The potential of risk from chemical ingredients in products is affected by the physical and chemical properties of the compound and the other substances in the product. For example, a chemical compound may be more or less hazardous, depending on its product formulation (that is, an impregnated solid suspension versus a chemical solution). Recently, there is been much interest in the role that the size of a particle plays in chemical hazard and exposure potential. In particular, do very small particles cause greater chemical risk than larger particles with the same chemical composition? For example, nanoparticles are less than 100 nm in at least one dimension. Do particles comprised of titanium dioxide (TiO2 that are smaller than 100 nm exhibit different toxicity or exposure than larger TiO2 particles?
Nanoparticles and derivative nanomaterials are pervasive in modern consumer products and are growing in number at over 243 new products per year, and currently estimated at 1317 products manufactured by 587 companies in over 30 countries. These consumer products span several major categories (health and fitness, home and garden, automotive, food and beverage, electronics and computers, appliances, goods for children), yet their full impact on product life-cycle and human health remains poorly understood, with a lack of harmonized standards on safety characterization and eco/human health assessments.
These emerging material additives have attracted considerable attention from scientists from the environmental exposure and health hazards communities. The source of these emerging materials in products, and their overall environmental fate and transport, environmental degradation, biodegradation, biological uptake and disposition, and effects remain poorly characterized. In fact, physiologically based pharmacokinetics and pharmacodynamics (PBPK/PD) research is ongoing in both the medical and environmental sciences. The manner and rates at which chemicals are absorbed, distributed, metabolized, and eliminated (ADME) are crucial in determining whether a molecule will reach the desired target, such as a chemotherapeutic compound reaching the tumor. Similarly, ADME informs the environmental toxicologist about the manner and rate that a chemical (xenobiotic) may reach an undesired target; for example, lead (Pb) reaching neurons in the brain and adversely affecting normal nerve activity.
Chemical manufacturers, pharmaceutical companies, and environmental researchers look for similar characteristics in chemical compounds that may allow them to “hide” from physiological processes as they find their way to the target cells. For example, nanoparticles for drug delivery consist of various biological substances such as albumin, gelatin, and phospholipids for liposomes and abiotic substances, including various polymeric and solid metal-containing nanoparticles. The potential interaction of these nanoparticles with tissues and cells is under investigation, but there appears to be both great promise and concern, depending on whether the target is drug delivery or potential toxicity. One aspect of more adequately addressing emerging concerns of nanomaterials is being able to properly characterize both their core and surface properties, variables that ultimately delineate many down-stream phenomena found in biological systems that have remained elusive in public health and environmental characterization.
There is a great need for reliable information as to whether a chemical ingredient may provide benefits, risks or, as is usually the case, both. The typical means of gaining such information is to compare a chemical to other chemicals with similar structures (known as quantitative structure activity relationships, QSAR). Unfortunately, only a small number of chemicals have been studied sufficiently from which to draw such comparisons. More importantly, QSAR cannot account for unique differences in even very similar compounds. For example, it is well known that chemicals with identical formulas, but with different configurations (for example, enantiomers) may either be efficacious or toxic as ingredients in medicines. Likewise, chiral compounds with the same composition but different handedness, will have very different environmental persistence (for example, the right-handed chiral may take years to biodegrade whereas the left-hand compound may degrade in a few weeks).
A particularly challenging knowledge gap is the role nanoparticle composite constituencies (that is, surface versus core) play in determining efficacy and toxicity. The particle may be a composite, with two distinct compartments: surface and core. It may also change in time and space, so that the core constituencies become surfaces with time, as the original surface is degraded (for example, during metabolism and environmental degradation).
Usually, the toxicity and other hazards associated with chemical ingredients is a function of the physical composition of the substance. This means that the properties of both the surface and the substance core help to determine the chemical risk. For example, surface properties drive the mobility and toxicity of engineered nanomaterials/particles, but the makeup of the material construct that has been coated is also important. To this extent, it has become more apparent that there are significantly more than nine factors used for similar-composition bulk materials alone that affect nanomaterial ADME and toxicity, some of which are nanomaterial specific are listed in the table.
Scientists are searching for reliable means of simultaneously characterizing core-surface coupled characteristics. Surface modifiers and passifiers must be added to engineering nanomaterials to reduce interparticle or material aggregation properties and to tailor the nanomaterials for their desired applications. That is, very small particles have large relative surface areas, so that they tend to aggregate readily compared to larger particles comprised of the same substances. Thus, engineers must coat these materials changing the electromagnetic properties, so that they repel one another (for example, coatings of electronegative cores with neutral organic compounds). However, the newly formed passivated nanomaterial core has a completely unique morphology and surface chemistry that modifies not only molecular driving forces from a materials integrity perspective, but elicits novel biological kinetics and responses as aggregation and surface modification or core leaching occurs.
Biological macromolecules (such as liposomes and micelles) can help provide clues to engineered molecular aggregates. For example, nanoparticles take on different forms, morphologies, phases, and shapes depending on their environment. Surface-core characterization is used in biomedical applications. For example, the use of liposomes in drug delivery is based on their ability to evade immunoresponse, allowing selective bioavailability of the drug at the target site. Methods for characterizing nanoparticles exist, such as electron microscopy. However, these methods tend to be limited to characterizing total morphology and chemical composition. Thus, there is a need to holistically capture core and surface responses and to develop models for testing the variety of surface modifiers or core components (including morphology and symmetry dimensions) to characterize both the environmental and physiological transport mechanisms, that is, through core-leaching, trans-surface modification.
One form of holistic characterization critical to environmental toxicology is to predict a substance’s ADME. The typical means of gaining information about ADME, aside from developed QSAR models and other tools for predicting whether a bulk material or compound will present risks, is to conduct in vitro, in vivo, and, more recently, in silico experimental methods. In vitro studies may look at cellular activity in a petri dish, whereas in vivo studies may expose rats to the chemical ingredient and observe effects. In silico studies use computational methods such as genomic and proteomic studies, data mining, molecular modeling, and quantitative structure–activity relationships. The PBPK/PD of a chemical or its modified progeny must be understood in order to determine how the particle and its components become bioavailable. Similarly, using biomimetics methods (such as lung-on-a-chip technology) and core-surface models such as the chirally perturbed particle in a box model (CPPIB), a variety of accelerated degradation studies can be performed on varied core-surface combinations and morphology domain size optimization that will call on microscopy and chromatography specialists and methods. These studies fully integrate a variety of core activities, research streams, and facilities to take on a major emerging challenge for this novel class of materials, from both a modeling and characterization perspective.
Nanomaterial domain-specific scoping and knowledge audits
Both Web 2.0 text and visual analytics tools in conjunction with open-access databases, such as PubMed or ChemSpider, can be combined to scope and outline the state of the science in any domain-specific research stream. Used appropriately, these informatics approaches can be used for nanomaterials to help study and to predict exposures and hazards from chemical ingredients. Such approaches can target information and enhance knowledge prior to an ingredient reaching the marketplace. That is, domain-specific scoping, or knowledge auditing, can capture key information assets needed by researchers. As such, informatics tools can prevent duplication of effort and can help to consolidate scarce research expertise. The domain-specific corpus of interest is the greater body of literature (Fig. 1) that relates to nanomaterial surface characterization methods. This query on pubmed.org provided a total of 790 articles (removing review articles). Extracting the abstracts and titles of all 790 articles and pasting the domain-specific corpus (DSC) into IBM's Many-Eyes (http://www.many-eyes.com) allows one to visualize a large amount of data in a streamlined manner (Fig. 1), focusing on key points and themes in nanomaterials characterization research. One may observe that there are two predominant techniques used to characterize nanomaterials: spectroscopy and microscopy. Curiously enough, microscopy is generally surface-related [for example, atomic force microscopy (AFM) and scanning tunneling microscopy (STM)] and spectroscopy is more intrinsically core related (for example, x-ray diffraction and plasmon resonance) in addition to surface characterization methods [for example infrared (IR) and Raman) that all work in unison to probe different compositions of the core-surface composite. In a similar context, the variations of surface modifications accessible from a Many-Eyes text analysis of a nanotoxicology research article (for example, L. Yan and et al., 2011) can also be useful to provide immediate insight into key research areas outlined within an article. For instance, in Fig. 2 the case of “surface modification” as applied to nanotoxicology becomes apparent from the context of both core-modifier details and the potential applications for which the materials were tailored. Briefly, both core and surface modifiers that are being actively explored for their intended purposes [(1) cores = titanium, palladium, gold, clay, silica colloids, and carbon; (2) surface modifiers = glucose, folate, octadecane, polyethylene glycol, resins, surfactants, amino-hexyl amino propyl methoxysilane, poly(ethylene oxide), and polyelectrolytes] can be rapidly outlined.
Another scoping technique is to compartmentalize the expertise and discipline domains of all web-accessible resources for a given subject area. For example, Fig. 3 shows at least seven different areas of interest in the topic of nanotechnology. From this display, more intensive investigation or broader searches can be made, depending on the question at hand. In this instance, since the interest is in core and surface properties of nanoparticles, the left bottom domain would be further explored at a higher level of detail.
[Disclaimer: The U.S. Environmental Protection Agency through the Office of Research and Development funded and managed some of the research described here. The present article has been subjected to the Agency's administrative review and has been approved for publication.]
See also: Chemometrics; Environmental engineering; Environmental toxicology; Mesoscopic physics; Nanoparticles; Nanotechnology; Risk assessment and management; Spectroscopy; Stereochemistry; Surface physics; Toxicology