Biomedical Engineering Reference
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responses in mice and rats to three forms of nano-titanium dioxide (nano-TiO 2 ) and three forms of
multiwalled CNTs (MWCNTs) showed some interlaboratory variability of the inflammatory response to
TiO 2 , but the relative potency of the MWCNTs was similar among all laboratories. Although some
agencies, such as NIST, are evaluating different protocols (NIST 2013b), the need for standard operating
procedures has not been fully met. Establishing such procedures for all phases of ENM preparation and
toxicity testing is required to increase consistency of results among laboratories.
Several studies have identified acute ecotoxic effects of ENM exposures and issues associated
with traditional nanotoxicity assays (see Klaine et al. 2008 and above references for review). However,
there is little information on effects on ecologically relevant species or on ecosystem-level effects of the
chronic low-dose exposures to ENMs that are expected in the environment (Bernhardt et al. 2010;
Gottschalk and Nowack 2011). Investigations of perturbations in whole-organism systems are also
lacking. Efforts have concentrated on oxidative stress, which may be a fleeting reaction of an organism to
ENM exposures and may not be the sole mechanism of effects. The committee's 2012 report called for
targeted assays for assessing nanotoxicity. Efforts to assess toxicity by using high-throughput assays at
the EPA-NSF funded centers (Lin et al. 2013; Nel et al. 2013) may provide some standard acute-toxicity
information on selected nanomaterials. The relevance of those assays to more realistic chronic low-dose
exposures and population-level effects has not been established. The committee specifically suggested
development of a standard battery of assays and novel assays that may be required to describe the various
effects of many types of nanomaterials, including ones that have new biologic activities. Standardized
assays for ecosystem effects of even standard chemicals are lacking. The EPA-NSF funded centers may
be an indication of support for those types of assays, but this is the only direct support identified for this
topic.
The committee considered that there was some research progress in this category, but the
progress was marked yellow because of the lack of identification of a set of methods to determine effects.
More information on the variety of potential mechanisms and research that elucidates these mechanisms
will move this indicator toward green.
Extent of joining of existing databases, including development of common informatics ontologies
Some progress has been made toward the development of informatics ontologies and sharing of
databases. For example, the Big Data Initiative was announced in March 2012 “to greatly improve the
tools and techniques needed to access, organize, and glean discoveries from huge volumes of digital data”
with support from NSF, NIH, the Department of Energy (DOE), the Department of Defense (DOD), the
Defense Advanced Research Projects Agency, and the US Geological Survey (OSTP 2012) . The new
program defines data as including data, publications, samples, physical collections, software, and models
(NSF 2010). The same comprehensive definition underpins the new NSF Nanotechnology Signature
Initiative for a Nanotechnology Knowledge Infrastructure (NKI) with participation by the Consumer
Product Safety Commission (CPSC), DOD, DOE, EPA, FDA, the National Aeronautics and Space
Administration, NIH, NIOSH, NIST, NSF, and the Occupational Safety and Health Administration
(OSHA). In addition, the NKI will support the new Materials Genome Initiative (MGI) (NSET 2012b) so
that informatics approaches, data curation workflows, protocols, and standards developed through MGI
activities may initially be explored for nanoscale activities by the NKI effort.
Coordination of activities in the United States and the EU has been established through the
Communities of Research (CoRs) by the National Nanotechnology Coordination Office (NNCO) and the
EU. The CoRs include “predictive modeling for human health, ecotoxicity testing and predictive models,
exposure through the life cycle, databases and ontology, risk assessment, and risk management and
control” (Finnish Institute of Occupational Health 2012). The ontology CoR is responsible for
coordinating informatics needs for all the CoRs, and its databases provide a mechanism for developing
prototype systems and applications to support information-sharing, annotation, validation, and curation
for experimental, computational, and theoretical efforts in nanotechnology. The EU-US CoRs represent
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