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OCR for page 48
2
A Conceptual Framework for
Considering Environmental, Health,
and Safety Risks of Nanomaterials
THE NATURE OF THE CHALLENGE
The rapid emergence of engineered nanomaterials (ENMs) and their use in
diverse products imply their eventual and inevitable appearance in the bio-
sphere. As discussed in Chapter 1, the environmental and human health risks
posed by these novel materials remain largely unknown, but the materials’ wide-
spread use provides a strong motivation for investment in research directed at
potential adverse effects. The vast variety of nanomaterials and their novel prop-
erties provide a strong basis for systematic, coordinated, and integrated research
efforts to understand what properties of the materials influence their hazard and
exposure potential and what applications present the greatest likelihood of expo-
sure and adverse effects on human health and the environment.
ENMs are a subset of the broader field of nanotechnology, which is defined
by the National Nanotechnology Initiative (NNI) as “the understanding and con-
trol of matter at dimensions between approximately 1 and 100 nanometers, where
unique phenomena enable novel applications. Encompassing nanoscale science,
engineering, and technology, nanotechnology involves imaging, measuring, mod-
eling, and manipulating matter at this length scale” (NSET 2010a).
Scale-specific properties and phenomena are at the heart of current interest
and investment in ENMs. A substance can be designed and engineered at the
nanoscale to behave in a particular and useful way, thereby potentially adding
value to an existing product or becoming the basis of a completely new product.
Scale-specific properties of nanomaterials expand the possibilities for making
new products. But the same scale-specific properties are at the center of
concerns about possible new risks: if a new material behaves in novel ways,
what are the chances that this behavior will lead to harm to people and the envi-
ronment?
48
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Environmental, Health, and Safety Aspects of Engineered Nanomaterials 49
The multiplicity of ENM variants makes material-by-material assessment
impractical. That heterogeneity in nanomaterials, characterized by distributions
of properties, has spurred efforts to generalize about exposure and hazard poten-
tial in relation to these properties, rather than considering risks for specific types
of materials. Initial attempts point to complexities in understanding risks of
ENMs (Dreher 2004). For example, the size range used to describe ENMs—1-
100 nm—has relatively little bearing itself in determining the risk to people or
the environment (see, for example, Auffan et al. 2009; Drezek and Tour 2010).
Risk “problems” associated with ENMs have been formulated in terms of estab-
lished “technologic” characteristics of ENMs (such as particle size) that do not
appropriately reflect the potential for harm.
Framing risks associated with an ENM in terms of established definitions
provides some insight into emergent risks. For example, exposure potential may
be enhanced as particle size decreases to the point where novel physicochemical
properties begin to dominate behavior. At the same time, a focus on particle size
may highlight issues that are not relevant while shifting attention from such
properties as reactivity that may be more relevant to determining risks (for ex-
ample, Maynard 2011; Maynard et al. 2011a). Consequently, there is substantial
uncertainty in understanding of the risks associated with the products of
nanotechnology, leading to confusion on prioritizing, and addressing these
risks—a confusion that is illustrated in many reports on risk. (See discussion in
Chapter 1.)
In making risk-based decisions—whether translating an innovative idea
into a new product, crafting new regulations, or developing a risk-research strat-
egy—effective problem formulation is essential (NRC 2009). Formulating the
environmental, health, and safety (EHS) “problems” presented by ENMs has
proved challenging, as documented by research efforts over the last decade.
DEVELOPING A STRATEGY AND A CONCEPTUAL FRAMEWORK
In addressing the challenges presented by ENMs, the committee notes that
there is a distinction between a research strategy and a research agenda. The
committee has developed a strategy that provides a principle-based approach to
sustaining an agenda for EHS research that will be accountable and adaptive as
ENMs change, diversify, and expand in use. In this chapter, the committee de-
scribes the research framework for its strategy; later chapters identify data gaps
to be addressed by the research strategy. The generation of findings for risk as-
sessment is considered here as an evolving process based on the integration of
various research efforts rather than as a static “deliverable.” There will be an
ongoing need to inform decision-making in advance of product development and
to consider uncertainty coming from incomplete information on future produc-
tion quantities, ENM properties, and uses of nanomaterials. An evolving and
iterative process provides feedback for adjusting research priorities and provides
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50 Considering Environmental, Health, & Safety Risks of Nanomaterials
the information needed to implement risk-management strategies aimed at re-
ducing the potential for harm to human health and the environment. That feed-
back also informs the design, manufacture, and use of future ENMs.
The conceptual framework, described later in this chapter, reflects a coor-
dinated, strategic research effort that is characterized by three key features:
A reliance on principles that help to identify emergent, plausible, and
severe risks resulting from designing and engineering materials at the nanoscale,
rather than an adherence to rigid definitions of ENMs.
A value-chain and life-cycle perspective that considers the potential
harm originating in the production and use of nanomaterials, nanomaterial-
containing products, and the wastes generated.
A focus on determining how nanomaterial properties affect key bio-
logic processes that are relevant to predicting both hazard and exposure; for ex-
ample, nanomaterial-macromolecular interactions that govern processes ranging
from protein folding (a basis for toxicity) to the adsorption of humic substances
(that may influence mobility or bioavailability of the materials).
Environmental and human health risk assessment of nanomaterials is se-
verely limited by lack of information on exposure to these materials (for exam-
ple, information on fate, transport, and transformations) and on the hazards that
they present. In contrast with previous research strategies that took a sequential
approach to evaluating exposure and hazard for assessing nanomaterial-related
risks, the committee’s framework considers evaluations of hazards and exposure
as processes that occur in tandem, and it accounts for the wide variety of matri-
ces and transformations of nanomaterials along the value chain and across the
life cycle (discussed in more detail later in this chapter).
The framework is to be implemented through a research agenda that be-
gins with understanding how nanomaterial properties may affect fundamental
processes—processes that are common in determining both exposures and haz-
ards. By focusing on these processes, the goal of advancing exposure and hazard
assessment under conditions of uncertainty can be addressed in a predictive and
generalizable fashion that helps to inform decision-making on current and future
nanomaterials. Knowledge of these processes has immediate applicability in
comparing risks among materials and providing criteria for establishing priori-
ties for research on nanomaterials that are on the market, for providing feedback
on research needs and priorities, and for providing evidence needed to reduce
the risks posed by nanomaterials that are on the market or are under develop-
ment.
The sections below address the utility of risk assessment in framing a re-
search strategy for the EHS aspects of nanomaterials, the conceptual framework
that is informed by risk assessment, and the principles for setting priorities
among research needs on the basis of the properties of nanomaterials.
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Environmental, Health, and Safety Aspects of Engineered Nanomaterials 51
RISK-ASSESSMENT CONSIDERATIONS
REGARDING NANOMATERIALS
In developing this chapter, the committee found useful guidance in Sci-
ence and Decisions: Advancing Risk Assessment (NRC 2009), which offers rec-
ommendations for addressing risks in the modern world. The report examines
near-term (2-5 y) and longer-term (10-20 y) solutions focusing on human health
risk assessment, but it also considers the implications for ecologic risk assess-
ment. The report focused on two broad goals in its evaluation: improving the
technical analysis that supports risk assessment and improving the utility of risk
assessment. Although that committee concluded that technical improvements are
necessary, it suggested retaining the four basic elements of risk assessment—
hazard identification, exposure assessment, dose-response assessment, and risk
characterization—originally articulated in Risk Assessment in the Federal Gov-
ernment: Managing the Process (NRC 1983). Technical improvements are
needed in approaches to uncertainty and variability analysis and in dose-
response analysis. With regard to improving the utility of risk assessment, the
committee authoring that report focused on improvements in scoping the prob-
lem at hand and understanding a broad set of risk-management options so that
the ensuing risk assessment would be more relevant to the questions that deci-
sion-makers might ask of the scientific-knowledge base. An important conclu-
sion of the committee’s work was that risk assessment, rather than being viewed
as an end in itself, should be considered as a method for informing research and
commercialization efforts and for evaluating the relative merits of various risk-
management options.
In the context of the development of an EHS risk-research strategy for
ENMs, NRC (2009) has much to offer in framing a research agenda. The prob-
lem is not equivalent to assessing a well-defined chemical substance for which
abundant data are available. An effective risk-research strategy for ENMs will
require the identification of data and models to assess risks as the sparse data
available are augmented. Careful planning, problem formulation, and considera-
tion of options for managing the risks, including application of green-chemistry
principles (see Box 2-1), can improve the utility of assessment for decision-
making (NRC 2009).
In Table 2-1, the committee applies the framework of NRC (2009) to po-
tential risks of ENMs. The general considerations of NRC (2009) are translated
into specific considerations related to ENMs.
Challenges of Defining Potential Risks
The diverse properties of nanomaterials present a challenge to addressing
potential EHS risks of ENMs. First, it is difficult to specify the composition of
ENMs, because of the variety of material types and variation within types.
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52 Considering Environmental, Health, & Safety Risks of Nanomaterials
BOX 2-1 Incorporating Green-Chemistry Principles
Into Nanomaterial Development and Application
An evolving risk-assessment process provides the best available infor-
mation needed to inform regulatory decision-making and future research
while providing a basis for precautionary actions that might otherwise be
ruled out because of data limitations. The limitations include
Lack of data and adequate models (for example, structure-activity
and other predictive models) for nanomaterials, which results in major uncer-
tainties in describing and quantifying nanomaterial hazard and exposure
potential.
Lack of understanding and of ability to track and keep abreast of the
rapid change, already evident and expected to increase, in the array of
nanomaterials and their applications.
The diversity of nanomaterial types and variants and the poor ability
to group materials for assessment purposes on the basis of known risk char-
acteristics that can be related to specific physical properties.
Difficulties in distinguishing between exposures and risks associated
with nanoscale and conventional forms of the same substances and between
naturally occurring and incidentally produced nanoscale materials and
ENMs.
Nanomaterial development, informed by an evolving risk assessment,
presents the opportunity to identify and reduce, at the design stage, the in-
herent potential for exposure to and the hazards of nanomaterials. Applica-
tion of green-chemistry principles and design practices to nanomaterial de-
velopment can help to ensure that nanomaterials are designed to minimize
risk whatever their application.
ENMs seem ideally suited to such approaches, given the ability to exert
precise control over composition and structure. Such atomic-scale manipula-
tion is the defining essence of nanotechnology and is what makes it possible
to impart such materials with specific properties related to function and per-
formance. In principle, the same ability should extend to identifying and ex-
erting control over the factors determining a nanomaterial’s potential for ex-
posure, such as persistence, mobility, or bioavailability. Similarly, it may be
possible to reduce risk by reducing the inherent hazard of a nanomaterial by
altering such factors as composition and reactivity. The potential to precisely
define and control nanomaterial composition and structure are directly rele-
vant to a number of Green Chemistry principles (ACS 2011) such as those
addressing atom economy; use of less hazardous substances in processes;
and designing for reduced toxicity, increased energy efficiency, enhanced
degradation, and inherent safety.
An evolving risk-assessment process enables the identification and de-
velopment of predictive tools and methods for screening nanomaterials at
early stages in the development process for inherent properties that are as-
sociated with high exposure or potentially damaging biologic activity.
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Environmental, Health, and Safety Aspects of Engineered Nanomaterials 53
TABLE 2-1 Risk-Related Concerns from NRC (2009) as Applied to
Nanomaterials
Topic from NRC (2009) Consideration for nanomaterials
Emphasis should be placed on “planning Emphasis on “planning and scoping” and “problem
and scoping” and “problem formulation” formulation” will allow scientists and research
in the early phases of risk assessment to managers to triage a wide array of materials to focus on
ensure that the right questions are being the ones that present the greatest probability of a risk to
asked of the assessment. health or the environment. For example, understanding
the hierarchy of information needs from physical
characteristics to potential for release to fate in the
environment should allow critical early decisions in the
assessment process. There may be a minimum set of
information needed to address these determinants of
hazard or risk for all nanomaterials, but in the near
term the committee’s research agenda might best focus
on accumulating information on materials that appear
to be reactive, likely to be released, likely to interact
with other toxic materials and serve as delivery
mechanisms, and likely to persist under typical
environmental conditions. This somewhat simplistic
example shows the importance of developing some
early decision rules for implementation of the EHS
research agenda. As is the nature of risk assessments,
these early rules would probably be refined as
experience in assessing ENMs accrues.
Refined approaches to addressing In designing the research strategy for ENMs, a
uncertainty and variability in all premium should be placed on a “value of information”
phases of the risk assessment from analysis that underscores how the information gleaned
characterizing potential release through from the research will be used to reduce uncertainty or
potential exposure to hazard and risk will to refine an appreciation of variability in exposure or
be a critical component of information risk. Methods for doing that are available and are
needs in this risk-research strategy. continuing to evolve (NRC 2009).
Providing a perspective on the role of For nanomaterials, research is needed to determine
“default” values and scenarios in risk whether the traditional bases of default assumptions
assessments will be critical. (for example, high to low dose, animal to human, and
individual human variability in response) will apply;
these issues will need to be addressed in considering
approaches that lead to predicting releases or exposures
that are unlikely to result in deleterious effects to
humans and the environment.
Cumulative (multiple agents, same route) For nanomaterials, research on releases of
and aggregate (single agents, different nanomaterials from multiple processes for different
routes) exposures need to be addressed. applications must be conducted to account for the
potential for total release to the environment.
Individual assessments of process-release scenarios
have the potential to underestimate environmental and
human exposures. Potential interactions of different
nanomaterials in common disease processes should
also be considered.
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54 Considering Environmental, Health, & Safety Risks of Nanomaterials
Countless assemblages of atoms and structures and a plethora of inorganic and
organic macromolecular coatings affect their surface chemistry and therefore
their behavior in the environment and their potential for biologic impact.
Second, nanoscale structures include both materials (for example, parti-
cles, fibers, or sheets) and macromolecules (for example, proteins or DNA).
Many nanomaterials are particles or designed structures, not molecules. The
heterogeneity of the materials profoundly affects efforts to detect or to measure
the ENMs or to assess their potential to cause harm. Large biomolecules that are
labeled as ENMs may be detected with high specificity using molecular recogni-
tion elements. Spectroscopic approaches may provide certifiable identification
for some large molecular ENMs. Such approaches will frequently fail with the
more complex structures. These materials may have highly uniform properties,
while many of the more complex structures will lead to a range of possible in-
teractions. However, the magnitude of forces and the resulting bond strengths
induced by interactions with ENMs may be different from those for molecules.
In addition to forces that show size dependence (for example, van der Waals
interactions), the presence of a separate phase introduces surface energies and
boundary effects (for example, discontinuity of crystal lattices at a particle sur-
face and resultant surface charge) that are not present with molecules in solu-
tion.
Also, the relative impacts of kinetic compared with thermodynamic factors
in controlling the environmental behavior of nanoparticles may be expected to
differ from conventional chemical species for which there has been success in
predicting phenomena, such as bioaccumulation or transport from, for example,
use of structure-function relationships to calculate fugacity.
Third, like many “conventional” contaminants, chemical transformations of
the nanomaterials and their coatings will occur in the environment and in organ-
isms, and such transformations are not well characterized or readily predictable.
Fourth, the surface properties of nanomaterials are defined in part by the
media in which they are dispersed; for example, surface water, lung fluid, salt
water, and air may affect these properties differently. Because the behavior of
nanomaterials may be controlled largely by surface properties, general predic-
tions about environmental behavior and effects cannot be readily made. Overall,
the lack of a clear and stable material identity makes it difficult to group materi-
als or classes of materials that may behave similarly with respect to fate, trans-
port, toxicity, and risk. Moreover, because most nanomaterials can be thought of
not only as chemical entities but as having separate phases, there is considerable
doubt regarding the appropriateness of applying or interpreting some of the con-
ventional parameters used in exposure assessment, such as octanol-water parti-
tion coefficients and volatility.
A CONCEPTUAL FRAMEWORK LINKED TO RISK ASSESSMENT
The committee developed Figure 2-1, which establishes a conceptual
framework for informing its research agenda in Chapter 5. The figure, which is
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Environmental, Health, and Safety Aspects of Engineered Nanomaterials 55
not intended to portray a linear, sequential process, begins with a value-chain
and lifecycle perspective. It depicts sources of nanomaterials originating
throughout the lifecycle and value chain, and therefore the environmental or
physiologic context that these materials are embedded in, and the processes that
they affect. The circle, identified as “critical elements of nanomaterial interac-
tions,” represents the physical, chemical, and biologic properties or processes
that are considered to be the most critical for assessing exposure and hazards
and hence risk. Those elements exist on many levels of biologic organization,
including molecular, cellular, tissue, organism, population, and ecosystem. The
committee asks, What are the most important elements that one would examine
to determine whether a nanomaterial is harmful? and has placed these elements
at the center of the proposed research framework. The critical elements in the
circle are not ordered, and the dynamic interactions among them are implied.
For example, factors that affect surface affinity may also affect persistence and
bioaccumulation and would not be appropriately reflected in any linear sequenc-
ing of the elements. Research needs relating to such critical elements are dis-
cussed in Chapter 3. Research priorities for addressing the critical elements are
summarized in Chapter 5.
FIGURE 2-1 Conceptual framework for informing the committee’s research agenda.
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56 Considering Environmental, Health, & Safety Risks of Nanomaterials
The lower half of the figure depicts tools needed to support an informative
research agenda on critical elements of nanomaterial interactions. Improved
tools will be integral products of the research agenda. The tools are materials
(standardized materials that embody a variety of characteristics of interest),
methods (standardized approaches for characterizing, measuring, and testing
materials), models (for example, for assessing availability, concentration, expo-
sure, and dose), and informatics (methods and systems for systematically captur-
ing, annotating, archiving, and sharing the research results). The vertical arrows
between the tools and the circle acknowledge the interplay between what is
learned through research about the processes that influence exposure and haz-
ards and the continuing evolution of the tools for carrying out research.
Inputs of nanomaterials depicted in Figure 2-1 represent releases of ENMs
along the entire value chain and life cycle. Activities along the value chain im-
ply inputs of energy and materials at each stage and the creation of waste
streams. Each nanomaterial or product containing nanomaterials along the steps
of the value chain has an associated life cycle of production, distribution, use,
and end-of-life releases that may affect human health and the environment. The
principle of including a value-chain and life-cycle perspective in the commit-
tee’s conceptual framework is fundamental for assessing the risks posed by
nanomaterials and is discussed in greater detail below. Understanding release
mechanisms in manufacturing, transport, and product use (for example, abra-
sion) is implicit in this value-chain and life-cycle perspective.
A LIFE-CYCLE AND VALUE-CHAIN PERSPECTIVE
WITHIN THE CONCEPTUAL FRAMEWORK
In developing the conceptual framework, the committee recognized the
importance of considering aspects of the life cycle of ENMs throughout the
value chain to understand the potential for exposure of humans and ecologic
receptors. (See Figure 2-2, an input into the conceptual framework, Figure 2-1).
The value chain extends beyond production of nanomaterials into primary and
secondary products based on the parent nanomaterials. Releases can come from
byproducts and wastes in addition to intended and unintended releases of the
parent nanomaterials that extend throughout each step of the value chain of
products that contain these materials and their life cycles. Examples of potential
releases include
Fugitive emissions of parent material.
Process releases of nanomaterials during production and finishing of a
product (for example, sawing or sanding).
Releases during transportation or accidents.
Releases during product or material use, recycling, recovery, or dis-
posal.
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Environmental, Health, and Safety Aspects of Engineered Nanomaterials 57
Byproducts and Byproducts and
Byproducts and
Wastes Wastes
Wastes
Nanomaterial
Nanomaterial Nanomaterial
Releasea
Primary
Releasea Releasea
Secondary
Products
ENM
Products
Containing
Production
ENMs
s
a
l
i
r
e
t
m s
a
l
i
r
e
t
m s
a
l
i
r
e
t
m
y
g
r
n
e y
g
r
n
e y
g
r
n
e
e
f
l
y
c
i
L
Life cycle
a
Intended and unintended releases
Value chain
FIGURE 2-2 Potential human and ecosystem exposure through the value chain and life
cycle of nanomaterial production, use, and disposal.
How nanomaterials are produced, used, reused, and disposed of largely
determines the risks that they may present to human health and the environment.
The risks are in two categories: risks stemming directly from exposure to nano-
materials and nanomaterial-containing products and risks produced by the “col-
lateral damage” associated with energy consumption, material use, and wastes
generated as nanomaterials are made, transported, processed, and treated for
disposal.
Risks Stemming Directly from Potential Exposure to Nanomaterials
The first category of risks is derived from the potential for exposure to
nanomaterials at any stage of fabrication, transport, processing, use, and end of
life—activities that make up what is referred to as the life cycle of nanomateri-
als. The nanomaterial value chain (represented along the horizontal axis in Fig-
ure 2-2) involves the production of basic building blocks of nanomaterials and
their incorporation (in later stages) into products of increasing complexity (Wi-
esner and Bottero 2011). For example, such ENMs as quantum dots (QDs) and
single-walled carbon nanotubes (SWCNTs) might be combined as QD-SWCNT
composites in primary products, such as thin films. Thin films might then be
incorporated into solar cells (secondary products), which are then used in hous-
ing materials (tertiary products). Each of those products has its own life cycle
associated with its fabrication, transport, processing, use, and end of life. Table
2-2 illustrates potential releases of and exposures to carbon nanotubes across the
value chain and life cycle of a textile application.
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58
TABLE 2-2 Illustration of Potential Releases of and Exposures to Carbon Nanotubes (CNTs) across the Value Chain and
Lifecycle of a Textile Application
Manufacture 1: Manufacture Manufacture 3:
Materials 2: Product Filling/
Raw material Distribution Use Recycle Disposal
Manufacture Fabrication Packaging
CNT Production of Textile Textile Preparing CNTs Transport of Use in textiles “Recycling” of Potential for
CNT manufacture fabrication for shipment to CNTs to (next row); also CNT raw materials release and
polymers and (next row). (next row). textile manufacturer. includes epoxy may entail release exposure during
master manufacturer. Potential for resin, batteries, during collection transport and waste
batches. Potential for release during adhesives, and and re-use of management (for
Potential for exposure during transfer or from coatings. remaining example, landfills,
exposure filling/packing spills. materials in incinerators).
during and unpacking. subsequent
synthesis, manufacturing.
which may
differ for
each
synthesis
method.
Product 1 Potential for Potential for Activities include Sending CNT- Transport of Use in garments Recycling of Disposal of unused
(Integrating exposure exposure during melting, spinning, treated textile to secondary (next row). fabric: or waste CNTs,
CNT into during processing to weaving, sizing, garment product (the shredding/cutting textile scraps.
Textile) incorporation make and apply knitting; manufacturer. garment) with and screening,
depending on a uniform bleaching, CNT already cleaning to reuse
physical form material; dyeing, printing, incorporated into materials in new
and handling. depends on washing, the fabric. blends; release is
degree of drying/fixing, possible from
automation and cutting, sewing, intensive
whether CNTs shaping, washing; treatments (for
are dry, in fibre production; example, heat,
suspension, or in finishing pressure, chemical)
masterbatch; (inspection, and exposure may
coating of textile cleaning, result from break-
with CNTs down or from
could lead to
OCR for page 59
release or washing and incorporation of
exposure. packing); fibers CNTs into a new
carrying CNTs fabric (cross-
may be shed contamination).
during these
processes.
Product 2 [N/A: CNT [N/A: Product 1 Pressure, Filling/packing of Transport of Degradation of Textiles sent to Landfills or
(Article of row]. row - primary chemicals, and secondary secondary product during second-hand stores incinerators.
Clothing) product]. heat of tailoring product (the product (the normal wear or developing
and finishing the garment). garment). and tear of countries; release
textile may lead garment or from and exposure
to release of UV, chemicals, through wear and
CNTs and water, oxidation tear described
resulting (for example, above; recycling of
exposure due to washing, fabric (previous
abrasion of fibers. ironing, heat, row).
sweat); direct
dermal
exposure
possible; form
of released
material a
question: single,
agglomerated
ENPs or nano-
or micro- scale
textile
containing
ENP.
Abbreviation: ENPs, engineered nanoparticles.
Sources: Chaudhry et al. 2009; EDF/DuPont 2007; Som et al. 2009.
59
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60 Considering Environmental, Health, & Safety Risks of Nanomaterials
Because of the potential for nanomaterial releases and exposures of hu-
mans or ecosystems at each stage of the value chain and life cycle, factors to
consider in assessing exposure include the nanomaterial form that will be pre-
sent in commercial products, the potential for the material to be released to the
environment, and the transformations of the material that may affect exposure
(Wiesner 2009). Analysis based on the value chain and the life cycle is rooted in
an assessment of which nanomaterials are being and are expected to be produced
and used.
An estimated “reservoir” of nanomaterial production can be used to obtain
first-order exposure estimates that are based on explicit, easily understood as-
sumptions regarding the quantities of nanomaterials that enter the environment
integrated over the life cycle of production through disposal (Robichaud et al.
2009; Wiesner 2009; Wiesner and Bottero 2011). Understanding the fate and
transport of these materials in the environment will lead to an understanding of
their ability to interact with biologic systems and help in assessing risk.
Potential Risks Associated with “Collateral Damages”
The second category of risks also extends across the life cycle of nanoma-
terial production, use, and disposal. At each stage of the value chain (and at the
links between stages of the value chain), there is consumption of energy and
materials, production of wastes, and the potential for disposal, reuse, and recy-
cling of the materials or products. Those life-cycle factors of nanomaterial pro-
duction and use throughout the value chain are depicted along the vertical axis
(and corresponding vertical arrows) in Figure 2-2 and may result in effects on
human health and ecosystems that are independent of the nanomaterials them-
selves and yet are directly connected to the production of nanomaterials and the
products that contain nanomaterials.
For example, the entropic penalties associated with creating order on the
atomic scale indicate that energy-intensive processes will commonly be needed
to produce nanomaterials (Wiesner 2009). The environmental effects of up-
stream energy production and use may include hazards to workers in mines, air
pollution, global warming, and so on. Material use may introduce risks associ-
ated with solvent handling and disposal (Robichaud et al. 2005). It has been
shown that the production of non-nanomaterial wastes from the production of
carbon nanotubes (Plata et al. 2008) may pose substantial hazards. Those “col-
lateral” risks to human health and the environment are as integral to an assess-
ment of risks associated with nanomaterials as is the potential for exposure to
and toxicity of the nanomaterials themselves. However, these factors have been
largely unexamined.
An assessment of the repercussions of activities and products throughout
the life cycle of production, use, disposal, and reuse of nanomaterials is needed
for sustainability planning and decision-making. For any given industrial prod-
uct, the life-cycle stages of resource extraction, raw-material production, product
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Environmental, Health, and Safety Aspects of Engineered Nanomaterials 61
manufacturing, transportation, use, and end of life can all be associated with
substantial costs and benefits to manufacturers, customers, and the environment.
(See Box 2-2 for a discussion of life-cycle assessment, life-cycle inventory, and
data needs.)
Although the committee recognizes that indirect collateral effects associ-
ated with the life cycle of materials and energy use in nanomaterial production
may in some cases be the dominant effects on human health and the environ-
ment, the committee’s research framework is focused on identifying EHS issues
resulting directly from contact with nanomaterials released along the value chain
and life cycle. Notably absent from the proposed framework is a consideration
of important issues relating to nanomaterial fabrication, complex nanostructures
and devices, and comprehensive life-cycle considerations concerning energy and
materials use, reflecting a deliberate focus of this committee on nanomaterials
rather than nanotechnology and a heavy emphasis on toxicologic research.
However, the framework and strategy proposed by this committee address sev-
eral key points raised in the NNI Signature Initiative of Sustainable Nanomanu-
facturing (NSET 2010b). In particular, the focus in this report on methodologic
tools supports the call for novel measurement techniques. Like the NNI Initia-
tive, the conceptual approach proposed here and the focus on nanomaterial
transformations occurring after release along the value chain aligns with the
NNI call for “Development of methodologies that enable accurate measurement
of nanomaterial evolution and transport during product manufacturing and use,
and across the material lifecycle (NSET 2010b, p. 4).”
PRINCIPLES FOR IDENTIFYING AND SETTING
PRIORITIES FOR RESEARCH NEEDS IN THE CONTEXT
OF THE CONCEPTUAL FRAMEWORK
One premise of the committee’s framework for research is that EHS re-
search priorities can be established on the basis of judgments regarding the rela-
tionships between nanomaterial properties and the processes that govern their
interactions with organisms and ecosystems. The nature of the interactions will
ultimately define the risk posed by the materials. The following section outlines
principles that the committee considered for setting research priorities for the
potential human health and environmental risks of ENMs. In many of the com-
mittee’s discussions, these principles were applied implicitly as the critical re-
search needs were considered.
Principles for Setting Priorities for Nanomaterial-EHS Research
In the paper “Towards a Definition of Inorganic Nanoparticles from an
Environmental, Health and Safety Perspective,” Auffan et al. (2009) illustrate
how principles can be used to identify materials that are of interest from a risk
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62 Considering Environmental, Health, & Safety Risks of Nanomaterials
BOX 2-2 Life-Cycle Assessment, Life-Cycle Inventory, and Data Needs
Life-cycle assessment (LCA) provides a formal framework for identifying
and evaluating the life-cycle effects of a product, process, or activity. Typi-
cally, effects on human health and ecosystem health and effects of pollutant
deposition in all environmental media are evaluated for each stage of the life
cycle, and an LCA may be performed on products at each stage of the value
chain. There are many variations in LCA methods, but arguably the most
broadly accepted is one formalized in the ISO-14040 series of standards
(ISO 1997; Guinee et al. 2010). Often referred to as formal LCA or full LCA,
the ISO method guides the quantitative assessment of environmental effects
throughout a product’s life cycle.
A major challenge in conducting formal LCA is to obtain reliable and
available data for a life-cycle inventory (LCI). The challenge is amplified for
the evolving nanomaterial industry in which production methods, markets,
and patterns of product use may be unknown and confidential. Efforts have
also been made to integrate consideration of social effects into LCA. The
ecoefficiency assessment of BASF corporation has recently been extended
to include social effects (Schmidt et al. 2005). Individual indicators of a prod-
uct’s effects on human health and safety, nutrition, living conditions, educa-
tion, workplace conditions, and other social factors are assessed and scored
relative to a reference (usually the product being replaced).
Although LCA based on a robust LCI may prove to be a useful tool in
assessing EHS risks posed by manufactured nanomaterials, it must be re-
membered that releases to the environment, representing an upper bound
on potential for exposure, will not equate to actual exposure of humans or
ecologic receptors. Fate, transport, and transformation processes of nano-
materials in the environment need to be considered. Data needs include
Characterizing commonly used nanomaterials.
Understanding the potential for release of nanomaterials throughout
the life cycle of the material and the value chain leading to products.
Placing potential releases into an exposure context.
Providing bases for assessing risk to human health and the envi-
ronment.
In addition, a broader framework that combines life-cycle assessment
and risk analysis may help to inform our understanding of potential risks and
environmental impacts of ENMs (Evans et al. 2002; Matthews et al. 2002;
Shatkin 2008).
Current knowledge needs to be assessed and a gap analysis performed
to understand critical research and data needs for addressing the EHS as-
pects of nanomaterials (see Chapter 3). Addressing the issues of modeling
vs monitoring—for example, releases, fate and transport, exposure, dose,
and potential effects—will be critical for the success of this effort (see dis-
cussion in Chapter 4).
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Environmental, Health, and Safety Aspects of Engineered Nanomaterials 63
perspective. Regarding important risk-related characteristics of ENMs, Auffan et
al. considered developing a risk-based definition of inorganic nanoparticles that
is founded on novel size-dependent properties. Contrary to the title of their pa-
per, Auffan et al. pose a set of principles for identifying materials of interest
rather than a rigid definition for classifying ENMs. The science-based approach
that they adopted allows materials presenting new or unusual risks to be distin-
guished from materials that present more conventional risks. Their approach
establishes criteria for determining the probability that a material measuring 1-
100 nm will exhibit novel properties that might lead to new or unusual risks.
Building on that idea, the present committee focuses on a set of principles
in lieu of definitions to help identify nanomaterials and associated processes on
which research is needed to ensure the responsible development and use of the
materials. The principles were adopted in part because of concern about the use
of rigid definitions of ENMs that drive EHS research and risk-based decisions
(Maynard 2011; Maynard et al. 2011a). The principles are technology-
independent and can therefore be used as a long-term driver of nanomaterial risk
research. They help in identifying materials that require closer scrutiny regard-
ing risk irrespective of whether they are established, emerging, or experimental
ENMs. The principles are built on three concepts: emergent risk, plausibility,
and severity; the principles are based on proposals articulated by Maynard et al.
(2011b).
Emergent risk, as described here, refers to the likelihood that a new mate-
rial will cause harm in ways that are not apparent, assessable, or manageable
with current risk-assessment and risk-management approaches. Examples of
emergent risk include the ability of some nanoscale particles to penetrate to bio-
logically relevant areas that are inaccessible to larger particles, the failure of
some established toxicity assays to indicate accurately the hazard posed by some
nanomaterials, scalable behavior that is not captured by conventional hazard
assessments (such as behavior that scales with surface area, not mass), and the
possibility of abrupt changes in the nature of material-biologic interactions asso-
ciated with specific length scales. Identifying emergent risk depends on new
research that assesses a novel material’s behavior and potential to cause harm.
Emergent risk is defined in terms of the potential of a material to cause
harm in unanticipated or poorly understood ways rather than being based solely
on its physical structure or physicochemical properties. Thus, it is not bound by
rigid definitions of nanotechnology or nanomaterials. Instead, the principle of
emergence enables ENMs that present unanticipated risks to human health and
the environment to be distinguished from materials that probably do not. It also
removes considerable confusion over how nanoscale atoms, molecules, and in-
ternal material structures should be considered from a risk perspective, by focus-
ing on behavior rather than size.
Many of the ENMs of concern in recent years have shown a potential to
lead to emergent risks and would be tagged under this principle and thus require
further investigation. But the concept also allows more complex nanomaterials
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64 Considering Environmental, Health, & Safety Risks of Nanomaterials
to be considered—those in the early stages of development or yet to be devel-
oped. These include active and self-assembling nanomaterials. The principle
does raise the question of how “emergence” is identified, being by definition
something that did not exist previously. However the committee recognized that
in many cases it is possible to combine and to interpret existing data in ways that
indicate the possible emergence of new risks. For example, some research has
suggested that surface area is an important factor that affects the toxic potency
of some ENMs; ENMs that have high specific surface area and are poorly solu-
ble might pose an emergent risk.
Plausibility refers in qualitative terms to the science-based likelihood that
a new material, product, or process will present a risk to humans or the envi-
ronment. It combines the possible hazard associated with a material and the po-
tential for exposure or release to occur. Plausibility also refers to the likelihood
that a particular technology will be developed and commercialized and thus lead
to emergent risks. For example, the self-replicating nanobots envisaged by some
writers in the field of nanotechnology might legitimately be considered an
emergent risk; if it occurs, the risk would lie outside the bounds of conventional
risk assessment. But this scenario is not plausible, clearly lying more appropri-
ately in the realm of science fiction than in science. The principle of plausibility
can act as a crude but important filter to distinguish between speculative risks
and credible risks.
The principle of severity refers to the extent and magnitude of harm that
might result from a poorly managed nanomaterial. It also helps to capture the
reduction in harm that may result from research on the identification, assess-
ment, and management of emergent risk. The principle offers a qualitative real-
ity check that helps to guard against extensive research efforts that are unlikely
to have a substantial effect on human health or environmental protection. It also
helps to ensure that research that has the potential to make an important differ-
ence is identified and supported.
Together, those three broad principles provide a basis for developing an
informed strategy for selecting materials that have the greatest potential to pre-
sent risks. They can be used to separate new materials that raise safety concerns
from materials that, although they may be novel from an application perspective,
do not present undetected, unexpected, or enhanced risks. They contribute to
providing a framework for guiding a prioritized risk-research agenda. In this
respect, the principles were used by the committee as it considered the pressing
risk challenges presented by ENMs.
When the principles are applied to existing and emerging ENMs, various
groups of materials that may warrant further study are evident. Those groups,
identified below, are not intended to be comprehensive, but they are the basis for
beginning to map out material properties that need to be addressed in a risk-
research strategy (Maynard et al. 2011b).
Materials that demonstrate abrupt scale-specific changes in biologic or
environmental behavior. Materials that undergo rapid size-dependent changes in
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Environmental, Health, and Safety Aspects of Engineered Nanomaterials 65
physical and chemical properties that affect their biologic or environmental be-
havior may pose a hazard that is not predictable based on what is known about
larger-scale materials of the same composition.
Materials capable of penetrating to normally inaccessible places. Ma-
terials that, on the basis of their size or surface chemistry or both, are able to
persist in or penetrate to places in the environment or body that are not accessi-
ble to larger particles of the same chemistry may present emergent risks. If there
is a credible scenario for accumulation of, exposure to, or an organ-specific dose
of a nanomaterial that is not expected according to the behavior of the dissolved
material or larger particles of the same material, a plausible and emergent risk is
possible.
Active materials. Materials that change their biologic behavior in re-
sponse to their local environment or a signal present dynamic risks that are not
well understood. Active materials might include materials whose surface charge
leads to association with other materials in the environment, which allows the
nanomaterial to function as an efficient delivery system for potentially toxic
materials, such as metals and polyaromatic hydrocarbons. Active materials
might also include materials whose enzymatic or catalytic processes pose a po-
tential hazard in biologic systems. In addition, it is plausible that nanomaterials
that have a three-dimensional structure, similar to natural ligands, could activate
receptor-mediated processes in humans and the environment.
Self-assembling materials. Materials that are designed to assemble into
new structures in the body or the environment on release pose issues that may
not be captured by current risk-assessment approaches.
Materials exhibiting a scalable hazard that is not captured by conven-
tional dose metrics. When hazard scales according to parameters that are not
typically used in risk assessment, emergent risks may arise because dose-
response relationships may be inappropriately quantified. For example, the haz-
ard presented by an inhaled material may scale with the surface area of the mate-
rial, but if risk assessment is based on mass, the true hazard may not be identi-
fied; the material has the possibility of causing unexpected harm.
Applying the Principles to the Value Chain and Life Cycle
of Nanomaterials and Products
The principles can be applied to both the value chain of materials and
products and their life cycle to identify context-specific risks that may arise and
require further research to assess and manage them. The concepts of plausibility,
emergence, and severity can help to differentiate between what may be consid-
ered more and less important risks. For example, generating and handling mul-
tiwalled carbon nanotubes in a workplace—materials that have demonstrated
novel properties that include, for example, strength and electric conductivity—
may present a plausible and emergent risk. It is only recently that production of
these materials has started commercially; there are indications that some forms
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66 Considering Environmental, Health, & Safety Risks of Nanomaterials
of carbon nanotubes are more harmful than their carbon base might indicate; and
there is a potential for human exposure (Maynard et al. 2004; Han et al. 2008;
Evans et al. 2010). However, riding a bicycle that incorporates multiwalled
nanotubes in the frame or using a cellular telephone with a battery containing
small quantities of nanotubes is unlikely to lead to important exposure. In those
cases, although the emergent risk might remain, the plausible risk is much re-
duced; nevertheless, when the products are disposed of or prepared for recy-
cling, a plausible and possibly severe risk may re-emerge as the material again
becomes potentially dispersible and biologically available.
Those examples demonstrate how the principles of plausibility, emergent
risk, and severity allow important risks or “hot spots” to be identified over the
value chain and life cycle of the material. The principles provide a systematic
basis for identifying and setting priorities among properties of nanomaterials as
research subjects in addressing risks.1
Criteria for Selecting Research Priorities
Each of the above types of materials (they are not exclusive), illustrates
key research questions that need to be addressed if emergent and plausible risks
are to be identified, characterized, assessed, and managed. The principles de-
scribed above can be applied to set priorities for the study of ENMs. However, a
comprehensive research strategy also will address both near-term and long-term
issues regarding the EHS aspects of nanomaterials, including identifying the
properties of ENMs that make them potentially hazardous; determining how to
harmonize collection and storage of pertinent but diverse data types to enable
risk-assessment modeling and risk management; developing new tools to meas-
ure ENMs in complex environmental and biologic matrices and to model expo-
sure and hazard pathways; and identifying justifiable simplifications that can
reduce the level of complexity to enable comprehensive risk assessment of
ENMs. And it should outline a path to address complex mixtures of ENMs, to
understand their transformations and interactions with existing environmental
contaminants, and to assess how the transformations and interactions affect their
behavior and effects.
In addition to the issues of life-cycle and value-chain perspective dis-
cussed earlier, the committee identified the following criteria as a basis of set-
ting priorities for research:
Research that advances knowledge of both exposure and hazard wher-
ever possible.
1
A similar definition-independent approach to addressing potential risks arising from
ENMs has previously been proposed in the Nano Risk Framework developed by the En-
vironmental Defense Fund and DuPont (Environmental Defense/DuPont 2007).
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Environmental, Health, and Safety Aspects of Engineered Nanomaterials 67
Research that leads to the production of risk information needed to in-
form decision-making on nanomaterials in the market place.
Research efforts to address short-term needs that serve as a foundation
for moving beyond case-by-case evaluations of nanomaterials and allows
longer-term forecasting of risks posed by newer materials expected to enter
commerce.
Research that promotes the development of critical supporting tools,
such as measurement methods, limitations of which hinder the conduct of re-
search in processes that control hazards and exposure.
Research on ecosystem-level effects that addresses exposure or hazard
scenarios that are underrepresented in the current portfolio of nanotechnology-
related EHS research; for example, impacts on ecosystem processes and on or-
ganisms representing different phyla and environments.
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