Treye A. Thomas

Release of Silver from Nanotechnology-Based Consumer Products for Children

We assessed the potential for childrens exposure to bioavailable silver during the realistic use of selected nanotechnology-based consumer products (plush toy, fabric products, breast milk storage bags, sippy cups, cleaning products, humidifiers, and humidifier accessory). We measured the release of ionic and particulate silver from products into water, orange juice, milk formula, synthetic saliva, sweat, and urine (1:50 product to liquid mass ratio); into air; and onto dermal wipes. Of the liquid media, sweat and urine yielded the highest amount of silver release, up to 38% of the silver mass in products; tap water yielded the lowest amount, ≤1.5%. Leaching from a blanket into sweat plateaued within 5 min, with less silver released after washing. Between 0.3 and 23 μg m(-2) of silver transferred from products to wipes. Aerosol concentrations were not significantly elevated during product use. Fabrics, a plush toy, and cleaning products were most likely to release silver. Silver leached mainly via dissolution and was facilitated in media with high salt concentrations. Levels of silver to which children may potentially be exposed during the normal use of these consumer products is predicted to be low, and bioavailable silver is expected to be in ionic rather than particulate form.

Characterization of silver nanoparticles in selected consumer products and its relevance for predicting children’s potential exposures

Due to their antifungal, antibacterial, antiviral, and antimicrobial properties, silver nanoparticles (AgNPs) are used in consumer products intended for use by children or in the home. Children may be especially affected by the normal use of consumer products because of their physiological functions, developmental stage, and activities and behaviors. Despite much research to date, childrens potential exposures to AgNPs are not well characterized. Our objectives were to characterize selected consumer products containing AgNPs and to use the data to estimate a childs potential non-dietary ingestion exposure. We identified and cataloged 165 consumer products claiming to contain AgNPs that may be used by or near children or found in the home. Nineteen products (textile, liquid, plastic) were selected for further analysis. We developed a tiered analytical approach to determine silver content, form (particulate or ionic), size, morphology, agglomeration state, and composition. Silver was detected in all products except one sippy cup body. Among products in a given category, silver mass contributions were highly variable and not always uniformly distributed within products, highlighting the need to sample multiple areas of a product. Electron microscopy confirmed the presence of AgNPs. Using this data, a childs potential non-dietary ingestion exposure to AgNPs when drinking milk formula from a sippy cup is 1.53 μg Ag/kg. Additional research is needed to understand the number and types of consumer products containing silver and the concentrations of silver in these products in order to more accurately predict childrens potential aggregate and cumulative exposures to AgNPs.

Nanoparticles-containing spray can aerosol: characterization, exposure assessment, and generator design

This is the first report demonstrating that a commercially available household consumer product produces nanoparticles in a respirable range. This report describes a method developed to characterize nanoparticles that were produced under typical exposure conditions when using a consumer spray product. A well-controlled indoor environment was simulated for conducting spray applications approximating a human exposure scenario. Results indicated that, while aerosol droplets were large with a count median diameter of 22 µm during spraying, the final aerosol contained primarily solid TiO2 particles with a diameter of 75 nm. This size reduction was due to the surface deposition of the droplets and the rapid evaporation of the aerosol propellant. In the breathing zone, the aerosol, containing primarily individual particles (>90%), had a mass concentration of 3.4 mg/m3, or 1.6 × 105 particles/cm3, with a nanoparticle fraction limited to 170 µg/m3, or 1.2 × 105 particles/cm3. The results were used to estimate the pulmonary dose in an average human (0.075 µg TiO2 per m2 alveolar epithelium per minute) and rat (0.03 µg TiO2) and, consequently, this information was used to design an inhalation exposure system. The system consisted of a computer-controlled solenoid ‘‘finger’’ for generating constant concentrations of spray can aerosols inside a chamber. Test results demonstrated great similarity between the solenoid ‘‘finger’’-dispersed aerosol compared to human-generated aerosol. Future investigations will include an inhalation study to obtain information on dose–response relationships in rats and to use it to establish a No Effect Exposure Level for setting guidelines for this consumer product.

Effects of Laser Printer–Emitted Engineered Nanoparticles on Cytotoxicity, Chemokine Expression, Reactive Oxygen Species, DNA Methylation, and DNA Damage: A Comprehensive in Vitro Analysis in Human Small Airway Epithelial Cells, Macrophages, and Lymphoblasts

Background Engineered nanomaterials (ENMs) incorporated into toner formulations of printing equipment become airborne during consumer use. Although information on the complex physicochemical and toxicological properties of both toner powders and printer-emitted particles (PEPs) continues to grow, most toxicological studies have not used the actual PEPs but rather have primarily used raw toner powders, which are not representative of current exposures experienced at the consumer level during printing. Objectives We assessed the biological responses of a panel of human cell lines to PEPs. Methods Three physiologically relevant cell lines—small airway epithelial cells (SAECs), macrophages (THP-1 cells), and lymphoblasts (TK6 cells)—were exposed to PEPs at a wide range of doses (0.5–100 μg/mL) corresponding to human inhalation exposure durations at the consumer level of 8 hr or more. Following treatment, toxicological parameters reflecting distinct mechanisms were evaluated. Results PEPs caused significant membrane integrity damage, an increase in reactive oxygen species (ROS) production, and an increase in pro-inflammatory cytokine release in different cell lines at doses equivalent to exposure durations from 7.8 to 1,500 hr. Furthermore, there were differences in methylation patterns that, although not statistically significant, demonstrate the potential effects of PEPs on the overall epigenome following exposure. Conclusions The in vitro findings obtained in this study suggest that laser printer–emitted engineered nanoparticles may be deleterious to lung cells and provide preliminary evidence of epigenetic modifications that might translate to pulmonary disorders. Citation Pirela SV, Miousse IR, Lu X, Castranova V, Thomas T, Qian Y, Bello D, Kobzik L, Koturbash I, Demokritou P. 2016. Effects of laser printer–emitted engineered nanoparticles on cytotoxicity, chemokine expression, reactive oxygen species, DNA methylation, and DNA damage: a comprehensive in vitro analysis in human small airway epithelial cells, macrophages, and lymphoblasts. Environ Health Perspect 124:210–219; http://dx.doi.org/10.1289/ehp.1409582

Consumer exposures to laser printer-emitted engineered nanoparticles: A case study of life-cycle implications from nano-enabled products

Abstract It is well established that printers emit nanoparticles during their operation. To-date, however, the physicochemical and toxicological characterization of “real world” printer-emitted nanoparticles (PEPs) remains incomplete, hampering proper risk assessment efforts. Here, we investigate our earlier hypothesis that engineered nanomaterials (ENMs) are used in toners and ENMs are released during printing (consumer use). Furthermore, we conduct a detailed physicochemical and morphological characterization of PEPs in support of ongoing toxicological assessment. A comprehensive suite of state of the art analytical methods and tools was employed for the physicochemical and morphological characterization of 11 toners widely utilized in printers from major printer manufacturers and their PEPs. We confirmed that a number of ENMs incorporated into toner formulations (e.g. silica, alumina, titania, iron oxide, zinc oxide, copper oxide, cerium oxide, carbon black among others) and released into the air during printing. All evaluated toners contained large amounts of organic carbon (OC, 42–89%), metals/metal oxides (1–33%), and some elemental carbon (EC, 0.33–12%). The PEPs possess a composition similar to that of toner and contained 50–90% OC, 0.001–0.5% EC and 1–3% metals. While the chemistry of the PEPs generally reflected that of their toners, considerable differences are documented indicative of potential transformations taking place during consumer use (printing). We conclude that: (i) Routine incorporation of ENMs in toners classifies them as nano-enabled products (NEPs); (ii) These ENMs become airborne during printing; (iii) The chemistry of PEPs is complex and it reflects that of the toner and paper. This work highlights the importance of understanding life-cycle (LC) nano-EHS implications of NEPs and assessing real world exposures and associated toxicological properties rather than focusing on “raw” materials used in the synthesis of an NEP.

Pulmonary and Cardiovascular Responses of Rats to Inhalation of Silver Nanoparticles

Exposure to wet aerosols generated during use of spray products containing silver (Ag) has not been evaluated. The goal was to assess the potential for cardiopulmonary toxicity following an acute inhalation of wet silver colloid. Rats were exposed by inhalation to a low concentration (100 μg/m3 ) using an undiluted commercial antimicrobial product (20 mg/L total silver; approximately 33 nm mean aerodynamic diameter [MAD]) or to a higher concentration (1000 μg/m3) using a suspension (200 mg/L total silver; approximately 39 nm MAD) synthesized to possess a similar size distribution of Ag nanoparticles for 5 h. Estimated lung burdens from deposition models were 0, 1.4, or 14 μg Ag/rat after exposure to control aerosol, low, and high doses, respectively. At 1 and 7 d postexposure, the following parameters were monitored: pulmonary inflammation, lung cell toxicity, alveolar air/blood barrier damage, alveolar macrophage activity, blood cell differentials, responsiveness of tail artery to vasoconstrictor or vasodilatory agents, and heart rate and blood pressure in response to isoproterenol or norepinephrine, respectively. Changes in pulmonary or cardiovascular parameters were absent or nonsignificant at 1 or 7 d postexposure with the exceptions of increased blood monocytes 1 d after high-dose Ag exposure and decreased dilation of tail artery after stimulation, as well as elevated heart rate in response to isoproterenol 1 d after low-dose Ag exposure, possibly due to bioavailable ionic Ag in the commercial product. In summary, short-term inhalation of nano-Ag did not produce apparent marked acute toxicity in this animal model.

Moving toward exposure and risk evaluation of nanomaterials: challenges and future directions

Nanotechnology, the commercial development of engineered nanomaterials, promises breakthrough innovations by enhancing the performance of existing consumer products and enabling development of new devices, architectures, and applications. Although these materials and applications are being developed at an explosive pace, a fundamental understanding of any potential human health and environmental risks resulting from exposure throughout the lifecycle of these materials has not advanced as rapidly. Past experience has demonstrated that successful introduction of a new technology occurs more readily if it is precipitated by a robust appreciation for any inherent risks associated with the technology. Such understanding allows the timely development of occupational and consumer exposure standards that might be needed to protect human health and the environment. Although risk is recognized as the product of hazard and exposure, too often exposure patterns are poorly characterized, and risk is based primarily or exclusively on the hazard characterization. The extent of exposure to nanomaterials in currently available commercial products is relatively unknown. Given the number of commercial products that claim to contain engineered nanomaterials, it is possible that human and environmental exposure to these materials is widespread. This paper is intended to highlight the importance of exposure assessment for determining the potential risks of nanomaterials. In essence, this is a call to action to the community of exposure scientists, toxicologists, and risk assessors to develop, consider, and incorporate requisite exposure information in the risk assessment of nanomaterials. Without an integrated approach, it will be difficult to meaningfully assess the risks of nanomaterials, realize their potential benefits, and foster their sustainable development.

Characterisation and potential migration of silver nanoparticles from commercially available polymeric food contact materials

The potential for consumer exposure to nano-components in food contact materials (FCMs) is dependent on the migration of nanomaterials into food. Therefore, characterising the physico-chemical properties and potential for migration of constituents is an important step in assessing the safety of FCMs. A number of commercially available food storage products, purchased domestically within the United States and internationally, that claim to contain nanosilver were evaluated. The products were made of polyethylene, polypropylene and polyphenylene ether sulfone and all contained silver (0.001–36 mg kg–1 of polymer). Silver migration was measured under various conditions, including using 3% acetic acid and water as food simulants. Low concentrations (sub-ppb levels) of silver were detected in the migration studies generally following a trend characterised by a surface desorption phenomenon, where the majority of the silver migration occurred in the first of three consecutive exposures. Silver nanoparticles were not detected in food simulants, suggesting that the silver migration may be due solely to ionic silver released into solution from oxidation of the silver nanoparticle surface. The absence of detectable silver nanoparticles was consistent with expectations from a physico-chemical view point. For the products tested, current USFDA guidance for evaluating migration from FCMs was applicable. Graphical Abstract

Development and characterization of an exposure platform suitable for physico-chemical, morphological and toxicological characterization of printer-emitted particles (PEPs).

Abstract An association between laser printer use and emissions of particulate matter (PM), ozone and volatile organic compounds has been reported in recent studies. However, the detailed physico-chemical, morphological and toxicological characterization of these printer-emitted particles (PEPs) and possible incorporation of engineered nanomaterials into toner formulations remain largely unknown. In this study, a printer exposure generation system suitable for the physico-chemical, morphological, and toxicological characterization of PEPs was developed and used to assess the properties of PEPs from the use of commercially available laser printers. The system consists of a glovebox type environmental chamber for uninterrupted printer operation, real-time and time-integrated particle sampling instrumentation for the size fractionation and sampling of PEPs and an exposure chamber for inhalation toxicological studies. Eleven commonly used laser printers were evaluated and ranked based on their PM emission profiles. Results show PM peak emissions are brand independent and varied between 3000 to 1 300 000 particles/cm3, with modal diameters ranging from 49 to 208 nm, with the majority of PEPs in the nanoscale (<100 nm) size. Furthermore, it was shown that PEPs can be affected by certain operational parameters and printing conditions. The release of nanoscale particles from a nano-enabled product (printer toner) raises questions about health implications to users. The presented PEGS platform will help in assessing the toxicological profile of PEPs and the link to the physico-chemical and morphological properties of emitted PM and toner formulations.

Pulmonary and cardiovascular responses of rats to inhalation of a commercial antimicrobial spray containing titanium dioxide nanoparticles

Our laboratory has previously demonstrated that application of an antimicrobial spray product containing titanium dioxide (TiO2) generates an aerosol of titanium dioxide in the breathing zone of the applicator. The present report describes the design of an automated spray system and the characterization of the aerosol delivered to a whole body inhalation chamber. This system produced stable airborne levels of TiO2 particles with a median count size diameter of 110 nm. Rats were exposed to 314 mg/m3 min (low dose), 826 mg/m3 min (medium dose), and 3638 mg/m3 min (high dose) of TiO2 under the following conditions: 2.62 mg/m3 for 2 h, 1.72 mg/m3 4 h/day for 2 days, and 3.79 mg/m3 4 h/day for 4 days, respectively. Pulmonary (breathing rate, specific airway resistance, inflammation, and lung damage) and cardiovascular (the responsiveness of the tail artery to constrictor or dilatory agents) endpoints were monitored 24 h post-exposure. No significant pulmonary or cardiovascular changes were noted at low and middle dose levels. However, the high dose caused significant increases in breathing rate, pulmonary inflammation, and lung cell injury. Results suggest that occasional consumer use of this antimicrobial spray product should not be a hazard. However, extended exposure of workers routinely applying this product to surfaces should be avoided. During application, care should be taken to minimize exposure by working under well ventilated conditions and by employing respiratory protection as needed. It would be prudent to avoid exposure to children or those with pre-existing respiratory disease.