Influence of different acids on the transport of CdSe quantum dots from

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Influence of different acids on the transport of CdSe quantum dots from polymer nanocomposites to food simulants Patrick J Gray, Jessica E. Hornick, Ashutosh Sharma, Rebecca G. Weiner, John L. Koontz, and Timothy V. Duncan Environ. Sci. Technol., Just Accepted Manuscript • DOI: 10.1021/acs.est.8b02585 • Publication Date (Web): 13 Jul 2018 Downloaded from http://pubs.acs.org on July 16, 2018

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Environmental Science & Technology

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Influence of different acids on the transport of CdSe quantum dots from polymer nanocomposites to food simulants

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Patrick J. Gray1, Jessica E. Hornick2, Ashutosh Sharma3, Rebecca G. Weiner1, John L. Koontz1, Timothy V. Duncan1*

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Center for Food Safety and Applied Nutrition, US Food and Drug Administration, Bedford Park IL 2 Biological Imaging Facility, Northwestern University, Evanston IL 3 Department of Food Science and Nutrition, Illinois Institute of Technology, Bedford Park IL *Corresponding author: Physical address: Center for Food Safety and Applied Nutrition, US Food and Drug Administration, 6502 South Archer Road, Bedford Park IL, 60516. Email: [email protected] ABSTRACT

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We fabricated polymer nanocomposites (PNCs) from low density polyethylene and

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CdSe quantum dots (QDs) and used these materials to explore potential exposure after

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long term storage in different acidic media that could be encountered in food contact

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applications. While low level release of QD-associated mass into all the food simulants

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was observed, exposure to dilute acetic acid resulted in more than double the mass

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transfer than occurred during exposure to dilute hydrochloric acid at the same pH.

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Conversely, exposure to citric acid resulted in a suppression of QD release. Permeation

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experiments and confocal microscopy were used to reveal mechanistic details

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underlying these mass transfer phenomena. From this work, we conclude that

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permeation of undissociated acid molecules into the polymer, limited by partitioning of

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the acids into the hydrophobic polymer, plays a larger role than pH in determining

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exposure to nanoparticles embedded in plastics. Although caution must be exercised

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when extrapolating these results to PNCs incorporating other nanofillers, these findings

ACS Paragon Plus Environment


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are significant because they undermine current thinking about the influence of pH on

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nanofiller release phenomena. From a regulatory standpoint, these results also support

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current guidance that 3% acetic acid is an acceptable acidic food simulant for PNCs

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fabricated from hydrophobic polymers, because the other acids investigated resulted in

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significantly less exposure.

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Table of Contents Graphic 36 37


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Introduction

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Polymer nanocomposites (PNCs) – polymeric materials incorporating nanoscale

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fillers – have received attention for their potential use in infrastructure and

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construction,1-2

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automotive and aerospace components.4,

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motivated calls for data on the diverse interactions between these materials and

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environmental systems. In particular, there is a need to determine the likelihood that

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humans or the environment may be exposed to embedded nanoparticles or their

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components, the form and quantity of released mass, and the environmental or other

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extrinsic factors that influence these processes.

packaging,3-6

biomedicine,7-9 13-15

textiles,10-12

and

high-performance

Commercial interest in PNCs has

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For PNCs intended for food packaging applications, additional information is

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needed on the effects of long term exposure of PNCs to liquid media under a wide

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variety of conditions relevant to food processing and/or storage. Previous experimental

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efforts have established that low concentrations of mass deriving from nanoparticles

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embedded in polymers are passively leached to liquid environments under many test

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conditions.16 Although PNCs intended to function as food contact surfaces have

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received significant attention,17-36 the diversity of host materials, nanofiller structure and

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composition, dispersion type (e.g., internally embedded versus surface immobilized

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nanofillers), and experimental conditions makes it challenging to construct broad

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predictive frameworks. Some studies on passive release phenomena have reported

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observing whole nanoparticles in food simulants during experimental timescales.

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However, recent theoretical37 and experimental38-39 efforts indicate that release of whole

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nanofillers originating from polymeric interiors is unlikely to occur over timescales



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relevant to intended product use cycles, owing to slow diffusion rates of nanoparticles

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through comparatively small polymeric void volumes. As a result, in most cases the

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released material is likely comprised of dissolved metal ions originating from the

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surfaces of embedded particles. Incidental release of whole nanoparticles weakly bound

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at the interface between the PNC and the food simulant or along cut edges of PNC test

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samples, or reconstitution of nanoparticles in environmental media from dissolved

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components under favorable redox conditions, may also be indicated.40

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Although long term storage of PNCs in liquid media constitutes a potential route

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of exposure to nanomaterials, even if in a dissolved state, questions remain about the

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factors likely to influence release rates. Most experimental studies have employed only

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a few simple test matrices, which limits understanding of how chemistry of the storage

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medium influences the embedded particle dissolution process. For example, virtually all

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studies, including our own, that investigated nanoparticle release from film-based PNCs

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into aqueous environments have observed significantly more release into acidified

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media.20,

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nanoparticles in low pH environments.42-44 However, in most of the passive release

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studies with PNCs, dilute aqueous acetic acid (HAc) was the only acidic food simulant

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that was tested, despite the fact that other acids are commonly found in foods. A deeper

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exploration of the relationship between pH of the storage medium and release

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characteristics is therefore warranted, particularly when one considers the complex role

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that the host material could play in mediating nanofiller dissolution and mass transport

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dynamics.

25, 29, 32-33, 36, 39, 41

This result has been attributed to the lower stability of


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In a previous study, we fabricated free-standing PNC films composed of

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core@shell semiconductor nanocrystals (quantum dots, QDs) embedded in low density

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polyethylene (LDPE) and used them as models to systematically study structure-

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function relationships that may play a deterministic role in mediating exposure profiles.39

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Although QDs are unlikely to be incorporated into commercial food contact materials,

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they are commercially available in narrow size distributions and possess unique optical

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properties that can be used as sensitive probes of interactions between polymer-

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embedded particles and different storage media. Dilute HAc was selected as the acidic

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test medium in our earlier study because it is among the food simulants recommended

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by the US Food and Drug Administration (FDA) for assessment of molecular migration

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from a new food contact substance under consideration for marketing in the United

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States.45 Recognizing that embedded nanoparticle dissolution dynamics may be more

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complex than often assumed, we sought to evaluate whether exposure of a PNC to HAc

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was representative of how PNCs may behave in other types of acids relevant to food

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systems. We hypothesized that acids may differ in the efficiency with which they

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penetrate into hydrophobic polymer phases, which could result in different exposure

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profiles. To test this hypothesis, we evaluated the environmental release of core-only

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(CdSe) QDs from LDPE-based free-standing PNC films under accelerated storage

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conditions during exposure to dilute hydrochloric (HCl), acetic (HAc), and citric acid

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(H3Cit) solutions at a pH value (2.5) that is characteristic of very acidic foods (e.g.,

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vinegar, citrus juice, or soda). Table 1 lists pKa values and other relevant information

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for these acids, showing that they differ substantially in both their degree of dissociation

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in water at equilibrium and their affinity for hydrophobic phases. After measuring release



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of QD mass into these food simulants, we used laser-scanning confocal microscopy

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(LSCM) and permeation experiments to show that acid permeation into the polymer –

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influenced in large part by the acid dissociation constant and partitioning of

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undissociated forms into the hydrophobic polymer phase – is a stronger determinant of

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potential exposure than the pH of the food medium.

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113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132

Table 1. Reference data for acidic food simulantsa Acid Molar mass pKab [HA]eqc Dissociationd log Ko/we log [g mol-1] [mol L-1] [%] Khxd/we -1 HAc 60.05 4.756 5.70 x 10 0.55 -0.31 -3.27 H3Cit 192.12 3.13 1.35 x 10-2 18.97 -1.72 n/a HClf 36.46 -0.9 to -6.1 99.96 0.25 -1.22 a This table provides reference data at 25 °C because in most cases experimental parameters recorded at the experimental temperature (75 °C) could not be found. Trends in the data are expected to be similar at the two temperatures. bValues for HAc and H3Cit were those listed in the CRC Handbook of Chemistry and Physics, 94th Edition. Only the first dissociation constant of triprotic H3Cit is listed here. The experimental pKa value for HCl is challenging to measure; a range in the table reflects values from the literature from Tagirov et al.46 and Gutknecht et al.47 c Estimated concentration of undissociated acid present in aqueous solution at equilibrium at pH = 2.5, determined from acid’s pKa value at 25 °C. This estimation ignores contributions from ionic strength and, for citric acid, dissociation of the 2nd and 3rd carboxylic acid groups. dDefined as 100x the concentration of dissociated acid molecules at equilibrium divided by the sum of the concentrations of dissociated and un-dissociated molecules at equilibrium. eKo/w and Khxd/w refer to the octanol/water and hexadecane/water partition coefficients, respectively. A larger (less negative) value on the logarithmic scale indicates a higher relative solubility in the hydrophobic phase. Ko/w values were taken from Leo et al.48 and Khxd/w were taken from Walter and Gutknecht.49 A Khxd/w value for citric acid could not be found. fHCl is generally considered a strong acid, meaning it is almost completely dissociated at equilibrium. The table lists a range of pKa values reported in the literature. The [HA]eq value listed for HCl was calculated from pKa = 0.9, but [HA]eq may as low as ~8 x 10-12 mol L-1 if pKa = -6.1 is used.

Materials and methods

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Materials. LDPE (density = 0.925 g mL−1 at 25 °C, melt index = 25 g/10 min,

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product # 428043, batch # MKBX4360V) was purchased from Sigma-Aldrich. This

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grade has a molecular weight of approximately 80 kDa. Core-only CdSe QDs with an

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emission maximum of 541 nm were purchased from Nano-Optical Materials. They were


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surface-modified with oleylamine, dispersed at ~5.7 mg/mL in toluene solution, and

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possessed a Cd/Se mass ratio of 2.2, as determined by inductively coupled plasma-

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atomic emission spectroscopy (ICP-AES) analysis (Supporting Information). For release

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tests, OptimaTM grade glacial HAc and concentrated HCl were used; for acid permeation

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experiments, HPLC grade HAc and ACS Plus grade HCl were used. H3Cit for both

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release tests and permeation experiments was anhydrous grade. All stock acids were

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purchased from Fisher Scientific and diluted to pH 2.5 ± 0.1 with deionized water. All

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water for release tests was deionized to 18.2 MΩ cm and dispensed from a Millipore-

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Sigma MilliQ Direct Q3 water purification system. The pH of deionized water was ~ 5.6

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at ambient temperature due to dissolution of atmospheric carbon dioxide, which

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produces carbonic acid.

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Fabrication of QD/LDPE PNCs. A DSM Xplore micro-compounder with a

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volume capacity of 15 mL was used to mix the QD-toluene dispersion with the polymer

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melt and subsequently extrude the nanocomposite into freestanding films. The

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procedure used to manufacture core-only CdSe QD/LDPE and neat LDPE films using

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this equipment is identical to the method reported previously for CdSe/ZnS core-shell

153

QD/LDPE films.39 The procedure is reproduced in this article’s Supporting Information

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section, which also includes details on the optical, thermal, and compositional analysis

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of the test materials, as well as optical characterization and compositional analysis of

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QDs prior to polymer processing. QD concentration in the QD/LDPE film was

157

determined by ICP-AES (Supporting Information).

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Release tests in food simulants. A protocol reported earlier39 was used to

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assess release of Cd and Se from QD/LDPE PNCs. This information is reproduced in



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the Supporting Information. Because release of QDs from PNCs was anticipated to be

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slow, tests were performed at 75 °C to accelerate the release process and reduce

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experiment timescales. It is noted that these conditions may exaggerate the total mass

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of material likely to be released under more realistic scenarios.

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Laser scanning confocal microscopy. LSCM was used to measure

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photoluminescence (PL) properties of QD/LDPE films before and after release tests.

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LSCM was used instead of benchtop fluorimetry because in the latter, PL was found to

167

be sensitive to QD/LDPE film orientation within the sample chamber and light scattering

168

artifacts. Because LSCM interrogates a thin optical slice within the polymer using a high

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intensity laser, it is less sensitive to these factors.

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To measurement of QD/LDPE PL properties using LSCM, sections of film

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samples (~0.5 cm x 0.5 cm) were mounted on standard microscope slides (Azer

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Scientific, Inc, ThermoFisher) using an immersion oil as a mounting medium (Cargille

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Type HF Immersion Oil, Cargille Laboratories) and a #1.5 glass coverslip (Gold Seal,

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Electron Microscopy Sciences). Samples were imaged on a Leica SP5 laser scanning

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confocal with Hybrid (HyD) detector (Gain: 100%) and a 405 nm diode laser excitation

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(25%), using a Leica HCX PL APO CS 100x 1.44NA objective. For spectral analysis,

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samples were excited with a 405 nm laser line and PL emission was detected across 5

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nm windows with center wavelengths ranging from 410 nm to 700 nm, using the

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Lambda scan function in the Leica LAS AF software, at a central focal plane. At least

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three separate regions for each sample were scanned. Images were analyzed using

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ImageJ (NIH) to measure the mean luminescence intensity at the location of QD or QD

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aggregates at each PL emission wavelength. Imaging was also done at the peak


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emission wavelength (λmax = 541 nm) using 405 nm excitation and emission detection at

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435-445 nm.

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Acid permeation experiments. Permeation of acids through LDPE films was

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measured using a liquid diffusion cell (Permegear, Inc.). The jacketed Side-Bi-Side cell

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consists of two chambers of approximately 55 mL internal volume each that are

188

separated by a polymer film of known thickness (40-50 µm) and contact area (13.2

189

cm2). The heat transfer medium was Duratherm S silicone oil and temperature was

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controlled with a 3 L oil bath circulator (Haake DC30-B3). The receptor chamber of the

191

diffusion cell was filled with deionized water and the donor chamber was filled with one

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of the three acid food simulants used in the release experiments. The deionized water

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chamber was stirred constantly at ~160 RPM using a magnetic stir plate (Corning PC-

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410D). The pH of the liquid in both the receptor and donor chambers was recorded

195

using an electronic pH meter (Mettler Toledo Seven Easy equipped with a Mettler

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Toledo LE422 micro pH electrode) and then the temperature of the diffusion cell was

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increased to 75 °C. At regular time intervals, ~3 mL aliquots were removed from the

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receptor and donor chambers, placed in small scintillation vials, and rapidly cooled to

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room temperature using a water bath. The pH of each aliquot was measured three

200

independent times and average values were recorded; aliquots were returned to the

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respective chamber of the diffusion cell after measurement to maintain constant volume

202

in the cell. The use of aliquots cooled to ambient temperature was required because the

203

pH meter was calibrated using standards that are certified only at 25 °C, and cooling the

204

entire permeation cell to 25 °C for each pH measurement was not practical. Permeation

205

tests for each acid were performed in triplicate using freshly sectioned LDPE films.



206

Results

207

QD/LDPE manufacture and characterization. Incorporation of QDs into LDPE

208

was accomplished via melt-compounding and extrusion of the molten mixture through a

209

heated cast film die to afford free-standing, luminescent QD/LDPE nanocomposite films.

210

In contrast to our earlier study,39 in which core@shell CdSe@ZnS QDs were employed,

211

here we used core-only CdSe QDs because it simplified the acquisition and

212

interpretation of release data. Moreover, the luminescence of CdSe particles is more

213

sensitive to changes in local environment than that of CdSe@ZnS particles, which are

214

coated with a protective ZnS shell. As before, LDPE was used as a host material

215

because it is easy to process, exhibits a relatively low melt temperature, finds common

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use in food contact and other industrial applications, and exhibits fast mass transfer

217

rates. QD/LDPE and control LDPE cast films produced for this study typically had mean

218

thicknesses of 40-50 µm and crystallinity content (measured by differential scanning

219

calorimetry, DSC) of ~40% (Supporting Information, Table S3).

220

Figure 1 displays electronic absorption and PL spectra of CdSe QDs in both

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toluene suspension and after incorporation into LDPE. Also shown are photographs of a

222

QD/LDPE film and dilute toluene suspension of QDs under illumination with a hand-held

223

UV lamp. In toluene, the QDs have a PL maximum of 541 nm and an E1S absorption

224

maximum of 527 nm, the latter value providing an estimate50 of the mean QD diameter

225

of ~2.7 nm. Electron microscopy images of related core-only QD/LDPE extruded

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materials (not shown) suggest that QDs are likely dispersed as a mixture of aggregates

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and individual particles, similar to the dispersion characteristics of core@shell QD

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variants in LDPE. A small (∆λmax ~ 2-3 nm) bathochromic shift and 32% broadening


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(~1150 cm-1 vs ~870 cm-1, measured at full-width-at-half-maximum) of the PL band was

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observed when the core-only QDs were dispersed in LDPE (Figure 1B), which is

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consistent with an inner-filter effect in the solid-state composite,51 QD aggregation,52

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and/or QD surface modification during high temperature film processing.

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Figure 1. Spectral data for the core-only CdSe QD/LDPE polymer nanocomposite film used to assess potential release into acidic environments. (A) Normalized UV-visible region absorption (grey line) and PL (blue line) of oleylamine-capped CdSe QDs dispersed in toluene with a concentration of ~30 µg/mL. The PL λmax was 541 nm. (B) Normalized PL spectra of QDs in toluene (solid blue line) and dispersed in LDPE at 0.068 ± 0.002 wt.% (dotted blue line). Photographs of a dilute toluene solution of QDs and QD/LDPE films (0.041 ± 80%) drop in peak intensity. A blue shift of the CdSe QD PL maximum is consistent

307

with oxidation of the QD surface, which reduces the QD diameter, confines excitons to a

308

smaller volume, and increases the optical bandgap.54-56 Conversely, a redshift of the PL

309

maximum is frequently caused by surface passivation. In the case of QDs dispersed in

310

polymer, prolonged storage at elevated temperature may result in changes to the local

311

polymer or ligand binding structure that outwardly shifts the effective potential boundary

312

experienced by the QD exciton.57 A control experiment in which QD/LDPE film sections

313

were stored at 75 °C in air for 15 days showed rapid (99.96% dissociated (at 25

384

°C, see Table 1), meaning there is very little molecular HCl present in solution at

385

equilibrium ( 60

392

fold) higher release of QD mass into simulated gastric fluid (predominantly HCl, pH =

393

1.12) than neutral pH solution. This contrast with our HCl results is resolved by

394

considering the polarity and swelling capacity of acrylate polymer compared to LDPE.

395

Liu et al. measured a 11% water infiltration during their release experiment, whereas in

396

our case the mass of water absorbed during the immersion test (in deionized water)

397

was measured to be 5 orders of

445

magnitude less membrane permeability than monocarboxylic analog lactic acid, which

446

only forms 5 hydrogen bonds per molecule.67 A similar effect is probably occurring here:

447

the large number of hydrogen bonds that must be broken in order for a neutral H3Cit

448

molecule to partition into the hydrophobic LDPE interior contributes to a large, rate

449

limiting activation energy for LDPE permeation. This hypothesis is supported by the low

450

octanol/water partition coefficient of H3Cit compared to HAc and especially HCl (Table

451

1), the latter of which is not an efficient hydrogen bond former. The computational

452

modelling experiments confirm that when the water/polymer partition coefficient (inverse

453

of polymer/water coefficient) is increased compared to the benchmark value for HAc,

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the amount of acid permeated through the polymer after 15 days at 75 °C is predicted to

455

be lowered significantly (Supporting Information, Figure S9), in agreement with the


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H3Cit permeation experiment (Figure 4). We note that our results are consistent with an

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earlier study that also reported significantly less permeation of citric acid (and other

458

polyproptic food acids) through LDPE packaging materials than HAc or proprionic acid,

459

which is also a monoprotic acid.68 These results suggest that acidic foods comprised

460

primarily of polyprotic acids, or other acids with low partition coefficients, may interact

461

less with polymer-embedded nanoparticles on a per-mole basis than those comprised of

462

monoprotic acids.

463

Conceptual model for QD/LDPE interactions with acids. A general model for

464

how different dilute organic acids may impact mass transfer into foods from polymer-

465

embedded QDs begins with nanoparticle decomposition. Environmental studies with

466

CdSe-based QDs69 and finely ground CdSe powder44 in aqueous dispersion have

467

shown an increase in dissolution rates (and, e.g., Cd2+ release) as pH is lowered, and

468

stability is reduced in aerobic environments. CdSe QD dissolution in aqueous media

469

has been attributed to a two step process.56 First, O2 oxidizes surface Se atoms to form

470

SeO2. Then, Cd atoms left dangling due to vacancies from Se depletion are vulnerable

471

to desorption or, especially in the presence of H+ in low pH media, oxidation to Cd2+.

472

Light exposure increases rates of QD dissolution via photosensitation of reactive

473

oxygen species,70 but surface oxidation has also been observed in the dark.54 To a first

474

approximation, nanoparticle oxidation chemistry is expected to be relatively similar

475

within a hydrophobic polymer phase, with the added complexity of the role the polymer

476

plays as a bottleneck for transport of oxidants to and dissolution products away from the

477

particle surfaces.



478

Nanoparticle dissolution in polymers has not been extensively studied, but work

479

on acid chemistry in nonpolar environments is relevant. Although weak Brønstead acids

480

exhibit minimal dissociation in nonpolar environments, the process is sensitive to trace

481

levels of moisture.71 Additionally, acid-base chemistry in nonpolar media occurs

482

efficiently via direct donation of protons from the neutral acid rather than an intermediate

483

charge-dissociation step.72 As such, we propose that any weak monoprotic acid, like

484

HAc, that exhibits a sufficiently low level of dissociation at equilibrium, may partition into

485

the polymer and facilitate embedded QD surface oxidation, possibly with the assistance

486

of minute amounts of permeated water. Dissolution products containing Cd and Se then

487

migrate back to the external environment, possibly in the form of neutral oxides or metal

488

chelates (e.g., Cd acetate44). Stronger acids are almost completely dissociated and

489

therefore have minimal interactions with embedded QDs; in this case nanofiller

490

oxidation is promoted only by dissolved oxygen and the release profile would be

491

expected to be similar to that observed in deionized water. This leads to the

492

counterintuitive conclusion that food simulants composed of weaker (monoprotic) acids

493

(as determined by pKa value) may be more efficient drivers for nanofiller mass transfer

494

than strong acids, at least at equivalent pH values. At the same pH value, weaker acids

495

also have a higher initial concentration of neutral molecular forms in solution, which

496

increases both the driving force for permeation (concentration gradient effect) and

497

ultimately the number of species available in the polymer film to participate in redox

498

chemistry with nanofiller surfaces.

499

Interestingly, H3Cit contradicts this simple model: it is intermediate in strength

500

between HAc and HCl, but QD/LDPE films released the lowest amount of QD-


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associated (sum of Cd and Se) mass into pH = 2.5 H3Cit solution (significantly lower

502

than even the water control). In consideration of its low permeation into a hydrophobic

503

phase (Figure 4), it is unlikely that enough H3Cit molecules are present in the polymer

504

to interact directly with QD surfaces. Therefore, the suppression of dissolution-mediated

505

release into dilute H3Cit is unlikely to be due to direct beneficial interaction between

506

H3Cit and QDs (e.g., passivation of QD surfaces). Rather, the effect is probably due to

507

some indirect mechanism, such as the scavenging of dissolved oxygen or an inhibition

508

of water absorption into LDPE, which may reduce the activity of permeated oxygen.

509

While our experiments therefore suggest that weaker acids may generally be more

510

efficient promoters of nanofiller release, other factors that influence partitioning of acids

511

into the hydrophobic phase or their ability to indirectly mediate the transport of oxidants

512

into or oxidation products out of the polymer likely complicate this picture.

513

Impacts and limitations. Our results establish that different acidic food

514

simulants exhibit different physicochemical interactions with polymer-dispersed QDs,

515

and these interactions directly impact QD mass release in a simulated long-term food

516

contact application. Although we describe QD/LDPE as a model system, it is important

517

to underscore that other nanofillers and polymer types may exhibit behavior different

518

from that reported here. It is possible that oxidation-assisted release of NP-associated

519

mass from polymers incorporating other types of NPs (e.g., noble metal or metal oxide

520

NPs) will exhibit a dependence on acid permeation dynamics similar to what we have

521

reported here for QD/LDPE. Nevertheless, modification of the nanofiller capping agent,

522

composition, and shape/size may significantly alter the thermodynamic (e.g., redox

523

potentials) or kinetic factors that impact release into foods or other acidic environments.



524

Additional studies, including those that explore release as a function of time to better

525

correlate mass transfer and acid permeation timescales, are ongoing to explore this

526

complex landscape.

527

Despite these limitations, we have shown that the QD model system is a useful

528

means of investigating whether additional factors may need to be taken into

529

consideration during experimental exposure assessments of nanotechnology-enabled

530

food contact materials. In the regulatory paradigm, in which a conservative exposure

531

estimate is required (i.e., one that errs on the side of overestimation), the results of this

532

study support the current guidance that 3% HAc is an acceptable acidic food simulant

533

for PNCs fabricated from hydrophobic polymers, because the other acids tested

534

resulted in significantly less exposure for the system under consideration in this study.

535

Further investigation of the phenomenon described here may yield additional insights

536

that could lead to the development of effective simulants for a variety of foods or for use

537

with other types of PNCs. More broadly, the QD model system highlights the complex

538

and sometimes unexpected exposure dynamics for nanotechnology-enabled materials,

539

and the results may have similar implications for plastics incorporating non-nanoscale

540

fillers as well.

541 542

Disclaimer

543

This article has been reviewed in accordance with the FDA's peer and

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administrative review policies and approved for publication. The statements made in this

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report do not represent the official position of any of the employers or affiliated

546

organizations of the experts. Certain commercial equipment, instruments, or materials


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are identified in this article to foster understanding. Such identification does not imply

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recommendation or endorsement by FDA, nor does it imply that the materials or

549

equipment identified are necessarily the best available for the purpose.

550 551

Acknowledgments

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The authors are grateful to Glenn J. Bastiaans, Ph.D., President of NanoOptical

553

Materials, for his helpful insight related to QD PL and surface chemistry. The authors

554

also thank FDA/CFSAN for financial support of this work. The Biological Imaging Facility

555

at Northwestern University is generously supported by the Chemistry of Life Processes

556

Institute and the Office for Research.

557 558 559

Supporting Information Additional

descriptions

of

experimental

methods,

additional

thermal

and

560

spectroscopic characterization of the QD/LDPE nanocomposites, tabulated release

561

data,

562

experiments.

additional

LSCM

images,

and

computational

modelling

of

permeation

563 564

References

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Influence of different acids on the transport of CdSe quantum dots from

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