Regulatory Science Perspective on the Analysis of Microplastics and Nanoplastics in Human Food.

Microplastics are increasingly reported, not only in the environment but also in a wide range of food commodities. While studies on microplastics in food abound, the current state of science is limited in its application to regulatory risk assessment by a continued lack of standardized definitions, reference materials, sample collection and preparation procedures, fit-for purpose analytical methods for real-world and environmentally relevant plastic mixtures, and appropriate quality controls. This is particularly the case for nanoplastics. These methodological challenges hinder robust, quantitative exposure assessments of microplastic and nanoplastic mixtures from food consumption. Furthermore, limited toxicological studies on whether microplastics and nanoplastics adversely impact human health are also impeded by methodology challenges. Food safety regulatory agencies must consider both the exposure and the risk of contaminants of emerging concern to ascertain potential harm. Foundational to this effort is access to and application of analytical methods with the capability to quantify and characterize micro- and nanoscale sized polymers in complex food matrices. However, the early stages of method development and application of early stage methods to study the distribution and potential health effects of microplastics and nanoplastics in food have largely been done without consideration of the stringent requirements of methods to inform regulatory activities. We provide regulatory science perspectives on the state of knowledge regarding the occurrence of microplastics and nanoplastics in food and present our general approach for developing, validating, and implementing analytical methods for regulatory purposes.

Surface defects and particle size determine transport of CdSe quantum dots out of plastics and into the environment.

Polymers incorporating quantum dots (QDs) have attracted interest as components of next-generation consumer products, but there is uncertainty about how these potentially hazardous materials may impact human health and the environment. We investigated how the transport (migration) of QDs out of polymers and into the environment is linked to their size and surface characteristics. Cadmium selenide (CdSe) QDs with diameters ranging from 2.15 to 4.63 nm were incorporated into low-density polyethylene (LDPE). Photoluminescence was used as an indicator of QD surface defect density. Normalized migration of QDs into 3% acetic acid over 15 days ranged from 13.1 ± 0.6-452.5 ± 31.9 ng per cm2 of polymer surface area. Migrated QD mass was negatively correlated to QD diameter and was also higher when QDs had photoluminescence consistent with larger surface defect densities. The results imply that migration is driven by oxidative degradation of QDs originating at surface defect sites and transport of oxidation products along concentration gradients. A semi-empirical framework was developed to model the migration data. The model supports this mechanism and suggests that QD surface reactivity also drives the relationship between QD size and migration, with specific surface area playing a less important role.

Sulfides mediate the migration of nanoparticle mass out of nanocomposite plastics and into aqueous environments.

We show that inorganic sulfides strongly influence transfer (migration) of nanoparticle mass out of polymer nanocomposites (PNCs) and into aqueous environments. We first manufactured two families of PNCs: one incorporating silver nanoparticles (AgNPs) and one incorporating CdSe quantum dots (QDs). Then, we assessed migration out of these PNCs and into aqueous media containing Na2S at concentrations ranging from 0 to 10-4 M. Results show that Na2S strongly suppressed migration of Ag from AgNP-based PNCs: the migration into water spiked with 10-6 M Na2S was 79% less than migration into water without Na2S, and no migration was detected (LOD ≈ 0.01 ng/cm2) in water spiked with Na2S at 10-5 M or 10-4 M. With CdSe QD-based PNCs, Na2S suppressed Cd migration but enhanced Se migration, resulting in only a small net effect on the total QD migration but a large shift of the leachate composition (from favoring Cd by an average of 5.8 to 1 in pure water to favoring Se 9.4 to 1 when Na2S was present at 10-4 M). These results show that common inorganic substances like sulfides may play a strong role in determining the environmental fate of polymer-dispersed nanoparticles and imply that migration tests conducted in purified water may not always accurately reflect migration into real environments.

Challenges and potential solutions for nanosensors intended for use with foods.

Nanotechnology-adapted detection technologies could improve the safety and quality of foods, provide new methods to combat fraud and be useful tools in our arsenal against bioterrorism. Yet despite hundreds of published studies on nanosensors each year targeted to the food and agriculture space, there are few nanosensors on the market in this area and almost no nanotechnology-enabled methods employed by public health agencies for food analysis. This Review shows that the field is currently being held back by technical, regulatory, political, legal, economic, environmental health and safety, and ethical challenges. We explore these challenges in detail and provide suggestions about how they may be surmounted. Strategies that may have particular effectiveness include improving funding opportunities and publication venues for nanosensor validation, social science and patent landscape studies; prioritizing research and development of nanosensors that are specifically designed for rapid analysis in non-laboratory settings; and incorporating platform cost and adaptability into early design decisions.

Food and Beverage Ingredients Induce the Formation of Silver Nanoparticles in Products Stored within Nanotechnology-Enabled Packaging.

Nanotechnology-based packaging may improve food quality and safety, but packages manufactured with polymer nanocomposites (PNCs) could be a source of human dietary exposure to engineered nanomaterials (ENMs). Previous studies showed that PNCs release ENMs to foods predominantly in a dissolved state, but most of this work used food simulants like dilute acetic acid and water, leaving questions about how substances in real foods may influence exposure. Here, we demonstrate that food and beverage ingredients with reducing properties, like sweeteners, may alter exposure by inducing nanoparticle formation in foods contacting silver nanotechnology-enabled packaging. We incorporated 12.8 ± 1.4 nm silver nanoparticles (AgNPs) into polyethylene and stored media containing reducing ingredients in packages manufactured from this material under accelerated room-temperature and refrigerated conditions. Analysis of the leachates revealed that reducing ingredients increased the total silver transferred to foods contacting PNC packaging (by as much as 7-fold) and also induced the (re)formation of AgNPs from this dissolved silver during storage. AgNP formation was also observed when Ag+ was introduced to solutions of natural and artificial sweeteners (glucose, sucrose, aspartame), commercial beverages (soft drinks, juices, milk), and liquid foods (yogurt, starch slurry), and the amount and morphology of reformed AgNPs depended on the ingredient formulation, silver concentration, storage conditions, and light exposure. These results imply that food and beverage ingredients may influence dietary exposure to nanoparticles when PNCs are used in packaging applications, and the practice of using food simulants may in certain cases underpredict the amount of ENMs likely to be found in foods stored in these materials.

Leveraging Extraction Testing to Predict Patient Exposure to Polymeric Medical Device Leachables Using Physics-based Models.

Toxicological risk assessment approaches are increasingly being used in lieu of animal testing to address toxicological concerns associated with release of chemical constituents from polymeric medical device components. These approaches currently rely on in vitro extraction testing in aggressive environments to estimate patient exposure to these constituents, but the clinical relevance of the test results is often ambiguous. Physics-based mass transport models can provide a framework to interpret extraction test results to provide more clinically relevant exposure estimates. However, the models require system-specific material properties, such as diffusion (D) and partition coefficients (K), to be established a priori for the extraction conditions. Using systems comprised high-density polyethylene and 4 different additives, we demonstrate that these properties can be quantified through standard extraction testing in hexane and isopropyl alcohol. The values of D and K derived in this manner were consistent with theoretical predictions for these quantities. Based on these results, we discuss both the challenges and benefits to leveraging extraction data to parameterize physics-based exposure models. Our observations suggest that clinically relevant, yet still conservative, exposure dose estimates provided by applying this approach to a single extraction measurement can be more than 100 times lower than would be measured under typical aggressive extraction conditions. However, to apply the framework on a routine basis, limiting values of D and K must be established for device-relevant systems either through the aggregation and analysis of more extensive extraction test data and/or advancements in theoretical and computational modeling efforts to predict these quantities.

A Quantum Dot Nanobiosensor for Rapid Detection of Botulinum Neurotoxin Serotype E.

Botulinum neurotoxins (BoNTs) are potent toxins produced by Clostridium bacteria that are responsible for the illness botulism and are listed as bioterrorism agents. BoNT serotype E (BoNT/E) is one of four BoNT serotypes that cause human botulism and is the second most frequent cause of foodborne botulism. Rapid detection and discrimination of BoNT serotypes implicated in human disease are critical for ensuring timely treatment of patients and identifying sources of toxins, but there have been few reported detection methods for BoNT/E and even fewer methods usable for BoNT serotyping. We report a nanobiosensor based on Förster resonance energy transfer (FRET) between semiconductor nanocrystals (quantum dots, QDs) and dark quencher-labeled peptide probes to detect biologically active BoNT/E in aqueous media. The peptide probes contain a specific cleavage site for active BoNT/E. QD photoluminescence, which changes intensity due to FRET when the peptide probe is cleaved, was used to indicate toxin presence and quantity. The detection of a BoNT/E light chain (LcE) and holotoxin was observed within 3 h. The limits of detection were 0.02 and 2 ng/mL for LcE and holotoxin, respectively. The nanobiosensor shows good specificity toward the target in tests with nontarget BoNT serotypes. The high sensitivity, simple operation, short detection time, and ability to be used in parallel with probes developed for other BoNT serotypes indicate that the nanobiosensor will be useful for rapid BoNT/E detection and serotype discrimination in food analysis.

Migration of Quaternary Ammonium Cations from Exfoliated Clay/Low-Density Polyethylene Nanocomposites into Food Simulants.

Clay/polymer nanocomposites (CPNs) are polymers incorporating refined clay particles that are frequently functionalized with quaternary ammonium cations (QACs) as dispersion aids. There is interest in commercializing CPNs for food contact applications because they have improved strength and barrier properties, but there are few studies on the potential for QACs in CPNs to transfer to foods under conditions of intended use. In this study, we manufactured low-density poly(ethylene) (LDPE)-based CPNs and assessed whether QACs can migrate into several food simulants under accelerated storage conditions. QACs were found to migrate to a fatty food simulant (ethanol) at levels of ∼1.1 µg mg-1 CPN mass after 10 days at 40 °C, constituting about 4% total migration (proportion of the initial QAC content in the CPN that migrated to the simulant). QAC migration into ethanol was ∼16× higher from LDPE containing approximately the same concentration of QACs but no clay, suggesting that most QACs in the CPN are tightly bound to clay particles and are immobile. Negligible QACs were found to migrate into aqueous, alcoholic, or acidic simulants from CPNs, and the amount of migrated QACs was also found to scale with the temperature and the initial clay concentration. The migration data were compared to a theoretical diffusion model, and it was found that the diffusion constant for QACs in the CPN was several orders of magnitude slower than predicted, which we attributed to the potential for QACs to migrate as dimers or other aggregates rather than as individual ions. Nevertheless, the use of the migration model resulted in a conservative estimate of the mass transfer of QAC from the CPN test specimens.

Influence of Different Acids on the Transport of CdSe Quantum Dots from Polymer Nanocomposites to Food Simulants.

We fabricated polymer nanocomposites (PNCs) from low-density polyethylene and CdSe quantum dots (QDs) and used these materials to explore potential exposure after long-term storage in different acidic media that could be encountered in food contact applications. While the low-level release of QD-associated mass into all the food simulants was observed, exposure to dilute acetic acid resulted in more than double the mass transfer compared to that which occurred during exposure to dilute hydrochloric acid at the same pH. Conversely, exposure to citric acid resulted in a suppression of QD release. Permeation experiments and confocal microscopy were used to reveal mechanistic details underlying these mass-transfer phenomena. From this work, we conclude that the permeation of undissociated acid molecules into the polymer, limited by partitioning of the acids into the hydrophobic polymer, plays a larger role than pH in determining exposure to nanoparticles embedded in plastics. Although caution must be exercised when extrapolating these results to PNCs incorporating other nanofillers, these findings are significant because they undermine current thinking about the influence of pH on nanofiller release phenomena. From a regulatory standpoint, these results also support current guidance that 3% acetic acid is an acceptable acidic food simulant for PNCs fabricated from hydrophobic polymers because the other acids investigated resulted in significantly less exposure.

High Throughput Quantification of Quaternary Ammonium Cations in Food Simulants by Flow-Injection Mass Spectrometry.

Background: A flow-injection MS (FI/MS) method was evaluated for the quantitation of quaternary ammonium cations (QACs) in simple food simulants. Methods: The calibration standard was dimethyldioctadecyl ammonium ion (C18-C18), and the internal standard was benzyldimethylhexadecyl (BDMHD) ammonium ion. Calibration standards based on the C18-C18 ion were prepared in ethanol with a range of 5 to 500 ppb and contained 100 ppb BDMHD. The mobile phase was 90 + 10 (v/v) acetonitrile-5 mM aqueous ammonium acetate and flowed directly into an electrospray source of the mass spectrometer. Detection was accomplished by single ion recording (SIR) in positive mode. Results: Calibration curves were linear with coefficients of determination above 0.995, and the LOQ was 5 ppb. Recoveries of four QACs derived from Arquad 2HT-75, a commercially available surfactant, were measured in common food simulants: ethanol, water, 10% (v/v) ethanol in water, and 3% (v/v) aqueous acetic acid. A solvent exchange procedure was employed for the three aqueous solvents, which included complete evaporation of the sample followed by reconstitution in ethanol prior to injection. The solvent exchange method minimized losses because of QAC adsorption on glass surfaces. Recoveries ranged from 74.4 ± 4.0 to 106.7 ± 6.6% for the two most abundant Arquad 2HT-75 component cations, dimethyldioctadecyl ammonium and dimethyloctadecyl-hexadecyl ammonium. Conclusions: This method is suitable to quantify trace levels of QACs in food simulants as part of exposure evaluations related to their use in emerging food contact materials.

Conservative Exposure Predictions for Rapid Risk Assessment of Phase-Separated Additives in Medical Device Polymers.

A novel approach for rapid risk assessment of targeted leachables in medical device polymers is proposed and validated. Risk evaluation involves understanding the potential of these additives to migrate out of the polymer, and comparing their exposure to a toxicological threshold value. In this study, we propose that a simple diffusive transport model can be used to provide conservative exposure estimates for phase separated color additives in device polymers. This model has been illustrated using a representative phthalocyanine color additive (manganese phthalocyanine, MnPC) and polymer (PEBAX 2533) system. Sorption experiments of MnPC into PEBAX were conducted in order to experimentally determine the diffusion coefficient, D = (1.6 ± 0.5) × 10-11 cm2/s, and matrix solubility limit, C s = 0.089 wt.%, and model predicted exposure values were validated by extraction experiments. Exposure values for the color additive were compared to a toxicological threshold for a sample risk assessment. Results from this study indicate that a diffusion model-based approach to predict exposure has considerable potential for use as a rapid, screening-level tool to assess the risk of color additives and other small molecule additives in medical device polymers.

Improving risk assessment of color additives in medical device polymers.

Many polymeric medical device materials contain color additives which could lead to adverse health effects. The potential health risk of color additives may be assessed by comparing the amount of color additive released over time to levels deemed to be safe based on available toxicity data. We propose a conservative model for exposure that requires only the diffusion coefficient of the additive in the polymer matrix, D, to be specified. The model is applied here using a model polymer (poly(ether-block-amide), PEBAX 2533) and color additive (quinizarin blue) system. Sorption experiments performed in an aqueous dispersion of quinizarin blue (QB) into neat PEBAX yielded a diffusivity D = 4.8 × 10-10 cm2  s-1 , and solubility S = 0.32 wt %. On the basis of these measurements, we validated the model by comparing predictions to the leaching profile of QB from a PEBAX matrix into physiologically representative media. Toxicity data are not available to estimate a safe level of exposure to QB, as a result, we used a Threshold of Toxicological Concern (TTC) value for QB of 90 µg/adult/day. Because only 30% of the QB is released in the first day of leaching for our film thickness and calculated D, we demonstrate that a device may contain significantly more color additive than the TTC value without giving rise to a toxicological concern. The findings suggest that an initial screening-level risk assessment of color additives and other potentially toxic compounds found in device polymers can be improved. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 310-319, 2018.

Detection and Quantification of Biologically Active Botulinum Neurotoxin Serotypes A and B Using a Förster Resonance Energy Transfer-Based Quantum Dot Nanobiosensor.

Botulinum neurotoxin (BoNT) is the most potent toxin known. The ingestion of food contaminated with biologically active BoNT causes foodborne botulism, which can lead to respiratory paralysis, coma, and death after ingestion of as little as 70 µg for a 70 kg human. Because of its lethality and challenges associated with current detection methods, there is an urgent need for highly sensitive rapid screening techniques capable of detecting biologically active BoNT. Here, we describe a Förster resonance energy transfer-based nanobiosensor that uses quantum dots (QDs) and two specific quencher-labeled peptide probes to detect and differentiate two biologically active forms of BoNT, serotypes A and B, which were responsible for 80% of human foodborne botulism cases in the U.S. from 2012 to 2015. Each peptide probe contains an enzymatic cleavage site specific to only one serotype. QDs were selected based on the spectral overlap with the quenchers. In the presence of the target BoNT serotype, the peptide probe is cleaved and the quenching of QD photoluminescence (PL) is reduced, giving a signal that is easily detected by a PL spectrophotometer. This sensor performance was evaluated with light chains of BoNT/A and BoNT/B (LcA and LcB), catalytic domains of the respective serotypes. LcA and LcB were detected in 3 h with limits of detection of 0.2 and 2 ng/mL, respectively. The specificity of the sensor was evaluated, and no cross-reactivity from nontarget serotypes was observed with 2 h of incubation. Because each serotype-specific peptide is conjugated to a QD with a unique emission wavelength, multiple biologically active BoNT serotypes could be detected in one PL spectrum. The sensor was also shown to be responsive to BoNT/A and BoNT/B holotoxins. Good performance of this sensor implies its potential application as a rapid screening method for biologically active BoNT/A and BoNT/B in the laboratory and in the field.

Nanoscale sensors for assuring the safety of food products.

As far as chemical analysis is concerned, foods are among the most difficult matrices to work with because they are complex, heterogeneous substances with a high degree of variety. Assaying foods for trace levels of chemical and microbiological substances is a challenge that often requires the application of time-consuming, expensive analytical instrumentation in dedicated facilities populated by highly trained personnel. Therefore there is a continued demand for new analytical technologies that can detect small concentrations of chemicals or microbes in a more cost- and time-effective manner, preferably in the field, on the production line, and/or non-destructively, with little to no sample pre-treatment, and possibly by individuals with scant scientific training. In the last decade, nanotechnology - a branch of science that takes advantage of the unique chemical and physical properties of matter on the nanoscale - has created new opportunities for both qualitative and quantitative detection of vapors/gasses, small molecules, biopolymers, and even living microbes in a fraction of the time and expense of traditional analytical techniques. This article offers a focused review of recent progress in nanotechnology-enabled biosensing as applied to foods and related matrices, paying particular attention to trends in the field, recent breakthroughs, and current areas of need. Special focus is paid to two primary categories of nanobiosensors - optical and electrochemical - and the discussion includes a comparison of their various strengths and weaknesses as they pertain ensuring the safety of the food supply.

Environmental release of core-shell semiconductor nanocrystals from free-standing polymer nanocomposite films.

Concomitant with the development of polymer nanocomposite (PNC) technologies across numerous industries is an expanding awareness of the uncertainty with which engineered nanoparticles embedded within these materials may be released into the external environment, particularly liquid media. Recently there has been an interest in evaluating potential exposure to nanoscale fillers from PNCs, but existing studies often rely upon uncharacterized, poor quality, or proprietary materials, creating a barrier to making general mechanistic conclusions about release phenomena. In this study we employed semiconductor nanoparticles (quantum dots, QDs) as model nanofillers to quantify potential release into liquid media under specific environmental conditions. QDs of two sizes were incorporated into low-density polyethylene by melt compounding and the mixtures were extruded as free-standing fluorescent films. These films were subjected to tests under conditions intended to accelerate potential release of embedded particles or dissolved residuals into liquid environments. Using inductively-coupled plasma mass spectrometry and laser scanning confocal microscopy, it was found that the acidity of the external medium, exposure time, and small differences in particle size (on the order of a few nm) all play pivotal roles in release kinetics. Particle dissolution was found to play a major if not dominant role in the release process. This paper also presents the first evidence that internally embedded nanoparticles contribute to the mass transfer, an observation made possible via the use of a model system that was deliberately designed to probe the complex relationships between nanoparticle-enabled plastics and the environment.

Large Hyperpolarizabilities at Telecommunication-Relevant Wavelengths in Donor-Acceptor-Donor Nonlinear Optical Chromophores.

Octopolar D2-symmetric chromophores, based on the MPZnM supermolecular motif in which (porphinato)zinc(II) (PZn) and ruthenium(II) polypyridyl (M) structural units are connected via ethyne linkages, were synthesized. These structures take advantage of electron-rich meso-arylporphyrin or electron-poor meso-(perfluoroalkyl)porphyrin macrocycles, unsubstituted terpyridyl and 4'-pyrrolidinyl-2,2';6',2″-terpyridyl ligands, and modulation of metal(II) polypyridyl-to-(porphinato)zinc connectivity, to probe how electronic and geometric factors impact the measured hyperpolarizability. Transient absorption spectra obtained at early time delays (tdelay < 400 fs) demonstrate fast excited-state relaxation, and formation of a highly polarized T1 excited state; the T1 states of these chromophores display expansive, intense T1 → T n absorption manifolds that dominate the 800-1200 nm region of the NIR, long (µs) triplet-state lifetimes, and unusually large NIR excited absorptive extinction coefficients [ε(T1 → T n ) ∼ 105 M-1 cm-1]. Dynamic hyperpolarizability (ßλ) values were determined from hyper-Rayleigh light scattering (HRS) measurements, carried out at multiple incident irradiation wavelengths spanning the 800-1500 nm spectral domain. The measured ßHRS value (4600 ± 1200 × 10-30 esu) for one of these complexes, RuPZnRu, is the largest yet reported for any chromophore at a 1500 nm irradiation wavelength, highlighting that appropriate engineering of strong electronic coupling between multiple charge-transfer oscillators provides a critical design strategy to realize octopolar NLO chromophores exhibiting large ßHRS values at telecom-relevant wavelengths. Generalized Thomas-Kuhn sum (TKS) rules were utilized to compute the effective excited-state-to-excited-state transition dipole moments from experimental linear-absorption spectra; these data were then utilized to compute hyperpolarizabilities as a function of frequency, that include two- and three-state contributions for both ß zzz and ß xzx tensor components to the RuPZnRu hyperpolarizability spectrum. This analysis predicts that the ß zzz and ß xzx tensor contributions to the RuPZnRu hyperpolarizability spectrum maximize near 1550 nm, in agreement with experimental data. The TKS analysis suggests that relative to analogous dipolar chromophores, octopolar supermolecules will be likely characterized by more intricate dependences of the measured hyperpolarizability upon irradiation wavelength due to the interactions among multiple different ß tensor components.

Release of engineered nanomaterials from polymer nanocomposites: the effect of matrix degradation.

Polymer nanocomposites-polymer-based materials that incorporate filler elements possessing at least one dimension in the nanometer range-are increasingly being developed for commercial applications ranging from building infrastructure to food packaging to biomedical devices and implants. Despite a wide range of intended applications, it is also important to understand the potential for exposure to these nanofillers, which could be released during routine use or abuse of these materials so that it can be determined whether they pose a risk to human health or the environment. This article is the second of a pair that review what is known about the release of engineered nanomaterials (ENMs) from polymer nanocomposites. Two roughly separate ENM release paradigms are considered in this series: the release of ENMs via passive diffusion, desorption, and dissolution into external liquid media and the release of ENMs assisted by matrix degradation. The present article is focused primarily on the second paradigm and includes a thorough, critical review of the associated body of peer-reviewed literature on ENM release by matrix degradation mechanisms, including photodegradation, thermal decomposition, mechanical wear, and hydrolysis. These release mechanisms may be especially relevant to nanocomposites that are likely to be subjected to weathering, including construction and infrastructural materials, sporting equipment, and materials that might potentially end up in landfills. This review pays particular attention to studies that shed light on specific release mechanisms and synergistic mechanistic relationships. The review concludes with a short section on knowledge gaps and future research needs.

Release of engineered nanomaterials from polymer nanocomposites: diffusion, dissolution, and desorption.

Polymer nanocomposites-polymer-based materials that incorporate filler elements possessing at least one dimension in the nanometer range-are increasingly being developed for commercial applications ranging from building infrastructure to food packaging to biomedical devices and implants. Despite a wide range of intended applications, it is also important to understand the potential for exposure to these nanofillers, which could be released during routine use or abuse of these materials, so it can be determined whether they pose a risk to human health or the environment. This article is the first in a series of two that review the state of the science regarding the release of engineered nanomaterials (ENMs) from polymer nanocomposites. Two ENM release paradigms are considered in this series: the release of ENMs via passive diffusion, desorption, and dissolution into external liquid media and release of ENMs assisted by matrix degradation. The present article focuses primarily on the first paradigm and includes (1) an overview of basic interactions between polymers and liquid environments and a brief summary of diffusion physics as they apply to polymeric materials; (2) a summary of both experimental and theoretical methods to assess contaminant release (including ENMs) from polymers by diffusion, dissolution, and desorption; and (3) a thorough, critical review of the associated body of peer-reviewed literature on ENM release by these mechanisms. A short outlook section on knowledge gaps and future research needs is also provided.

Measurement Methods to Evaluate Engineered Nanomaterial Release from Food Contact Materials.

This article is one of a series of 4 that report on a task of the NanoRelease Food Additive project of the Intl. Life Science Inst. Center for Risk Science Innovation and Application to identify, evaluate, and develop methods that are needed to confidently detect, characterize, and quantify intentionally produced engineered nanomaterials (ENMs) released from food along the alimentary tract. This particular article focuses on the problem of detecting ENMs that become released into food indirectly from food contact materials. In this review, an in-depth analysis of the release literature is presented and relevant release mechanisms are discussed. The literature review includes discussion of articles related to the release phenomenon in general, as experimental methods to detect ENMs migrating from plastic materials into other (nonfood) complex matrices were determined to be relevant to the focus problem of food safety. From the survey of the literature, several "control points" were identified where characterization data on ENMs and materials may be most valuable. The article concludes with a summary of findings and a discussion of potential knowledge gaps and targets for method development in this area.

Measurement Methods for the Oral Uptake of Engineered Nanomaterials from Human Dietary Sources: Summary and Outlook.

This article is one of a series of 4 that report on a task of the NanoRelease Food Additive (NRFA) project of the International. Life Science Institute Center for Risk Science Innovation and Application. The project aims are to identify, evaluate, and develop methods that are needed to confidently detect, characterize, and quantify intentionally produced engineered nanomaterials (ENMs) released from food along the alimentary tract. This particular article offers an overview of the NRFA project, describing the project scope and goals, as well as the strategy by which the task group sought to achieve these goals. A condensed description of the general challenge of detecting ENMs in foods and a brief review of available and emerging methods for ENM detection is provided here, paying particular attention to the kind of information that might be desired from an analysis and the strengths and weaknesses of the various approaches that might be used to attain this information. The article concludes with an executive summary of the task group's broad findings related to the 3 topic areas, which are covered in more detail in 3 subsequent articles in this series. The end result is a thorough evaluation of the state of ENM measurement science specifically as it applies to oral uptake of ENMs from human dietary sources.