Getting to Green - Research Progress on Environmental Health and Safety Aspects of Engineered Nanomaterials - page 61

Additional shortcomings in available ENM toxicity data are related to the need to shift
experimental study designs and models to gain more realistic and useful data for mechanistic
understanding of ENMs. The preponderance of published studies provides information of questionable
relevance to the health and environmental effects of realistic ENM exposures. Many findings are based on
acute, high-dose exposures of single cells under in vitro conditions and so provide little or no information
on relevant dose or dosimetry (for humans), on potential sustained effects (key to understanding potential
toxicity vs short-term injury resulting from reactive oxidation species or an inflammatory response), on
dose-response characteristics that provide mechanism insights, and on issues related to route of exposure
or to life cycle. Similarly, many of the animal bioassay data come from studies involving high-dose acute
exposures with limited time-course information or data on mechanisms or important end points, such as
development and reproduction. In addition, there are minimal studies of community-level or ecosystem
effects. Studies are limited to a few organisms, but uptake and mechanisms of action may differ among
species. Those issues need to be explored further in relation to establishing standardized assays.
To generate study results that can provide useful information on potential health and
environmental risks associated with ENMs and that can be validated by other researchers in the field, it
will be important to expand and redirect the focus of experiments to provide greater relevance on EHS
issues, considering the chronic low-dose exposure scenarios that prevail for people and ecosystems. The
results should be shared with other investigators, and results of in vivo studies (at relevant concentrations)
should be compared with results of in situ and in vitro screening assays to foster development of more
expedient testing strategies. However, there is a paucity of useful in vivo data to establish a foundation for
development of better screening tools. Consequently, the committee graded progress in experimental
research in organisms that is relevant to community or ecosystem level effects as yellow. Research is
ongoing in Environmental Protection Agency-National Science Foundation (EPA-NSF) centers, but
there is little emphasis on the effects of ENM exposures on interactions among organisms (community-
level effects) or on the interactions of multiple communities with the abiotic environment, including how
ENMs may change such interactions and how ENMs may be changed when interacting within the
ecosystem (ecosystem-level effects).
There is an absence of validated screening tools that are needed to apply data gained from
experiments to challenging risk-related questions in humans and ecosystems (that is, transitioning from
the laboratory world to the real world). There is a need to scale from laboratory systems to whole
organisms and to the full ecosystem. Progress may need to be tied to a federal effort, inasmuch as
individual laboratories may not have the incentive to participate in this methods development. One way to
begin to address that shortcoming may be to use the data generated in the comprehensive Organisation for
Economic Co-operation and Development program that involves 12 ENMs (representative of materials
found in commerce). This program collects extensive in vivo health effects data in accordance with
robust scientific guidelines (OECD 2013); the results could be used as benchmarks for toxicologic
evaluation of unknown ENMs. New assays under development could be compared with that rich
database. The lack of mechanistic understanding is a further barrier that limits certainty as to which types
of assays should be developed. Supporting more mechanistic research and giving individual laboratories
the opportunity to build on the few existing assays that have been tried with a subset of ENMs is
necessary to bridge this gap.
Steps to Improve Progress in Understanding Nanomaterial Interactions
in Complex Systems Ranging from Subcellular Systems to Ecosystems
The development of relevant in vivo hazard data based on appropriate routes of exposure and
realistic exposure concentrations is an excellent starting point for understanding ENM interactions in
complex systems. The ENM test material should be well characterized, and concentrations or doses
administered to the organism should be based on data obtained from exposure-assessment studies and
appropriate dose metrics (if available). Dose-response and time-course (temporal) characteristics should
be built into the experimental design of these in vivo studies, and benchmark materials should be used as