Biomedical Engineering Reference
In-Depth Information
considered. In addition, studies have focused on acute short-term effects, and little is known about the
persistence of such effects in vivo. Moreover, effects of chronic low-dose exposure are not well
established. Phenomena observed at high doses may not be entirely relevant in vivo inasmuch as dose
may influence mechanisms (Slikker et al. 2004).
Formulation of time-course studies will be essential for in vivo and in vitro evaluations. They are
necessary for documenting the possible transformations of ENM characteristics within the life cycle and
for assessing the persistence of measured responses in organisms. The latter issue will be essential for
identifying and characterizing hazards. The mixed progress in these subjects led the committee to assess
this indicator as yellow.
Extent of use of experimental research results in initial models for predicting nanomaterial
behavior in complex biologic and environmental settings
The fate and effects of ENMs in complex environments will be determined by a set of
interactions between the materials and the properties of the environments. Identifying mechanisms by
which those interactions occur requires integration of the mechanistic understanding gained from studies
on a laboratory scale in well-controlled environments and the understanding obtained from research
conducted in environments of varied complexity. Predictive models can then be developed on the basis of
the mechanisms identified in relevant exposure scenarios. In contrast with the development of models for
specific behaviors (such as aggregation and agglomeration) in relatively well-characterized environments,
development of models for predicting nanomaterial behavior in complex biologic and environmental
systems has seen little progress. One key limitation is the lack of resources for conducting long-term
experiments in large-scale environmental systems, such as mesocosms
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, or for performing in vivo studies.
Another is the absence of a central structured database for consistent documentation of research results
that permits datasets to be compared and used in models. Some efforts are under way in EPA-NSF
funded centers to develop models for predicting nanomaterial behavior in complex biologic and
environmental systems, but they are disjointed. Data collected in the various systems (environments and
organisms) are not characterized in the same manner and are therefore not readily usable for modeling. In
addition, the focus has been on only a few ENMs, so comparisons among ENMs that have different
chemical composition are not possible. The committee therefore identified this indicator as red.
Nanomaterial Interactions in Complex Systems Ranging from Subcellular Systems to Ecosystems
In its first report, the committee recognized the need to investigate and increase the understanding
of interactions of ENMs in a variety of complex systems. Complex systems can range from subcellular
organelles to cells to organisms to ecosystems. These elements may act independently, synergistically, or
antagonistically in response to ENM exposures. Research efforts that focus on system-level approaches to
investigate potential ENM effects on human health and the environment are needed. Indirect effects may
also result from direct interactions with ENMs. For example, ENM transformations that occur in
environmental systems—for example, through weathering in ecosystems or metabolism in organisms and
ecosystems—may have unexpected effects on other organisms along the food chain or indirectly in organ
systems. Specifically quantum dots have been found to be toxic to a variety of systems, but weathering of
quantum dots can induce antibiotic resistance in some bacterial strains that could in turn affect organisms
that are susceptible to these bacteria (Yang et al. 2012). In mammals, inhaled ENMs that are deposited in
the distal lung or alveolar epithelial sites may interact with lung lining fluids to form nanomaterial-corona
complexes that may alter the disposition and biologic activity of the ENM. Therefore, a first step is to
identify relevant exposure sources, concentrations, and cellular and ecologic targets so that potential
effects on complex systems can be addressed. Research progress indicators for this category ranged from
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A means of studying the natural environment under controlled conditions.
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