Metal oxide nanomaterials: health and environmental effects

10 Metal oxide nanomaterials: health and environmental effects J.E. CAÑAS-CARRELL, S. LI, A.M. PARRA and B. SHRESTHA, Texas Tech University, USA DOI: 10.1533/9780857096678.3.200 Abstract: Metal oxide nanomaterials have unique properties that allow for numerous applications and uses in industry and consumer products. However, these materials also potentially pose a risk to humans, aquatic and terrestrial organisms, and the environment. This chapter will briefly identify applications of metal oxide nanomaterials. However, the major focus of the chapter will be a literature review of human health and ecotoxicology studies conducted with metal oxide nanomaterials. Key words: toxicity, nano-ZnO, nano-TiO2, aquatic toxicity, terrestrial toxicity.

10.1

Introduction

Metal oxide nanomaterials represent a growing asset in many industries, especially with their heightened chemical, physical, and electronic properties compared with their bulk counterparts. Metal oxide nanomaterials are versatile materials that can be used in applications such as environmental remediation, medical technology, energy, water treatment, and personal care products (Table 10.1), with their applications projected to increase. Studies show that three to four consumer products are released per week that may contain metal oxide nanomaterials (Project on Emerging Nanotechnologies, 2008). Nanotechnology is projected to contribute US $1 trillion to the US economy by 2015 (LUX, 2004). Becoming increasingly popular in their usage, exposure of metal oxide nanomaterials to people and the environment through occupational processes and consumer products is likely. Therefore, it is important to investigate how these nanomaterials affect human health and the environment. The following sections will include an overview of the applications and potential toxicity to humans, aquatic organisms, and terrestrial organisms of several metal oxide nanomaterials, including two of the most widely used metal oxides – nano-ZnO and nano-TiO2.

10.2

Nano-zinc oxide

Zinc oxide (ZnO) is a widely used compound in many household, electrical, and industrial products. Though naturally occurring in the mineral zincite, most 200 © 2014 Woodhead Publishing Limited

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Table 10.1 Applications of metal oxide nanomaterials Nanomaterial

Products and applications

Source

Nano-TiO2

Sunscreens, cosmetics, and self- cleaning coatings Pharmaceuticals, pigments, food additives, and solar cells Food additives, paints, pigments, and adhesives Medical disinfection and environmental remediation Sunscreens and cosmetics

Sharma (2009)

Nano-TiO2 Nano-ZnO Nano-ZnO Nano-ZnO Nano-FeOx Nano-MnO Nano-Al2O3 Nano-CeO2 Nano-CeO2 Nano-CuOx Nano-CuOx

Wastewater treatment and bioremediation Wastewater treatment Water-resistant coating and gas- discharge lamps Televisions, glass mirrors, and ophthalmic lenses Fuel additives Antimicrobial studies Solar cells, catalysts, and sensors

Ju-Nam and Lead (2008), Sugibayashi et al. (2008) Ma et al. (2012a) Hoffmann et al. (1995) Franklin et al. (2007), Ma et al. (2012a) Deliyanni et al. (2004) Takamatsu et al. (1985), Kawashima et al. (1986) ObservatoryNano (2008) Reinhart and Winkler (2002) Park et al. (2008) Esteban-Cubillo et al. (2006) Filipic and Cvelbar (2012)

production originates from anthropogenic sources. Nano-sized ZnO (nano-ZnO) can be produced by the grinding of bulk ZnO, where it takes on a wurtzite crystalline structure that can then be utilized for a number of applications. NanoZnO serves as an n-type semiconductor due to its wide-bandgap (~3.37 ev) (Hahn, 2011). Based on electric, thermal, and chemical stability, piezoelectric and superconductive properties, nano-ZnO has many applications in devices such as piezoelectric cells (Minne et al., 1995), cholesterol and glucose biosensing (Umar et al., 2009), solar cells (Keis et al., 2002), and photovoltaic transducers (Martin et al., 2000). When in a powder form, nano-ZnO can be mixed into foods, paints, pigments, and adhesives (Ma et al., 2012b), medical disinfection, and environmental remediation (Hoffmann et al., 1995). Due to UV-Vis luminescence and UV blocking properties, nano-ZnO is used in personal care products, such as sunscreens and cosmetics (Franklin et al., 2007; Ma et al., 2012b). Production of nano-ZnO and other metal oxides have been found to be popular for cosmetic applications with an estimated 1000 tons per year during 2005–2010 (Pitkethly, 2004).

10.2.1 Human health effects Given that one of the main applications of nano-ZnO is in sunscreens, a few studies have investigated the ability of nano-ZnO to be absorbed through the skin.

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An in vitro study with porcine skin found that nano-ZnO was not able to penetrate the stratum corneum reducing the possibility for absorption through the skin (Gamer et al., 2006). Other studies have also demonstrated that nano-ZnO does not penetrate normal or compromised human (or animal) skin (Nohynek et al., 2007, 2010; Filipe et al., 2009). Numerous in vitro studies with human cell lines have been conducted with nano-ZnO to elucidate the potential toxicity. Nano-ZnO exhibited cytotoxicity in human renal culture cells in a dose-dependent manner and effects were highly correlated with metal composition, size, and solubility (Pujalte et al., 2011). A study with human cardiac microvascular endothelial cells also observed that nano-ZnO produced cytotoxicity in a dose-dependent manner, caused permeability of the plasma membrane, and elicited an inflammation response (Sun et al., 2011). Cytotoxicity and oxidative stress were also observed in human colon carcinoma cells exposed to nano-ZnO (De Berardis et al., 2010). Xia et al. (2008) also observed the production of reactive oxygen species and then subsequent cytotoxicity and cell death in human bronchial epithelial cells exposed to nanoZnO. In addition, nano-ZnO was cytotoxic to human dermal fibroblasts and had the potential to induce apoptosis in these cells (Meyer et al., 2011). Similar effects of nano-ZnO were also observed in human lung epithelial cells and human fetal lung fibroblasts (Karlsson et al., 2008; X.Q. Zhang et al., 2011). In contrast, no cytotoxicity was observed in human nasal mucosa mini organ cultures, but repetitive exposure to low concentrations of nano-ZnO resulted in persistent DNA damage (Hackenberg et al., 2011). Only one study has investigated the genotoxicity of nano-ZnO in vivo, and following a 14 day exposure in mice there was oxidatively induced DNA damage similar to that observed in vitro (Klien and Godnic-Cvar, 2012). Overall, nano-ZnO is highly cytotoxic and additional studies are warranted.

10.2.2 Environmental effects Aquatic toxicity Valued for their unique antimicrobial properties, catalytic capacities, odor-fighting properties, and many other characteristics, metal-based nanomaterials have been applied in a wide range of products (Moore, 2006; Ma et al., 2012b). However, these same properties could also pose a risk to aquatic organisms. Hence, aquatic toxicity data are needed for environmental risk assessment and regulation of metal-based nanomaterials. This section reviews current knowledge of aquatic toxicity of metal-based nanomaterials. A summary of lethal effects of metal oxide nanomaterials to aquatic organisms is presented in Table 10.2. Based on material flow analysis, estimated nano-ZnO concentrations in surface water could reach the ng/L range (Gottschalk et al., 2009). Several review papers have demonstrated the emerging concerns of nano-ZnO toxicity in different taxa

Table 10.2 Summary of lethal effects of metal- based nanomaterials to aquatic organisms Nanomaterial

Particle size (nm) Species

Lethality

Source

Nano-TiO2 Nano-TiO2 Nano-TiO2 Nano-TiO2 Nano-TiO2

<150* <25 20 30 20

Daphnia magna Daphnia magna Caenorhabditis elegans Zebrafish Danio rerio

LC50, 48 h value > 100 mg/L LC50, 48 h value of 143 mg/L LC50, 24 h value of 80 mg/L LC50, 96 h value of 124.5 mg/L LC50, 10 d value > 10 mg/L

Nano-TiO2

25

Fatal damage

Nano-TiO2 Nano-TiO2 Nano-ZnO Nano-ZnO Nano-ZnO Nano-ZnO Nano-ZnO Ag nanoparticles

25 25 20 50–70 67, 820, 44 000* 50–70 50–70 10, 20, 30, 50

Artemia salina and Chattonella antigua Daphnia magna Japanese medaka Daphnia magna Daphnia magna Daphnia magna Thamnocephalus platyurus Thamnocephalus platyurus Daphnia magna

Warheit et al. (2007) Zhu et al. (2009) Wang et al. (2009) Xiong et al. (2011) Palaniappan and Pramod (2010) Matsuo et al. (2001)

Ag nanoparticles

10

Pimephales promelas

Al nanoparticles Cu nanoparticles Cu nanoparticles

20–30 30 30

Daphnia magna Daphnia magna Thamnocephalus platyurus

* Particle size in water suspension.

LC50, 48 h value of 29.8 μg/L LC50, 48 h value of 2.2 mg/L LC50, 48 h value of 1.5 mg/L LC50, 48 h value of 3.2 mg/L LC50, 73 h value of 0.2 mg/L LC50, 48 h value of 0.14 mg/L LC50, 24 h value of 0.18 mg/L LC50, 48 h values of 4.31–30.35 μg total Ag/L LC50, 96 h value of 89.4 μg total Ag/L LC50, 48 h value > 162 mg/L LC50, 48 h values of 3.2 mg/L LC50, 48 h values of 2.1 mg/L

Ma et al. (2012a) Ma et al. (2012a) Zhu et al. (2009) Heinlaan et al. (2008) Adams et al. (2006) Blinova et al. (2010) Heinlaan et al. (2008) Hoheisel et al. (2012) Hoheisel et al. (2012) Zhu et al. (2009) Heinlaan et al. (2008) Heinlaan et al. (2008)

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(Cattaneo et al., 2009; Ma et al., 2012a). Unfortunately, toxicity studies with nano-ZnO in aquatic organisms are still limited (Cattaneo et al., 2009; Ma et al., 2012b). Based on current studies, nano-ZnO is generally more toxic than nano-TiO2 under laboratory conditions. For D. magna, Zhu et al. (2009) and Heinlaan et al. (2008) reported relatively low LC50,48 h values of 1.5 mg/L and 3.2 mg/L, respectively. Adams et al. (2006) observed an even lower LC50,73 h value of 0.2 mg/L for D. magna. For fairy shrimp, Thamnocephalus platyurus, a LC50,48 h value (0.18 mg/L) and a LC50,24 h value (0.14 mg/L) have also been reported (Heinlaan et al., 2008; Blinova et al., 2010). Compared with acute toxicity studies, chronic studies of nano-ZnO are even more rare. A very recent study reported that 1 mg/L nano-ZnO could affect survival, growth, and reproduction of a marine amphipod, Corophium volutator (Fabrega et al., 2012). The exact mode of action of nano-ZnO toxicity is still under debate. Brunner et al. (2006) suggested at least three distinct mechanisms: particle dissolution, surface interaction with media, and surface interaction with organisms. Most studies believe that dissolution contributes to most of the nano-ZnO toxicity (Brunner et al., 2006; Heinlaan et al., 2008). In addition, reactive oxygen species (ROS), with or without photo-activation, have also been suggested as possible mechanisms for toxicity of nano-ZnO (Ma et al., 2011; Navarro and Sigg, 2011). Future studies should focus on investigating to what extent these distinct mechanisms contribute to toxicity. Terrestrial toxicity Ecotoxicology studies of metal oxide nanomaterials in terrestrial environments are limited to soil invertebrates and plants. Soil is considered an ultimate sink for nanomaterials (Klaine et al., 2008; Tiede et al., 2009; Dinesh et al., 2012). Nanomaterials can be released into and enter soil mostly through application of sewage sludge received from wastewater treatment plants (Tourinho et al., 2012). This section incorporates various toxicity studies conducted with soil invertebrates and plants. Media effects on nano-ZnO toxicity to earthworms were observed in a study in which 100% earthworm mortality was observed in agar at the highest concentration (1000 mg/kg) while mortality decreased with an increase in concentration in the filter paper test (Li et al., 2011). Size-dependent toxicity of nano-ZnO in the nematode Caenorhabditis elegans was observed in a study; LC50 values for nano-ZnO particles <25 nm and <100 nm were 0.32 mg/L and 2 mg/L, respectively (Khare et al., 2011). Very few studies have been conducted with nano-ZnO and soil invertebrates other than earthworm and nematodes. A recent study with the ostracod Heterocrypris incongruens observed 100% mortality after exposure to nano-ZnO for 6 days, but no adverse effects of 230 mg/kg nano-ZnO on Folsomia candida reproduction were observed (Manzo et al., 2011).

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Studies on ecotoxicological effects of metal oxide nanomaterials in plants have shown mixed results of negative effects, positive effects, and no effects. Most of the studies have been conducted in agar, water suspensions or hydroponically, although recent studies have been conducted in soil. Nano-ZnO accumulated in leaves, stem, and roots of velvet mesquite (Prosopis juliflora-velutina) and caused an increase in catalase and ascorbate peroxidase activities (Hernandez-Viezcas et al., 2011). Nano-ZnO inhibited root elongation in Allium sepa following exposure to 5, 10, and 20 g/L (Ghodake et al., 2011). Nano-ZnO (2000 mg/L) negatively affected seed germination in ryegrass and corn (Lin and Xing, 2007). Nano-ZnO caused a negative effect on root elongation in garden cress and genotoxicity in broad bean (Manzo et al., 2011). Kim et al. (2011) observed a decrease in biomass and an increase in oxidative stress in Cucumis sativus exposed to nano-ZnO. Similarly, Du et al. (2011) observed reduced biomass of wheat. Based on the few contrasting studies conducted with nano-ZnO and terrestrial invertebrates, the effects of nano-ZnO on invertebrates depend on the experimental setup, nano-ZnO size, and invertebrate species. In general, based on the limited plant studies that have been conducted, nano-ZnO exhibits mostly negative effects on plant species; nano-ZnO affected seed germination, root elongation, decreased biomass, and increased oxidative stress in various plant species.

10.3

Nano-titanium dioxide

Also known for photocatalytic properties, nano-titanium dioxide (nano-TiO2) serves as a useful nanomaterial in industry today. Nano-TiO2 and bulk TiO2 have both been studied based on their roles as photocatalysts. Nano-TiO2, the more chemically reactive of the two, can serve in both oxidative and reductive processes in the removal of organic and inorganic compounds in wastewater. One study has shown nano-TiO2 to play a successful role in the adsorption of heavy metals (Cu, Cd, Ni, Pd, Zn) from spiked San Antonio tap water samples (Engates and Shipley, 2011). Additionally, nano-TiO2 can be used in the removal of metal ions and nonbiodegradable organics (Kabra et al., 2004) and total organic carbon degradation using UV light (Chitose et al., 2003) from synthetic wastewater. Nano-TiO2 is included in many consumer products due to its ability to absorb UV radiation and is widely used in sunscreens, cosmetics, and self-cleaning coatings for antimicrobial properties (Sharma, 2009). Nano-TiO2 can also be found in pharmaceuticals, pigments, food additives, and solar cells (Ju-Nam and Lead, 2008; Sugibayashi et al., 2008).

10.3.1 Human health effects Due to the widespread applications (cosmetics, sunscreens, body care products, etc.) and the stability of nano-TiO2 in the environment, it is one of the most studied nanomaterials (Som et al., 2011) in terms of its effect on human health. Recent

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studies have demonstrated that nano-TiO2 cannot cross the skin and be absorbed (Gamer et al., 2006; Filipe et al., 2009; Nohynek et al., 2010; Pinheiro et al., 2007). However, inhaled nano-TiO2 was able to cross the air–blood barrier and a small amount of the total particles were distributed throughout the body (Kapp et al., 2004; Geiser et al., 2005). Compared with other nano-metal oxides, nano-TiO2 is one of the least cytotoxic (Jin et al., 2008; Lai et al., 2008; De Berardis et al., 2010; Pujalte et al., 2011). However, a few studies have observed cytotoxicity (cellular mitochondrial dysfunction, induction of apoptosis, cell proliferation, and cell viability) following exposure to nano-TiO2 in human fetal lung fibroblasts, human lung cells, and human bronchial epithelium cells (Huang et al., 2010; Kim et al., 2010; X.Q. Zhang et al., 2011). Despite the low cytotoxicity, a few studies have observed an increase in the production of ROS following exposure to nano-TiO2 in human bronchial epithelium cells and mouse brain microglial cells (Long et al., 2006; E. Park et al., 2008). Numerous studies involving human bronchial, human lung, and human epidermal cells exposed to nano-TiO2 also observed genotoxicity (DNA damage) as a result of exposure (Gurr et al., 2005; Karlsson et al., 2008; Shukla et al., 2011). Other studies with rat and mouse models, however, showed conflicting results with the majority of the studies finding DNA damage following exposure to nano-TiO2 (Trouiller et al., 2009; Sycheva et al., 2011; Saber et al., 2012) and two studies reporting no DNA damage (Landsiedel et al., 2010; Naya et al., 2012). In summary, at present the most likely route of exposure for nano-TiO2 is through inhalation. Recent in vitro studies with human bronchial, lung, and bronchial epithelium cells indicated that nano-TiO2 is not very cytotoxic, but these nano-metal oxides may exhibit genotoxicity and increase the production of ROS.

10.3.2 Environmental effects Aquatic toxicity Nano-TiO2 has been widely used in sunscreens, cosmetics, and self-cleaning coatings because of its antimicrobial and UV-absorbing properties (Sharma, 2009). Direct evidence of nano-TiO2 emission into the aquatic environment has been reported (Kaegi et al., 2008; Windler et al., 2012). While nano-TiO2 is one of the most widely used metal-based nanomaterials, aquatic toxicity studies with nano-TiO2 are relatively limited. Most aquatic toxicity studies with nano-TiO2 were conducted under laboratory conditions in the presence of fluorescence light. In these studies, nano-TiO2 exhibited no or low toxicity to various aquatic organisms. For example, Warheit et al. (2007) reported that for Daphnia magna, nano-TiO2 with Si/Al coatings had an EC50,48 h value greater than 100 mg/L. Zhu et al. (2009) observed a LC50,48 h value of 143 mg/L and an EC50,48 h value of 35 mg/L for D. magna. For Caenorhabditis

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elegans, Wang et al. (2009) reported a LC50,24 h value of 80 mg/L, which is less than that of bulk TiO2 (136 mg/L). Toxicological effects of nano-TiO2 have also been examined in fish. Xiong et al. (2011) found low acute toxicity of nano-TiO2 (LC50,96 h value of 124.5 mg/L) to zebrafish. Palaniappan and Pramod (2010) observed no mortality of adult Danio rerio during a 14 day exposure period of 10 mg/L nano-TiO2. However, photo-induced toxicity of nano-TiO2 is attracting more attention because photoreactivity of nano-TiO2 might significantly increase the risk of nano-TiO2 to aquatic organisms (Ma et al., 2012a). If nano-TiO2 is exposed to radiation with energy greater than the band gap energy of nano-TiO2 (3.2 ev, anatase crystal form), an ‘electron-hole pair’ system will form and lead to the formation of ROS (Fujishima et al., 2000; Ma et al., 2012a). Biomacromolecules will be attacked by ROS and this process could trigger various toxic processes in organisms, such as lipid peroxidation and DNA damage (Riley, 1994). A few aquatic studies have demonstrated phototoxicity of nano-TiO2 under UV exposure. Matsuo et al. (2001) tested phototoxicity of 1 g/L nano-TiO2 under a UV (365 nm) lamp on marine plankton. After 60–100 minutes of exposure, fatal damage was observed for both species. Ma et al. (2012a) observed a two- to four-fold increase in toxicity of nano-TiO2 to D. magna (LC50,48 h value of 29.8 μg/L) and Japanese medaka (LC50,48 h value of 2.2 mg/L) when exposed to simulated solar radiation. In summary, nano-TiO2 exhibits no to low toxicity in aquatic organisms in the absence of UV irradiation. However, under natural sunlight, phototoxicity of nano-TiO2 will be triggered and will potentially pose a risk to organisms in aquatic systems. Future risk assessment of nano-TiO2 should be evaluated based on various exposure conditions. Terrestrial toxicity Most of the nano-TiO2 toxicity studies with soil invertebrates have been conducted in earthworms and nematodes. Nano-TiO2 caused oxidative stress, DNA damage, and mitochondrial damage in earthworms following exposure to greater than 1.0 g/kg in soil (Hu et al., 2010). In another study, nano-TiO2 inhibited reproduction in Eisenia foetida after a 4 week exposure (Canas et al., 2011). However, one study observed that exposure to 200 and 10 000 mg/kg nano-TiO2 in field and artificial soil had no significant effects on juvenile survival and growth, adult earthworm survival, or reproduction (McShane et al., 2012). This study also observed avoidance of nano-TiO2 soil by earthworms. Growth and reproduction were also inhibited by nano-TiO2 in the nematode Caenorhabditis elegans (Wang et al., 2009). A recent study observed that size was an important parameter that influenced the toxic behavior of nano-TiO2 to nematodes (Li et al., 2012). Smaller sized nano-TiO2 (4 and 10 nm) were more toxic to nematodes than larger sized nano-TiO2 (60 and 90 nm). Nano-TiO2 (4 and 10 nm) significantly reduced locomotion in nematodes. A similar trend was

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observed by another study with C. elegans where the LC50 for smaller nano-TiO2 (< 25 nm) was 77 mg/L, but no toxicity was observed following exposure to larger sized nano-TiO2 (<100 nm) (Khare et al., 2011). Roh et al. (2010) also found that smaller nano-TiO2 particles (7 nm) were more toxic to C. elegans than larger particles (45 nm). Despite toxicity in earthworms and nematodes, nano-TiO2 exposure (1000 μg/g) to isopods (Porcellio scaber) did not cause any toxic effects (Drobne et al., 2009). Many toxicity studies with nano-TiO2 observed no toxic effects or positive effects on plants. Spinach growth increased after exposure to nano-TiO2 due to enhanced photosynthesis and nitrogen fixation (Yang et al., 2007). Lu et al. (2002) observed an increase in nitrate reductase activity in soybeans in a mixed SiO2 and TiO2 treatment. Wheat germination and growth was enhanced at 2 and 10 mg/kg nanoTiO2, but no effect or a slight inhibitory effect was observed at higher concentrations (Feizi et al., 2012). No effects of nano-TiO2 on willow tree seedling growth were observed (Seeger et al., 2009). Larue et al. (2011) observed nano-TiO2 uptake in wheat (Triticum aestivum), oilseed rape (Brassica napus), and Arabidopsis thaliana, but no adverse effects were observed on root elongation and germination. Some phytotoxicity studies have observed adverse effects of nano-TiO2 on plants. In one study in Allium cepa roots, malonaldehyde concentration increased (4.5 times) and oxidative stress increased following exposure to nano-TiO2 (Asli and Neumann, 2009; Ghosh et al., 2010). Similarly, Asli and Neumann (2009) observed accumulation of nano-TiO2 in maize root cell walls that caused significant reduction in the cell pore diameter.

10.4

Other metal oxides

Additional metal oxide nanomaterials have been of interest due to their unique properties. Aside from nano-ZnO and nano-TiO2, nano-ferric oxides (nano-FeOx) are one of the most widely used nanomaterials in industry. Stemming from the ubiquitous source of iron, nano-FeOx compounds have been used in wastewater treatment and bioremediation of toxic metal contaminated sites with little risk of secondary contamination (Deliyanni et al., 2004). Other metal oxide nanomaterials, such as nano-magnesium oxide (nano-MgOx), can be used in heavy metal adsorption in wastewater treatment. Nano-MgOx has been used as an absorbent for catatonic and ionic compounds such as phosphates (Kawashima et al., 1986) and arsenates (Takamatsu et al., 1985) in natural waters. Nano-aluminum oxide (nano-Al2O3) particles are used as a wear-resistant coating for tools and gas discharge lamps due to their inert properties (ObservatoryNano, 2008). Known also for UV-blocking and catalytic properties, cerium dioxide (nanoCeO2) nanoparticles are used in commercial uses such as polishing agents for television tubes, glass mirrors, and ophthalmic lenses (Reinhart and Winkler, 2002). Nano-CeO2 can also serve as a fuel additive, resulting in decreased emissions (B. Park et al., 2008). Lastly, copper oxide nanoparticles (nano-CuOx),

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which are known for their semiconductive, catalytic, and electronic properties, are used in applications such as antimicrobials (Esteban-Cubillo et al., 2006) and solar cells, catalysts, and gas and liquid sensors (Filipic and Cvelbar, 2012).

10.4.1 Human health effects In addition to nano-ZnO and nano–TiO2, several other metal oxide nanomaterials have been evaluated for effects linked to human health. However, since studies are limited for each type, results of various studies with other metal oxide nanomaterials are summarized in Table 10.3. Aquatic toxicity In addition to nano-TiO2 and nano-ZnO, concerns are beginning to emerge related to other metal-based nanomaterials, such as silver, aluminum, and copper nanoparticles. Compared with nano-TiO2 and nano-ZnO, toxicity data for these nanomaterials are sparse. Briefly, Hoheisel et al. (2012) reported LC50,48 h values from 4.31 to 30.35 μg total Ag/L of multiple sizes (10, 20, 30, and 50 nm) of silver nanoparticles for D. magna; toxicity increased with decreasing particle size. This study suggested that toxicity of silver nanoparticles could be explained by cooccurring silver ions, while no mechanism of nano-scale toxicity was observed. Several other studies have also confirmed toxicity of ionic silver contributing to the overall toxicity of silver nanoparticles (Lok et al., 2007; Liu and Hurt, 2010). Zhu et al. (2009) reported a D. magna LC50,48 h value greater than 162 mg/L for aluminum nanoparticles. Heinlaan et al. (2008) reported copper nanoparticles LC50,48 h values of 3.2 mg/L and 2.1 mg/L for D. magna and T. platyurus, respectively. In summary, the study of aquatic toxicity of metal-based nanomaterials is still in its infancy. Current understanding of their toxicity is largely limited by the lack of a toxicological database and standardized guidelines. Terrestrial toxicity Lee et al. (2010) observed no effects of Al2O3 nanoparticles on root elongation and growth in Arabidopsis plants. Nano-CuO and nano-NiO inhibited lettuce, radish, and cucumber seed germination, while nano-Fe2O3 and nano-Co3O4 caused no effects; nano-Co3O4 (5 g/L) had a positive effect on root elongation of radish (Wu et al., 2012). While no negative effects of nano-Fe3O4 on pumpkin plants were observed, nano-Fe3O4 exposure resulted in higher oxidative stress and antioxidative enzyme activity than bulk Fe3O4 particles (Wang et al., 2010). Nano-CuO decreased biomass and caused oxidative stress in Cucumis sativus (Kim et al., 2011, 2012). In freshly germinated sunflower seeds injected with aqueous suspensions of magnetic colloidal nanoparticles of Fe3O4, CoFe2O4, and ZnFe2O4, the mitosis rate decreased and chromosomal aberrations increased in root tips cells (Vochita et al., 2012).

Table 10.3 Effects of metal oxide nanomaterials related to human health Nanomaterial

Endpoint/effect

Source

Iron oxide (FeO)

Generated and elevated levels of ROS in human cell lines

Iron oxide (FeO)

Reduced ROS present in the cell

Iron oxide (FeO)

Affected cellular cytoskeleton network and structure

Iron oxide (FeO) Iron oxide (FeO) Iron oxide (FeO) Iron oxide (FeO)

No or little genotoxicity No effect on stem cell differentiation Inhibition of stem cell differentiation Exhibited genotoxicity and disrupted cellular functions

Iron oxide (FeO)

No cytotoxicity, permeability or induction of inflammation in human cardiac endothelial cells No or low cytotoxicity and genotoxicity Exhibited cytotoxicity Permeability and induction of inflammation in human cardiac endothelial cells Caused DNA damage and an increase in ROS Caused apoptosis and cell death in respiratory cells Cytotoxic in a concentration- and time- dependent manner Increased ROS production No cytotoxicity, permeability or induction of inflammation in human cardiac endothelial cells Exhibited cytotoxicity in a dose- dependent manner Dose-related DNA breakage, micronuclei formation, and chromosomal aberrations Exhibited cytotoxicity in a dose- dependent manner Suppressed production of ROS and increased cellular resistance to oxidative stress Protected nerve cells from oxidative stress

Stroh et al. (2004), Arbab et al. (2005), Soenen et al. (2010) Gao et al. (2007), Huang et al. (2009), Nel et al. (2009) Gupta and Curtis (2004), Gupta and Gupta (2005), Soenen et al. (2009), Wu et al. (2010), Buyukhatipoglu and Clyne (2011) Auffan et al. (2006), Karlsson et al. (2008) Arbab et al. (2005) Kostura et al. (2004), Chen et al. (2010) Pisanic et al. (2007), Kedziorek et al. (2010), Soenen et al. (2010), Puppi et al. (2011) Sun et al. (2011)

Iron oxide (FeO) Copper oxide (CuO) Copper oxide (CuO) Copper oxide (CuO) Copper oxide (CuO) Magnesium oxide (MgO) Magnesium oxide (MgO) Aluminum oxide (Al2O3 ) Aluminum oxide (Al2O3 ) Aluminum oxide (Al2O3 ) Silicon dioxide (SiO2) Cerium oxide (CeO2) Cerium oxide (CeO2)

Karlsson et al. (2008) Karlsson et al. (2008), Sun et al. (2011) Sun et al. (2011) Karlsson et al. (2008) Sun et al. (2012) Sun et al. (2011) Sun et al. (2011) Sun et al. (2011) Zhang et al. (2011) Balasubramanyam et al. (2009a, 2009b) Zhang et al. (2011) Xia et al. (2008) Schubert et al. (2006)

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A study of in vivo effects of nano-CeO2 (8.5 nm) on C. elegans observed that nano-CeO2 could induce ROS accumulation and oxidative damage in C. elegans even at an exposure level of 1 nM (H. Zhang et al., 2011). Nano-CeO2 significantly inhibited root growth in tomato and alfalfa seedlings at higher concentrations (López-Moreno et al., 2010).

10.5

Conclusion and future trends: metal oxide nanomaterial regulation and risk assessment

Given the current use of metal oxide nanomaterials, the increasing number of applications, and the current toxicity data, there is a continued, urgent need to fully assess the potential effects of these nanomaterials on humans and organisms in aquatic and terrestrial environments. More data are needed for a more robust hazard and exposure assessment; however, it is unclear if or how well standard toxicity testing can be used to assess nanomaterial toxicity (Aschberger et al., 2011). In addition, many questions remain, including whether each form of a nanomaterial (individual particles vs. agglomerates or functionalized vs. nonfunctionalized) needs to be assessed for toxicity, as differences in toxicity arise based on size, surface characteristics, and impurities (Aschberger et al., 2011). Aschberger and colleagues (2011) recommend some key research priorities to generate data for a more effective risk assessment of nanomaterials in general that can be applied to metal oxide nanomaterials. Currently, metal oxide nanomaterials are not regulated in the United States. One of the major challenges for regulation in the USA is how to classify nano-metal oxides, especially compared with their bulk counterparts. In contrast, the European Union (EU) has seen significant progress in regulating nanomaterials. Nanomaterial legislation first began in 2004 with an EU document addressing the regulation of nanomaterials (COM(2004)338, 2004). The document provided insight on creating an efficient industry in nanotechnology, while concurrently maintaining a safe environment. By 2010, legislation was passed that defined a nanomaterial by its (1) size distribution, (2) surface area, and (3) size of internal structural elements (Lovestam et al., 2010). In addition to these criteria, the REACH regulation provided by the EU implements the Registration, Evaluation, Authorization, and Restriction of Chemical substances. Since 2009, nanomaterials have become a part of this list (European Commission, 2012) and guidance is provided on Information Requirements (Hankin et al., 2011) and Chemical Safety Assessment (Aitke et al., 2011) concerning these nanomaterials.

10.6

Sources of further information and advice

The following resources have additional information related to nano-metal oxides as well as other nanomaterials.

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Websites for general information

• • • • •

The Project for Emerging Nanotechnology (http://www.nanotechproject. org/) ObservatoryNano (http://www.observatorynano.eu/project/) EPA’s Nanomaterial Research Strategy (http://www.epa.gov/nanoscience/) OECD Database on Research into the Safety of Manufactured Nanomaterials (http://webnet.oecd.org/NanoMaterials/Pagelet/Front/ Default.aspx) DaNa (http://www.nanopartikel. info/cms/lang/en/page3.html)

Government documents

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Regulation of Nanomaterials Today and Tomorrow (www.intertek.com/ articles/ regulation-of-nanomaterials/) EPA: Environmental, Health, and Safety Research Needs for Engineered Nanoscale Materials (http://www.nano.gov/NNI_EHS_research_needs.pdf) EPA Needs to Manage Nanomaterial Risks More Effectively (http://www.epa. gov/oig/reports/2012/20121229–12-P-0162.pdf) European Commission – Second Regulatory Review on Nanomaterials (http://ec.europa.eu/nanotechnology/pdf/second_regulatory_review_on_ nanomaterials_com(2012)_572.pdf) European Commission – Types and Uses of Nanomaterials, including Safety Aspects (http://eurlex.europa.eu/LexUriServ/LexUriServ.do?uri=SWD:2012: 0288:FIN:EN:PDF)

Books Houdy, P., Lahmani, M. and Marano, F. 2011. Nanoethics and Nanotoxicology. Berlin: Springer. Zhao, Y. and Singh-Nalwa, H. 2006. Nanotoxicology: Interactions of Nanomaterials with Biological Systems. Valencia, CA: American Scientific Publishers.

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