Feasibility study on the use of probabilistic migration modeling in support of exposure assessment from food contact materials

The use of probabilistic approaches in exposure assessments of contaminants migrating from food packages is of increasing interest but the lack of concentration or migration data is often referred as a limitation. Data accounting for the variability and uncertainty that can be expected in migration, for example, due to heterogeneity in the packaging system, variation of the temperature along the distribution chain, and different time of consumption of each individual package, are required for probabilistic analysis. The objective of this work was to characterize quantitatively the uncertainty and variability in estimates of migration. AMonte Carlo simulation was applied to a typical solution of the Fick’s law with given variability in the input parameters. The analysis was performed based on experimental data of a model system (migration of Irgafos 168 from polyethylene into isooctane) and illustrates how important sources of variability and uncertainty can be identified in order to refine analyses. For long migration times and controlled conditions of temperature the affinity of the migrant to the food can be the major factor determining the variability in the migration values (more than 70% of variance). In situations where both the time of consumption and temperature can vary, these factors can be responsible, respectively, for more than 60% and 20% of the variance in the migration estimates. The approach presented can be used with databases from consumption surveys to yield a true probabilistic estimate of exposure.info:eu-repo/semantics/acceptedVersio

Modelling migration from paper into a food simulant

The migration of components from paper into Tenax (R) was studied to determine the influence of molecular size and chemical character of the migrant and the influence of paper characteristics in the migration process The Weibull model was applied because Fick s 2nd law of diffusion gave poor fits in some cases The migration pattern depended on the migrants molecular size and was independent of temperature in the studied range The migration rate decreased with the migrant molecular size The influence of the migrants character (polarity and vapour pressure) on the migration behaviour was also studied nonpolar migrants with high vapour pressure presented low relative migration values and polar migrants presented high values of relative migration Results indicated that the apparent partition coefficient between paper and the simulant Tenax (R) increased with the migrant vapour pressure and with both the paper grammage and the recycled pulp contentinfo:eu-repo/semantics/acceptedVersio

Practical guidelines on the application of migration modelling for the estimation of specific migration

The aim of this practical guidance document is to assist the users of the described diffusion models to predict conservative, upper bound specific migration values from plastic food contact materials for compliance purposes. Explanatory guidance tables and practical examples of migration modelling are provided. This document is an updated version of the report "Estimation of specific migration by generally recognised diffusion models in support of EU Directive 2002/72/EC" (Simoneau, 2010) concerning the current legal basis (Regulation (EU) No 10/2011) and the use of migration models for the estimation of specific migration from plastic multi-layers. This document represents the current validity of the models based on constant periodical evaluations of new experimental migration data performed by the Task Force on Migration Modelling chaired by the Directorate General Joint Research Centre of the European Commission on behalf of Directorate General Health and Consumers. The members of the Task Force are R. Brandsch, C. Dequatre, E.J. Hoekstra, P. Mercea, M.R. Milana, A. Schäfer, C. Simoneau, A. Störmer, X. Trier and O. Vitrac.JRC.I.1-Chemical Assessment and Testin

Training workshop "Safety of food contact materials: Technical Guidelines for Testing Migration under Regulation EU No 10/2011"

This report outlines the results of the Workshop Technical Guidelines on Migration Testing under Regulation EU No 10/2011JRC.I.1-Chemical Assessment and Testin

Impact of Partitioning in Short-Term Food Contact Applications Focused on Polymers in Support of Migration Modelling and Exposure Risk Assessment

Food contact materials (FCMs) can transfer chemicals arising from their manufacture to food before consumption. Regulatory frameworks ensure consumer safety by prescribing methods for the assessment of FCMs that rely on migration testing either into real-life foods or food simulants. Standard migration testing conditions for single-use FCMs are justifiably conservative, employing recognized worst-case contact times and temperatures. For repeated-use FCMs, the third of three consecutive tests using worst-case conditions is taken as a surrogate of the much shorter contact period that often occurs over the service life of these items. Food contact regulations allow for the use of migration modelling for the chemicals in the FCM and for the partitioning that occurs between the FCM and food/simulant during prolonged contact, under which steady-state conditions are favored. This study demonstrates that the steady-state is rarely reached under repeated-use conditions and that partitioning plays a minor role that results in migration essentially being diffusion controlled. Domains of use have been identified within which partitioning does not play a significant role, allowing modelling based upon diffusion parameters to be used. These findings have the potential to advance the modelling of migration from repeated-use articles for the benefit of regulatory guidance and compliance practices

Analysis of mathematical models to describe the migration of additives from packaging plastics to foods

The mathematical modeling of migration of additives from plastics to food simulants was studied using experimental data published in the literature, following two routes: the conventional approach using the solution of Fick’s 2nd law, and a kinetic model based on the Weibull distribution function. The objective of this comparison was to permit using a mathematically simpler model equally able to describe migration data, and that could have a generally wider applicability by describing situations more complex than those that simple diffusional phenomena can describe. The relationship between the parameters of the two models was analyzed by regression of data generated by Fick’s law using the Weibull model. The results show that the time constant parameter is related to the diffusion coefficient and the material thickness.It depends on temperature and on the molecular weight of the migrant in a similar manner to the diffusion coefficient. The activation energy presented values from 72 to 125 kJ/mol. The shape parameter is a function of the contribution of the mass transfer resistance at the interface. It was independent of temperature and of the migrant, assuming a global constant value of 0.67, for the systems and conditions studied. The results indicate that the Weibull model can be used to describe and analyze the migration of additives from plastics to foods with a meaning of the parameters in terms of the underlying physical phenomena.info:eu-repo/semantics/publishedVersio

Identification of a Disulfide Bridge Essential for Transport Function of the Human Proton-coupled Amino Acid Transporter hPAT1*

The proton-coupled amino acid transporter 1 (PAT1, SLC36A1) mediates the uptake of small neutral amino acids at the apical membrane of intestinal epithelial cells after protein digestion. The transporter is currently under intense investigation, because it is a possible vehicle for oral drug delivery. Structural features of the protein such as the number of transmembrane domains, the substrate binding site, or essential amino acids are still unknown. In the present study we use mutagenesis experiments and biochemical approaches to determine the role of the three putative extracellular cysteine residues on transport function and their possible involvement in the formation of a disulfide bridge. As treatment with the reducing reagent dithiothreitol impaired transport function of hPAT1 wild type protein, substitution of putative extracellular cysteine residues Cys-180, Cys-329, and Cys-473 by alanine or serine was performed. Replacement of the two highly conserved cysteine residues Cys-180 and Cys-329 abolished the transport function of hPAT1 in Xenopus laevis oocytes. Studies of wild type and mutant transporters expressed in human retinal pigment epithelial (HRPE) cells suggested that the binding of the substrate was inhibited in these mutants. Substitution of the third putative extracellular nonconserved cysteine residue Cys-473 did not affect transport function. All mutants were expressed at the plasma membrane. Biotinylation of free sulfhydryl groups using maleimide-PEG11-biotin and SDS-PAGE analysis under reducing and nonreducing conditions provided direct evidence for the existence of an essential disulfide bond between Cys-180 and Cys-329. This disulfide bridge is very likely involved in forming or stabilizing the substrate binding site