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Detection and Characterization of SiO2 and TiO2 Nanostructures in Dietary Supplements Jin-Hee Lim, Patrick N. Sisco, Thilak K. Mudalige, Germarie Sanchez-Pomales, Paul C. Howard, and Sean Walker Linder J. Agric. Food Chem., Just Accepted Manuscript • DOI: 10.1021/acs.jafc.5b00392 • Publication Date (Web): 04 Mar 2015 Downloaded from http://pubs.acs.org on March 10, 2015

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Journal of Agricultural and Food Chemistry

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Detection and Characterization of SiO2 and TiO2

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Nanostructures in Dietary Supplements

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Jin-Hee Lim1*, Patrick Sisco1, Thilak K. Mudalige1, Germarie Sánchez-Pomales1, Paul C. Howard2, and

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Sean W. Linder1*

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NCTR Road, Jefferson, Arkansas 72079, United States

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Administration, 3900 NCTR Road, Jefferson, Arkansas 72079, United States

Office of Regulatory Affairs, Arkansas Regional Laboratory, US Food and Drug Administration, 3900

National Center for Toxicological Research, Office of Scientific Coordination, US Food and Drug

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*Corresponding author

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Email Address: [email protected]

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Phone: +1-870-543-4660

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Fax: +1-870-543-4041

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Email Address: [email protected]

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Phone: +1-870-543-4667

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Fax: +1-870-543-4041

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1

ACS Paragon Plus Environment


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Abstract

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Nanomaterials are beginning to enter our daily lives through various consumer products as the result of

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technology commercialization. The development of methodologies to detect the presence of

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nanomaterials in consumer products is an essential element in understanding our exposure. In this study,

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we have developed methods for the separation and characterization of silicon dioxide (SiO2) and titanium

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dioxide (TiO2) nanostructures in dietary supplements marketed in products specifically targeted for

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women. A total of twelve commercial products claiming the inclusion of SiO2 and TiO2, but not making

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any claims regarding the particle size, were randomly selected for purchase through various retailers. In

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order to isolate nanostructures from these products, a simple methodology which combines acid digestion

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and centrifugation was utilized. Once isolated, the chemical composition, size, morphology, and crystal

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structure were characterized using mass spectroscopy, light scattering, electron microscopy, and x-ray

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diffraction techniques. SiO2 and TiO2 nanostructures were detected in eleven of twelve products using

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these methods. Many of the isolated nanoscale materials showed a high degree of aggregation; however,

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identified individual structures had at least one dimension below 100 nm. These robust methods can be

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used for routine monitoring of commercial products for nanoscale oxides of silica and titanium.

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Keywords: Nanotechnology, Nanomaterials, Silicon dioxide, Titanium dioxide, Dietary supplements

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Introduction

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Nanotechnology is an emerging field of research that has attracted tremendous amounts of

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interest from both the academic and industrial communities, and development of nanoparticles with new

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properties has resulted in the inclusion of nanoparticles into a wide variety of consumer products.1-4 This

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research interest stems from the unique physicochemical properties associated with nanomaterials. The

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physical and chemical properties of materials at the nano-scale (i.e. 1-100 nm) are tunable as a function of

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nanoparticle size, shape, structure, and coating materials. As a result, the nano-platform can be

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“customized” and is ideal for a variety of applications including therapeutic delivery, coloration, sensing,

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and imaging.5,6 Experimental data has indicated that nanoscale materials can penetrate cells, tissues, and

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organs that their bulk counterparts cannot, and this could lead to “nanoscale specific” adverse health

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effects.7-12 When the size of engineered particles is reduced to the nanometer scale, these materials can

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exhibit different physicochemical properties as compared to their bulk materials. This decrease in particle

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size (e.g. from micron-scale to nanoscale) results in a substantial increase in the total surface area per unit

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mass of material (i.e. m2/g), which can lead to increase a chemical reactivity per unit mass, or could alter

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absorption/excretion rates in environmental and biological systems.13 In recent years, numerous

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publications have reported the potential impact of nanomaterials on the environment and public health.14-

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One emerging market for applications of nanotechnology is dietary supplements, for which

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manufacture and consumption has increased dramatically over the past several decades, resulting in

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approximately one-half of all U.S. adults reporting the use of one or more supplements.18-20 Additional

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demographic studies have reported that the use of dietary supplements is more prevalent within the

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female population.20-22 Many of these supplements are marketed specifically for women, with a wide

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variety of market claims such as improved sexual function, increased or rapid weight loss, and decreased

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symptoms associated with menopause. Supplements containing metal/metal oxide nanomaterials (e.g. Fe, 3



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Cu, Zn, Ag, Pt, Au, Si, and Ti) are prevalent in the commercial marketplace and are increasingly coming

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under scrutiny due to lack of clear and consistent conclusions regarding their toxicity.7,23-27 Micron-sized

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titanium dioxide (TiO2) and silica dioxide (SiO2) are commonly utilized in dietary supplements and

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many food commodities28, and nanoscale sizes of these metal oxides have also been detected.29-31 These

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materials are typically used as a coloring agents due to their unique bright white color, are used as anti-

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caking components of powders, and have found other uses such as flavor enhancer.

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In order to address knowledge gaps and perform science based risk assessments, analytical

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methodologies must be developed to isolate, identify, quantitate, and thoroughly characterize nanoscale

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materials in complex matrices, including food products such as dietary supplements. General concern

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exists about the use of nanomaterials in these products, as substantial scientifically-based safety and

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efficacy data has not been published, and established methods for the detection and characterization of

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nanomaterials within these products have not been well documented in the literature.

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To date, several detection and separation techniques have been reported by researchers to address

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these needs, specifically for SiO2 or TiO2 nanomaterials in food products.2,9,31-35 Lozano et al34

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documented an ion beam technique, particle-induced x-ray emission (PIXE), for the quantification of

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SiO2 nanoparticles dispersed in water, coffee, and milk. This technique offers fast measurements, minimal

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sample preparation, and parts per million (ppm) levels of sensitivity. Dekkers et al35 described the

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presence of nanoscale SiO2 (known as food additive, E551) in several food products (e.g., sugar, noodle,

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soup, seasoning mix) and discussed the potential risks of the intake of nanoscale SiO2 through the food

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chain. Chen et al.2 applied a centrifugation method to separate TiO2 nanoparticles in sugar coated chewing

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gum and described several characterization techniques for TiO2 nanostructures. Although centrifugation is

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a relatively simple and cost-effective method to isolate nanomaterials without altering particle size or

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shape, the potential for many other interfering compounds and/or particles remaining with the target

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nanostructures is of concern. Other methods with high efficiency are still needed to separate nanometer

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particles, especially for nanoscale SiO2 and TiO2 in foods, including dietary supplements.

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In this study we describe a simple and unique method to separate and characterize SiO2 and TiO2

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nanomaterials in dietary supplements marketed specifically for women. A total of twelve dietary

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supplements claiming the inclusion of SiO2 and TiO2, but not providing any information related to

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particle size in their products, were purchased through various retailers. SiO2 and TiO2 nanostructures

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were selectively separated from the products using a simple acid digestion and centrifugation step, in

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which other metallic particles were dissolved during the process. The resulting nanostructures were

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characterized using multi-techniques including dynamic light scattering (DLS), field emission scanning

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electron microscopy (FESEM), transmission electron microscopy (TEM), energy dispersive spectroscopy

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(EDS), and x-ray diffraction (XRD). Nanometer sized SiO2 and TiO2 particles were detected in eleven

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products and many of those particles were aggregated. The methods that were developed can be utilized

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to detect and characterize the physicochemical properties of these nanoparticles within other consumer

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products.

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Experimental Section

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Materials and Reagents

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SiO2 (amorphous, 20-60 nm in diameter) and TiO2 (rutile, 10-30 nm) nanoparticles were purchased from

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Skyspring Nanomaterials, Inc. (Houston, TX, USA) to use as reference materials. TiO2 nanopowder

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(anatase, diameter below 25 nm) was purchased from Sigma Aldrich (St. Louis, MO, USA). Polystyrene

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(PS) standard nanoparticles, 50 nm and 500 nm in diameter, were purchased from Thermo Fisher

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Scientific Inc. (Waltham, MA, USA). Nitric acid (HNO3, Optima 67-70%), hydrogen peroxide (H2O2,

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30%), and ethanol (C2H6O) were purchased from Fisher Scientific (Houston, TX, USA). Type I ultra-pure 5



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water (18 MΩ·cm) was available through a Thermo Scientific Barnstead Nanopure System (Waltham,

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MA, USA).

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Detection and Characterization of SiO2 and TiO2 particles

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Isolation of SiO2 and TiO2 particles: To separate SiO2 and TiO2 particles from complex matrices, a

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digestion solution consisting of 10 mL of hydrogen peroxide and 0.5 mL of nitric acid was prepared in a

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15 mL conical tube. Approximately 100 mg of each dietary supplement and 3 mL of the digestion

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solution were mixed and heated in a sand bath at 120 °C. When the sample volume was reduced to 2 mL,

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the solution was allowed to cool to room temperature. The sample was then transferred into a 2 mL

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centrifuge tube and ultra-sonicated for 1 minute (Branson 2510, Danbury, CT, USA). The white particles

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were centrifuged at approximately 10,000 g for 20 minutes (Eppendorf Centrifuge 5430R, Hauppauge,

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NY, USA). The supernatant was carefully removed and the precipitate was resuspended in 2 mL of

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ethanol. The extraction processes repeated twice with the isolated particles being redispersed in ethanol or

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ultra-pure water.

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Dynamic Light Scattering (DLS): For particle size and size distribution analysis, DLS measurements

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were carried out using a ZetaPALS from Brookhaven Instruments Corp. (Holtsville, NY, USA), with

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particle sizing software version 5.23. All particles were diluted with ultra-pure water and ultra-sonicated

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for 3 minutes. The instrument was operated at a laser wavelength of 658 nm, and a temperature of 23°C.

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The data collection period was set at 2 minutes and replicated 5 times (total elapsed time=10 minutes).

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Field Emission Scanning Electron Microscopy (FESEM):

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nanostructures were characterized by a Zeiss-Merlin FESEM (Thornwood, NY, USA) under high vacuum

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conditions. Before characterization, the particles were dispersed in ethanol, ultra-sonicated for 1 minute

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(Branson 2510), and directly placed on a standard Zeiss sample holder. The dispersion was allowed to

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evaporate to dryness and a very thin layer (approximately 4 nm) of Au/Pd was sputtered onto the sample

The shape and morphology of the

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using a Denton Vacuum Desk V (Moorestown, NJ, USA). The presence of Si and Ti in the SiO2 and

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TiO2 particles, respectively, was confirmed using an EDAX Apollo XL (EDAX Inc., Mahwah, NJ)

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energy dispersive x-ray spectroscope (EDS) while the sample was irradiated in the FESEM.

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Transmission Electron Microscopy (TEM): TEM samples were prepared by adding 5-10 µL of the

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specimen dispersed in ethanol on 300-mesh carbon coated copper grids purchased from Electron

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Microscopy Sciences (Hatfield, PA, USA) and the samples allowed to dry at room temperature. TEM

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images were acquired using a JEOL 2100 TEM (Peabody, MA, USA) operated at an acceleration voltage

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of 80 kV. Particle shape, size, and size distribution were characterized using multiple images of each

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sample with the reported statistics based on a minimum of 500 particles. The elemental composition of

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the nanostructures was determined by an EDS detector (EDAX Genesis 2000).

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X-Ray Diffraction (XRD): The crystalline structure of the particles, separated from dietary supplements,

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was determined using an Bruker AXS (Madison, WI, USA) XRD D2 Phaser operated at 30 kV and 10

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mA at 24 °C.

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Richmond, CA, USA) were dried overnight at room temperature. XRD patterns were obtained from 20°

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to 80° (2 Theta) using a Lynxeye detector and CuKα (λ=1.541 Å) radiation.

Samples placed onto the zero diffraction silicon sample holder (MTI Corporation;

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Results and Discussion

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Twelve dietary supplements (arbitrarily assigned DS-1 through DS-12) were randomly selected and

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procured from national retailers. A list of the products can be found in Table 1 including the

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corresponding formulation type, market claim, and labeling information on the inclusion of SiO2 and/or

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TiO2. None of the supplements included in this report contained labeling which specifically indicates the

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presence or absence of nanosized materials as dietary ingredients, preservatives, or colorants.

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The products selected for analysis contain a variety of active ingredients and excipients (e.g.,

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vitamins, botanicals or herbs, amino acids, dietary substances) which are problematic for the isolation of

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the SiO2 and TiO2 nanostructures. To overcome this obstacle, a combination of acid digestion and

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centrifugation was adopted from Chen et al.2 and used to isolate SiO2 and TiO2 simultaneously. A solution

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of nitric acid and hydrogen peroxide was used to dissolve or decompose the various components of the

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products at high temperature, leaving only SiO2 and TiO2. It has been well documented that SiO2 and

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TiO2 are not dissolved without a presence of HF.36 The remaining particles were rinsed three times with

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ethanol (collection by centrifugation) and suspended in ethanol or ultra-pure water. This simple and

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facile method was able to isolate the metal oxide particles, while not altering the particle size and

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morphology of the separated materials (see Supporting Information Figures SI1and SI2).37 The average

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size, morphology, size distribution, and crystal structure of the isolated particles were further

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characterized using multiple techniques as described below.

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DLS is a technique that is commonly used to measure particle size or particle size distributions

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due to its rapid and simple operation. The particle size can be analyzed and reported based on the number

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or intensity average with multimodal size distribution. A summary of the particle size analysis is shown in

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Table 2. The size of the nanoparticles isolated from the dietary supplements was very polydisperse. This

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is indicated by the differences in the modes of analysis of the DLS data (number versus intensity) and a

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high polydispersity index (P) as shown in Table 2. The smallest particle sizes of three samples including

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DS-3, DS-11, and DS-12 were below 100 nm. As shown in Figure 1, the actual size of the nanoparticles

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was closer to the number based particle size in DLS. In this case, the hydrodynamic particle size

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calculated by intensity based mode is highly dependent on the larger particles because the intensity (I) of

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light scattered is proportional to d6 and 1/λ4 from the Rayleigh approximation, where d is a particle

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diameter and λ is a laser wavelength.38,39 For instance, as shown in Supporting Information Figure SI3,

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the particles have a narrow size distribution showed very close numbers in both number and intensity

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based modes. However, when the particles with 50 nm and 500 nm in diameter were mixed, large 8


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different mean diameters were observed in the two modes and the P value was also larger than 0.3. This

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occurred because the intensity of the 500 nm particles would be 106 times higher than that of the 50 nm

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particles.39 Larger particles exhibit a greater instrumental response compared to smaller particles and the

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signal corresponding to the smaller particles can be masked. It is important to note that when the value of

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polydispersity index is higher than 0.3, the size information obtained by DLS calculations is not always

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accurate.39,40 In addition, the shape of the particles can also play a role in the experimental determination

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of the hydrodynamic size, as the principles of DLS are based on the Stokes-Einstein relationship which

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has two fundamental assumptions: (1) that the particle shape is spherical, and (2) the particles are in

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Brownian motion.38 As shown in Figures 2-4, the SiO2 and TiO2 particles were not spherical, with many

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single particles being barrel-shaped, and many primary particles aggregated into small clusters.

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In order to characterize the morphology and size of separated particles from each product,

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microscopic imaging techniques were adopted. Nanometer scale particles were found in a total of 11

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products, with the exception of DS-7. Although DLS of DS-7 indicated that nanometer scale materials

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were present, advanced imaging via FESEM and TEM could not locate these particles in this size domain.

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FESEM images in Figure 2 showed both spherically shaped and irregularly shaped nanoparticles with

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various particle sizes. By using the X-ray emission spectra from FESEM-EDS, it was determined that the

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isolated particles were consistent with the presence of Si and Ti. The samples containing TiO2: DS-1, DS-

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2, DS-4, DS-5, DS-8, DS-10, and DS-12, showed 50 nm to 200 nm sized individual particles; however,

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several those particles were found within aggregates. Unlike TiO2 particles, the size of individual SiO2

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particles in DS-2, DS-3, DS-4, DS-6, DS-9, DS-11, and DS-12 were smaller than 100 nm, but they were

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likewise found in a state of aggregation. Clusters of SiO2 nanoparticles showed size ranges of several

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nanometers to micrometers. FESEM images suggest that individual SiO2 nanoparticles are much smaller

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than TiO2 nanoparticles.

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products containing SiO2 as compared to other products (Table 2). Figure 3 shows that both SiO2 and

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TiO2 nanoparticles could be found within the same samples, as was the case in DS-2, DS-4, and DS-12. 9

The degree of aggregation supports the large polydispersity observed in



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TEM images (Figure 4) were consistent with the morphology and size information obtained using

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FESEM. The TiO2 particles separated from products DS-1, DS-2, DS-4, DS-5, DS-8, DS-10, and DS-12,

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were found to have at least one dimension below 100 nm in size and a round shape. An analysis of the

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size showed that 94% of the TiO2 particles showed size ranges between 50-200 nm, and 99% of SiO2

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nanoparticles found in DS-2, DS-3, DS-4, DS-6, DS-9, DS-11, and DS-12 were less than 100 nm in

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diameter and present in large aggregates. As it can be seen in Figures 2 and 4, no nanosized structures

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were found in DS-7.

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In Figure 5, EDS analysis showed the presence of elements (i.e. Si, Ti, and O peaks indicating

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SiO2 or TiO2) in the specific area corresponding to TEM images in Figure 4. The C, Cr, and Cu peaks

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were from the sample grid and instrument. Taken together, the FESEM, TEM and EDS data demonstrated

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that the particles isolated from 11 products consist of nanosized SiO2 and/or TiO2.

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In order to assess the crystal structure of the isolated particles, XRD was used in conjunction with

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the reference data file, Joint Committee on Powder Diffraction Standards (JCPDS) card. XRD data

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presented in Figure 6 reveals that SiO2 nanoparticles exhibit a 2θ broad peak from 20° to 25°

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corresponding to amorphous SiO2 (broad peaks near 55° to 70° are from the sample holder). TiO2

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particles show diffraction peaks at 2θ = 25.3°, 36.9°, 37.8°, 38.5°, and 48.1°, which can be indexed to the

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(101), (103), (004), (112), and (200) planes. The diffraction peak positions are consistent with the

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standard diffraction pattern of anatase TiO2 (JCPDS card no. 21-1272).41 In the case of DS-2 and DS-4,

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both SiO2 and TiO2 peaks were detected even though the labeling on product DS-2 discloses only SiO2

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and the labeling on product DS-4 discloses only TiO2. These results suggest that the isolated particles

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were a mixture of amorphous SiO2 and anatase TiO2 particles. Furthermore, DS-12 showed both

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amorphous SiO2 and anatase TiO2 peaks as claimed.

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A comparison between experimentally determined data and product labeling showed that

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unexpected TiO2 and SiO2 nanoparticles were detected in DS-2 and DS-4, respectively. DS-10 claims the 10


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inclusion of both SiO2 and TiO2, but only anatase TiO2 was detected. All TiO2 nanoparticles detected and

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characterized in this study were found in the anatase phase, which is reported to be more toxic than the

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rutile phase.42,43 The concentration of Si and Ti contents in each product were experimentally determined

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by inductively coupled plasma-mass spectrometry (ICP-MS) and can be seen in Supporting Information

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Table SI1.

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Herein we developed a simple and low temperature acid digestion method to isolate SiO2 and

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TiO2 nanomaterials in commercially available dietary supplements. The isolated SiO2 and TiO2 particles

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were characterized using several complimentary techniques. The analytical data demonstrated that 11 of

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the 12 dietary supplements contained nanometer scale SiO2 and/or TiO2 particles. Interestingly, the

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properties of TiO2 nanomaterials detected in this study are very close to those identified in several

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different commercial products, for example, foods2, cosmetics44, textiles45, or personal care products46

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recently reported in the literature. It is important to note that all of those products did not indicate the

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presence of nanomaterials on their labels. A recent survey released by ‘As you Sow’ concluded that most

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manufactures are uncertain whether nanomaterials are used within their products.47 Although this is a

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small number of studies to represent a global market, it is possible that a large amount of SiO2 and TiO2

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nanomaterials are included in various commercial products without proper labeling.

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We expect that the developed methodologies can be applied to properly isolate and characterize

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the physicochemical properties of SiO2 and TiO2 nanoparticles within consumer products, and can assist

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in the critical assessment of public health risk and science-based regulation of products using

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nanotechnology based ingredients.

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Abbreviations Used

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PIXE, particle-induced x-ray emission; PPM, parts per million; PS, polystyrene; DLS, dynamic light

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scattering; P, polydispersity index; FESEM, field emission scanning electron microscopy; TEM, transmit

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electron microscopy; EDS, energy dispersive x-ray spectroscopy; XRD, X-ray diffraction; JCPDS, Joint

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Committee on Powder Diffraction Standards; ICP-MS, inductively coupled plasma-mass spectrometry;

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FDA, U.S. Food and Drug Administration.

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Acknowledgments

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This work was conducted using the Nanotechnology Core Facility (NanoCore) located on the U.S. Food

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and Drug Administration’s Jefferson Laboratories campus (Jefferson, Arkansas), which houses the FDA

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National Center for Toxicological Research and the FDA Office of Regulatory Affairs Arkansas Regional

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Laboratory. This work was graciously supported by the FDA Office of Women’s Health. We gratefully

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thank Yvonne Jones for the assistance in performing TEM. This project was supported in part by an

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appointment to the Research Participation Program at the Office of Regulatory Affairs/Arkansas Regional

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Laboratory, U.S. Food and Drug Administration, administered by the Oak Ridge Institute for Science and

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Education through an interagency agreement between the U.S. Department of Energy and FDA. The

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views expressed in this manuscript are those of the authors and should not be interpreted as the official

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opinion or policy of the U.S. Food and Drug Administration, Department of Health and Human Services,

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or any other agency or component of the U.S. government. The mention of trades names, commercial

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products, or organizations is for clarification of the methods used and should not be interpreted as an

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endorsement of a product or manufacturer.

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Associated Content

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Supporting Information

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Supporting Information Available: Additional figures dipicting TEM images of commercial SiO2 and

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TiO2 nanoparticles, DLS data of polystyrene (PS) standard nanoparticles, and experimentally determined

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Si and Ti contents per capsule/tablet by ICP-MS. This material is available free of charge via the Internet

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at http://pubs.acs.org.

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References

280

1. Bradley E.; Castle, L.; Chaudhry, Q. Applications of nanomaterials in food packaging with a

281

consideration of opportunities for developing countries. Trends Food Sci. Technol. 2011, 22, 604-

282

610.

283

2. Chen, X.-X.; Cheng, B.; Yang, Y.-X.; Cao, A.; Liu, J.-H.; Du, L.-J.; Liu, Y.; Zhao, Y.; Wang, H.

284

Characterization and preliminary toxicity assay of nano-titanium dioxide additive in sugar-coated

285

chewing gum. Small 2012, 9, 1765-1774.

286 287

3. Napierska, D.; Thomassen, L. C.J.; Lison, D.; Martens, J. A.; Hoet, P. H. The nanosilica hazard: another variable entity. Part. Fibre Toxicol. 2010, 7:39, 1-32.

288

4. Yang, Y.; Doudrick, K.; Bi, X.; Hristovski, K.; Herckes, P.; Westerhoff, P.; Kaegi, R.

289

Characterization of Food-Grade Titanium Dioxide: The Presence of Nanosized Particles. Environ.

290

Sci. Technol. 2014, 48, 6391-6400.

291

5. Lim, J.-H.; Rotaru, A.; Min, S.-G.; Malkinski, L.; Wiley, J. B. Synthesis of mild-hard AAO

292

templates for studying magnetic interactions between metal nanowires, J. Mater. Chem. 2010, 20,

293

9246-9252.

13



294

6.

Page 14 of 29

Jung, J.-S.; Lim, J.-H.; Choi, K.-H.; Oh, S.-L.; Kim, Y.-R.; Lee, S.-H.; Smith, D. A.; Stokes, K.

295

L.; Malkinski, L.; O'Connor, C. J. CoFe2O4 nanostructures with high coercivity, J. Appl. Phys.

296

2005, 97, 10F306-1-10F306-3.

297

7. Nel, A.; Xia, T.; Mädler, L.; Li, N. Toxic potential of materials at the nanolevel. Science 2006, 311, 622-627.

298

299

8. Cushena, M.; Kerryb, J.; Morrisc, M.; Cruz-Romerob, M,; Cummins E. Nanotechnologies in the

300

food industry-Recent developments, risks and regulation. Trends Food Sci. Technol. 2012, 24,

301

30-46.

302

9.

Blasco, C.; Picό Y. Determining nanomaterials in food. Trends Anal. Chem. 2011, 30, 84-98.

303

10. Sadrieh, N.; Wokovich, A. M.; Gopee, N. V.; Zheng, J.; Haines, D.; Parmiter, D.; Siitonen, P. H.;

304

Cozart, C. R.; Patri, A. K.; McNeil, S. E.; Howard, P. C.; Doub, W. H.; Buhse, L. F. Lack of

305

significant dermal penetration of titanium dioxide from sunscreen formulations containing nano-

306

and submicron-size TiO2 particles. Toxicol. Sci. 2010, 115, 156-166.

307

11. Karlsson, H. L.; Gustafsson, J.; Cronholm, P.; Möller, L. Size-dependent toxicity of metal oxide

308

particles-A comparison between nano- and micrometer size. Toxicology Lett. 2009, 188, 112-118.

309

12. Tyner, K. M.; Wokovich, A. M.; Doub, W. H.; Buches, L. F.; Sung, L.P.; Watson S. S.; Sadrieh,

310

N. Comparing methods for detecting and characterizing metal oxide nanoparticles in unmodified

311

commercial sunscreens. Nanomedicine 2009, 4, 145-159.

312

13. Auffan, M.; Rose, J.; Bottero, J.-Y.; Lowry, G. V.; Jolivet, J.-P.; Wiesner, M. R. Towards a

313

definition of inorganic nanoparticles from an environmental, health and safety perspective.

314

Nature Nanotech. 2009, 4, 634-641.

14


Page 15 of 29


315

14. Mastronardi, M. L.; Hennrich F.; Henderson, E. J.; Maier-Flaig, F.; Blum C.; Reichenbach, J.;

316

Lemmer, U.; Kübel, C.; Wang D.; Kappes, M. K.; Ozin, G. A. Preparation of monodisperse

317

silicon nanocrystals using density gradient ultracentrifugation. J. Am. Chem. Soc. 2011, 133,

318

11928.

319

15. Hagendorfer, H.; Kaegi, R.; Parlinska, M.; Sinnet, B.; Ludwig, C.; Ulrich, A. Characterization of

320

silver nanoparticle products using asymmetric flow field fractionation with a multidetector

321

approach – a comparison to transmission electron microscopy and batch dynamic light scattering.

322

Anal. Chem. 2012, 84, 2678-2685.

323

16. Nischwitz, V.; Goenaga-Infante, H. Improved sample preparation and quality control for the

324

characterisation of titanium dioxide nanoparticles in sunscreens using flow field flow

325

fractionation on-line with inductively coupled plasma mass spectrometry. J. Anal. At. Spectrom.

326

2012, 27, 1084-1092.

327 328

17. Soto-Alvaredo, J.; Montes-Bayón, M.; Bettmer, J. Speciation of silver nanoparticles and silver (I) by reversed-phase liquid chromatography coupled to ICPMS. Anal. Chem. 2013, 85, 1316.

329

18. Bailey, R. L.; Gahche, J. J.; Lentino, C. V.; Dwyer, J. T.; Engel, J. S.; Thomas, P. R.; Betz, J. M.;

330

Sempos, C. T.; Picciano, M. F. Dietary supplement use in the United States. 2003-2006. J. Nut.

331

2011, 141, 261-266.

332 333

19. Bailey, R. L.; Gache, J. J.; Miller, P. E.; Thomas, P. R.; Dwyer, J. T. Why US Adults Use Dietary Supplements. JAMA Intern. Med. 2013, 173, 355-361.

334

20. Timbo, B. B.; Ross, M. P.; McCarthy, P. V.; Lin, C. J. Dietary Supplements in a National Survey:

335

Prevalence of Use and Reports of Adverse Events. J. Am. Diet. Assoc. 2006, 106, 1966-1974.

15



Page 16 of 29

336

21. Qato, D. M.; Alexander, G. C.; Conti, R. M.; Johnson, M.; Schumm, P.; Lindau, S. T. Use of

337

Prescription and Over-the-counter Medications and Dietary Supplements Among Older Adults in

338

the United States. JAMA, 2008, 300, 2867-2878.

339 340

341 342

22. . Raiten, D. J.; Picciano, M. F.; Coates, P. M. Dietary Supplement Use in Women: Current Status and Future Directions-Introduction and Conference Summary. J. Nutr. 2003, 133, 1957S-1960S. 23. Albanese, A.; Tang, P. S.; Chan, W. C.W. The effect of nanoparticle size, shape, and surface chemistry on biological systems. Annu. Rev. Biomed. Eng. 2012, 14, 1-16.

343

24. Chen J.: Saeki F.: Wiley B. J.: Cang H.: Cobb M. J.: Li Z. Y.: Au L.: Zhang H.: Kimmey M. B.:

344

Li X.: Xia Y. Gold nanocages: bioconjugation and their potential use as optical imaging contrast

345

agents. Nano Lett, 2005, 5, 473–477.

346 347

348 349

25. Su S.; Wu W.; Gao J.; Lu J.; Fan C. Nanomaterials-based sensors for applications in environmental monitoring. J. Mater. Chem. 2012, 22, 18101-18110. 26. Cho K.; Wang X.; Nie S.; Chen Z.; Shin D. M. Therapeutic nanoparticles for drug delivery in cancer. Clin Cancer Res, 2008, 14, 1310–1316.

350

27. Sánchez-Pomales, G.; Mudalige, T. K.; Lim, J.-H.; Linder, S. W. Rapid Determination of Silver

351

in Nanobased Liquid Dietary Supplements Using a Portable X-ray Fluorescence Analyzer. J.

352

Agric. Food Chem. 2013, 61, 7250-7257.

353

28. IFST information statement- Nanotechnology, December 2013, Institute of Food Science & http://ifst2.pseltd.com/documents/misc/Nanotechnologydec2013.pdf

354

Technology,

355

November 18, 2014)

(accessed

356

29. Peters, R.; Bemmel, G.; Herrera Raivera, Z.; Helsper, H. P. F. G.; Marvin, H. J. P.; Weigel, S.;

357

Tromp, P. C.; Oomen, A. G.; Rietveld, A. G.; Bouwmen, H. Characterization of Titanium 16


Page 17 of 29


358

Dioxide Nanoparticles in Food Products: Analytical Methods To Define Nanoparticles. J. Agric.

359

Food Chem. 2014, 62, 6285-6293.

360

30. Heroul, J.; Nischwitz, V.; Bartczak, D.; Goenaga Infante, H. The potential of asymmetric flow

361

field-flow fractionation hyphenated to multiple detectors for the quantification and size

362

estimation of silica nanoparticles in a food matrix. Anal. Bioanal. Chem. 2014 406, 3919-3927.

363

31. Peters, R.; Kramer, E.; Oomen, A. G.; Herrera Rivera, Z. E.; Oegema, G.; Tromp, P. C.; Fokkink,

364

R.; Rietveld, A.; Marvin, H. J. P.; Weigel, S.; Peijnenburg, A. A. C. M.; Bouwmeester, H.

365

Presence of Nano-Sized Silica during In Vitro Digestion of Foods Containing Silica as a Food

366

Additive. ACS Nano, 2012, 6, 2441- 2451.

367

32. Kammer, F.; Legros, S.; Hofmann, T.; Larsen, E. H.; Loeschner, K. Separation and

368

characterization of nanoparticles in complex food and environmental samples by field-flow

369

fractionation. Trends Anal. Chem. 2011, 30, 425-436.

370

33. Dudkiewicz, A.; Tiede, K.; Loescher, K.; Jensen, L. H. S.; Jensen, E.; Wierzbicki, R.; Boxall, A.

371

B.A. Characterization of nanomaterials in food by electron microscopy. Trends Anal. Chem.

372

2011, 30, 28-43.

373

34. Lozano, O.; Mejia, J.; Tabarrant, T.; Masereel, B.; Dogné, J.M.; Toussanint, O.; Lucas, S.

374

Quantification of nanoparticles in aquous food matrices using Particle-Induced X-ray Emission.

375

Anal. Bioanal. Chem. 2012, 403, 2835-2841.

376

35. Dekkers, S.; Krystek, P.; Peters, R. J.; Lankveld, D. P.; Bokkers, B. G.; van Hoeven-Arentzen, P.

377

H.; Bouwmeester, H.; Oomen A. G. Presence and risks of nanosilica in food products.

378

Nanotoxicology, 2011, 5, 393-405.

17



379 380

Page 18 of 29

36. Wet chemical etching; chemical and physical mechanisms-revised 11/25/2005, MicroChemicals, http://www.microchemicals.de/secret/etching.pdf (accessed October 31, 2014)

381

37. Regonini, D.; Jaroenworaluck, A.; Stevens, R.; Bowen, C.R. Effect of heat treatment on the

382

properties and structure of TiO2 nanotubes: phase composition and chemical composition. Surf.

383

Interface Anal. 2010, 42, 139-144.

384

38. Hassellöv, M.; Readman, J. W.; Ranville, J. F.; Tiede K. Nanoparticle analysis and

385

characterization methodologies in environmental risk assessment of engineered nanoparticles.

386

Ecotoxicol. 2008, 17, 344-361.

387 388

389

39. Dynamic

light

scattering

technical

note,

MRK656-01,

Malvern

Instruments

Ltd.,

http://www3.nd.edu/~rroeder/ame60647/slides/dls.pdf (accessed November 18, 2014). 40. Nanocomposix’s guide to dynamic light scattering measurements and analysis, Guidelines for

390

dynamic

light

scattering

measurements,

Setember

391

http://nanocomposix.com/sites/default/files/nanoComposix%20Guidelines%20for%20DLS%20M

392

easurements%20and%20Analysis.pdf (assessed November 18, 2014).

2012,

V1.3,

nanoComposix,

393

41. Reyes-Coronado, D.; Rodríguez-Gattorno, G.; Espinosa-Pesqueira, M. E.; Cab, C.; de Coss, R.;

394

Oskam, G. Phase-pure TiO2 nanoparticles: anatase, brookite and rutile. Nanotechnology 2008, 19,

395

145605-145614.

396

42. Braydich-Stolle, L. K.; Schaeublin, N. M.; Murdock, R. C.; Jiang, J.; Biswas, P.; Schlager, J. J.;

397

Hussain, S. M. Crystal structure mediates mode of cell death in TiO2 nanotoxicity. J. Nanopart.

398

Res. 2009, 11, 1361–1374.

18


Page 19 of 29


399

43. Yeo, M.-K.; Kang, M. The biological toxicities of two crystalline phases and differential sizes of

400

TiO2 nanoparticles during zebrafish embryogenesis development. Mol. Cell Toxicol. 2012, 8,

401

317-326.

402

44. Contado, C.; Pagnoni, A. TiO2 nano-and micro-particles in commercial foundation creams: Field

403

Flow-Fractionation techniques together with ICP-AES and SQW Voltammetry for their

404

characterization. Anal. Methods 2010, 2, 1112–1124.

405

45. Winder, L.; Lorenz, C.; Goets, N.; Hungerbühler, K.; Amberg, M.; Heuberger, M.; Nowack, B.

406

Release of titanium dioxide form textiles during washing. Environ. Sci. Technol. 2012, 46, 8181-

407

8188.

408 409

410 411

46. Weir, A.; Westerhoff P.; Fabricius, L.; Hristovski, K.; Goetz, N. Titanium dioxide nanoparticles in food and personal care products. Environ. Sci. Technol. 2012, 46, 2242-2250. 47. Nanomaterials in Foods, As you sow, http://www.asyousow.org/health_safety/gmosnano.shtml (accessed November 18, 2014)

412

413

414

415

416

417 418 419 19



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420

Figure Captions

421

Figure 1. (a) Number and intensity based hydrodynamic particle size of sample DS-3 analyzed by DLS

422

and (b) representative FESEM image of sample DS-3.

423

Figure 2. FESEM images of SiO2 and TiO2 particles separated from each product labeled as DS-1 to DS-

424

12. The dietary supplements were digested and SiO2 and TiO2 particles isolated, suspended in ethanol, and

425

placed on FESEM platform for analysis.

426

Figure 3. FESEM images and EDS spectrum of SiO2 and TiO2 nanoparticles in DS-2, DS-4, and DS-12.

427

Al peaks are associated background signal of the sample holder.

428

Figure 4. TEM images of SiO2 and TiO2 particles in DS-1 to DS-12.

429

Figure 5. EDS spectrum of particles in TEM images (Figure 2). The C, Cr, and Cu peaks are associated

430

with background signal of the sample holder.

431

Figure 6. XRD analysis of samples DS-1 to DS-12. Reference patterns for anatase (JCPDS No. 21-1272)

432

and rutile (JCPDS No. 21-1276) TiO2 peaks are provided along with the pattern observed from the zero

433

diffraction silicon XRD sample holder.

434 435 436 437 438 439 440 441 442

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443

Tables

444

Table 1. List of dietary supplements investigated. Sample

Formulation

DS-1

Solid/Tablet

Market Claim

Labeling of SiO2 or TiO2 as Ingredients

Sexual health formula for women TiO2 Supports energy production

445 446

DS-2

Solid/Tablet

Support hormonal balance

SiO2

DS-3

Solid/Capsule

Maximum strength enhancement

SiO2

DS-4

Liquid/Soft gel

Passion and pleasure boost

TiO2

DS-5

Solid/Capsule

Menopause support

TiO2

DS-6

Solid/Capsule

Enhances fertility and desire

SiO2

DS-7

Solid/Capsule

Female fertility support

SiO2

DS-8

Solid/Capsule

Balances yeast and bacteria to maintain feminine health

TiO2

DS-9

Solid/Tablet

Menopause support

SiO2

DS-10

Solid/Capsule

Urinary tract health

SiO2, TiO2

DS-11

Solid/Capsule

Urinary tract support

SiO2

DS-12

Solid/Capsule

Pleasure enhancer for women

SiO2, TiO2

The dietary supplements (DS) were given arbitrary numbers and reviewed for (a) physical condition, (b) intent of use, and (c) indications of contents containing SiO2 or TiO2 based on product labeling.

447 448 449 450 451 452 453 21



454

Page 22 of 29

Table 2. Particle size and size distribution measured by Dynamic Light Scattering (DLS). Particle Size

455 456 457 458

Sample ID

Number based mean diameter (nm)

Intensity based mean diameter (nm)

Size distribution (nm)

Polydispersity (P)

DS-1

308

557

260 – 1255

0.20

DS-2

282

2146

236 – 3590

0.38

DS-3

100

4275

87 – 7288

0.40

DS-4

142

500

121 – 834

0.30

DS-5

328

542

202 - 705

0.20

DS-6

344

2701

281 – 4019

0.43

DS-7

441

2736

237 – 4617

0.37

DS-8

156

869

136 - 1418

0.38

DS-9

254

2496

213 – 3680

0.45

DS-10

146

350

120 – 416

0.10

DS-11

47

4905

41 - 6840

0.41

DS-12

57

403

53 - 533

0.29

The dietary supplements (DS) were given arbitrary numbers. A solution of nitric acid and hydrogen peroxide was used to dissolve the various components of the products at high temperature, leaving only SiO2 and TiO2. The particles sizes were characterized by DLS following suspension and ultra-sonication in ultra-pure water.

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Detection and Characterization of SiO2 and TiO2 ... - ACS Publications

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