A Research Strategy for Environmental, Health, and Safety Aspects of Engineered Nanomaterials (2012) / Chapter Skim
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4 New Tools and Approaches for Identifying Properties of Engineered Nanomaterials That Indicate Risks
4 New Tools and Approaches for Identifying Properties of Engineered Nanomaterials That Indicate Risks
Pages 107-142
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From page 107... ...
(The research needs presented here are summarized according to categories of tools at the end of this chapter, Table 4-1.) CHARACTERIZED NANOMATERIALS FOR NANOTECHNOLOGYRELATED ENVIRONMENTAL, HEALTH, AND SAFETY RESEARCH Identifying ENM properties that influence biologic and environmental interactions will require well-characterized libraries of materials for hypothesistesting and reference or standard test materials that may be used as benchmarks for comparison among studies, to validate protocols or measurements, or to test 107
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. Reference Materials Reference materials are developed for hypothesis-driven research or for use as benchmarks to compare results among various tests or assays or among laboratories.
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However, because these materials typically represent specific, narrow structural types that are not easily manipulated to access a broad range of structural features, it is difficult to develop more general design rules from studies of these materials. Libraries Libraries are collections of reference materials in which structural or compositional variables are systematically varied throughout a series of members of the library.
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TOOLS, STANDARDIZED CHARACTERIZATION METHODS, AND NOMENCLATURE OF ENGINEERED NANOMATERIALS Protocols for Measuring and Reporting a Minimum Set of Material Properties for Pristine Engineered Nanomaterials Used in Nanotechnology-Related Environmental, Health, and Safety Research With regard to characterization of research and commercial samples for EHS testing, there is a need for systematic approaches for adequately and systematically defining the structure, composition (including surface chemistry) , and purity of samples so that data reported through the nanotechnology-related EHS research community ultimately can be used to correlate structure and composition of nanomaterials with their behaviors and effects.
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For example, for a ligand-stabilized inorganic nanoparticle, transmission electron microscopy (TEM) and small-angle x-ray scattering can be used to define nanoparticle cores (von der Kammer et al.
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As discussed in Chapter 3, these properties will depend on the media in which they are dispersed so methods should be tailored to the exposure conditions. The surface properties of ENMs will determine their interactions with environmental and biologic media.
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Many existing analytic techniques from material science and other disciplines are applicable to ENMs, but their use in measuring and characterizing low concentrations and heterogeneous matrices will require additional development or in some cases, development of completely new approaches. A recent review by von der Kammer et al.
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Strategies and tools for detecting and tracking materials are needed. These strategies should include combinations of techniques to detect and characterize ENMs in complex matrices, and to differentiate between naturally occurring ENMs and naturally occurring nanomaterials (von der Kammer 2012)
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Develop analytic tools and processes that can detect ENMs at low (relevant) concentrations in situ or in vivo, followed by tools to track and characterize ENM properties (for example, reactivity, reactive surface area, nanometer and subnanometer surface features, aggregation-agglomeration, and adsorption of organic macromolecules)
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Research is needed to elucidate those toxicity mechanisms for representative organisms, considering appropriate dosimetry (see above) and well-characterized ENMs, so that ENM properties can be correlated with mechanisms of injury.
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Research Needs for Development of New Protocols or Modification of Existing Protocols for Determination of Population and Ecosystem Effects Develop and validate a suite of standard tests that can indicate the potential for population or ecosystem effects of chronic ENM exposure on specific organisms. Develop methods for understanding ecosystem effects (that is, effects on systems of systems)
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Standard protocols need to be developed to "weather" or "age" ENMs in environmental and biologic media and to determine the rate and extent of transformation expected as a function of environmental and ENM properties. The aging procedures should consider expected transformations for ENMs, including dissolution, sulfidation, oxidation-reduction, adsorption of organic matter and biomacromolecules, biodegradation, and photodegradation.
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Research Needs for Development of New Protocols or Modification of Existing Protocols for Exposure Assessment Develop and validate standard protocols for measuring and reporting attachment of ENMs to biologic and environmental surfaces. Establish protocols that can be applied to pristine ENMs to identify and classify their stability in the environment.
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Specific research needs to decrease uncertainty in exposure models are described below. Sources of Engineered Nanomaterials in the Environment The expected concentration of ENMs in environmental compartments cannot be predicted without reasonable estimates of the quantity of ENMs released and an understanding of the medium into which they are released (for example, air or water)
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Methods for quantifying and characterizing ENMs in each source stream should be developed to validate models that have been constructed to predict ENM environmental releases. The models should be informed by large-scale efforts, such as the Nanomaterial Registry that is being supported by the National Institute of Biomedical Imaging and Bioengineering, the National Institute of Environmental Health Sciences, and the National Cancer Institute (Ostraat 2011)
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Exposure models need to be updated to improve estimation of the dilution behavior of ENMs released into the environment, because the choice of assumptions about dilution will influence the prediction of ENM concentrations by the models. The models need to include aggregation, deposition, and sedimentation.
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A major ecotoxicology modeling goal has been the development of reliable, predictive models whereby the chemical structure of a compound can be used to predict the harm that it will cause. That is particularly challenging for ENMs given the breadth of ENM types and the lack of understanding of ENM transformations in the environment and in organisms.
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Develop models to link the biochemical pathway responses to ENMs and ENM properties (beyond oxidative stress) to adverse outcomes.
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That is a formidable task because bioavailability and bioconcentration will probably depend in part on ENM properties, route of exposure, and dispersion media. Thus, the ENM properties and environmental conditions affecting bioavailability and bioconcentration of ENMs in long-term exposure need to be determined and incorporated into exposure models.
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Stakeholders and regulators who make risk-management decisions regarding ENMs will need to become familiar with probabilistic models and interpretation of their results. Research Needs for Incorporating Uncertainty into Models and Reporting Uncertainty in Exposure Modeling Identify key uncertainties surrounding exposure-assessment models and estimate the ranges of the uncertainties.
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Approaches and informatics requirements are described as they are related to method development and validation, model development and validation, and data management and data-sharing. Research priorities to develop the knowledge base and data-sharing capabilities are presented in Chapter 5.
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Because of those compounded difficulties in the development and dissemination of validated standard methods, recent ILSs of new protocols by the Asia Pacific Economic Forum, the American Society for Testing and Materials, and the International Alliance for NanoEHS Harmonization have shown that the reliability and reproducibility of published nanotechnology data are problematic (Hackley et al. 2009; Murashov and Howard 2011)
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needs that require new approaches and mechanisms to ensure collaborative participation. Informatics needs that require enhancement of traditional method development and validation procedures include the ability to collect, organize, curate, and share data on The methods used, including links to standard protocols.
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Each of the models incorporates submodels of different types -- models of in situ environments; cellular, tissue, organ, system, organism, and ecosystem models; and models of ENM structure that use basic descriptors, detailed molecular structures, or both and that use different numerical and statistical applications and tools. Although it may appear that the requirements for model development and validation are similar to those for method development and validation, there is a striking difference: the models are in a computer-usable form.
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is a relevant example. The wwPDB was originally designed to serve both as a repository for protein molecular structures and as a collaborative mechanism to curate and validate structural models and to improve predictive models of protein structure, conformation, binding, and activity in different environments (Berman et al.
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Adding semantic content about the meanings and relationships of the search terms is the aim of the Semantic Web, sponsored by the World Wide Web Consortium of informatics systems providers and users (W3C Semantic Web 2011)
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Moving all the data to a central site has been tried and is usually very difficult because of issues involving data rights and security and the need to agree on common formats, procedures, and rules for governance. Informatics Needs for Data-Sharing Use existing pilots to demonstrate the capability to federate the different sites through the use of semantic web technologies, including ontology development to enable data curation by experts in the data, and access control by the owners of the data.
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Who will generate the data for informatics, and what are the incentives for them to participate? From one perspective, the information used to populate the databases for nanoinformatics efforts will be developed by specialists using standard protocols and working with defined reference materials.
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without introducing experimental artifacts in exposure and toxicity studies; and standard reference materials to use in calibrating assays and measurement tools. METHODS Develop and validate new or modify existing standard toxicity-testing protocols for ENMs, including relevant cell types and organisms, appropriate dosimetry and toxicity end points (for example, chronic effects)
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concentrations in situ or in vivo, followed by methods to track and characterize ENM properties (for example, reactivity, reactive surface area, nanometer and subnanometer surface features, aggregation, and adsorption of organic macromolecules)
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2010. Considerations in evaluating the physicochemical properties and transformations of inorganic nanoparticles in water.
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Creative Industries Knowledge Transfer Network, University of Arts, London [online]
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2010. State-of-the-Science Report on Predictive Models and Modeling Approaches for Characterizing and Evaluating Exposure to Nanomaterials.
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Poster Notes of the Second International Semantic Web Conference (ISWC 2003) , October 20 23, 2003, Sanibel Island, FL [online]
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and surface modification decrease the toxicity of nanosized zerovalent iron. Environ.
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. von der Kammer, F., P.L.
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