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Keywords:

  • environmental risk assessment;
  • genomics;
  • industrial ecology;
  • metabolomics;
  • proteomics;
  • toxicology

Summary

  1. Top of page
  2. Summary
  3. Introduction
  4. Routes of Nanoparticles Into the Aquatic Environment
  5. Detection in the Environment
  6. Bioavailability
  7. Environmental and Biological Fate
  8. Bioaccumulation
  9. Potential Mechanisms of Nanoparticle Toxicity
  10. Potential Effects of Nanoparticles on Aquatic Organisms
  11. Genomic, Proteomic, and Metabolomic Risk Assessment Tools
  12. Acknowledgements
  13. References
  14. About the Author

Nanotechnology has great potential for revolutionizing the treatment of disease, optimizing manufacturing processes and consumer products, and remediating polluted environments. Increased use and disposal of products containing nanoparticles will inevitably result in their accumulation in aquatic ecosystems via direct input and runoff from contaminated soils. Aquatic organisms are particularly susceptible to pollutants due to their large, fragile respiratory epithelium. This potential toxicity can be exacerbated by common stressors, such as changes in water temperature, salinity, pH, and oxygen levels, and must be considered in environmental risk assessments. The unique properties of manufactured nanoparticles present serious problems for risk assessment strategies, and there is a concern in the regulatory community that standard toxicological methods may be inadequate to address these compounds. Our capacity to detect and quantify nanoparticles is extremely limited, especially in complex biological, soil, or water samples. The distinctive chemistry and physical structure of each nanomaterial will determine its bioavailability, and these parameters can be altered over time or with changes in water chemistry. The use of advanced analytical techniques, such as functional genomics, proteomics, and metabolomics, can provide a global assessment of the biological response to a novel chemical and will be important in determining the potential toxicity of nanoparticles. Industry should adopt a proactive approach to identifying potential risks to aquatic ecosystems so that the benefits of nanotechnology can be fully realized.


Introduction

  1. Top of page
  2. Summary
  3. Introduction
  4. Routes of Nanoparticles Into the Aquatic Environment
  5. Detection in the Environment
  6. Bioavailability
  7. Environmental and Biological Fate
  8. Bioaccumulation
  9. Potential Mechanisms of Nanoparticle Toxicity
  10. Potential Effects of Nanoparticles on Aquatic Organisms
  11. Genomic, Proteomic, and Metabolomic Risk Assessment Tools
  12. Acknowledgements
  13. References
  14. About the Author

In the past, perceived but untested human and environmental health risks have greatly slowed the introduction of novel technologies with possible widespread societal benefits. Nanotechnology has great potential for reducing society's impact on the natural environment by increasing the efficiency of industrial and manufacturing processes, optimizing products used in everyday life, and even remediating polluted environments (Liu 2006). Although nanoparticles do occur naturally, concerns have been raised over the potential environmental impact of manufactured nanoparticles. Manufactured nanoparticles are usually defined as any synthetic material with one or more dimensions smaller than 100 nm (Thomas and Sayre 2005), examples of which include carbon nanotubes, fullerenes, and quantum dots (Rieger et al. 2005). Nanoparticles are similar in size to cellular components such as ribosomes (∼20 nm) and, as such, may allosterically interact with proteins, DNA, or RNA. These interactions could potentially disrupt vital processes, such as enzyme function and gene translation/transcription.

Manufactured nanoparticles are engineered to optimize specific physicochemical and surface characteristics that give them unique electrical, thermal, mechanical, and imaging properties different from those of their non-nanosized counterparts (Rieger et al. 2005; Liu 2006). This makes them potentially subject to regulatory approval through government agencies.1 The novel properties that make manufactured nanoparticles desirable for use in industrial and commercial applications may also render them uniquely hazardous for organisms and the environment. There is a concern in regulatory agencies that standard toxicological models and testing methods may be inadequate to assess the potential impacts of nanoparticles (Holsapple et al. 2005; EPA 2007).

In spite of the growing and widespread use of these materials, their impacts on the environment and on human health are largely unknown (Colvin 2003; Powers et al. 2006). Understandably, considerable attention is being focused on increasing our awareness of the human health and safety risks associated with nanotechnology (Thomas and Sayre 2005; Gwinn and Vallyathan 2006), with particular reference to the consequences of workplace exposure (Maynard et al. 2004). The risks of nanotechnology to the environment have been acknowledged (e.g., Colvin 2003; Liu 2006), but relatively little work has focused on aquatic ecosystems and the characteristics that may make them susceptible to nanoparticle pollution (Moore 2006). This article highlights a number of important issues pertaining to nanotechnology and its potential effects on aquatic and marine ecosystems. We suggest proactive approaches to identifying these unique ecological problems so that the benefits of nanotechnology can be fully realized without harm to the environment. If the nanotechnology industry is provided with clear data on potential mechanisms of toxicity early in the product development cycle, the specific properties of each nanoparticle can be tailored to minimize any unwanted effects but maintain the commercially desirable properties of the material.

Routes of Nanoparticles Into the Aquatic Environment

  1. Top of page
  2. Summary
  3. Introduction
  4. Routes of Nanoparticles Into the Aquatic Environment
  5. Detection in the Environment
  6. Bioavailability
  7. Environmental and Biological Fate
  8. Bioaccumulation
  9. Potential Mechanisms of Nanoparticle Toxicity
  10. Potential Effects of Nanoparticles on Aquatic Organisms
  11. Genomic, Proteomic, and Metabolomic Risk Assessment Tools
  12. Acknowledgements
  13. References
  14. About the Author

The increased use and disposal of engineered nanoparticles will eventually result in their accumulation in air, soil, water, and organisms. Direct release of nanoparticles may occur during their manufacturing or purification processes or through their direct application to soil and water for contaminant remediation. As of April 2008, it is estimated that there are currently greater than 610 available consumer products utilizing nanomaterials (Project on Emerging Nanotechnologies 2008), and this figure is undoubtedly going to increase markedly as manufacturers exploit the beneficial properties of nanomaterials. It follows that the disposal of these products (e.g., personal care products, pharmaceuticals, electronic and sporting equipment) will increase in the coming years and that nanoparticle pollutants will inevitably accumulate in aquatic environments. Airborne nanomaterials will end up in soil and the aquatic environment through direct input via wet deposition and gravitational settling. Runoff from contaminated terrestrial environments, such as landfills and industrial sites, will also be a significant input source of nanomaterials into aquatic environments. The manufacturing processes utilized for some nanoparticles2 employ metals such as iron, nickel (Lam et al. 2004), and cadmium (Choi et al. 2007) as well as other potentially toxic compounds (Vallhov et al. 2006). Even highly purified nanoparticles can still contain significant levels of free metals as impurities (Lam et al. 2004). These impurities can pose an additional risk to ecosystems if released in sufficient quantities.

Detection in the Environment

  1. Top of page
  2. Summary
  3. Introduction
  4. Routes of Nanoparticles Into the Aquatic Environment
  5. Detection in the Environment
  6. Bioavailability
  7. Environmental and Biological Fate
  8. Bioaccumulation
  9. Potential Mechanisms of Nanoparticle Toxicity
  10. Potential Effects of Nanoparticles on Aquatic Organisms
  11. Genomic, Proteomic, and Metabolomic Risk Assessment Tools
  12. Acknowledgements
  13. References
  14. About the Author

Our capacity to detect and quantify nanoparticles in the environment is extremely limited and remains one of the most critical priorities for the advancement of research into the toxicity of these compounds. There is currently no reliable way to distinguish between manufactured and naturally occurring nanoparticles. There are also no simple methods to characterize the exact molecular structure of an unknown nanoscale particle in a complex mixture of other compounds, such as a biological sample or a soil or water sample (Burleson et al. 2004). Electron microscopy can provide information on the shape of a nanoparticle, but getting representative, quantitative data on sample composition and the concentration of specific particles requires meticulous sample preparation and the examination of thousands of particles (Powers et al. 2006). In addition, preparation of samples for electron microscopy can change the aggregation characteristics of nanoparticles and may not give an accurate picture of the state of these materials in the original sample (Burleson et al. 2004). The inability to accurately determine the presence and/or chemical structure of manufactured nanomaterials may severely hinder efforts to investigate the impact of these compounds once they are released into an uncontrolled environment. Obtaining accurate information about the physical and chemical makeup of an unknown environmental toxicant will aid in predicting its bioactivity and ecosystem effects and help in deciding on the most appropriate remediation action. The following sections outline several processes that may affect the distribution and fate of nanoparticles in the environment. These processes may alter our capacity for characterizing nanoparticles in complex samples and should be carefully considered when in examination of detection methods.

Bioavailability

  1. Top of page
  2. Summary
  3. Introduction
  4. Routes of Nanoparticles Into the Aquatic Environment
  5. Detection in the Environment
  6. Bioavailability
  7. Environmental and Biological Fate
  8. Bioaccumulation
  9. Potential Mechanisms of Nanoparticle Toxicity
  10. Potential Effects of Nanoparticles on Aquatic Organisms
  11. Genomic, Proteomic, and Metabolomic Risk Assessment Tools
  12. Acknowledgements
  13. References
  14. About the Author

The surface chemistry and physical structure of each nanomaterial will be the major determinant of its bioavailability, and these parameters will be different for every type of particle (Powers et al. 2006). The physical and chemical properties of the soil and water that a particular nanoparticle comes into contact with will also play a critical role in determining the fate of that particle in the environment (EPA 2007). Nanoparticles are prone to aggregation and sorption onto organic and inorganic material due to their small size and reactive surface characteristics (Holsapple et al. 2005). Adsorption onto soil components may result in a significant accumulation of nanoparticles in terrestrial environments. Soil composition, as well as the characteristics of the water it is exposed to, will determine whether a particular particle will be washed out by groundwater and runoff or remain bound to the soil. The characteristics of particle coatings must be carefully considered, as they change the nature of these interactions and significantly influence the environmental fate of particles. Knowledge about the fate of surface coatings in the environment will be critical in assessing the potential bioactivity of a specific material (Balshaw et al. 2005). Finally, nanoparticles are engineered with a huge variety of structural and chemical characteristics, which makes it impossible to formulate a general hypothesis regarding their toxicity in aquatic environments. Predictions about the safety of each material should be made on an individual basis and should account for changes in the structural and chemical makeup of the specific compound that can occur over time or as a result of biological and/or environmental factors (Kashiwada 2006).

Exposure routes for aquatic animals will depend largely on their particular feeding and life history strategies. Ingestion of particles bound to food sources or suspended sediments represents a significant risk, particularly to filter-feeding animals that process large volumes of water for both respiratory gas exchange and feeding. Intestinal uptake has been documented for a number of nanoparticles (des Rieux et al. 2006), and this will likely be a major route of exposure for many aquatic organisms. The uptake of nanoparticles directly through the skin is also possible. Several studies have observed dermal penetration of nanoparticles under certain circumstances (Bennat and Müller-Goymann 2000; Tinkle et al. 2003), and potential uptake via the olfactory bulb has been suggested (Oberdörster 2004). Amphibians may be particularly susceptible to dermal nanoparticle exposure via their well-vascularized, membranous skin, which is an important organ for gas exchange (Feder and Burggren 1985). The potential for absorption of nanoparticles into the chorion of fish eggs and their persistence into the adult animal have been demonstrated (Kashiwada 2006), although the exposure doses used in this study are unlikely to be environmentally relevant.

The fragile respiratory epithelium of water-breathing aquatic organisms is prone to damage from suspended toxicants, and manufactured nanoparticles may pose a significant risk to this tissue. Animals living in an aquatic environment require a substantial surface area for gas and ion exchange, and this is accomplished in large part by the gills (Perry 1997). The gills maintain a very short distance for transit between the outside environment and the blood, averaging approximately 5 to 15 μM. This large surface area with a small diffusion distance provides a direct route for the rapid transfer of a number of contaminants into the organism (Wood et al. 2002). The implications of these anatomical features on the potential toxicity of nanomaterials will be discussed further in the following text.

Environmental and Biological Fate

  1. Top of page
  2. Summary
  3. Introduction
  4. Routes of Nanoparticles Into the Aquatic Environment
  5. Detection in the Environment
  6. Bioavailability
  7. Environmental and Biological Fate
  8. Bioaccumulation
  9. Potential Mechanisms of Nanoparticle Toxicity
  10. Potential Effects of Nanoparticles on Aquatic Organisms
  11. Genomic, Proteomic, and Metabolomic Risk Assessment Tools
  12. Acknowledgements
  13. References
  14. About the Author

Little information is available regarding the breakdown and/or biological deactivation of nanoparticles in the environment. It is unlikely that inorganic nanoparticles such as titanium dioxide (TiO2) will be subject to biological degradation; however, surface coatings and attached functional groups may be altered enzymatically or chemically (Borm et al. 2006). Altering these coatings significantly changes the bioactivity of the particle. For example, minor differences in the structure of fullerene nanoparticles can result in a 7 orders of magnitude change in the lethal dosage in human cell lines (Sayes et al. 2004). The effects of temperature, pH, dissolved gases, and ion concentrations in aquatic environments will undoubtedly play a major role in the rate of environmental depuration (purification) of nanoparticles. Heat-sensitive degradation processes could proceed at considerably slower rates in the cold, stenothermal3 Arctic and Antarctic oceans or bodies of freshwater in subpolar regions. Oxidative degradation of nanomaterials may be limited or absent in hypoxic and anoxic environments, such as those common in marine (Wu 2002) and freshwater (MacCormack et al. 2003) ecosystems. Aquatic environments can also exhibit pHs ranging from acidic to basic, and the concentration of dissolved ions in surface waters ranges from near-distilled to hypersaline (up to three times as salty as normal seawater). These extremes in water chemistry are common and should be considered in any attempt to predict the fate of nanoparticles in the environment.

Equally little is known about the depuration of nanoparticles from organisms. In one study, single-walled carbon nanotubes persisted in the lungs of mice for at least 90 days following exposure via intratracheal instillation (Lam et al. 2004). Normally, elimination of particles from the body occurs via mucus, urine, or bile secretion into the feces. The kidney is capable of filtering some nanoparticles from the circulation and excreting them in the urine (Nigavekar et al. 2004), although its efficiency will largely depend on the individual physical and chemical characteristics of the particle in question.

Bioaccumulation

  1. Top of page
  2. Summary
  3. Introduction
  4. Routes of Nanoparticles Into the Aquatic Environment
  5. Detection in the Environment
  6. Bioavailability
  7. Environmental and Biological Fate
  8. Bioaccumulation
  9. Potential Mechanisms of Nanoparticle Toxicity
  10. Potential Effects of Nanoparticles on Aquatic Organisms
  11. Genomic, Proteomic, and Metabolomic Risk Assessment Tools
  12. Acknowledgements
  13. References
  14. About the Author

Bioaccumulation of nanoparticles is a significant possibility given that many are inorganic, are specifically engineered for strength and durability, and have a tendency to sorb onto larger particles. It is likely that a number of types of nanoparticles will enter the food chain by being eaten by primary consumers, such as zooplankton, which are known to ingest nanoscale particles (Borm et al. 2006). Larger animals subsequently eat these primary consumers, in addition to detritus with adsorbed nanoparticles. Toxicant burden increases higher in the food chain, with top predators typically accumulating the most significant concentrations (Henriksen et al. 2001; Kelly et al. 2006). In this manner, nanoparticles that may be present in the environment in extremely low levels can accumulate to the point where they become bioactive and significantly impact an ecosystem. This phenomenon is well illustrated by examples of persistent, low-level toxins such as polychlorinated biphenyls (PCBs) and metals, which accumulate in the tissues of higher organisms and eventually reach toxic concentrations (Muir et al. 1992).

Potential Mechanisms of Nanoparticle Toxicity

  1. Top of page
  2. Summary
  3. Introduction
  4. Routes of Nanoparticles Into the Aquatic Environment
  5. Detection in the Environment
  6. Bioavailability
  7. Environmental and Biological Fate
  8. Bioaccumulation
  9. Potential Mechanisms of Nanoparticle Toxicity
  10. Potential Effects of Nanoparticles on Aquatic Organisms
  11. Genomic, Proteomic, and Metabolomic Risk Assessment Tools
  12. Acknowledgements
  13. References
  14. About the Author

Nanoparticles are often engineered with highly reactive surface chemistries that may permit them to exert toxic effects without actually entering the cells of an organism. The physical dimensions of nanoparticles may allow them to interact with cellular receptors or transport proteins (Moore 2006) that face the environment. In aquatic animals, such as fish, the respiratory and ion transport surface area can be greater than 60% of the total surface area of the animal (Rombough and Moroz 1997), presenting a large area for potential interaction with nanoparticles. The toxicity of metals in aquatic animals results from an interaction of the metal with gill ion transport mechanisms, resulting in ionoregulatory failure (Pane et al. 2004), and this may represent an important mechanism of toxicity for nanoparticles as well. Interactions between nanoparticles and epithelial proteins may not occur in a manner that can be predicted by their chemical structure alone. This is due to large surface area per unit mass of nanoparticles and the fact that a significant percentage of their atoms are exposed at the surface of the molecule (Powers et al. 2006).

Numerous studies have noted an increase in the production of reactive oxygen species (ROS) in tissues exposed to specific nanoparticles (Oberdörster 2004; Sayes et al. 2004; Hussain et al. 2005; Lin et al. 2006), and this is considered an important mechanism of toxicity for several forms of TiO2 particles (Tsuji et al. 2006). No evidence of increased ROS production or toxicity is observed in cells exposed to nanodiamonds (Schrand et al. 2007). Aquatic organisms are very sensitive to oxidative pollutants (Valavanidis et al. 2006); therefore, their capacity to deal with ROS may be a key factor in determining the potential effects of nanoparticles on individual ecosystems.

A number of nanoparticles are specifically designed to insert into biological membranes (Tarek et al. 2003; Nednoor et al. 2005) and can act as transporters or ionophores. In biological terms, ionophores are used to pass ions across membranes. Many antibiotics function as specific ionophores by inserting themselves into the plasma membrane and disrupting established ionic gradients, thereby killing the target cells. Given that membrane biology is a dynamic process, with production, insertion, and recycling of components occurring continuously, a large potential exists for nanoparticles to be transported into the animal (Sawant et al. 2006) and exert profound cellular effects once present.

Nanoparticles with a desirable biological trait, such as the ability to traverse a membrane or a marked tissue specificity, can be functionalized through attachment to pharmacological agents, DNA, or proteins (Yeh and Hummer 2004) or even by encapsulating active enzymes inside them (Sharma et al. 2005). Features such as these have led to considerable research into the use of nanoparticles as targeted drug and gene delivery systems (Gwinn and Vallyathan 2006), with the aim of increasing the potency and specificity of treatments with the promise of decreasing unwanted side effects. These technologies have the potential to revolutionize the diagnosis and treatment of disease. Developing technologies that will be able to assess the specificity of the particle within biological systems is absolutely necessary to fulfill this promise. This will reduce the possibility of releasing particles that have adverse, unpredicted side effects when applied in a clinical setting or when subsequently released into the environment. For instance, several nanoparticles have been shown to facilitate the transport of pharmacological agents across the blood–brain barrier (BBB) (Silva 2007). Under certain conditions, however, the potentiation of BBB transport is not specific to the pharmacological agent in question, and nanoparticles can disrupt the membrane potential and result in a general increase in BBB permeability (Lockman et al. 2004). In addition to their explicit potential for detrimental effects, it is conceivable that these nanoparticles may also increase the toxicity of other pollutants by allowing them access to the normally well-protected nervous system. If released into the environment, these agents could induce complex, species-specific pathogenic responses that would be extremely difficult to predict.

Potential Effects of Nanoparticles on Aquatic Organisms

  1. Top of page
  2. Summary
  3. Introduction
  4. Routes of Nanoparticles Into the Aquatic Environment
  5. Detection in the Environment
  6. Bioavailability
  7. Environmental and Biological Fate
  8. Bioaccumulation
  9. Potential Mechanisms of Nanoparticle Toxicity
  10. Potential Effects of Nanoparticles on Aquatic Organisms
  11. Genomic, Proteomic, and Metabolomic Risk Assessment Tools
  12. Acknowledgements
  13. References
  14. About the Author

The risks of nanotechnology to the environment are increasingly well recognized; however, most studies have concentrated on the effects of nanoparticles on organisms under steady-state physiological conditions. In reality, organisms are constantly adapting to a multitude of changes in their environment. Aquatic and marine species in particular naturally face extreme changes in temperature, oxygen, salinity, and pH in addition to anthropogenic threats. The effects of toxicants are often subtle and difficult to detect because of the complexity of the physiological response to these environmental changes. Efforts should be made to predict the potential effects of novel nanomaterials on these adaptive responses and experimentally confirm their safety before decisions are made regarding proper utilization and disposal practices. A few examples of the potential risks of engineered nanomaterials to aquatic organisms in the context of their adaptation to environmental stressors are provided here.

The dynamic temperature regime encountered by ectothermic organisms should be an important consideration in assessment of environmental issues related to nanomaterials. Animals have the capacity to physiologically compensate for temperature changes, so that many biochemical reaction rates can be maintained over a wide temperature range. This type of thermal compensation is common in ectotherms and is achieved by a change of enzyme levels or a switch to a more appropriate isoform of that enzyme. The symptoms of exposure to an engineered nanoparticle that affects a specific enzyme may therefore change significantly with changing environmental temperature.

Cell membrane structure is also altered during temperature changes by variation of the content of unsaturated fatty acids, cholesterol, and other factors to maintain membrane fluidity and preserve the function of membrane-bound proteins. Nanoparticles that are designed to insert into biological membranes may interfere with these adaptative processes and reduce the capacity of membrane proteins to function following a temperature change. In ectotherms, such as fish, the characteristics of cellular energy metabolism also change with changing temperatures (Driedzic and Gesser 1994). This is even observed in some mammalian species that decrease their body temperature during hibernation (Carey et al. 2003). To our knowledge, the effects of nanoparticles on metabolic processes during temperature challenges have not been addressed. Given that many nanoparticles are specifically engineered to insert into membranes and alter their physiology, we feel that temperature-dependent effects of these particles must be studied to gain a better understanding of their potential environmental impacts.

Aquatic organisms can also be faced with significant changes in salinity, particularly diadromous species that migrate between freshwater and seawater or those inhabiting estuarine environments. Fish adapt to changes in salinity largely through morphological and physiological modifications of their gill membranes in order to maintain the homeostasis of their body fluids (Goss et al. 1998). These adaptations can change the permeability characteristics of the gill membrane and potentially affect an organism's exposure or response to environmental nanoparticles. Salinity has significant effects on the bioaccumulation of toxicants in estuarine bivalves (García-Luque et al. 2007).

The limited solubility of oxygen in water and its dependence on environmental influences commonly results in low oxygen availability (hypoxia) in aquatic environments (Wu 2002). Aquatic and marine organisms exhibit physiological responses to hypoxia that can make them much more vulnerable to nanoparticle exposure and toxicity. In fish and other aquatic vertebrates, the response to hypoxia manifests itself in the form of increased ventilatory effort, coupled with the cardiovascular changes necessary to exploit those adjustments. These factors can make animals more vulnerable to environmental toxicants. Prolonged exposure to hypoxia can be associated with increased gill surface area (Fernandes 1996; Sollid et al. 2003). In amphibians, cutaneous respiration is an important source of oxygen, and decreased oxygen availability triggers a thinning of the skin (Boutilier et al. 1992) and an increase in body surface area (Feder and Burggren 1985). In several species, the skin grows into folds that hang off the body, increasing the effective surface area of the animal (Boutilier et al. 1992). In larval frogs exposed to hypoxia, skin capillary density doubles, and the capillary mesh moves outward, improving the efficiency of cutaneous oxygen uptake (Feder and Burggren 1985). In the context of these survival strategies, it is clear that decreased oxygen availability in an aquatic system can greatly increase an organism's risk of dermal or respiratory exposure to suspended or colloidal nanoparticles.

Responses to systemic oxygen debt also occur at the cellular level, and some nanoparticles have the potential to directly affect the signaling pathways responsible for these adaptive responses. Hypoxia Inducible Factor-1α (HIF-1α) is an oxygen-sensitive transcription factor that plays a critical role in cell signaling at the onset of hypoxia, leading to a number of adaptive changes that aid in survival (Chandel and Budinger 2007). A genetically modified, oxygen-insensitive form of HIF-1α is a therapeutic agent that has shown promise in promoting angiogenesis for the treatment of myocardial ischemia and for the facilitation of cell transplantation therapies (Trentin et al. 2005, 2006). This is achieved by using nanoparticles to deliver the gene for the oxygen-insensitive HIF-1α to specific sites where vascular development is required (Trentin et al. 2006). Although unlikely, the release of an agent of this type into the environment is conceivable and could result in a complex series of detrimental effects to nontarget organisms. The unintended introduction of a gene such as oxygen-insensitive HIF-1α into species normally tolerant to environmental stressors could impair that organism's ability to adapt and survive in a dynamic habitat. It is clear from this example that conventional toxicology testing methods would be inappropriate for assessing the environmental risks of nanoparticle-based gene-delivery systems. The potential therapeutic benefits of gene therapy are immense; however, rapid inactivation and/or biodegradation must be a critical safety consideration in the design of nanoparticle gene-delivery systems.

Genomic, Proteomic, and Metabolomic Risk Assessment Tools

  1. Top of page
  2. Summary
  3. Introduction
  4. Routes of Nanoparticles Into the Aquatic Environment
  5. Detection in the Environment
  6. Bioavailability
  7. Environmental and Biological Fate
  8. Bioaccumulation
  9. Potential Mechanisms of Nanoparticle Toxicity
  10. Potential Effects of Nanoparticles on Aquatic Organisms
  11. Genomic, Proteomic, and Metabolomic Risk Assessment Tools
  12. Acknowledgements
  13. References
  14. About the Author

The ability to provide a rapid form of environmental risk assessment for each type of nanoparticle is a growing issue in nanotechnology research. By immediately developing a strong scientific framework for assessing exposure mechanisms and potential impacts of nanotechnology, we can facilitate development of nanotechnology and avoid many of the problems associated with negative public perceptions, thus benefiting both industry and society. Each new compound that is manufactured will undoubtedly require both an environmental and a biological safety assessment before it can be released as a commercial agent. It is clear from the above discussion, however, that most current toxicological testing methods will not adequately address the potential problems associated with novel nanomaterials.

Toxicological testing is generally performed via time-consuming techniques whereby model organisms are exposed to environmentally relevant doses of a novel agent for varying periods of time and then a few physiological parameters are measured. The unique chemistry of engineered nanoparticles will make it extremely difficult to predict their mechanism or mechanisms of action and the appropriate physiological parameter to monitor. The use of advanced analytical techniques such as functional genomics, proteomics, and metabolomics4 will give a much broader assessment of the specific biological responses to a novel chemical (Olden 2006; Benninghoff 2007). These tools sensitively characterize the expression patterns of many genes, proteins, and metabolites under different physiological conditions. When used in concert, they can provide a nearly complete, instantaneous snapshot of the physiological status of an organism.

Our lab is currently utilizing these powerful techniques to investigate the potential effects of manufactured nanoparticles on the zebrafish (Danio rerio). Zebrafish are widely available and easy to maintain, which makes them desirable for use as a model animal in commercial toxicology bioassays. These animals also have a fully sequenced and annotated genome, which is essential for genomic and proteomic analyses. We are currently exploiting these methods to quantitatively assess changes in the levels of specific genes, proteins, and metabolites that can then be used as biomarkers to quickly identify whether an organism has been exposed to a specific nanoparticle. Cellular responses to stress or toxicants result in alterations in gene expression and the levels of specific proteins and metabolites that create “fingerprints” exclusive to particular stimuli. These characteristic patterns of changes can then be used to develop microarray technologies for environmental risk assessments. The aim is to build an accessible database of responses to multiple classes of nanomaterials and their associated surface coatings and functional groups. In preliminary work with healthy zebrafish liver tissue, we were able to identify greater than 1,200 proteins in the cytosolic (water-soluble) fraction alone (Wang et al. 2007).

Given the technical difficulties associated with identifying and characterizing unknown nanoscale materials in complex mixtures (Burleson et al. 2004), zebrafish bioassays, in combination with the genomic methods discussed above, are an efficient means of elucidating the biologically relevant features of an unknown nanoparticle or novel toxicant. The use of genomic, proteomic, and metabolomic tools with a number of model systems, including mammalian cell lines, zebrafish, daphnia, and representative plant and microbial models, will ensure that potential ecosystem effects are identified rapidly and thoroughly. These methods will also identify potential genotoxic effects of nanoparticles (Marple et al. 2004) that would otherwise require a difficult and time-consuming generational analysis of a population. Creating advanced, robust, and accessible risk assessment tools for emerging pollutants such as nanoparticles is absolutely necessary to allow these technological developments to move forward with the conviction that potential health and environmental risks have been clearly identified.

Acknowledgements

  1. Top of page
  2. Summary
  3. Introduction
  4. Routes of Nanoparticles Into the Aquatic Environment
  5. Detection in the Environment
  6. Bioavailability
  7. Environmental and Biological Fate
  8. Bioaccumulation
  9. Potential Mechanisms of Nanoparticle Toxicity
  10. Potential Effects of Nanoparticles on Aquatic Organisms
  11. Genomic, Proteomic, and Metabolomic Risk Assessment Tools
  12. Acknowledgements
  13. References
  14. About the Author

Tyson J. MacCormack was funded by postdoctoral fellowships from the Natural Sciences and Engineering Research Council of Canada and the Isaak Walton Killam Foundation. This work was funded by an Alberta Ingenuity Centre for Water Research grant to Greg G. Goss.

Notes
  • 1

    Whether and how nanomaterials are subject to existing environmental laws is currently a matter of debate. See, for example, the study by Davies (2006).

  • 2

    Editor's note: A review of nanomanufacturing methods and some of their environmental impacts can be found in an article by Şengül and colleagues (2008) in this issue.

  • 3

    Stenothermal refers to environments where organisms are capable of living or growing only within a limited range of temperatures.

  • 4

    Genomics refers to techniques in genetics and molecular biology for the genetic mapping and DNA sequencing of sets of genes or the complete genomes of selected organisms (“Genomics” n.d.). Proteomics refers to techniques of molecular biology, biochemistry, and genetics for the analysis of the structure, function, and interactions of the proteins produced by the genes of a particular cell, tissue, or organism (“Proteomics” n.d.). Metabolomics refers to techniques for the detection and quantification of low-molecular-weight molecules, known as metabolites, produced by living cells under different conditions and times in their life cycles (“Metabolomics” n.d.).

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  1. Top of page
  2. Summary
  3. Introduction
  4. Routes of Nanoparticles Into the Aquatic Environment
  5. Detection in the Environment
  6. Bioavailability
  7. Environmental and Biological Fate
  8. Bioaccumulation
  9. Potential Mechanisms of Nanoparticle Toxicity
  10. Potential Effects of Nanoparticles on Aquatic Organisms
  11. Genomic, Proteomic, and Metabolomic Risk Assessment Tools
  12. Acknowledgements
  13. References
  14. About the Author
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About the Author

  1. Top of page
  2. Summary
  3. Introduction
  4. Routes of Nanoparticles Into the Aquatic Environment
  5. Detection in the Environment
  6. Bioavailability
  7. Environmental and Biological Fate
  8. Bioaccumulation
  9. Potential Mechanisms of Nanoparticle Toxicity
  10. Potential Effects of Nanoparticles on Aquatic Organisms
  11. Genomic, Proteomic, and Metabolomic Risk Assessment Tools
  12. Acknowledgements
  13. References
  14. About the Author

Tyson J. MacCormack is a Killam Postdoctoral Fellow in the Biological Sciences Department at the University of Alberta in Edmonton, Alberta, Canada. Greg G. Goss is a professor in the Biological Sciences Department at the University of Alberta.