Engineered Nanoparticles in Consumer Products: Understanding a NewIngredient

British chef and food activist Jamie Oliver ignited a firestorm in January 2011 when he mentioned on the Late Show with David Letterman that castoreum, a substance used to augment some strawberry and vanilla flavorings, comes from what he described as “rendered beaver anal gland.”1 The next year, vegans were outraged to learn that Starbucks used cochineal extract, a color additive derived from insect shells, to dye their strawberry Frappuccino® drinks2 (eventually, the company decided to transition to lycopene, a pigment found in tomatoes3). Although substances like castoreum and cochineal extract may be long on the “yuck factor,”4 research has shown them to be perfectly safe for most people; strident opposition arose not from safety issues but from the ingredients’ origins. But these examples demonstrate that the public often lacks significant knowledge about the ingredients in foods and where they come from. This is not a new development; the public relationship to food additives has a long history of trust lost, regained, and in some cases lost again. The Federal Food, Drug, and Cosmetic (FD&C) Act of 19385 was passed shortly after the deaths of 100 people who took an untested new form of a popular drug, which contained what turned out to be a deadly additive.6 The new law was consumer oriented and intended to ensure that people knew what was in the products they bought, and that those products were safe. The law has been amended over the years in attempts to streamline and bring order to the sprawling task of assessing and categorizing the thousands of substances used in foods, drugs, and cosmetics. One result of this streamlining is that under current U.S. law, companies can add certain types of ingredients to foods without premarket approval from the thin-stretched Food and Drug Administration (FDA). In other words, there are substances in the food supply that are unknown to the FDA. In 2010 the Government Accountability Office (GAO) concluded that a “growing number of substances … may effectively be excluded from federal oversight.”7 Is this a problem? The answer depends on whom you ask.

Engineered nanomaterials (ENMs) have a large economic impact in a range of fields, but the concerns about health and safety of occupational activities involving nanomaterials have not yet been addressed. Monitoring exposure is an important step in risk management. Hence, the interest for reviewing studies that reported a potential for occupational exposure. We systematically searched for studies published between January 2000 and January 2015. We included studies that used a comprehensive method of exposure assessment. Studies were grouped by nanomaterial and categorized as carbonaceous, metallic, or nanoclays. We summarized data on task, monitoring strategy, exposure outcomes, and controls in a narrative way. For each study, the strength of the exposure assessment was evaluated using predetermined criteria. Then, we identified all exposure situations that reported potential occupational exposure based on qualitative or quantitative outcomes. Results were synthesized and general conclusion statements on exposure situations were formulated. The quality of evidence for the conclusion statements was rated as low, moderate, or high depending on the number of confirmed exposure situations, the strength of the exposure assessment, and the consistency of the results. From the 6403 references initially identified, 220 were selected for full-text screening. From these, 50 studies describing 306 exposure situations in 72 workplaces were eligible for inclusion (27 industrial-scale plants and 45 research or pilot-scale units). There was a potential for exposure to ENMs in 233 of the exposure situations. Exposure occurred in 83% (N = 107) of the situations with carbonaceous ENMs, in 73% (N = 120) of those with metallic ENMs and in 100% (N = 6) of those with nanoclay. Concentrations of elemental carbon in the workers' breathing zone ranged from not detected (ND) to 910 µg m(-3) with local engineering controls (LEC), and from ND to 1000 µg m(-3) without those controls. For carbon nanofibres (CNFs), particle counts ranged from ND to 1.61 CNF structures cm(-3) with LEC, and from 0.09 to 193 CNF structures cm(-3) without those controls. The mass concentrations of aluminium oxide, titanium dioxide, silver, and iron nanoparticles (NPs) were ND, 10-150, 0.24-0.43, and 32 µg m(-3) with LEC, while they were <0.35, non-applicable, 0.09-33, and 335 µg m(-3) without those controls, respectively. Regarding the potential of exposure in the workplace, we found high-quality evidence for multiwalled carbon nanotubes (CNTs), single-walled CNTs, CNFs, aluminium oxide, titanium dioxide, and silver NPs; moderate-quality evidence for non-classified CNTs, nanoclays, and iron and silicon dioxide NPs; low-quality evidence for fullerene C60, double-walled CNTs, and zinc oxide NPs; and no evidence for cerium oxide NPs. We found high-quality evidence that potential exposure is most frequently due to handling tasks, that workers are mostly exposed to micro-sized agglomerated NPs, and that engineering controls considerably reduce workers' exposure. There was moderate-quality evidence that workers are exposed in secondary manufacturing industrial-scale plants. There was low-quality evidence that workers are exposed to airborne particles with a size <100nm. There were no studies conducted in low- and middle-income countries.

Pick up a tube of sunscreen, a tennis racquet, an iPod, or any number of other consumer products, and there’s a good chance that it’s been “nano-enabled,” meaning it contains nanoscale particles designed to give it some beneficial feature. An estimated $147 billion worth of nano-enabled commercial and consumer products were sold in 2007, according to Lux Research, a market analysis firm in New York City. Citing the firm’s latest estimates, Lux analyst David Hwang predicts that figure could top $3.1 trillion by 2015, reinforcing a broad view that nanotechnology is fueling a new industrial revolution. Yet nanotechnology’s spread through the market has been met with mounting concerns over the potential human health effects of these miraculous materials. Because of their small size—100 nano-meters or less—nanomaterials have unique physical properties that can influence their uptake, distribution, and behavior in the body. Indeed, some nano-particles have been shown to penetrate into cells, where they can trigger inflammatory responses and oxidative stress. Canada and California recently took the unprecedented step of imposing mandated disclosure requirements on nanomaterial use and toxicity assessment. Issued 29 January 2009, Canada’s law targets domestic companies and institutions that manufacture or buy more than 1 kilogram of nanomaterial per year. According to the new regulations, these entities must now reveal how much nanomaterial they use, how they use it, and what they know about its toxicity. California’s law, issued 2 February 2009, limits its scope to carbon nanotubes, a class of nanomaterial used in electronics, optics, and biomedical applications. Under the new regulation, by February 2010 companies that manufacture, import, or export carbon nanotubes in California must disclose information about the toxicity and environmental impacts of their products. Meanwhile, experts in nanotoxicology and risk assessment have become increasingly polarized, represented on one side by the National Research Council (NRC) and on the other by the National Nanotechnology Initiative (NNI), a government-wide collaboration coordinated by the National Science and Technology Council in the Executive Office of the President. In February 2008, the Nanotechnology Environmental and Health Implications (NEHI) Working Group of the NNI released a document titled Strategy for Nanotechnology-Related Environmental, Health, and Safety Research. This document is meant to present the U.S. government’s agenda for studying nano-particle hazards, and describes 246 related projects that were ongoing in 2006, representing a combined investment for that year of $68 million. The document also purports to “address prioritized research areas . . . and to advance knowledge and support risk decision-making—both of which are essential for the responsible development of nanotechnology.” Clayton Teague directs the National Nano-technology Coordination Office, which was responsible for drafting the federal strategy. He says the strategy was developed in extensive consultation with regulatory agencies, research organizations, the business community, and nongovernmental organizations. “We believe the strategy represents needs and agreements about what the agencies plan to do,” he says. “Funding agencies are telling us that they’re using the document to formulate solicitations for future research in this area.” But on 25 February 2009, a panel assembled by the NRC issued its own report, describing what it calls serious shortcomings in the strategy document. According to the NRC panel, which was assembled at the request of the NNI, the strategy exposes weaknesses in the government’s understanding of potential nanotechnology risks today and does not adequately address how they will be assessed in the future. NRC panel member Mark Weisner, a professor of civil and environmental engineering at Duke University, claims that many of the research programs described in the NNI’s document don’t actually address environmental, health, and safety (EHS) concerns. “If you take this portfolio at face value, it overstates the true level of effort in federally financed [nano-technology-related] EHS research,” he says.

Effects of microplastic and engineered nanomaterials on inflammatory bowel disease: A review

Engineered nanomaterials (ENMs) are increasingly incorporated into a variety of commercial applications and consumer products; however, ENMs may possess cytotoxic properties due to their small size. This study assessed the effects of two commonly used ENMs, zinc oxide nanoparticles (ZnONPs) and silver nanoparticles (AgNPs), in the model eukaryote Saccharomyces cerevisiae. A collection of ≈4600 S. cerevisiae deletion mutant strains was used to deduce the genes, whose absence makes S. cerevisiae more prone to the cytotoxic effects of ZnONPs or AgNPs. We demonstrate that S. cerevisiae strains that lack genes involved in transmembrane and membrane transport, cellular ion homeostasis, and cell wall organization or biogenesis exhibited the highest sensitivity to ZnONPs. In contrast, strains that lack genes involved in transcription and RNA processing, cellular respiration, and endocytosis and vesicular transport exhibited the highest sensitivity to AgNPs. Secondary assays confirmed that ZnONPs affected cell wall function and integrity, whereas AgNPs exposure decreased transcription, reduced endocytosis, and led to a dysfunctional electron transport system. This study supports the use of S. cerevisiae Gene Deletion Array as an effective high-throughput technique to determine cellular targets of ENM toxicity.

Nanotechnology is currently at the forefront of scientific research and technological developments that have resulted in the manufacture of novel consumer products and numerous industrial applications using engineered nanomaterials (ENMs). With the increasing number of applications and uses of ENMs comes an increasing likelihood of nanoscale materials posing potential risks to the environment and engineered technical systems such as wastewater treatment plants (WWTPs). Recent scientific data suggests that ENMs that are useful in, for example, medical applications due to their novel physicochemical properties, may also cause adverse effects to the bacterial populations used in wastewater treatment systems. In this review, the toxicological effects of titanium nanoparticles (nTiO(2)), zinc oxide (nZnO), carbon nanotubes (CNTs), fullerenes (C(60)) and silver nanoparticles (AgNPs) to bacteria were examined. The results suggest that the potential ENMs risks to bacteria are non-uniform (need to be assessed case-by-case), and are dependent on numerous factors (e.g. size, pH, surface area, natural organic matter). Currently available data are therefore insufficient for evaluating the risks that ENMs pose in WWTPs. To fill these knowledge gaps, we recommend scenario specific studies aimed at improving our understanding on: (i) estimated volumes of ENMs in effluents, (ii) the antibacterial sensitivity of cultures within WWTPs towards selected ENMs, and (iii) processes improving the stability of ENMs in solutions. Two factors that merit consideration for elucidating the potential risks systematically are the toxicity mechanisms of ENMs to bacteria, and the influencing factors based on inherent physicochemical properties and environmental factors. Furthermore, the complexity of behaviour and fate of ENMs in real WWTPs requires case studies for assessing the ENMs risks to bacteria in vivo. The current laboratory results derived using simplified exposure media do not reflect actual environmental conditions.

Chapter 3 - Environmental Fate and Exposure Modeling of Nanomaterials

Increases in the use and the progressive manufacture of new Engineered Nanomaterials (ENMs) lead to inquire about their impact on the environment. Due to the small size, high reactivity inside organisms and the unusual physicochemical properties of the ENMs, the predictions of toxicity are very complex. The zebrafish (Danio rerio) has been granted as a practical alternative to study the toxicity of ENMs. In this article the toxic effects of silver nanoparticles, titanium oxide nanoparticles, zinc oxide nanoparticles, carbon nanotubes, copper nanoparticles, gold nanoparticles, cadmium nanoparticles and nano plastics were reviewed trough the most recent literature available. Every ENMs should be studied in depth independently, considering co-exposures, environmental matrices, the effects of variations in size and concentrations, the potential effects of prolonged exposure, the coverage of ENMs, specific organism and targeted organs. This information will help to identify deficiencies in research trends and reinforce the safest ways to use ENMs.

Background: Little justification is generally provided for selection of in vitro assay testing concentrations for engineered nanomaterials (ENMs). Selection of concentration levels for hazard evaluation based on real-world exposure scenarios is desirable.Objectives: Our goal was to use estimates of lung deposition after occupational exposure to nanomaterials to recommend in vitro testing concentrations for the U.S. Environmental Protection Agency’s ToxCast™ program. Here, we provide testing concentrations for carbon nanotubes (CNTs) and titanium dioxide (TiO2) and silver (Ag) nanoparticles (NPs).Methods: We reviewed published ENM concentrations measured in air in manufacturing and R&D (research and development) laboratories to identify input levels for estimating ENM mass retained in the human lung using the multiple-path particle dosimetry (MPPD) model. Model input parameters were individually varied to estimate alveolar mass retained for different particle sizes (5–1,000 nm), aerosol concentrations (0.1 and 1 mg/m3), aspect ratios (2, 4, 10, and 167), and exposure durations (24 hr and a working lifetime). The calculated lung surface concentrations were then converted to in vitro solution concentrations.Results: Modeled alveolar mass retained after 24 hr is most affected by activity level and aerosol concentration. Alveolar retention for Ag and TiO2 NPs and CNTs for a working-lifetime (45 years) exposure duration is similar to high-end concentrations (~ 30–400 μg/mL) typical of in vitro testing reported in the literature.Conclusions: Analyses performed are generally applicable for providing ENM testing concentrations for in vitro hazard screening studies, although further research is needed to improve the approach. Understanding the relationship between potential real-world exposures and in vitro test concentrations will facilitate interpretation of toxicological results.

Chemical basis of interactions between engineered nanoparticles and biological systems.

A state-of-the-science review was undertaken to identify and assess sampling and analysis methods to detect and quantify selected nanomaterials (NMs) in the ambient atmosphere. The review is restricted to five types of NMs of interest to the Office of Research and Development Nanomaterial Research Strategy (U.S. Environmental Protection Agency): cerium oxide, titanium dioxide, carbon nanostructures (carbon nanotubes and fullerenes), zero-valent iron, and silver nanoparticles. One purpose was determining the extent to which present-day ultrafine sampling and analysis methods may be sufficient for identifying and possibly quantifying engineered NMs (ENMs) in ambient air. Conventional sampling methods for ultrafines appear to require modifications. For cerium and titanium, background levels from natural sources make measurement of ENMs difficult to quantify. In cases where field studies have been performed, identification from bulk analysis samples have been made. Further development of methods is needed to identify these NMs, especially in specific size fractions of ambient aerosols.

The number of technologies and consumer products that incorporate engineered nanomaterials (ENMs) has grown rapidly. Indeed, ENMs such as carbon nanotubes and nano-silver, are revolutionizing many commercial technologies and have already been incorporated into more than 800 commercial products, including polymer composites, cell phone batteries, sporting equipment and cosmetics. The global market for ENMs has grown steadily from $7.5 billion in 2003 to $12.7 billion in 2008. Over the next five years, their market value is expected to exceed $27 billion. This surge in demand has been responsible for a corresponding increase in the annual production rates of ENMs. For example, Bayer anticipates that single and multi-walle d carbon nanotubes (SWNT a nd MWNT) production rates will reach 3,000 tons/yr by 2012. Inevitably, some of these synthetic materials will enter the environment either from incidental release during manufacture and transport, or following use and disposal. Consequently, intense scientific research is now being directed towards understanding the environmental, health and safety (EHS) risks posed by ENMs. I will highlight some of the key research challenges and needs in this area, include (i) developing structure-property relationships that will enable physicochemical properties of ENMs to be correlated with environmentally releva nt behavior (e.g. colloidal properties, toxicity), (ii) determining the behavior of nanoproducts, and (iii) developing anal ytical techniques capable of detecting and quantifying the concentration of ENMs in the environment. Keywords: Engineered nanomaterials, health, environment, surface chemistry, car bon nanotubes, nano-Ag, structure-property relationships, nanoproducts, release rates, detection

Investigation of twenty metal, metal oxide, and metal sulfide nanoparticles' impact on differentiated Caco-2 monolayer integrity

Engineered nanomaterials (ENMs) are defined as having at least one dimension ≤100 nm 1. When ENMs have three dimensions ≤100 nm they are called nanoparticles (NPs). ENMs have attracted a great deal of attention recently because their many technologically interesting properties have led to technological growth with ensuing economic rewards 2. Technologies involving ENMs are envisaged to become the cornerstone for a number of industrial sectors, such as micro-electronics, materials, paper, textiles, energy, cosmetics and medical devices, all capable of incorporating some nanoscale-enabled properties into their products 2. By 2015, the annual profit from ENM-based products is estimated to be US$1.1–2.5 trillion 3. Today, ENMs can be found in more than 1,000 consumer products 4. By 2015, 2 million workers will be needed to support nanotechnology industries worldwide 5. However, some of the properties of ENMs that are unique and beneficial for technological applications may also endanger human health, inducing cyto- and genotoxic effects, inflammation and even cancer 6–12. Inflammatory effects are particularly important 13–15. Free radical activity or oxidative capacity of particulate matter might be essential for provoking these inflammatory responses. The physico-chemical features of ENMs that account for their deleterious health effects include a large ratio of surface area to mass and associated increased surface reactivity, altered physico-chemical properties, such as changes in melting point, solubility or electrical conductivity, or changes, for example, in the crystalline structure of the materials 16–20. Therefore, detailed evaluation of these characteristics is critical for the understanding of the mechanisms by which ENMs elicit biological responses. The respiratory system is a critical route of exposure to aerosolised ENM, by accident or by occupational exposure. A rapidly increasing number of studies have evaluated the respiratory effects …

Too small to matter? Physicochemical transformation and toxicity of engineered nTiO2, nSiO2, nZnO, carbon nanotubes, and nAg