from the commonly used aromatic dicarboxylic acid terephthalic acid (TPA) are provided by in vitro experiments. Three cyclic polyester oligomers originated from PET (trimer) and PBT (dimer and trimer) were extracted from the raw materials, isolated and subjected to a simulated intestinal digestion. A fast cleavage (≥75% of the initial amount) of all three cyclic oligomers into their linear counterparts was detected already within the first hour of in vitro intestinal incubation. Subsequent hydrolysis to shorter chained linear oligomers was determined especially for the PET cyclic trimer. Degradation down to the monomer TPA was not observed. In terms of risk assessment and prioritisation for non-evaluated NIAS, the threshold of toxicological concern (TTC) concept is an appropriate tool. While cyclic polyester oligomers based on TPA are assigned to the TTC Cramer class III (high potential concern, exposure threshold 1.5 µg/kg body weight per day), the corresponding linear oligomers are expected to be of a lower probable toxicological concern (Cramer class I, 30 µg/kg body weight per day). A cleavage of cyclic polyester oligomers under human intestinal conditions, which was assessed to be likely by the provided in vitro experiments, could consequently affect the risk assessment on polyester oligomers.
Content may be subject to copyright.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... Two terephthalates were included in the study; the PET oligomer bis(2-hydroxylethyl) terephthalate (BHET) was shown to degrade by 69.9% after a 4 h incubation in an intestinal-fluid simulant while the plasticizer di(ethylhexyl) terephthalate degraded by 35.1% after the simulation with both the gastric juice and intestinalfluid simulant. Eckardt et al. (2019) investigated the hydrolyzability of cyclic PBT oligomers; a cleavage of approximately 99% (cyclic dimer, CT 2 B 2 ) and 96% (cyclic trimer, CT 3 B 3 ) was observed after a 4 h incubation in the intestinalfluid simulant with an addition of 1-2% organic solvent to improve the solubility. A lower degradation rate of approximately 74% (CT 2 B 2 ) was observed without a solvent addition, proving that the solubility of the oligomer is a significant factor for the hydrolysis rate (as proposed by Ulrich et al. [2018]). ...
... These results suggest that the strict assessment of cyclic oligomers as Cramer III substances may be inappropriate because these are possibly hydrolyzed in the gastrointestinal tract, yielding Cramer I-class linear oligomer species. Hydrolysis down to the monomers (terephthalic acid and 1,4-butanediol) was not observed by Eckardt et al. (2019) and no specification of degradation products was made by Ulrich et al. (2018). Furthermore, the hydrolysis of oligomers is yet to be confirmed in vivo. ...
... The worst-case scheme is possibly overestimating the concern connected to the oligomer consumption as the Cramer III cyclic oligomers may be hydrolyzed to linear species. The best-case scheme is probably underestimating the risk because it considers all oligomers to be linear, which is probably not the case due to an incomplete cleavage of cyclic oligomers as observed during the in vitro experiments (Ulrich et al. 2018;Eckardt et al. 2019). Therefore, the two schemes frame a range of risk. ...
Article
Oligomers are a significant group of migrating substances from food contact materials made of polyesters like polybutylene terephthalate (PBT). Twenty-three cyclic and linear oligomers with different end groups including olefin-terminated oligomers, which are associated with thermal stress of the material, were tentatively identified in PBT extracts by high-performance liquid chromatography with mass spectrometry and diode array detection. Quantification approaches based on chromophore concentration, relative response factors, and overall oligomer determination after hydrolysis to the monomer terephthalic acid were employed. An exhaustive extraction of thirteen PBT samples yielded an overall oligomer content of 1.87–6.10 mg/g material (sum of individual oligomers < 1,000 Da) with a predominant content of cyclic over linear oligomers. Migration experiments were performed according to Regulation (EU) No. 10/2011 using the official food simulants as well as cows’ milk. A total of 218 µg cyclic oligomers/L milk were detected in the third migrate relevant for risk assessment of repeated-use articles under hot-fill conditions (70 °C, 2 h). The official food simulant for milk, 50% ethanol, was found to overestimate the actual migration into milk by a factor of four. Frying conditions using sunflower oil as the food simulant (200 °C, 10 min) resulted in a migration of 7.5 mg cyclic oligomers/kg oil. The exposure to migrating oligomers is critical in some scenarios when evaluated by the threshold of toxicological concern concept; however, the toxicological evaluation poses a challenge due to the possible hydrolysis of cyclic oligomers in the human gastrointestinal tract. Our experiments display the need for a toxicological evaluation of PBT oligomers because the migration of cyclic oligomers is expected to exceed the current in silico–based thresholds under foreseeable conditions of use.
... Due to the different Cramer Class assignments of linear and cyclic oligomers the above-mentioned factors influencing the migration of linear and cyclic oligomers into different types of foods are important for the risk assessment of migrating PES oligomers. Additionally, it has to be considered that a hydrolysis of cyclic polyester oligomers by enzymes of the gastro intestinal tract, as shown by Eckardt et al. (2019) for the cyclic dimer and trimer of PBT and the cyclic trimer of PET, would result in the formation of linear oligomers mostly assigned to Cramer Class I. ...
... Further, a hydrolysis of cyclic PBT and PET oligomers by enzymes of the gastro intestinal tract yielding linear oligomers has been shown by Eckardt et al. (2019). Since more than 100 oligomers were identified in polyesters of PET, PETG and Tritan™, it may be obvious that a routine analysis of these will be difficult and a toxicological assessment of each identified substance impossible. ...
Article
Polyesters are commonly used as food contact materials. During manufacture of polyesters different low molecular mass oligomers (<1000 Da) are formed in the polymer melt. These so-called non-intentionally added substances (NIAS) are potential migrants into foods. In this work, different polyester samples made of polyethylene terephthalate (PET), glycol-modified PET (PETG) and Tritan™ were investigated on their qualitative and quantitative oligomer composition. The analysis of acetonitrile extracts by HPLC-DAD/ESI-MS revealed the presence of about 100 linear (different combinations of hydroxyl-, carboxyl-, methyl ester end groups) and cyclic oligomers depending on the main and co-monomers. The identified oligomers were quantified in different extracts and after reprecipitation by HPLC-DAD using bis-hydroxyethylene terephthalate (BHET) as external standard. The amount of oligomers isolated by reprecipitation ranged between 0.80 and 3.4% in the respective polyester. Cyclic oligomers generally made up 90% or more of the isolated oligomers. Compared to the exhaustive extracts the leaching of oligomers into 20% ethanol (1 h, 60 °C) resulted in a considerable change of the oligomer distribution with a predominant detection of linear oligomers. This suggests linear oligomers to be relevant for migration into aqueous foods despite the dominant amount of extractable cyclic oligomers in polyesters. Analysis of the extractable oligomers of a PET preform and a PETG container and their corresponding raw material pellets revealed that the injection moulding process did not significantly change the amount of cyclic oligomers but did increase the amount of low molecular mass linear oligomers about twofold.
... PET oligomers are considered as non-intentionally added substances (NIAS) and have shown to migrate from the plastic material into the food (Brenz et al., 2017;Eckardt, Schneider, & Simat, 2019;Genualdi, Nyman, & Begley, 2014;Heimrich, Nickl, Bönsch, & Simat, 2015;Kappenstein et al., 2018;Tsochatzis, Alberto, Kappenstein, Tietz, & Hoekstra, 2020). A mixture of some PBT cyclic oligomers (dimer to pentamer) is included in the positive list of Regulation (EU) No. 10/2011as FCM substance No. 885 (Regulation (EU) No. 10/, 2011EFSA, 2009), but its use as additive is restricted to FCMs made of PET, PBT, polycarbonate, polystyrene and rigid poly(vinyl chloride) in concentrations up to 1% w/w. ...
... They reported that cleavage of certain cyclic polyester oligomers to linear ones is occurring under human intestinal conditions, down to a plateau. The subsequent degradation of these linear products into smaller linear oligomers would again increase the probability of high intestinal absorption of the molecules (Eckardt et al., 2019). ...
Full-text available
Article
of PBT and PET cyclic oligomers in extracts of coffee capsules and food simulants by a HPLC-UV/FLD method, Food Chemistry (2020), doi: https://doi. Abstract A HPLC-UV/FLD method was validated for the quantification of six polyethylene terephthalate (PET) and four polybutylene terephthalate (PBT) oligomers. PBT oligomers are EU regulated, while the PET ones are considered non-intentionally added substances (NIAS). LOQs were higher than 0.4 and 3.5 μg kg-1 for the simulants and in the polymer extracts, respectively. Recoveries ranged from 95-114 % with RSDs below 12 %. Migration testing of PBT and polypropylene coffee capsules were performed with H 2 O and simulant C, and extracts were obtained with accelerated solvent extraction (ASE). For the latter legislative limits weren't surpassed. As no migration limits are existing for the analytes, both EFSA's toxicological threshold of concern (TTC) and sum of oligomers approaches were applied. The majority of oligomers were below the TTC (90 µg/person/day), but the limit value of 50 µg/kg food was surpassed for some capsules, which indicates a significant intake in both single and multiple consumption.
... The hydrolytic cleavage of these ester bonds leads to a change in the composition of the PET oligomers and therefore strongly influences the exposure. This phenomenon has already been observed with PET oligomers and is therefore considered an important information for chemical risk assessment (Eckardt et al., 2019). Migration of chemicals into food and beverages is a commonly used method to support and estimate oral exposure and is therefore a relevant study concept in this SEM. ...
Full-text available
Preprint
Background Polyethylene terephthalate (PET) oligomers are ubiquitous in PET used in food contact applications. Consumer exposure by migration of PET oligomers into food and beverages is documented. However, no specific risk assessment framework or guidance for the safety evaluating of PET oligomers exist to date. Aim The aim of this systematic evidence map (SEM) is to identify and organize existing knowledge clusters and associated gaps in hazard and exposure information of PET oligomers. Research needs will be identified as an input for chemical risk assessment, and to support future toxicity testing strategies of PET oligomers and regulatory decision-making. Search strategy and eligibility criteria: Multiple bibliographic databases (incl. Embase, Medline, Scopus, and Web of Science Core Collection), chemistry databases (SciFinder-n, Reaxys), and gray literature sources will be searched, and the search results will be supplemented by backward and forward citation tracking on eligible records. The search will be based on a single-concept PET oligomer-focused strategy to ensure sensitive and unbiased coverage of all evidence related to hazard and exposure in a data-poor environment. A scoping exercise conducted during planning identified 34 relevant PET oligomers. Eligible work of any study type must include primary research data on at least one relevant PET oligomer with regard to exposure, health, or toxicological outcomes. Study selection: For indexed scientific literature, title and abstract screening will be performed by one reviewer. Selected studies will be screened in full-text by two independent reviewers. Gray literature will be screened by two independent reviewers for inclusion and exclusion. Study quality assessment: Risk of bias analysis will not be conducted as part of this SEM. Data extraction and coding: Will be performed by one reviewer and peer-checked by a second reviewer for indexed scientific literature or by two independent reviewers for gray literature. Synthesis and visualization: The extracted and coded information will be synthesized in different formats, including narrative synthesis, tables, and heat maps. Systematic map protocol registry and registration number: Zenodo: 10.5281/zenodo.6224302
... In another work, Eckardt et al. studied the in vitro intestinal digestion of individual cyclic PET and PBT oligomers. The results showed a cleavage of the ester group of these cyclic oligomers after 4 h of simulated intestinal incubation, pointing to an expected similar occurrence in real human intestinal conditions [17]. However, in order to evaluate human exposure and hazard assessment, accurate analytical tools are required. ...
Article
Food contact materials (FCM) polyethylene terephthalate (PET) and polybutylene terephthalate (PBT) used extensively in food packaging may contain cyclic oligomers which may migrate into food and thus cause toxic effects on human health. A simple, fast, and sensitive ultra-high-performance liquid chromatography method quadrupole time-of-flight mass spectrometer was developed for the analysis of 7 cyclic oligomers in post-mortem blood samples. The targeted analytes were separated on a Waters BEH C18 (150 × 2.1 mm, 1.7 µm) analytical column by gradient elution. Calibration curves were constructed based on standard solutions and blood samples and Student’s t-test was applied to evaluate the matrix effect. The LODs ranged from 1.7 to 16.7 μg mL−1, while the method accuracy was assessed by recovery experiments and resulting within the range 84.2–114.6%. Such an analytical method for the determination of PET and PBT cyclic oligomers in biological samples is reported for the first time. The developed methodology allows the determination of these oligomers in blood providing a useful analytical tool to assess the exposure and thus the potential hazard and health risks associated with these non-intentionally added substances (NIAS) from PET and PBT FCM through food consumption. The method was validated and successfully applied to the analysis of 34 post-mortem whole blood samples. Polyethylene terephthalate trimer was detected in four of them, for the first time in literature.Graphical abstract
... Cyclic dimers, are sensitive to hydrolysis, and in general, it is assumed that the cyclic oligomers (classified as Cramer III in toxicity class) are transformed to linear, which are less toxic (Cramer I toxicity class). A recent study demonstrated that after digestion in the human body, the linear oligomers are predominant (Eckardt et al., 2019). Table 1 summarizes some of the most commonly found contaminants in both virgin and recycled food-grade PET, as well as the analytical techniques used for their determination. ...
Article
Polyethylene terephthalate (PET) is a polymer deemed safe to be mechanically recycled and used in food contact applications. Its recycled form (rPET) can be used as a food contact material (FCM). Although this is an obvious positive step towards a more circular economy, the development of an appropriate analytical toolbox to experimentally assess and evaluate the various steps during end of life and mechanical recycling is still at its infancy. The safety of the decontamination process is currently evaluated following a conventional modelling approach applied to a specific number of compounds (challenge test). However, additional compounds, quality markers and process controls are needed, with respect to migrating substances, potential non-intentionally added substances (NIAS), contaminants and known polymeric degrading compounds. This would ensure an additional level of safety and provide recomendations for the application of appropriate methods when ensuring full compliance with safety standards for rPET. This review presents the current regulatory framework and the most recent developments in analytical methodologies related to compliance testing. It also highlights some of most described chemical substances found in food-grade rPET.
... The content of PET cyclic trimer is higher than that of other oligomers because of its high chemical and thermal stability and easy aggregation and crystallization during dyeing [16,17]. Not only is the melting point of cyclic trimer as high as 310 • C [18], its solubility in water is also very low [19]. ...
Full-text available
Article
As a promising new dyeing process without using water, the non-aqueous medium dyeing of polyester has attracted people's attention and some progress has been made in related research. However, the oligomers of polyester fiber can affect the dyeing of polyester during the use of a silicone waterless dyeing system. Based on this point, the oligomer problem in the silicone waterless dyeing system was investigated. The oligomers of some different types of polyester were extracted by solvent extraction. A treatment method with little influence on the fiber was used to reduce the oligomer content in polyester. The improvement of the dyeing effect of polyester after treatment in silicone medium was studied, and the influence of the oligomer on polyester dyeing was also analyzed. For the dyeing of disperse blue 366, the dye exhaustion was increased by 3.25-3.71%, and the color depth of the dyed sample was increased by 6-13%. Moreover, the colorfastness to rubbing was also improved. In the comparison, the changes in thermal properties and crystallization properties of polyester were tested by differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), and X-ray diffraction analysis (XRD). The results showed that the thermal and crystalline properties of polyester fiber were not changed before and after solvent extraction.
... An Expert Group of the International Life Sciences Institute (ILSI Europe) has examined the TTC principle for its broader applicability in food safety evaluation, and they have concluded that this approach can be applied for low concentrations of chemicals in the food that lack toxicity data, provided that there is an intake estimate [7]. The authors used the TTC approach to estimate NIAS Risk Assessment in recent literature [116,[136][137][138]. ...
Full-text available
Article
Several food contact materials (FCMs) contain non-intentionally added substances (NIAS), and most of the substances that migrate from plastic food packaging are unknown. This review aimed to situate the main challenges involving unknown NIAS in plastic food packaging in terms of identification, migration tests, prediction, sample preparation, determination methods and risk assessment trials. Most studies have identified NIAS in plastic materials as polyurethane adhesives (PU), polyethylene terephthalate (PET), polyester coatings, polypropylene materials (PP), multilayers materials, plastic films, polyvinyl chloride (PVC), recycled materials, high-density polyethylene (HDPE) and low-density polyethylene (LDPE). Degradation products are almost the primary source of NIAS in plastic FCMs, most from antioxidants as Irganox 1010 and Irgafos 168, following by oligomers and side reaction products. The NIAS assessment in plastics FCMs is usually made by migration tests under worst-case conditions using food simulants. For predicted NIAS, targeted analytical methods are applied using GC-MS based methods for volatile NIAS and GC-MS and LC-MS based methods for semi- and non-volatile NIAS; non-targeted methods to analyze unknown NIAS in plastic FCMs are applied using GC and LC techniques combined with QTOF mass spectrometry (HRMS). In terms of NIAS risk assessment and prioritization, the threshold of toxicological concern (TTC) concept is the most applied tool for risk assessment. Bioassays with sensitive analytical techniques seem to be an efficient method to identify NIAS and their hazard to human exposure; the combination of genotoxicity testing with analytical chemistry could allow the Cramer class III TTC application to prioritize unknown NIAS. The scientific justification for implementing a molecular weight-based cut-off (
... Nevertheless, the possibility of potential hydrolysis that might occur during sample preparation/extraction has to be taken always into consideration, especially for cyclic and low molecular mass oligomers of PET and PBT (i.e. dimers) (Brenz et al., 2018;Dehouck et al., 2018;Eckardt, Schneider & Simat, 2019;Tsochatzis, Alberto Lopes, Dehouck et al., 2020). Hence, MgSO 4 and NaCl were added to the extraction process, both to serve as a salting-out agent and to remove potential excess of H 2 O (Anastassiades et al., 2003;Otoukesh et al., 2020;Tsochatzis, Karayannakidis et al., 2019). ...
Article
An Ultra High-Performance Liquid chromatography method quadruple time-of-flight mass spectrometry has been developed for the analysis of 11 cyclic polyesters oligomers, following a modified QuEChERS clean-up with alumina/primary secondary amine, in pasta. Target analytes were polyethylene terephthalate (PET) 1st series cyclic dimer to heptamer, polybutylene terephthalate (PBT) dimer to pentamer and a polyurethane oligomer. Standard addition method was applied for the calibration, and the limits of quantification ranged from 3.2 to 17.2 ng g⁻¹. Recoveries ranged from 86.4 - 109.8 %, RSDs were lower than 12 % for all analytes, and matrix effect never exceeded ± 2.5 %. The method was successfully applied to real commercial pasta samples, where the PET 1st series cyclic trimer was the most abundant oligomer, being found in all tested samples. The 1st series PET cyclic dimer and tetramer, as well as 1,4,7-trioxacyclotridecane-8,13-dione, were found in considerable amounts. Traces of the 2nd and 3rd series PET cyclic dimers were also found.
Article
The techniques for the detection and control of cyclic esterification (CE) in biodegradable polyesters are presented. It is pointed out that CE can be extracted by extraction or migration and then detected using GC-MS or LC-MS depending on their volatility, with LC-MS techniques being more commonly used due to the generally poor volatility of CE. CE was detected in several typical biodegradable polyesters such as poly(lactic acid) (PLA), poly(butylene succinate) (PBS) and poly(butylene adipate-terephthalate) (PBAT) with repeating units less than 10; both the improvement of the polymerization process and the use of organic solvents to wash the biodegradable polyester particles can effectively reduce the content of CE, and the washing strategy is relatively more convenient and efficient.
Article
Polyester yarn is successfully dyed with disperse dye in a low-pressure non-aqueous medium dyeing system. However, oligomers with different low molecular mass are formed during manufacture of polyesters, which can diffuse into the dyeing bath or be adsorbed on the dyeing machine during dyeing process. In this investigation, oligomers of different polyester yarns were extracted with tetrachloroethane solution, and analyzed using Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance (NMR), thermogravimetric analysis (TGA), high performance liquid chromatography (HPLC), and liquid chromatography-mass spectrometry (LCMS). The amount of oligomer that was isolated by reprecipitation method ranged from 1.83 % to 4.07 % (on the weight of yarn) in the respective yarn, and more than 80 % of the components are cyclic oligomers. The thermal profile of oligomer showed it had a faster weight loss at 183 °C and 470 °C which was compared with polyester (473 °C). HPLC and LC-MS analysis results further indicated that 99 % of the oligomers were cyclic trimers during dyeing. Moreover, the dyeing color depth of dyed yarn and the uptake of dye would be greatly improved after the oligomer of polyester yarn was removed. Otherwise, the oligomer may affect the color fastness and levelness of the dyed polyester samples.
Thesis
D’après la littérature scientifique, les plastiques présents en mer libèrent des micro et nano-plastiques ainsi des substances chimiques, potentiellement transférées ou bioaccumulées dans les organismes marins, ce qui constitue une source potentielle de préoccupation. Par ailleurs, l’aquaculture marine utilise de nombreux équipements en plastique, devant être recyclés en fin de vie (cf. Directive (UE) 2019/904). Dans ce contexte, tout nouvel équipement en plastique conçu pour l’aquaculture doit être éco-conçu et s’inscrire dans une économie circulaire. Le présent travail propose une méthodologie d’éco-conception, systémique et pilotée par l’usage, développée pour maîtriser l’innocuité, la durabilité et la recyclabilité des matériaux polymères utilisés en aquaculture, et comprenant 4 étapes : 1- une évaluation scientifique des risques liés à l’usage du matériau, 2- l’identification des points de contrôle de ces risques, 3- le développement d’actions préventives, 4- la définition de procédures de vérification de leur maîtrise, incluant la réalisation d’analyses biométriques et chimiques dans le cadre d’une expérimentation in situ.
Thesis
Ces travaux s’inscrivent dans le cadre du développement d’une nouvelle pièce ostréicole en plastique. Leur objectif est de proposer une méthodologie, spécifiquement développée pour l’écoconception des matériaux plastiques utilisés en ostréiculture, en vue de garantir : 1 – Leur innocuité vis-à-vis des huîtres, des consommateurs d’huîtres et des écosystèmes marins, 2 - Leur durabilité, ou maintien de leur intégrité physique dans le temps, afin d’optimiser leur durée d’utilisation et ralentir leur dégradation dans le milieu, 3 - Leur recyclabilité post utilisation, en vue d’assurer leur intégration dans une économie circulaire. Le développement de cette méthodologie s’est organisée autour d’un cadre général de gestion des risques, comprenant 5 étapes au niveau desquelles les données scientifiques, toxicologiques et écotoxicologiques, ainsi que les méthodes et outils d’aide à la décision identifiés comme étant les plus pertinents ont été utilisés, adaptés ou développés, pour identifier, évaluer et maîtriser les dangers potentiels. Pour faciliter son intégration dans une démarche d’écoconception, les attentes technico-économiques et le rôle de chaque acteur de la chaîne de valeur du matériau ont été pris en compte. La mise en œuvre de cette méthodologie a permis la sélection de 2 matrices polymères et de 2 formulations. Les 3 matériaux expérimentaux obtenus ont été testés in situ, dans le cadre d’un cycle de culture expérimentant le prototype du système de production en développement. Les premiers résultats obtenus suggèrent que la recyclabilité, la durabilité et les niveaux d’émission de substances dans le milieu peuvent être maîtrisés. Développé pour l’ostréiculture, cette méthodologie reposant sur l’établissement de scénarios de devenir, d’exposition et d’effets des composants des polymères, devrait être adaptable à d’autres usages
Article
Since the decline of the use of bisphenol A, the chemistry of the varnishes and coatings which are applied to the inner surfaces of metallic food contact materials is poorly documented. We hypothesised that can coatings are now diverse and bring forth various non-intentionally added substances (NIAS) to be described. Investigating complex components such as NIAS requires demanding non-targeted approaches. We investigated the coatings of 12 vegetable cans from the French market. More than 125 substances were pinpointed, among them 84 oligoester combinations from 8 diols and 4 diacids. Thus, oligoesters were the dominant family. Additives such as epoxidised soybean oil, bisphenol A diglycidyl ether and benzoguanamine derivatives and phenol-formaldehyde oligomers were also identified. A software for exploring databases of theoretical combinations of polyester and phenol-formaldehyde resin components (NIAS-db 1.0) was made available. The stepwise organic synthesis of native and deuterated combinations of neopentyl glycol and isophthalic acid (4 and 8 units, linear and cyclic) enabled a higher confidence level and monitoring in vegetable extracts. Migration of oligoesters averaged 330 µg/kg in the drained vegetables (43 to 1600 µg/kg). This study sheds light on the need to fulfil a proper risk assessment on this NIAS family (exposure and hazard characterisation).
Full-text available
Article
The Scientific Committee confirms that the Threshold of Toxicological Concern (TTC) is a pragmatic screening and prioritisation tool for use in food safety assessment. This Guidance provides clear step-by-step instructions for use of the TTC approach. The inclusion and exclusion criteria are defined and the use of the TTC decision tree is explained. The approach can be used when the chemical structure of the substance is known, there are limited chemical-specific toxicity data and the exposure can be estimated. The TTC approach should not be used for substances for which EU food/feed legislation requires the submission of toxicity data or when sufficient data are available for a risk assessment or if the substance under consideration falls into one of the exclusion categories. For substances that have the potential to be DNA-reactive mutagens and/or carcinogens based on the weight of evidence, the relevant TTC value is 0.0025 lg/kg body weight (bw) per day. For organophosphates or carbamates, the relevant TTC value is 0.3 lg/kg bw per day. All other substances are grouped according to the Cramer classification. The TTC values for Cramer Classes I, II and III are 30 lg/kg bw per day, 9 lg/kg bw per day and 1.5 lg/kg bw per day, respectively. For substances with exposures below the TTC values, the probability that they would cause adverse health effects is low. If the estimated exposure to a substance is higher than the relevant TTC value, a non-TTC approach is required to reach a conclusion on potential adverse health effects.
Full-text available
Article
Regulatory agencies across the world are facing the challenge of performing risk-based prioritization of thousands of chemicals in commerce. Here, we present an approach using the Threshold of Toxicological Concern (TTC) combined with heuristic high-throughput exposure (HTE) modelling to rank order chemicals for further evaluation. Accordingly, for risk-based prioritization, chemicals with exposures > TTC would be ranked as higher priority for further evaluation whereas substances with exposures < TTC would be ranked as lower priority. An initial proof of concept, using a dataset of 7986 substances with previously modeled median and upper 95% credible interval (UCI) total daily median exposure rates showed fewer than 5% of substances had UCI exposures > the Cramer Class III TTC (1.5 μg/kg-day). We extended the analysis by profiling the same dataset through the TTC workflow published by Kroes et al (2004) which accounts for known exclusions to the TTC as well as structural alerts. UCI exposures were then compared to the appropriate class-specific TTC. None of the substances categorized as Cramer Class I or Cramer Class II exceeded their respective TTC values and no more than 2% of substances categorized as Cramer Class III or acetylcholinesterase inhibitors exceeded their respective TTC values. The modeled UCI exposures for the majority of the 1853 chemicals with genotoxicity structural alerts did exceed the TTC of 0.0025 μg/kg-day, but only 79 substances exceeded this TTC if median exposure values were used. For substances for which UCI exposures exceeded relevant TTC values, we highlight possible approaches for consideration to refine the HTE : TTC approach. Overall, coupling TTC with HTE offers promise as a pragmatic first step in ranking substances as part of a risk-based prioritization approach.
Full-text available
Article
To be effective as a drug, a potent molecule must reach its target in the body in sufficient concentration, and stay there in a bioactive form long enough for the expected biologic events to occur. Drug development involves assessment of absorption, distribution, metabolism and excretion (ADME) increasingly earlier in the discovery process, at a stage when considered compounds are numerous but access to the physical samples is limited. In that context, computer models constitute valid alternatives to experiments. Here, we present the new SwissADME web tool that gives free access to a pool of fast yet robust predictive models for physicochemical properties, pharmacokinetics, drug-likeness and medicinal chemistry friendliness, among which in-house proficient methods such as the BOILED-Egg, iLOGP and Bioavailability Radar. Easy efficient input and interpretation are ensured thanks to a user-friendly interface through the login-free website http://www.swissadme.ch. Specialists, but also nonexpert in cheminformatics or computational chemistry can predict rapidly key parameters for a collection of molecules to support their drug discovery endeavours.
Full-text available
Article
Apart from efficacy and toxicity, many drug development failures are imputable to poor pharmacokinetics and bioavailability. Gastrointestinal absorption and brain access are two pharmacokinetic behaviors crucial to estimate at various stages of the drug discovery processes. To this end, the Brain Or IntestinaL EstimateD permeation method (BOILED-Egg) is proposed as an accurate predictive model that works by computing the lipophilicity and polarity of small molecules. Concomitant predictions for both brain and intestinal permeation are obtained from the same two physicochemical descriptors and straightforwardly translated into molecular design, owing to the speed, accuracy, conceptual simplicity and clear graphical output of the model. The BOILED-Egg can be applied in a variety of settings, from the filtering of chemical libraries at the early steps of drug discovery, to the evaluation of drug candidates for development.
Full-text available
Article
Cross-linked polyester resins are being introduced into the market as alternatives to epoxy resins as coatings for metal food cans. Identification of potential migrants, from these coatings into food, is a significant analytical challenge due to the diversity of substances employed in the manufacture of the coatings. However, such identification is required to assess migration from the can coating into the food and quantify dietary exposure. Polyester can coatings were extracted with acetonitrile at 40 °C for 24 h and the extracts were analyzed by a variety of analytical techniques, including GC-MS, HPLC-DAD/MS, HPLC-DAD/CAD and UHPLC-HRMS. Twenty nine non-volatile oligomers were tentatively identified using retention times, UV spectra, and accurate mass measurements. Identified oligomers suggest the coating in use for food cans is a polyester coating and is mainly based on the monomers isophthalic acid, terephthalic acid and nadic acid. To give confidence in the identification, one of the tentatively identified oligomer was synthetized and analyzed by 13C and 1H NMR and UHPLC-HRMS. The NMR and HRMS results, confirmed the presence of this compound in the can extracts. Finally, to determine if rapid, direct detection of the oligomers was practical, the coatings were analyzed by DART-HRMS. Twenty three out of the 29 oligomers were identified in the coating by direct measurement with DART-HRMS in few minutes.
Full-text available
Article
The migration of total levels of poly(ethylene terephthalate) (PET) oligomers into a diverse range of foods has been determined using an analytical approach that involves hydrolysis of oligomers to terephthalic acid, methylation, and analysis as dimethyl terephthalate by stable isotope dilution GC/MS. Aspects of use of PET materials examined in this study include roasting bags, PET trays (for conventional and microwave oven use), and 'suspector pads' for microwave browning applications. Total levels of migration of PET oligomers were found to range from 0.02 to 2.73 mg/kg depending on the foodstuff and the temperature attained during cooking. On repeated-use of PET trays for heating olive oil there was a decline in migration of oligomers from the first to second and subsequent uses of the container. Migration of oligomers was found to occur at only very low levels from PET bottles into alcoholic and carbonated beverages.
Full-text available
Article
We present a new atom type classification system for use in atom-based calculation of partition coefficient (log P) and molar refractivity (MR) designed in part to address published concerns of previous atomic methods. The 68 atomic contributions to log P have been determined by fitting an extensive training set of 9920 molecules, with r(2) = 0.918 and sigma = 0.677. A separate set of 3412 molecules was used for the determination of contributions to MR with r(2) = 0.997 and sigma = 1.43. Both calculations are shown to have high predictive ability.
Full-text available
Article
A quantitative method has been developed to measure the migration of polyethylene terephthalate (PET) cyclic oligomers from aluminized PET susceptor film-type food packaging into several food types. Microwaveable French fries, popcorn, fish sticks, waffles and pizza sold in susceptor-type packaging were purchased in local markets, cooked according to package instructions and analysed for PET oligomers. Appropriate food blanks were cooked in glass containers. Quantities of PET oligomers found in the foods ranged from less than 0.012 micrograms/g to approximately 7 micrograms/g.
Full-text available
Article
The threshold of toxicological concern (TTC) is a pragmatic risk assessment tool that is based on the principle of establishing a human exposure threshold value for all chemicals, below which there is a very low probability of an appreciable risk to human health. The concept that there are levels of exposure that do not cause adverse effects is inherent in setting acceptable daily intakes (ADIs) for chemicals with known toxicological profiles. The TTC principle extends this concept by proposing that a de minimis value can be identified for many chemicals, in the absence of a full toxicity database, based on their chemical structures and the known toxicity of chemicals which share similar structural characteristics. The establishment and application of widely accepted TTC values would benefit consumers, industry and regulators. By avoiding unnecessary toxicity testing and safety evaluations when human intakes are below such a threshold, application of the TTC approach would focus limited resources of time, cost, animal use and expertise on the testing and evaluation of substances with the greatest potential to pose risks to human health and thereby contribute to a reduction in the use of animals. An Expert Group of the European branch of the International Life Sciences Institute-ILSI Europe-has examined the TTC principle for its wider applicability in food safety evaluation. The Expert Group examined metabolism and accumulation, structural alerts, endocrine disrupting chemicals and specific endpoints, such as neurotoxicity, teratogenicity, developmental toxicity, allergenicity and immunotoxicity, and determined whether such properties or endpoints had to be taken into consideration specifically in a step-wise approach. The Expert Group concluded that the TTC principle can be applied for low concentrations in food of chemicals that lack toxicity data, provided that there is a sound intake estimate. The use of a decision tree to apply the TTC principle is proposed, and this paper describes the step-wise process in detail. Proteins, heavy metals and polyhalogenated-dibenzodioxins and related compounds were excluded from this approach. When assessing a chemical, a review of prior knowledge and context of use should always precede the use of the TTC decision tree. The initial step is the identification and evaluation of possible genotoxic and/or high potency carcinogens. Following this step, non-genotoxic substances are evaluated in a sequence of steps related to the concerns that would be associated with increasing intakes. For organophosphates a TTC of 18microg per person per day (0.3 microg/kg bw/day) is proposed, and when the compound is not an OP, the TTC values for the Cramer structural classes III, II and I, with their respective TTC levels (e.g. 1800, 540 and 90 microg per person per day; or 30, 9 and 1.5 microg/kg bw /day), would be applied sequentially. All other endpoints or properties were shown to have a distribution of no observed effect levels (NOELs) similar to the distribution of NOELs for general toxicity endpoints in Cramer classes I, II and III. The document was discussed with a wider audience during a workshop held in March 2003 (see list of workshop participants).
Full-text available
Article
Cyclic oligomers were identified in PET bottles used for mineral water and fruit juice using MS and (1)H and (13)C NMR: a first series cyclic trimer, a first series cyclic tetramer, a first series cyclic dimmer and a second series cyclic trimer. An analytical method to determine first series cyclic trimer in these bottles was developed and validated, using HPLC. The first series cyclic trimer levels were 316-462 mg/100g of PET bottle.
Article
Coatings for cans or closures are essential to protect the metal from corrosion and the food from migration of hazardous metal ions. Since coatings are no inert materials, they can release substances of potential health concern into food. In the present study, a comprehensive analysis is presented for a complex two-layered polyester–phenol-coating commercially used for metal closures of complementary infant food in sterilised glass jars. Focussed on the identity and migration of cyclic polyester oligomers as a kind of predictable non-intentionally added substances, polyester resin raw materials (n = 3) as well as individual coating layers (n = 3) were characterised by several analytical strategies (size exclusion chromatography, high-performance liquid chromatography mass spectrometry, diode array detection, charged aerosol detection, monomer determination after alkaline hydrolysis, overall migrate). The main polyester monomers were terephthalic acid, isophthalic acid, trimellitic acid, ethylene glycol, diethylene glycol, neopentylglycol, 2-methyl-1,3-propanediol, 1,4-butanediol and tricyclodecanedimethanol. The coatings were extracted with solvents acetonitrile and ethanol (24 h, 60°C), food simulants 50% ethanol, 20% ethanol and water (1 h, 121°C) as well as homemade and commercial baby food (1 h, 121°C). The released total polyester content determined by alkaline hydrolysis ranged from 288 µg/dm² (water, 1 h, 121°C) to 6154 µg/dm² (acetonitrile, 24 h, 60°C). However, individual cyclic oligomers, mainly dimers, were released from the coating to up to about 140 µg/dm². Migration into infant food was best represented by the food simulants water (up to 1% fat) and 20% ethanol (up to 5% fat). Cyclic polyester oligomers are classified as Cramer III substances by the threshold of toxicological concern concept associated to an exposure threshold of 1.5 µg/kg body weight per day. Exposure to cyclic polyester oligomers might be a potential concern for highly exposed infants.
Article
Polyethylene naphthalate and polybutylene terephthalate were investigated regarding their oligomer content. Based on their accurate mass and fragmentation spectra ten oligomers have been identified in extracts of PBT material and seven oligomers in extracts of PEN material. These oligomers were found to be cyclic and linear for both polymers. They consist of the respective diacid and monoglycol monomers as well as diglycol monomers. The total oligomer content in the polyesters was determined with LC-UV using the cyclic PET trimer as external standard and was found to be 0.81% for PEN and 0.34% for PBT. Migration of PBT oligomers was studied into 20% ethanol (v/v) at 40 °C and 60 °C and the diffusion coefficients thus derived were compared to theoretically determined ones. To estimate the PEN and PBT oligomer migration at 23 °C under long time storage conditions the diffusion coefficients were calculated using the approaches by Welle and Piringer. For cyclic PBT oligomers the Welle model underestimates the migration, for one linear PBT oligomer the Piringer model might be suitable to determine the migration. In the chosen scenario the resulting total oligomer migration was below 30 μg kg⁻¹ for both materials.
Article
In terms of risk assessment especially for known and unknown substances migrating from food contact materials, quantification without corresponding reference substances currently poses a challenge. In the present study, the opportunity of a universal response quantification approach was evaluated by using a corona charged aerosol detector (CAD) for liquid chromatography combined with inverse gradient compensation. Characteristics of CAD detection in dependence of substance properties were analyzed with 46 randomly chosen reference substances. An almost equal CAD response (±20%) was achieved for non-volatile substances with a molecular weight of minimum 400 g/mol and a vapor pressure of maximum 10−8 Torr. We empirically defined an analytical parameter, Q50/35, the quotient of CAD peak areas at CAD evaporator temperatures of 50 °C and 35 °C, to predict the adequacy of the CAD universal response approach for quantification of known and unknown analyte substances. Exemplarily, we applied the CAD universal quantification approach for the determination of extractable oligomers below 1000 g/mol from a variety of food contact polycondensate plastic materials (e.g. polyesters like polyethylene terephthalate, polybutylene terephthalate, Tritan copolyester, polyamides 6, 6.6 and 6 T/6I and polyarylsulfones polyphenylsulfone and polyethersulfone). Quantitative results for in total 44 oligomers out of 11 materials were compared with established material-specific quantification methods using extracted oligomer mixtures as well as individual oligomers isolated from the mixtures. CAD-based quantification results were generally in accordance to published quantification approaches for polyamide oligomers and oligomers from polyarylsulfones. For oligomers extracted and isolated from polyester materials a slight underestimation was determined by CAD universal response approach. In terms of detection limits and accuracy, the universal CAD approach exhibits no advantages compared to established UV-methods, to date.
Article
The polymeric coating used in metal packaging such as cans for foods and beverages may contain residual amounts of monomers used in the production of the coating, as well as unreacted linear and cyclic oligomers. Traditionally, although designed for use with plastic food contact materials, food simulants have been used to determine the migration of monomers from coatings into foodstuffs. More recently food simulants have also been used to determine oligomeric species migrating from can coatings. In the work reported here, the migration of both monomers and oligomers from polyester-based can coatings into food simulants and foodstuffs, some of which were towards the end of their shelf-life, are compared. The concentrations of monomers and selected oligomers in canned foods at the end of their shelf life were found to be significantly lower than those in food simulants, which in turn was lower than those in the extraction solvent acetonitrile.
Article
An untargeted strategy aiming at identifying non-intentionally added substances (NIAS) migrating from coatings was developed. This innovative approach was applied to two polyester-polyurethane lacquers, for which suppliers previously provided the identity of the monomers involved. Lacquers were extracted with acetonitrile and analyzed by liquid chromatography-high resolution mass spectrometry (LC-HRMS). Data, acquired in the full scan mode, were processed using an open-source R-environment (xcms and CAMERA packages) to list the detected features and deconvolute them in groups related to individual compounds. The most intense groups, accounting for more than 85% of cumulated feature intensities, were then investigated. A homemade database, populated with predicted polyester oligomer combinations from a relevant selection of diols and diacids, enabled highlighting the presence of 14 and 17 cyclic predicted polyester oligomers in the two lacquers, including three mutual combinations explained by common known monomers. Combination hypotheses were strengthened by chromatographic considerations and by the investigation of fragmentation patterns. Regarding unpredicted migrating substances, four monomers were hypothesised to explain several polyester or caprolactam oligomer series. Finally, considering both predicted and tentatively elucidated unpredicted oligomers, it was possible to assign hypotheses to features representing up to 82% and 90% of the cumulated intensities in the two lacquers, plus 9% and 3% (respectively) originating from the procedural blank. Graphical abstractElucidation of non-intentionally added substances Elucidation of non-intentionally added substances
Article
Polybutylene terephthalate (PBT) is a polyester (PES) gaining more importance on the food contact material (FCM) market. However, little is known about the potential migration of PBT oligomers which are formed during the polymer production. In this work, PBT pellets and a slotted spoon manufactured from this material by injection moulding were analysed on extractable oligomers and their migration potential into hydrophilic foods. Overall 27 oligomers (cycles and linears) could be identified in different extracts by HPLC-DAD/ESI-MS data, but without confirmation by reference substances. The oligomers were quantified by HPLC-DAD using bis(2-hydroxyethyl) terephthalate (BHET) as external standard and the total amount of oligomers isolated by reprecipitation from the pellets and the spoon were 0.69 and 0.71 %, respectively. While cyclic oligomers made up for approx. 90 % of the extractable oligomers, linear oligomers proved to be more relevant for migration into aqueous foodstuffs. Furthermore, it was shown that hydrolysis of oligomers can take place in water at elevated temperatures. Consequently, the qualitative and quantitative composition of PBT oligomers in aqueous foods from FCMs does not only depend on migration but also on hydrolysis. Migration testing of the PBT spoon under repeat use conditions with water at 100 °C for 2 h resulted in 0.29 mg item⁻¹ of linear oligomers and 0.05 mg item⁻¹ of the cyclic PBT dimer in the third migrate.
Article
p>Synthetic and naturally occurring substances present in food and feed, together with their possible breakdown or reaction products, represent a large number of substances, many of which require risk assessment. EFSA’s Scientific Committee was requested to evaluate the threshold of toxicological concern (TTC) approach as a tool for providing scientific advice about possible human health risks from low level exposures, its applicability to EFSA’s work, and to advise on any additional data that might be needed to strengthen the underlying basis of the TTC approach. The Scientific Committee examined the published literature on the TTC approach, undertook its own analyses and commissioned an in silico investigation of the databases underpinning the TTC approach. The Scientific Committee concluded that the TTC approach can be recommended as a useful screening tool either for priority setting or for deciding whether exposure to a substance is so low that the probability of adverse health effects is low and that no further data are necessary. The following human exposure threshold values are sufficiently conservative to be used in EFSA’s work; 0.15 μg/person per day for substances with a structural alert for genotoxicity, 18 μg/person per day for organophosphate and carbamate substances with anti-cholinesterase activity, 90 μg/person per day for Cramer Class III and Cramer Class II substances, and 1800 μg/person per day for Cramer Class I substances, but for application to all groups in the population, these values should be expressed in terms of body weight, i.e. 0.0025, 0.3, 1.5 and 30 μg/kg body weight per day, respectively. Use of the TTC approach for infants under the age of 6 months, with immature metabolic and excretory systems, should be considered on a case-by-case basis. The Committee defined a number of exclusion categories of substances for which the TTC approach would not be used.</p
Article
Background: Over the last years the variety of food and beverage packaging has increased with the development of new plastic materials and (co)polymer modifications. Oligomers which are always present in polymers evoke attention as potential migrants, from a qualitatively and quantitatively viewpoint. Scope and approach: This article deals with oligomers as potential migrants from plastics food contact materials and reviews their occurrence as well as analytical methods for their identification and quantification. Additionally a section about migration summarizes literature providing oligomer levels in food simulants and foods. Special attention was given to polycondensates since these represent a rapidly expanding polymer field due to increased numbers of (co)-monomers authorized by the EU. Key findings and conclusions: Evaluating a polymer regarding the content and migration potential of its oligomers several factors like the separation of oligomers from the material, the choice of suitable separation and detection techniques for identification and quantification and the choice of an appropriate standard have to be considered. Generally, MS technologies coupled to liquid chromatography have been shown to represent the analytical approach of choice. This is, so far as the authors are aware of, the first review exclusively focusing on analytical methods for oligomers as polymer specific substances, which suggests to consider them as a separate polymer related and polymer type specific group besides the so-called non-intentionally added substances (NIAS).
Chapter
Poly(ethylene terephthalate) (PET) is widely used as a packaging material for all kinds of foodstuff. Low diffusivity of the polymer combined with the limited number of additives and their low concentrations lead to very limited mass transfer (migration) of monomers, catalysts, or impurities from the PET polymer into food. This mass transfer (migration) for monomers, oligomers, catalysts, additives and non-intentionally added substances (NIAS) is discussed within this study. Based on the data given in the scientific literature it could be concluded that overall migration tests as well as specific migration tests for monomers and catalysts, like ethylene glycol, diethylene glycol, terephthalic acid, iso-phthalic acid and antimony are superfluous, because their migration limits cannot be exceeded, even if worst case conditions and swelling simulants like 95% ethanol are applied. A more suitable procedure for evaluation of the food law compliance of PET is the determination of migration relevant substances in PET and calculation of their migration by use of migration models. In addition, the analytical screening for low molecular weight migrants (like NIAS) gives an additional safety factor, because such NIAS were not determined using the conventional migration testing procedures.
Article
The types and contents of monomers and oligomers in polyethylene terephthalate (PET) food containers were analyzed using HPLC-ESI-MS after being extracted with 50% acetonitrile or dichloromethane using an accelerated solvent extraction unit. The types of cyclic oligomers were classified into first and second series. The first series represented a type of [TG]n composed of terephthalic acid (TPA; T) and monoethylene glycol (EG; G) at a ratio of 1:1. The second series showed a type of [TG]nG in which a single G unit was substituted by diethylene glycol (DEG; GG). The oligomer level extracted using dichloromethane was measured at 4024–11576 mg kg−1. The first series cyclic oligomers, second series cyclic oligomers and linear oligomers constituted 83.0–90.6%, 7.8–14.7% and 1.3–2.8%, of the total extracted oligomers, respectively. The extracted amounts of TPA, monohydroxyethyl terephthalate and bishydroxyethyl terephthalate using 50% acetonitrile were 3.0–28.2 mg kg−1, 16.8–118.2 mg kg−1 and 3.9–26.7 mg kg−1, respectively. The A2, A3, S2 and S3 groups as modified oligomers were detected as 42.9–221.4 mg kg−1, 17.2–250.3 mg kg−1, 1.1–48.1 mg kg−1 and 1.0–19.8 mg kg−1, respectively. The results of this study demonstrate an advanced analytical approach to determine the residual oligomers and monomers in PET products for food use and imply their potential migration to foodstuffs.
Article
The dependence of the enzymatic degradation of aliphatic–aromatic copolyesters on the polymer structure has been investigated. A number of defined model copolyesters containing terephthalate units as aromatic component were synthesized. The model polymers included random copolyesters, block copolyesters and also strictly alternating copolyesters, which were made from especially synthesized and purified pre-building blocks. The biodegradability was evaluated applying a laboratory degradation test under well-defined conditions with a lipase from Pseudomonas sp.It could clearly be proven that the selectivity of the lipase concerning the aliphatic or aromatic environment near the ester bonds is not the predominant factor controlling the biodegradability of the copolyesters. As already described for aliphatic homo polyesters the biodegradation rate of the copolyesters is mainly controlled by the chain mobility of the polymers, being correlated with the difference between the melting point of the polyester and the degradation temperature. The presence of longer aliphatic domains, e.g., in block copolyesters does not facilitate the hydrolytic attack by the lipase, but longer aromatic sequences, which control the melting point of the crystalline regions, reduce the biodegradation rate. The concept of chain mobility seems to be a quite universal way to describe and predict the biodegradation rate of synthetic polyesters, independent on their composition or micro-structure.
In einer Reihe von Polyestern aus Diolen und aromatischen Dicarbonsäuren wurden die cyclischen Oligomeren isoliert und mit Hilfe der Hochdruckflüssigkeitschromatographie quantitativ bestimmt.Der Gehalt an cyclischen Oligomeren hängt von der chemischen Struktur der Polyester und vom Kondensationsverfahren ab. Hauptkomponente ist das cyclische Dimere, bei Poly(ethylenterephthalat), Poly(1,4-dimethylencyclohexanterephthalat) und Poly(1,4-dimethylenbenzolterephthalat) aus Ringspannungsgründen das cyclische Trimere.Bei technischem Poly(1,4-dimethylencyclohexanterephthalat) gelang eine Auftrennung der stereoisomeren cyclischen Oligomeren, die durch die Verwendung eines trans/cis-1,4-Cyclohexandimethanol-Gemisches entstehen.Die cyclischen Oligomeren der Copolyester mit Diolethern enthalten bei niedrigem Modifizierungsgrad nur einen Dioletherrest.Cyclic oligomers have been separated and determined quantitatively by high pressure liquid chromatography on a number of polyesters of the diol-aromatic dicarbonic acid-type.Percentage of cyclic oligomers is related to the chemical structure of the polyesters as well as to the technology of polycondensations. Main component proved to be the cyclic dimer except in case of poly(ethyleneterephthalate), poly(1,4-dimethylenecyclohexaneterephthalate) and poly(1,4-dimethylenebenzeneterephthalate). Here — due to reasons of ring tension — cyclic trimers are predominant.Separation of stereoisomer cyclic oligomers, resulting from use of a trans/cis-1,4-cyclohexanedimethanol blend, could be achieved.Cyclic oligomers of copolyesters with diolethers, if modified to a low degree, only have one diolether group.
Article
The condition of time and temperature under which PET (polyethylene terephthalate) is used in food contact applications is reviewed. The effect upon overall migration into fat simulants of varying temperature, time, thickness and crystallinity of the PET is discussed, with experimental data. Specific migration of monomers, catalyst residues, colourants and acetaldehyde from PET into food simulants is reported.
Article
The in vitro hydrolysis of poly(1,2-propylene adipate) by digestive fluid liquids was studied to assess the safety of polymeric plasticizers that could migrate into food. A high extent of hydrolysis was obtained with freshly prepared intestinal fluid solutions. High performance size exclusion chromatography analysis indicated that the bulk plasticizer completely disappeared and that low molecular weight oligomers were formed within 4 h. Hydrolysis did not result in a significant conversion to the free monomers, like adipic acid, as was shown by gas-phase chromatography. Measurements by NMR indicated that the cleavage selectively occurred at primary ester linkages. Fractionation of the hydrolysis products on silica gel gave six oligomeric fractions, which were recovered and analyzed. The absolute molecular weight of the plasticizers and the average molecular weight of the hydrolysis products were evaluated using proton NMR. Hydrolysis did not take place (<2%) under simulated gastric and saliva conditions. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 83: 956–966, 2002
Article
The bio-catalysed cleavage of ester bonds in low molecular mass model esters and aliphatic polyesters was studied in detail with the aim to gain improved information about the underlying mechanism and the parameters controlling polyester degradation. Among various hydrolytic enzymes the lipase of Pseudomonas species (PsL) was chosen for the investigations. In the heterogeneous phase system the specific hydrolysis rate of the esters was constant as long as free substrate surface was available. In addition to aliphatic low molecular mass model esters, also cycloaliphatic and aromatic esters were cleaved by PsL, indicating that a steric hindrance of the enzymatic ester cleavage is not the predominant controlling factor in polyester degradation. However, the cleavage rates of the aliphatic model esters are larger by more than an order of magnitude. For aliphatic polyesters the temperature difference between the melting point of the polymer and the temperature where degradation takes place (ΔTmt), turned out to be the primary controlling parameter for polyester degradation with the lipase. Only if ΔTmt<30 °C, a measurable enzymatic degradation rate is found. ΔTmt can be regarded as a measure of the mobility of the polyesters chains in the crystalline domains, necessary for the access of the esters to the active site of the lipase. Though aliphatic homopolyesters are seemingly very similar with regard to their chemical structure and reactivity of the ester bonds, their enzymatic degradation rates still differ significantly even at the same ΔTmt. These differences have obviously to be attributed to small changes in the chemical structure, as, for instance, the C number of the aliphatic diacid.
Article
The degradation of several aliphatic and aromatic polyesters with lipases from Candida cylindracea (CcL) and Pseudomonas species (PsL) was investigated applying nanoparticles of the polymers. Nanoparticles (diameters 50 nm to 250 nm) of a particle concentration up to 6 mg/ml could be prepared by a precipitation technique without adding any stabilizing agents in the aqueous solutions. Using a titration system to monitor ester cleavage, enzymatic degradation experiments could be performed in the time scale of some minutes. A kinetic model is proposed which is based on a surface erosion process dependent on molar ester bond density and enzyme loading. Experimental evidence provided that degradation of the particles occurs uniformly at the surface after a Langmuir type adsorption of the enzyme. Rate constants and the maximal enzyme loadings of enzyme were estimated from the kinetic model for different polyesters and the rate constants correlate well with the length of the diacid component of the polyester. Comparison of degradation rates of polyester films and nanoparticles revealed that nanoparticles of aliphatic polyesters are in the amorphous state. Hence, differences of the rate constants reflect the direct influence of the polymer structure on the enzymatic hydrolysis not overlaid by effects of crystallinity.
Article
The Threshold of Toxicological Concern (TTC) is a level of human intake or exposure that is considered to be of negligible risk, despite the absence of chemical-specific toxicity data. The TTC approach is a form of risk characterisation in which uncertainties arising from the use of data on other compounds are balanced against the low level of exposure. The approach was initially developed by the FDA for packaging migrants, and used a single threshold value of 1.5 microg/day (called the threshold of regulation). Subsequent analyses of chronic toxicity data resulted in the development of TTC values for three structural classes with different potentials for toxicity (1,800, 540 and 90 microg/day). These TTC values have been incorporated into the procedure that is used internationally for the evaluation of flavouring substances. Further developments included additional TTC values for certain structural alerts for genotoxicity (0.15 microg/day), and for the presence of an organophosphate group (18 microg/day). All of these TTC values were incorporated into an extended decision tree for chemicals, such as contaminants, which might be present in human foods. The TTC approach has been shown to have potential applications to risk assessments of cosmetic ingredients, household products and impurities in therapeutic drugs.
Article
The General Solubility Equation (GSE) is a QSPR model based on the melting point and log P of a chemical substance. It is used to predict the aqueous solubility of nonionizable chemical compounds. However, its reliance on experimentally derived descriptors, particularly melting point, limits its applicability to virtual compounds. The studies presented show that the GSE is able to predict, to within 1 log unit, the experimental aqueous solubility (log S) for 81% of the compounds in a data set of 1265 diverse chemical structures (-8.48 < log S < 1.58). However, the predictive ability of the GSE is reduced to 75% when applied to a subset of the data (1160 compounds -6.00 < log S < 0.00), which discounts those compounds occupying the sparsely populated regions of data space. This highlights how sparsely populated extremities of data sets can significantly skew results for linear regression-based models. Replacing the melting point descriptor of the GSE with a descriptor which accounts for topographical polar surface area (TPSA) produces a model of comparable quality to the GSE (the solubility of 81% of compounds in the full data set predicted accurately). As such, we propose an alternative simple model for predicting aqueous solubility which replaces the melting point descriptor of the GSE with TPSA and hence can be applied to virtual compounds. In addition, incorporating TPSA into the GSE in addition to log P and melting point gives a three descriptor model that improves accurate prediction of aqueous solubility over the GSE by 5.1% for the full and 6.6% for the reduced data set, respectively.
Article
Poly(bisphenol-A carbonate) (PC) was degraded in solution at various temperatures $(26-70^ \circ C)$ by different lipases, Candida Rugosa (CR), Hog Pancreas (HP), Lipolase (LL), and Novozyme (NV), in various solvents. The degradation of PC was monitored using gel permeation chromatography (GPC). The molecular weights of oligomers obtained were around \sim 1,400 irrespective of the lipases used. Continuous distribution kinetics was proposed to determine the rate coefficients of the polymers and deactivation of the enzyme. The FTIR analysis of the polymer before and after degradation showed that there is large reduction of carbonate linkages and generation of hydroxyl and acidic groups in the broken chains. The optimal temperatures for HP and other lipases were 50 and $60^ \circ C$, respectively. HP showed higher degradation activity at lower temperatures and the overall degradability of the lipases was in the order of LL > CR > NV > HP. The effect of viscosity and polarity of the solvents on the degradation of the polycarbonate was also investigated. While the degradation rate decreased with viscosity, it increased with polarity for the solvents.
Article
Safety evaluation is caught in a frustrating circle. It is neither possible nor sensible to try to obtain the information needed to assess every imaginable toxic risk associated with every substance, and pursuit of greater safety therefore demands the setting of priorities as well as sensible limits for investigation. To do this with confidence requires possessing the very information that is lacking and that can be won only slowly on a few substances at a time, with significant uncertainty and at considerable cost. This requires priorities, and completes the circle of frustration. Individual texicologists deal with this problem by using ‘experience’, a personal synthesis of accumulated knowledge of structure-activity relationships, metabolic mechanisms, chemical reactivity, human exposure and other relevant information. Such expert judgement is often very effective in distinguishing potential risks worth pursuing from problems on which effort would be wasted but, because it is usually so inexplicit and subjective, it is seldom able to invoke the public confidence most decisions now require.
Article
Temperatures have been measured using a fluoro-optic probe at the food/container or food/packaging interfaces as appropriate, for a range of foods heated in either a microwave or a conventional oven. Reheating ready-prepared foods packaged in plastics pouches, trays or dishes in the microwave oven, according to the manufacturers' instructions, resulted in temperatures in the range 61-121 degrees C. Microwave-active materials (susceptors) in contact with ready-prepared foods frequently reached local spot temperatures above 200 degrees C. For foods cooked in a microwave oven according to published recipes, temperatures from 91 degrees C to 200 degrees C were recorded, whilst similar temperatures (92-194 degrees C) were attained in a conventional oven, but over longer periods of time. These measurements form the basis for examining compliance with specific and overall migration limits for plastics materials. The testing conditions proposed depend on the intended use of the plastic - for microwave oven use for aqueous foods, for all lidding materials, and for reheating of foods, testing would only be required with aqueous simulants for 1 h at 100 degrees C; for unspecified microwave oven use, testing with olive oil would be required for 30 min at 150 degrees C; and for unspecified use in a conventional oven testing with olive oil would be required for 2 h at 175 degrees C. For microwave-active materials, it is proposed that testing is carried out in the microwave oven using a novel semi-solid simulant comprising olive oil and water absorbed onto an inert support of diatomaceous earth. The testing in this instance is carried out with the simulant instead of food in a package and heating in the microwave oven at 600 W for 4 min for every 100 g of simulant employed. There is an option in every case to test for migration using real foods rather than simulants if it can be demonstrated that results using simulants are unrepresentative of those for foods. The proposed testing conditions were validated as being realistic by measurement of the specific migration of various components from different plastics into foods under actual conditions of use and comparing with migration into simulants. Migration of plasticizers from PVC and VC/VDC copolymer films was monitored for both microwave reheating and cooking of foods. Total oligomer concentrations were measured from poly(ethylene terephthalate) (PET) trays, and volatile aromatics from thermoset polyester trays, using both types of container in microwave and conventional ovens.(ABSTRACT TRUNCATED AT 400 WORDS)
Article
Molecular polar surface area (PSA), i.e., surface belonging to polar atoms, is a descriptor that was shown to correlate well with passive molecular transport through membranes and, therefore, allows prediction of transport properties of drugs. The calculation of PSA, however, is rather time-consuming because of the necessity to generate a reasonable 3D molecular geometry and the calculation of the surface itself. A new approach for the calculation of the PSA is presented here, based on the summation of tabulated surface contributions of polar fragments. The method, termed topological PSA (TPSA), provides results which are practically identical with the 3D PSA (the correlation coefficient between 3D PSA and fragment-based TPSA for 34 810 molecules from the World Drug Index is 0.99), while the computation speed is 2-3 orders of magnitude faster. The new methodology may, therefore, be used for fast bioavailability screening of virtual libraries having millions of molecules. This article describes the new methodology and shows the results of validation studies based on sets of published absorption data, including intestinal absorption, Caco-2 monolayer penetration, and blood-brain barrier penetration.
Article
Polymers, which undergo a controlled biological degradation by micro-organisms came to remarkable interest during the last years. Composting for instance could so be established as an alternative waste management system for parts of the plastic waste. Within this group of innovative polymer, polyesters play a predominant role, due to their potentially hydrolyzable ester bonds. While aromatic polyesters such as poly(ethylene terephthalate) exhibit excellent material properties but proved to be almost resistant to microbial attack, many aliphatic polyesters turned out to be biodegradable but lack in properties, which are important for application. To combine good material properties with biodegradability, aliphatic-aromatic copolyesters have been developed as biodegradable polymers for many years. This article reviews the attempts to combine aromatic and aliphatic structures in biodegradable plastics and work, which has been done to evaluate the degradation behaviour and environmental safety of biodegradable polyesters, containing aromatic constituents.
Article
Metal cans for food use can be coated with lacquers based on polyester resins. Recent research has focussed on the identification and quantification of migrants released by coatings that are potentially absorbable (below 1000 Da). The presented method describes a procedure that was optimized to hydrolyse the polyester migrants into their monomers, polyvalent acids and polyols. The polyols were identified by gas chromatography with flame ionization detection GC-FID and the acids by high-performance liquid chromatography (HPLC) coupled with an ultraviolet and an electrospray ionization-mass selective detector (HPLC-ESI-MSD/UVD), respectively. With the knowledge of the polyester monomers, it was possible--at least tentatively--to identify the main components in the migrate as cyclic oligoesters by HPLC-ESI-MSD/UVD. A cyclic oligomer, CYCLO [3IPA (isophthalic acid) 3EG (ethylene glycol)] was synthesized and characterized by infrared, nuclear magnetic resonance and mass spectrometry as well as by elementary analysis for further confirmation. To determine the amount of migrating cyclic oligoesters, the response of the migrating substances was compared using different detectors, UVD, MSD and evaporative light scattering detector (ELSD). The response of the ELSD was dependent on the molecular weight of the analytes that reduced the accuracy of this detection type. The wavelength with the same absorption coefficient for IPA and terephthalic acid (TPA) was obtained at 232 nm. The UV(232nm) response of an oligoester is proportional to the number of its IPA/TPA moieties, which was verified for several TPA/IPA esters. The amount of the migrating oligoesters was determined using an UV(232nm) calibration of a commercially available TPA ester and the number of IPA/TPA moieties molecules gained from the ESI-MSD spectra. According to this method, the amount of migrating oligoesters below 1000 Da in the 95% ethanol migrate varied from 0.1 to 0.6 mg dm(-2) (0.6-3.6 mg kg(-1) food) in the examined coatings. The determined amounts account for about 50% of the total migrate below 1000 Da.
  • EFSA CEF Panel
on plastic materials and articles intended to come into contact with food
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. OJEU. 12:1-89.
Identification of oligomers in polyethyleneterephthalate bottles for mineral water and fruit juice
  • Alm Nasser
  • Lmx Lopes
  • M N Eberlin
  • M Monteiro
Nasser ALM, Lopes LMX, Eberlin MN, Monteiro M. 2005. Identification of oligomers in polyethyleneterephthalate bottles for mineral water and fruit juice. J Chromatogr A. 1097:130-137.