The Novelty of Nano

THE NOVELTY OF NANO AND THE REGULATORY CHALLENGE OF NEWNESS

Abstract:

A great deal has been made of the question of whether nano-materials provide a unique set of ethical challenges. Equally important is the question of whether they provide a unique set of regulatory challenges. In the last ten months, the US Environmental Protection Agency has begun the process of trying to meet the regulatory challenge of nano using the Toxic Substances Control Act (1976)(TSCA). In this central piece of legislation, ‘newness’ is a critical concept. Current EPA policy, we argue, does not adequately deal with the novelty of nano. This paper is an exploration of how to do a better job of accounting for nano-materials as ‘new.’ We explore three alternative ways that nano-materials might fall under the TSCA regulatory umbrella. Since nanomaterials are of interest precisely because of the exciting new properties that emerge at the nano-scale, each of these three alternatives must meet what we call the ‘novelty condition’ and avoid what we call the ‘central paradox’ of existing regulatory policy. We examine both the strengths and weaknesses of each alternative in order to illuminate both the conceptual and practical challenges of novelty.

Keywords:

Central regulatory paradox, emergent properties, nanomaterial, newness, novelty condition, Toxic Substances Control Act.

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The Novelty of Nano

THE NOVELTY OF NANO AND THE REGULATORY CHALLENGE OF NEWNESS

The enormous excitement generated by the development of nanotechnology is, by

now, almost too well trumpeted to require repeating. The $1.5 billion dollars of public

money budgeted to support research and development in the US National

Nanotechnology Initiative (NNI) for 2009 indicates the central role the federal

government predicts nanotechnology will play in national security and economic

prosperity over the coming decades. At the same time as nanotechnology’s star has risen,

the possible perils associated with the development of nanomaterials have also gained a

prominent place in the minds of researchers and the interested public.

From its inception, the NNI had a budget line directed towards work on the

societal and ethical dimensions of nanotechnology, suggesting an early appreciation of

the need to have an informed discussion about the risks and challenges associated with

the technology’s development. This early appreciation was partly prudential. David

Rejeski, director of the Project on Emerging Nanotechnologies, identified the huge

potential cost of omitting the social and ethical discussions. In testimony before a US

Senate Science and Technology subcommittee in 2008, Rejeski remarked that ‘[P]ublic

trust is the “dark horse” in nanotechnology’s future. If government and industry do not

work to build public confidence in nanotechnology, consumers may reach for the “No-

Nano” label in the future’ (PEN 2008). Everybody involved in the development of

nanotechnology has an interest in heading-off the public relations debacle that plagued

agricultural biotechnology two decades earlier (David and Thompson 2008). The recent

addition of a separate Environment, Health, and Safety (EHS) component to the NNI’s

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strategic plan clearly indicates it is not just the watchdog sector that wants an accurate

account of the risks associated with nanomaterials.

At a time when the commercial promise of nanomaterials is just starting to be

realized – more than 800 consumer products containing nanomaterials are now on the

market1 - the precise nature and extent of the hazards associated with engineered

nanomaterials remains frustratingly unclear (Rejeski and Lekas 2008). While enough is

known to establish the presence of some risk (Oberdörster et al. 2005, Oberdorster et al.

2007, Maynard et al. 2006, Nel et al. 2006), the full extent of the risk is far from certain.2

As a result, some form of risk management through regulation would appear to be both

morally and economically prudent. Morally prudent because neither the public nor those

involved in the production of nanomaterials should rightly be exposed to substances

whose possible dangers are not well understood. Economically prudent because the

backlash against the industry – should cases of actual (or perceived) harm emerge – has

the potential to cost the industry far more than a well-considered, pre-emptive regulatory

regime.

The Current Regulatory Paradox of Nano.

While an entirely new regulatory mechanism may well be needed at some point in

the future (Davies 2009), the most important piece of legislation currently in place to

govern the regulation of nanomaterials in the U.S. is the Toxic Substances Control Act

(TSCA) of 1976. This act is the primary vehicle for regulating ‘chemical substances and

1 See the Project on Emerging Nanotechnology Consumer Products Inventory (accessible at http://www.nanotechproject.org/inventories/consumer). 2 Current research on nanomaterial health and safety is collected at the Organization of Economic Cooperation and Development website (http://webnet.oecd.org/NanoMaterials/Pagelet/Front/Default.aspx?) An inventory of environment, health, and safety research is also available at the Project on Emerging Nanotechnologies (http://www.nanotechproject.org/inventories/ehs).

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mixtures which present an unreasonable risk of injury to health or the environment.’

While TSCA is not the only law with potential regulatory impact over nanomaterials –

the Consumer Product Safety Act, the Federal Insecticide, Fungicide, and Rodenticide

Act, and the Federal Food Drug and Cosmetic Act are others – it is TSCA that gives the

US Environmental Protection Agency (EPA) the most basic starting point for regulating

chemical substances involved in commerce. To effect this regulation, TSCA employs

various means ranging from simple record-keeping, to testing, to various restrictions on

manufacture, processing, distribution, use, and disposal. Clarence Davies, an expert on

US environmental regulatory policy who was involved at the inception of both the EPA

and TSCA, accordingly describes it as ‘the only law that, at least potentially, could

provide oversight for nanotechnology in general’(Davies 2008).3 It does this through

regulating at the ‘front end’ (i.e. a substance’s manufacture and distribution as opposed to

its use in particular products). In late 2008 and 2009, a flurry of regulatory actions on

nanomaterials by EPA4 has confirmed that TSCA lies at the very center of nanoregulation

in the US. Indeed, the four recent decisions made under the authority of TSCA –

concerning carbon nanotubes, silica and alumina nanoparticles – are part of only a

handful of regulatory actions taken by the US government on nanomaterials to date.

The most pertinent provision of TSCA with regard to nano-regulation is that the

Act mandates the maintenance of a Chemical Substances Inventory of materials that are

3 We will not consider in this paper the effectiveness of TSCA as a whole, only the mechanisms it contains for regulating nanomaterials. Questions about TSCA’s effectiveness (e.g. the workload it involves, the burden of proof it imposes) need to be addressed elsewhere. A congressional hearing on TSCA by the U.S. House Subcommittee on Trade, Commerce, and Consumer Protection held on 02/26/09 probed the effectiveness of the 33 year old act. Many at the hearing suggested that the TSCA needed updating, independent of the challenges presented by nanomaterials.4 See the decisions by EPA on nanomaterials and TSCA issued on 10/31/08 (73 Federal Register, 64946-7), 11/05/08 (73 Federal Register, 65743, 65751-2), and 6/24/09 (74 Federal Register, 29982-29998). The EPA also issued a consent order to British firm Thomas Swan in September 2008 to commence commercial production of carbon nanotubes at its facility in New Jersey.

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manufactured, processed, imported, distributed, used, and/or disposed of in the course of

U.S. commerce. This inventory is at the front line of the regulation of potentially

hazardous materials and serves as an important resource for several federal agencies

including both the EPA and the Food and Drug Administration (FDA). The key provision

of TSCA, as it relates to nanotechnology, is the criterion by which a manufactured

material gets labeled an ‘existing’ or a ‘new’ chemical for the purpose of consideration

for the inventory. If a material qualifies as a new chemical, the company manufacturing

or importing it needs to submit to EPA a Pre-Manufacture Notice (PMN) at least 90 days

before commencing manufacture (or import) of that substance. On the basis of a PMN,

the EPA determines what restrictions and what additional information might be required

before the new substance can be introduced into commerce. Particularly significant for

nanomaterials is the fact that, if the chemical substance is determined to be the same as a

substance already on the inventory, then no PMN is required and no additional

restrictions on production, beyond what has already been specified for the existing

chemical, are required. The question of novelty, then, lies at the heart of the regulation of

nanomaterials under TSCA.

In January of 2008, EPA distributed a position paper concerning their general

approach to listing engineered nanomaterials on the TSCA inventory. The general

approach stated that ‘a chemical substance with the same molecular identity as a

substance listed on the Inventory is considered to be an existing chemical substance.’

(EPA 2008). Molecular identity, the paper goes on, is determined by considerations such

as the ‘types and number of atoms in the molecule, the types and number of chemical

bonds, the connectivity of the atoms in the molecule, and the spatial arrangement of the

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atoms within the molecule.’ The criterion essentially means that the same method for

determining whether a chemical is new at the macro scale – namely the criterion of

molecular identity – is used to determine whether a nanomaterial counts as a new

chemical.

For a few nanomaterials, this general approach will work fine. For example, on

October 31st, 2008 the EPA put the manufacturers of carbon nanotubes on notice that the

different molecular identity of a carbon nanotube means that it will be considered a new

chemical by EPA under TSCA and subject to a PMN.5 For the vast majority of

nanomaterials, however, the molecular identity approach will in all probability allow the

nano-chemical to evade regulatory scrutiny. Many nanomaterials have the same

molecular identity as their macro counterparts, differing only in terms of their particle

size. This ensures that they will be deemed to be ‘existing chemicals’ and, as such, will

not be subject to any manufacturing restrictions beyond those already in place for the

corresponding macro-level material.

While the decision to use the criterion of molecular identity to determine whether

an engineered nanomaterial is a new substance appears chemically reasonable on the

surface, it leads to what we will call ‘the central paradox’ in existing nanotechnology

regulation through TSCA. The central paradox lies in the inconsistency between the scale

at which nano-properties emerge and the scale at which the chemicals are regulated.

Perhaps the most significant aspect of nanomaterials is that – due, in part, to the rapidly

increasing surface area to volume ratios as a material is reduced in size – scale really

does make a difference in the physical, chemical, and biological properties of a material.

The NNI’s introductory webpage on nanotechnology admits as much when stating that

5 Federal. Register, 73, 64946-7.

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‘[U]nusual physical, chemical, and biological properties can emerge in materials at the

nanoscale. These properties may differ in important ways from the properties of bulk

materials and single atoms or molecules’ (emphasis in original) (NNI 2008). This

difference is responsible for creating what we are calling the central paradox. The

determination of whether a nanomaterial gets listed as a new chemical on the Chemical

Substances Inventory appears to ignore this scalar criterion, thereby creating an

extraordinary inconsistency. On the one hand, the very purpose of creating engineered

nanomaterials is to exploit the powerful and novel properties that emerge in some

materials at the nanoscale. On the other hand, the determination of whether these novel

materials need to fall under the regulatory umbrella of TSCA is based on properties that

exist at the macro scale.

Our assumption in what follows is that the central paradox in the EPA’s position

strongly suggests a different approach is required for determining whether nanomaterials

count as new chemicals for the Chemical Substances Inventory. We suggest that the

decision about whether a nanomaterial requires a PMN and the attendant regulatory

scrutiny must in some fashion reflect the very properties that make an engineered

nanomaterial commercially promising. The novel properties that make the nanomaterial

worth exploiting must be taken into account in the decision to manage the chemical under

TSCA. We will call this requirement the ‘novelty condition’ for nano-regulation.

Utilizing a methodology developed for a National Science Foundation funded project in

ethics education, we consider three alternative ways that nanomaterials might be

regulated under TSCA to meet the novelty condition. We refer to them as ‘Size-only,’

‘Size-plus-one,’ and ‘Significant-new-use.’ We consider these three options not for the

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purpose of specifying exactly how the regulatory mechanism would work. This would

require details about regulatory policy that are better discussed elsewhere. Our

exploration is more theoretical, designed to illuminate 1) the conceptual challenges

involved in describing nanotechnology as ‘new’ from a regulatory standpoint, and 2) the

practical difficulties that the regulation of nanomaterials presents for meeting the novelty

condition and avoiding the central paradox at the same time. Since all of these options

present a considerable regulatory burden, we also include a brief discussion of a method

for reducing this burden that could be employed at a later date when more information on

the health and safety effects of nanomaterials becomes available.

Regulating nanomaterials based on a size-only criterion

As the name itself makes clear, the property of nanomaterials that makes them

stand apart is their size. The approximate range of 1-100 nm is commonly offered as the

definition of a nanoscale object (NNI 2009, BSI 2007). As everyone in the field knows, at

this scale a variety of novel properties can emerge (Roduner 2006).

Material scientists and engineers working with nanomaterials are usually most

interested in their new physicochemical properties. These properties can be subdivided

into two main categories: surface effects and quantum size effects (Roduner, 2006). The

former are due to the activity of the surface atoms/molecules of the material. As size

decreases, the fraction of surface molecules relative to their total number becomes larger,

and surface effects become more prominent. This change can create unusual properties. A

common example is the increased catalytic activity of nanoparticles. Gold, for example,

regarded as a ‘noble’ metal by the ancients due to its inertness, becomes a very active

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The Novelty of Nano

catalyst when particle size is scaled down to tens of nanometers (Cortie & van der Lingen

2002). With quantum effects, the difference between nanomaterials and their bulk

counterparts can be understood by contrasting their energy levels. Extremely large

numbers of atoms or molecules create blurred energy bands in bulk materials, while more

well-defined discrete energy levels emerge in smaller particles. At this scale, their

behavior becomes similar to that of single atoms. A well-known example is quantum

dots. They are made up of clusters typically containing on the order of thousands of

atoms. Upon laser excitation, they fluoresce at a specific wavelength (i. e. with a specific

color), in stark contrast with the broad spectra of bulk materials (Kaji et al. 2007,

Roduner 2006).

The last two decades of research have revealed a number of potentially harmful

effects of nanomaterials (Oberdorster et al. 2005, Buzea et al. 2007, Klaine et al. 2008).

These potential harms include asthma from airborne nanoparticles (Hester & Harrison

2007), carcinogenetic effects (Kostarelos 2008), pulmonary lesions (Lam et al. 2004),

and fibrosis and/or thrombosis (Buzea et al. 2007). The enhanced catalytic activity of

certain nanomaterials also appears to cause the generation of reactive oxygen species in

organisms, potentially leading to damage of DNA and proteins (Nel et al. 2006). In many

cases, the toxicity of nanoparticles has been correlated directly with their size (small) and

surface area (relatively large) (Buzea et al 2007, Nel et al. 2006). Carbon nanotubes

(CNTs), the nanomaterial perhaps best known to the general public, present a supporting

example. They are praised for their remarkable electrical and mechanical properties –

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qualities that bulk carbon lacks. However, adverse health effects of CNTs have been

linked to their extremely unusual size and aspect ratio (Lam et al. 2006).6

Though just enough is known about potential harms at the nanoscale to create

anxiety about the toxicological properties and environmental impact of nanomaterials,

actionable data on this subject is still patchy (Hester & Harrison 2007, EPA 2007). To

address this shortfall, funding for the environmental, health, and safety effects (EHS) of

nanomaterials in the NNI has more than doubled in the three years from 2005-2008 and

more is urgently needed. While waiting for this data to emerge, some sort of oversight

through EPA and TSCA appears appropriate.

Whether caused by novel physicochemistry or simply by size, the nearly

ubiquitous causa prima of the concern caused by nanomaterials is their dimension. In our

terms, the novelty of nano is a direct consequence of size. It therefore seems plausible to

specify size as the criterion that would trigger the regulatory mechanisms of TSCA. In a

report addressed to the incoming administration in 2008, Clarence Davies appears to

advocate this line when he recommends that all nanomaterials simply be ‘defined as

“new” chemicals under the Toxic Substances Control Act.’ (Davies 2008).

Such a regulatory approach to nanomaterialas would be maximally inclusive and,

in principle, conceptually simple. An amendment to TSCA would certainly be required

involving an additional definition of a new chemical substance at Section 3(2)(A) to

function alongside the existing ‘molecular identity’ definition. This amendment could be

achieved with the following text that adds a size-based criterion for defining a material as

new:

6 Aspect ratio, for chemicals and nanomaterials, is usually defined as the ratio of depth to width, or diameter to length, depending on how the material is being observed and categorized.

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‘(iii) any material produced in a form where one or more dimensions is less than

100 nanometers, even if such material has the same molecular identity as a

chemical already on the inventory, unless a substantially identical nanomaterial is

already on the inventory.’7

With this definition of a new chemical, all manufacturers of nanomaterials would be

required to submit PMNs and the EPA would have the opportunity to make requests for

information from the manufacturer and, if necessary, impose restrictions on the

production and distribution of a particular nanomaterial.

The application of a size-only criterion, though appearing conceptually

straightforward, is not quite a simple as it first seems. There is nothing sacrosanct about

the definition of nanosized (1-100 nm). For regulatory purposes, it would be essential to

have an agreement about the dimension at which a material becomes ‘nano.’ A simple

dimensional definition of size is made more complex by the fact that mass-produced

nanoparticles are typically heterogeneous in size. Most probably, the definition needed to

trigger PMNs would have to include reference to the size distribution of the particles,

with a certain predetermined value of a dispersity index8 falling in the nano range, being

required before TSCA takes effect.

Due to its inclusiveness, the down-side of a size-only criterion would obviously

be the significant regulatory burden it would create. Every nanomaterial with a

distribution of particle sizes that fell below a certain threshold would require a PMN and 7 This text is amended from language used in Davies (2008, 28).8 A dispersity index is a measure of the distribution of molecular mass in a given sample of the material. To this end, section 8(a)(2) of TSCA would also need to specify that the manufacturer submit information on size distribution of the new chemical to EPA.

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a 90 day evaluation by EPA. Since EPA already struggles with the resources to make

timely decisions on new chemicals, a size-only criterion would require considerable

additional resources, resources that there is little reason to think are available. As more

and more nanomaterials enter the market and require screening, the burden on the EPA

and the manufacturers would increase. The logjam created by such a burdensome

regulatory regime may slow down the speed at which new products can be marketed and

the attendant motivation to innovate. Arguably this is an outcome to avoid, especially in

the light of increasing competitiveness among the major world players on the nanotech

market.

Once within the PMN process, the regulatory burden is intensified by the dearth

of available information on nanoparticle toxicity. Due to the impossibility of determining

potential risks of even every macro-sized chemical substance, the current EPA approach

for assessing new chemicals relies on comparisons between the structures of proposed

chemicals and those of chemicals with known toxicological effects. A Structural Activity

Relationship (SAR) is used to evaluate new, little-tested substances. An estimate of a new

substance’s toxicity is based on structural relations between it and other better known

substances. EPA makes its decisions based on the entire body of available evidence for

all similar chemicals, attempting to assign appropriate weight to each piece of evidence.

While plausible at the macro scale, there are difficulties with using SARs at the

nanoscale. The current lack of information on the toxicology of nanomaterials would

initially make such SAR comparisons a challenge. Nor is it clear which relationships

would be used to compare new materials to existing ones with known toxicological

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problems. The similarities that matter at the macroscale, may not be the same as the

similarities that matter at the nanoscale.

Standardized TSCA exemptions also present a challenge. In the three decades that

TSCA has been in force, approximately 25% of the PMNs submitted have achieved

exemptions from reporting requirements under certain standardized exemptions (OPPT

2007). The ‘low-volume exemption’ to TSCA that relieves manufacturers from reporting

requirements if they produce less than 10,000 kg per of the substance per year would be

inappropriate for nanomaterials for obvious reasons. The ‘low release, low exposure’

exemption that relieves manufacturers from reporting requirements if human exposure

falls below a certain threshold would also likely have to be rethought for nanomaterials

since ‘low’ takes on new meaning at the nanoscale.

An additional, though more subtle, reason to be cautious of the size-only criterion

is that it creates the presumption of danger surrounding all nanomaterials. The idea that a

nanomaterial requires significant regulatory scrutiny simply because it is nano-sized

connects the word ‘nano’ automatically to the word ‘hazard.’ Such a presumption would

damage the public image of nanomaterials regardless of the actual dangers, leading to the

‘no-nano’ worry mentioned by Rejeski previously. Not every nano-sized material has

novel properties that create special hazards. For example, the vast majority of drugs and

pharmaceuticals ultimately operate at the nanoscale in living systems. Their effects are

sometimes due to their size directly, but often due to their biological and/or chemical

effect on the tissues and processes. Size can, of course, be a positive or negative factor as

a result of they way it allows some materials to cross traditional biological barriers such

as the blood-brain barrier (Veiseh, 2009).

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In sum, the size-only criterion for identifying nanomaterials as new substances for

the Chemical Substances Inventory has the advantages of conceptual simplicity and

inclusivity. It would also, by default, meet the novelty condition by ensuring that every

nano-sized material receives regulatory scrutiny. It would, however, involve significant

regulatory burden at a time when existing resources and existing research on nanotoxicity

are clearly inadequate. It would also require a number of departures from the

qualifications and exemptions that have been established alongside the existing TSCA

framework.

Regulating Nanomaterials on a ‘size-plus-one’ emergent property basis

In a report written to evaluate the Food and Drug Administration’s (FDA) ability

to regulate the use of nanomaterials in drugs, medical devices, dietary supplements, and

cosmetics, Michael Taylor proposed that FDA consider the ‘functional properties’ of

nanomaterials as the basis of differentiating them from their conventional counterparts

(Taylor 2006). Similarly, during an American Bar Association teleconference in 2006,

EPA’s Jim Alwood referred to the possibility of looking for the ‘unique properties’ of

nanomaterials relative to their macro-sized counterparts as a basis for regulating them as

new chemicals. These ‘functional’ or ‘unique’ properties of nanomaterials, are products

of a nanomaterial’s physicochemical characteristics and/or simply of the particle’s shape

and size. Properties such as these, that do not appear at higher dimensions, could usefully

be referred to as a nanomaterial’s ‘emergent properties.’ A second alternative, then, is for

a ‘size-plus-one-emergent-property’ (or ‘size-plus-one’) criterion to be used to define a

nanomaterial as new for the purposes of listing on the Chemical Substances Inventory.

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There are several reasons why the emergent property criterion is an intuitively

plausible alternative to the size-only regulatory framework. First, emergent properties are

the very reason for exploring the nano world. They are also the same properties that

demand closer examination for their EHS effects. By specifying the emergent property as

the trigger for regulatory scrutiny, a size-plus-one approach directly meets the novelty

condition (rather than meeting it by default). The current molecular identity criterion used

by EPA fails to make the distinction between the composition and the chemistry of nano-

particles (Buzea et al. 2007). Even though composition of these particles remains the

same as their bulk counterparts, their chemistry may be very different due to their other

physical parameters. This difference in chemistry, as previously discussed, can be

brought about by factors such as different aspect ratio, different crystalline construction,

and the state of aggregation. It is this different chemistry that creates the interesting – and

potentially worrisome – properties. An emergent property criterion has the advantage of

directing attention towards the actual chemistry of nanomaterials.

Although size alone can enable nanomaterials to travel different environmental

and physiological pathways, often other emergent properties are also responsible for

creating the potential hazards of these materials. For example, even though nanoparticles

have the same composition as their macro-sized counterparts, some of them have

unexpected crystalline structures not present in other forms of the material. This is

observed in nanoparticles of the minerals rutile and anastase which are both polymorphs

of titanium dioxide. These two nanomaterials have different crystalline structures and

display different physicochemical properties. Rutile nanoparticles have been found to

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induce oxidative DNA damage in absence of light, but anastase nanoparticles do not

(Gurr et al. 2005).

The justification of including emerging properties as a criterion for nanoparticle

regulation is reinforced by several studies which have specifically correlated various

emergent physicochemical properties of nanoparticles with their toxicity (Buzea et al.

2007). From the earlier experience of toxicological properties of fibrous particles (such as

asbestos), it had been expected that the most critical parameters in determining adverse

health effects of nano-particles would be dose, dimension, and durability (Oberdörster

2002). However recent studies have indicated a correlation between specific emergent

physicochemical properties of nanoparticles and associated health effects. For example,

carbon nanotubes, having diameter from 0.4 and 100nm, have been found to be toxic for

living cells due to their hydrophobicity and tendency to aggregate (Dai 2002). Surface

modification can also have profound effect on cytotoxicity of nanoparticles. For example,

the toxicity of silica nanoparticles is associated with generation of surface free radicals

and reactive oxygen species (Hoet et al. 2004). These free radicals are extremely

damaging to cellular process and are associated with actions of many carcinogens.

Just as was the case with the size-only alternative, TSCA would require an

amendment so that nanomaterials with an emergent property could be defined as new

chemicals. The following language, used in a different context by Davies,9 might suffice:

‘(iii) any material produced in a form where one or more dimensions is less than

100 nanometers and where physical, chemical, or biological properties differ 9 The language below was suggested by Davies for amending TSCA to cover all nanomaterials. However, it appears that Davies’ language is qualified to apply only to nanomaterials that have ‘significant’ emergent properties. The language we used above (pps. 9-10) for a size-only TSCA amendment is the more inclusive phrasing. We use Davis’ language here to cover the size-plus-one case.

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significantly from similar materials with the same chemical identity due to its

nanometer structure, even if such material has the same molecular identity as a

chemical already on the inventory, unless a substantially identical nanomaterial is

already on the inventory’ (emphasis added).

While the idea of relying on emergent properties to trigger the regulatory

authority of TSCA seems chemically appropriate, it is clearly not as conceptually simple

as the size-only criterion. It is not immediately clear what is to count as a relevant

emergent property. Nor is it clear whether every emergent property is ‘significant.’ If, for

example, a nanoshell solution changes its color as it is reduced in size (Oldenburg et al.

1998), would this count as an emergent property that triggers regulatory scrutiny? Or is it

merely an interesting effect? Under what conditions might such a property be deemed

‘significant’ in the future?

Even though a clear-cut demarcation of these significant properties has yet to be

made, it might be possible to draw up a list of relevant properties based on what is known

about the potential pathways for harmful chemical effects. For example, the following

nanoparticle properties appear to be linked to their toxicity: (i) Aggregation (Oberdörster

et al. 2005), (ii) Particle chemistry and crystalline structure (Gurr et al. 2005), (iii) Aspect

ratio (Oberdörster 2002, Muller et al. 2005), (iv) Surface coating and functionalization

(Gupta and Gupta 2005, Risom et al. 2005). In addition to these four properties, attention

has also been drawn to properties such as shape and electrical charge. All of these

properties are, in some sense, emergent at the nanoscale and are candidates for the trigger

in a size-plus-one account of a new chemical. Without considerable additional

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toxicological data, however, it remains unclear how to make a workable judgment about

which properties should genuinely raise a red flag.

If the list of relevant emergent properties does become clearer over time, it would

be likely be desirable to rank them according to their risk. In a similar fashion to how

structural activity ratios are used to identify potentially dangerous substances, particular

emergent properties could be identified as especially worrisome from a toxicological or

environmental perspective. Supportive of this end, several high throughput screening

methods are being worked upon by researchers to meet the demands for efficient

nanoparticle screening systems (Jan et al.2008).

By introducing an additional criterion, regulating according to a size-plus-one

(emergent-property) characterization creates a more targeted approach than the size-only

strategy. As noted in the previous section, not every nano-sized material has novel

properties that create special hazards. This is a solid pragmatic reason for preferring the

addition of an ‘emergent property’ to the ‘size-only’ criterion - avoiding the over-

regulation of small particles that may not be dangerous. By utilizing a regulatory system

based on size and the presence of one or more emergent properties it will be possible to

keep many nano-sized particles outside of the regulatory regime hence reducing the

regulatory burden that might preempt commercialization of non-toxic nanoparticles.

On the other hand, as noted above, size can be the sole cause for concern. For

example, some mixes of nano and non-nano materials such as dusts, aerosols and other

air-borne particulates create cellular damage and breathing difficulties when inhaled into

the lungs. Nano-sized particles may be capable of traveling from the lungs directly into

the bloodstream, potentially causing other damage or issues (Nemmar et al. 2001). For

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this reason, a regulatory system using a size-plus-one criterion, may require some form of

additional mechanism to flag those cases where size alone might create a hazard.10

Regulating Nanomaterials as a ‘Significant New Use’ under TSCA

The two alternatives described above provide a means for listing nanomaterials as

‘new substances’ for purposes of the Chemical Substances Inventory. In the absence of a

nanomaterial making it onto the Chemical Substances Inventory in its own right, an

alternative to the new substances route already exists within TSCA. Regulatory

governance under TSCA can be initiated under the Significant New Use Rules (SNURs)

contained in Section 5(e) of the Act. If an existing chemical is going to be put to a

‘significant new use,’ TSCA allows the EPA to impose more or less the same regulatory

requirements on a company engaging in this new use as they would on one intending to

manufacture an entirely new chemical substance. Under section 5(a)(1)(B) of TSCA,

manufacturers must submit a Significant New Use Notice (SNUN) to EPA at least 90

days before they manufacture, import, or process a substance for a significant new use.

As with a PMN, the company must await a consent order from EPA and then abide by

any conditions attached to that order.

Since the whole point of discovering the novel properties that emerge at the

nanoscale is to use materials in new and useful ways, it seems plausible to regulate

nanomaterials according to the provision of TSCA that mandates attention to a significant

new use of a chemical already on the inventory. This approach would indirectly meet the

novelty condition since it recognizes how the novel properties of nanomaterials permit

10 The unresolved question this raises is whether the size-plus-one criterion will, de facto, revert to the size-only criterion.

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novel uses. One could argue that nanosizing a substance does not necessarily create an

entirely new chemical and so no new entry on the Chemical Substances Inventory should

be required. While the SNUR approach would not class the nanomaterial as a new

chemical per se, it would acknowledge something significantly new about the purpose for

which the substance was being produced. Since the toxicological and environmental

worries stem as much from the use to which a substance is put as they do from the nature

of the chemical material itself, this might be an appropriate way to trigger TSCA

oversight.

Some observers think the SNUR provision already provides the most effective

way to regulate nanomaterials. An American Bar Association report on nanotechnology

and TSCA is confident enough about the SNUR mechanism that it states ‘the Section 5(a)

(2) SNUR process appears to offer EPA adequate authority to effectively regulate

nanoscale versions of materials that are already on the TSCA Inventory’ (ABA 2006).

Similarly, in his 2007 report on regulating nanomaterials with existing laws, Clarence

Davies suggested that ‘most, if not all, nanomaterials could be designated under the

significant new use provision’ (Davies 2007).

Recent EPA actions confirm the promise of this approach. In November of 2008,

the EPA for the first time categorized the use of two nanomaterials (siloxane modified

silica nanoparticles and siloxane modified alumina nanoparticles) as significant new uses

of the macro forms of these materials, citing ‘concern for lung effects’ and ‘potential

systemic effects from dermal exposure’ as reasons for putting certain restrictions on the

production of the chemicals.11 Companies wishing to use these chemicals now have to

11 See the decision by EPA issued on 11/05/08 (73 Federal Register, 65743, 65751-2).

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submit a SNUN, after which EPA must issue a Consent Order that may put restrictions on

the production and distribution of the substance. On June 24, 2009 EPA issued a different

SNUR for multi-walled and single-walled carbon nanotubes that generalized provisions

of the consent order to British firm Thomas Swan and Co. for nanotube production issued

the previous Fall.12

Before EPA can issue a SNUR for an existing substance, it must do one of two

things. It must either show it now has special reason for health/environmental concern

according to a list of specified ‘concern criteria’ or it must show that the extent of

human/environmental exposure is likely to change significantly with the new use. To

show the latter, EPA must consider four factors: (a) the projected volume of

manufacturing and processing of a chemical substance, (b) the extent to which a use

changes the type or form of exposure to human beings or the environment to a chemical

substance, (c) the extent to which a use increases the magnitude and duration of exposure

of human beings or the environment to a chemical substance, and (d) the reasonably

anticipated manner and methods of manufacturing, processing, distribution in commerce,

and disposal of a chemical substance. Any of these four factors can individually trigger

the classification of a use as significant and new in addition to the case where new

information of concern has emerged.

While the recent EPA orders certainly demonstrate the possibility of regulating

certain nanomaterials under the SNUR provision, the approach raises several questions.

On the one hand, the mechanism clearly recognizes that nanomaterials provide new

challenges due to the new uses to which they can be put. There is no pretense that

12 See the decision made by EPA on carbon nanotubes issued on 06/24/09 (74 Federal Register, 29982-29998.

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The Novelty of Nano

existing macro scale regulations are always already adequate. On the other hand, by

focusing on the use to which a substance is put, rather than the chemical substance itself,

the SNUR approach only indirectly acknowledges the fact that nanomaterials possess

fundamentally different properties from their macro scale counterparts. Some might

argue that this misses something important about the novelty of nano. By failing to

directly address the question of whether anything has changed chemically at the

nanoscale, the SNUR mechanism fails to directly confront the central paradox.

This sounds like a merely conceptual quibble but the way TSCA has functioned in

the past suggests that directly identifying hazardous properties of chemicals should take

priority over identifying potentially hazardous uses. Of the nearly 1300 SNURs issued in

the life of TSCA, 56% were issued for chemicals that had restrictions already in place on

production of the chemical.13 In other words, the majority of SNURs are issued in relation

to worrisome properties previously identified (i.e. chemicals with known hazards). This

does not bode well for dangers that may only emerge at the nanoscale. The problem is

particularly clear for nanomaterials whose macro-sized counterparts are deemed

relatively safe and permitted to be manufactured with little or no restriction. In the

absence of compelling new data, it is unlikely that additional restrictions will be

generated for nanomaterials whose macroscale counterparts are in common use. For

example, the nanosizing of titanium dioxide and zinc oxide to create more aesthetically

pleasing sunscreens did not generate any assessment or restrictions under TSCA’s SNUR

provisions since these materials were already in common use at the macroscale. Yet the

health effects of rubbing these nanoparticles directly on the skin has not been determined.

13 These are known as 5(e) Consent Order SNURs. See EPA’s TSCA Summary of Accomplishments, available at http://www.epa.gov/oppt/newchems/pubs/accomplishments.htm.

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Compounding this concern about the SNUR approach is that, with so little

currently known about the toxicological and environmental effects of nanomaterials, it is

not clear which new uses should really count as ‘significant.’ Without adequate data, the

reasons for special concern at the nanosize have not yet been comprehensively

determined. The four criteria used to raise red flags about changes in use with

macroscized materials may not be entirely helpful. The ‘volume of manufacture [criterion

(a)]’ and the ‘magnitude of exposure [criterion (c)]’ are likely to be relatively low with

nanomaterials compared to their macrosized counterparts making it unlikely that these

two criteria could be invoked. The ‘form of exposure [criterion (b)]’ for a nanomaterial

may be no different from the form of exposure for the macro chemical even though

nanosizing might create a new risk. Using these criteria, the red flags for a significant

new use may not get raised. The fact that the red flags stay down may not, however,

ensure a safe level of exposure since the properties of the nanomaterial – and the

toxicological pathways - can be so different. With the relative paucity of current

information about these pathways, the existing criteria for significant new uses may not

be of much help. It is likely the criteria will have to be upgraded in order to better

account for what the term ‘significant’ really means at the nanoscale.

An additional problem with the SNUR approach is the track record of EPA in

actually uncovering new uses of chemicals that need regulating. SNURs do not get issued

very often. As mentioned above, the majority of SNUR rules are issued for chemicals that

already have restrictions on their manufacture but even this is not a large number. Only

729 of the 43,000 new chemicals brought to the EPA’s notice in the life of TSCA have

had SNURs attached to their original consent to manufacture notices (known as ‘5(e)

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SNURs’).14 As indicated above, these SNURs may not always be helpful since

nanomaterials are likely to have strikingly different properties from their macroscale

counterparts.

The other type of SNUR, rather than applying to chemicals whose consent to

manufacture came with restrictions, applies to novel uses that may create entirely new

risks. On the surface, this type of SNUR sounds like it may be more useful for

nanomaterials. The problem is that these SNURs are even more infrequent than the other

type. Only 570 of these ‘non-5(e) SNURs’ have been issued in the entire history of the

act. For these non-5(e) SNURs, the burden falls entirely on the regulatory authority to

identify a new potential hazard. In the case of the SNURs recently promulgated for

carbon nanotubes,15 there happened to be enough accumulation of evidence to suggest

that EPA had special reason for concern. Carbon nanotubes are, after all, one of the most

studied nanomaterials. For numerous other nanomaterials there will be considerably less

data available. Given the existing shortage of resources at EPA, and the lack of toxicity

studies available at this time, it seems unlikely that many new SNURs will be issued

under the current regulatory paradigm.

A final practical problem with the whole SNUR approach is its cumbersome legal

nature. There must be appropriate public comment and review periods for every new use

rule issued. SNURs are already known to be time consuming and confusing. If each

nanomaterial required its own significant new use rule, an enormous amount of EPA

action would be required. In 1989, under sections 5 and 26(c) of TSCA, EPA created an

expedited process for issuing significant new use rules for certain chemical substances to

14 See http://www.epa.gov/oppt/newchems/pubs/accomplishments.htm (accessed 7/3/09)15 This ruling was, in fact, for a 5(e) SNUR.

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The Novelty of Nano

ensure that the issuance of SNURs did not cause a bureaucratic logjam. Without some

categorical rules for nanomaterials (Davies 2007) the delays inherent in the SNUR

mechanism might be crippling.

In short, the SNUR approach has the attraction of recently proving itself to be

capable regulating some nanomaterials. The fact that it makes use of existing provisions

of TSCA and does not immediately require any amendments to the Act are clearly

advantages. The problem of fully coming to grips with the different aspects of the novelty

of nanomaterials means, however, that it is hard to determine what should count as a

significant-new-use. A material might be relatively benign and able to be produced

without restriction at the macroscale, but may not be so benign at the nanoscale. Even if

there are legitimate reasons for a red flag to be raised at the nanoscale, it may be hard to

muster the regulatory resources to actually know enough to trigger the SNUR provision.

Coda for the Future

As noted in each of the preceding discussions, the regulatory burden imposed by

all of the three suggested alternatives is high. Methods for reducing this burden would

surely be needed. As data on the toxicological properties of various nanomaterials

accumulates, it may be possible for EPA to simplify their task by making some

categorical groupings within the review process. A framework available within TSCA for

doing that would be to give nanomaterials their own designation as, say, Class 4

substances.

Currently the EPA divides all substances regulated under TSCA into 3 classes: a)

Class 1 substances have a single component chemical and that chemical can be described

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The Novelty of Nano

by a chemical formula; b) Class 2 substances are complex combinations of chemicals,

which cannot be described by a chemical formula; c) Class 3 substances are polymers.

This class structure recognizes common features pertaining to a large group of

chemical substances. A class grouping recognizes common properties between

substances without relying on SARs, which tend to be much more specific. Somewhat

different procedures and exemptions can be applied to different classes of materials based

on these common properties thus streamlining the review process. For example, certain

polyesters, most polymers with a molecular weight bigger than 10 kDa, and some

polymers with molecular weight bigger than 1 kDa, have been exempt from the PMN

review (Polymer Exemption, 40 CFR 723.250), as they have been found to present very

low risk for human health and environment.

The categorizing of certain polymers as their own special class of chemical

substances started in 1984, 8 years after TSCA had been enacted. Given the evidence that

certain polymers were most likely to be toxicologically harmless, EPA created a special

polymer exemption, which simplified PMN review for those chemicals. The polymer

exemption is not universal but targeted towards those types whose relative safety has

been established. Many other classes of polymers remain subject to the full PMN review

(e. g. positively charged polymers, unstable polymers, polymers with reactive functional

groups and others (Powell J. C. 2003)). Between 1984 and 1995 when the reporting

requirements changed, 2530 polymer exemptions were issued (28% of the total number

of exemptions) (EPA OPPT 2007). The easing of the regulatory burden that resulted is

evidenced by the fact that in 1995 EPA extended the exemptions further (40 CFR

723.250).

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The Novelty of Nano

A similar categorization by class could take place with respect to nanomaterials,

potentially striking a balance between over- and under-regulation. Certainly, substantial

additional information on toxicity would have to be accumulated by EPA in order for it to

designate exemptions for particular categories of nanoparticles. This information is in

most cases not currently available. If the Class 4 tool were to be implemented, we would

anticipate a time delay between the beginning of regulation of nanomaterials as 'new

chemicals' and the introduction of first exemptions.

Concluding Remarks

Each of the three alternatives described above – Size-only, Size-plus-one, and

Significant New Use – provides a way to regulate nanomaterials by working within the

existing legal structure provided by TSCA.16 Each of the recommended alternatives

manages to avoid the central paradox of existing nano-regulation while simultaneously

meeting the novelty condition (though the SNUR alternative does not meet it head on).

Furthermore, one of the three alternatives – SNUR – has recently been implemented by

EPA to provide regulatory oversight for silica and alumina nanoparticles and for carbon

nanotubes. When considered alongside the warning by EPA that certain forms of carbon

nanotubes count as new chemical substances under the traditional criteria, it becomes

clear that some nanomaterials can be regulated today without any amendments to the

language of TSCA at all.

The case of carbon nanotubes as a new chemical substance, however, is unlikely

to be typical for nanomaterials. The molecular identity of many nanosized particles will

remain the same as their macro scale counterparts. This means that these two recent steps

16 Size-only and size-plus-one do require minor amendments as noted above.

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The Novelty of Nano

forward in nano-regulation do not yet signal an adequate regulatory regime. Most

nanomaterials will not count as new substances under the general approach that EPA has

proposed since they have the same molecular identity as their macroscale counterparts.

Furthermore, many uses of nanomaterials will not count as SNURs since the four criteria

that determine a new use may not do enough to account for the novel toxicological

pathways of nanomaterials. Outside of the few cases this past year of EPA regulating

nanomaterials as new chemicals or with the SNUR mechanism, the central paradox is

likely to remain in place with the existing regulatory framework. This points in the

direction of the need to amend TSCA to bring the Size-only and Size-plus-one

alternatives into play.

As indicated at the start of this paper, there may be good reasons to question

whether TSCA is the appropriate place to regulate nanomaterials in the first place.

Testimony before the US Congress House subcommittee on Commerce, Trade and

Consumer Protection in February of 2009 highlighted just how hard it has proven to be to

regulate chemical substances under this law. A proposed ban on the production of

asbestos, for example, a known threat to pulmonary health, was overturned in the courts17

on the grounds that EPA had failed to show ‘substantial evidence’ of ‘unreasonable risk’

despite a ten year study and a 100,000 page administrative record. The court also decided

that it could not be proven that a ban was the ‘least burdensome’ alternative.18 The failure

to ban asbestos under TSCA raises a legitimate question concerning whether the burden

of proof placed on EPA by TSCA is too high. A second burden of proof issue for TSCA

17 Environment News Service, 2009 - http://www.ens-newswire.com/ens/feb2009/2009-02-26-10.asp 18 Testimony of John Stephenson, Director, Natural Resources and the Environment, Government Accountability Office at the House Subcommittee on Commerce, Trade, and Consumer Protection hearing on TSCA (2/26/09). Text available at: http://energycommerce.house.gov/index.php?option=com_content&task=view&id=1505&Itemid=95 (accessed 7/15/09).

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arises over the question of where obligation to show toxicity should fall. Unlike the

European REACH program for regulation of chemicals, TSCA puts the responsibility on

the regulatory authorities to show harm, as opposed to the commercial manufacturer to

show no harm.19 Since US regulation under TSCA is currently required to be minimally

burdensome to the manufacturers of a chemical substance, the EPA is obliged to apply

enormous administrative effort relative to its European counterparts.

The problems with TSCA notwithstanding, it is important to recognize that the

Act remains the primary regulatory regime in the US for new chemicals. Given that

nanomaterials with possible EHS implications are entering the marketplace today, it

remains important to determine what can be done in the present to mitigate worries about

the worst effects of nanomaterials on public and environmental health. The EPA policy

outlined in the January 2008 letter on TSCA Inventory Status of Nanoscale Materials

clearly does not meet the novelty condition and therefore falls foul of the central paradox.

Whether or not any of the three alternatives outlined above ultimately prove to be the

most effective way to regulate nanomaterials, they each provide plausible regulatory

avenues and can serve as valuable guides along the path towards a more successful

regulatory framework.

19 Also in the ENS article cited above. For specifics on REACH and Nanotechnology regulation, see http://www.safenano.org/nanoREACH.aspx (accessed 7/15/09).

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