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This Master's Project
Risk Assessment and Nanotoxicology: Life Cycle Exposure Analysis and
Management Implications for Carbon Nanotubes and Nano-sized Titanium
by
Dan Rompf
is submitted in partial fulfillment of the requirements
for the degree of:
Master of Science in
Environmental Management
at the
University of San Francisco
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Table of Contents
Chapter 1 Introduction..................................................................................................................7
1.1 Defining Nanotechnology ...................................................................................................7
1.2 Unique Properties and Applications for Nanotechnology................................................8
1.3 Hazard Assessment and Toxicology...................................................................................9
1.4 Regulatory Management and Oversight..........................................................................10
1.5 Human Exposure Routes and Nanomaterials Lifecycle.................................................11
1.6 Environmental Fate and Transport .................................................................................12
1.7 Descriptions and Background for Nano-sized TiO2 and CNTs.....................................13
1.7.1 Titanium dioxide (TiO2).................................................................................................14
1.7.2 Carbon nanotubes (CNTs) and nanofibers................................................................15
Chapter 2 Applications and Potential Exposure Pathways..........................................................18
2.1 Applications for Nano-sized Titanium Dioxide and Carbon Nanotubes.....................18
2.1.2 Materials sciences and applications ......................................................................18
2.1.3 Medical applications and cosmetics ......................................................................19
2.1.4 Environmental remediation applications and ecological benefits......................20
2.1.5 Energy efficiency and less toxic materials usage..................................................22
2.2 Lifecycle of Nanomaterials and End of Life...................................................................23
Chapter 3 Human Health Hazard Assessment to Nanomaterials: TiO2 and CNTs . .............25
3.1 Introduction and Hazards Identification........................................................................25
3.2 Hazard Identification: Source, Fate, Transport and Exposure Routes ......................25
3.3 Dose Response Assessment: Toxicity of CNT exposure ................................................26
3.4 Physical and Chemical Composition and Manufacturing Methods.............................28
3.5 Toxicology and Primary Exposure Route: Inhalation ..................................................29
3.6 Dose Response Assessment: Toxicity of Nano-sized TiO2 Exposure...........................30
3.7 Toxicity for Dermal and Ingestion Exposure Routes ....................................................36
Chapter 4 Nanotechnology Risk Management: Current Management Techniques and
Regulatory Approaches ........................................................................................................................38
4.1 Exposure Monitoring Practices and Methods................................................................38
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4.2 Hazard Management: Occupational Exposures to CNTs and TiO2 ...........................41
4.3 Administrative Controls, Engineering Controls and PPE............................................44
4.4 Detection and Monitoring of TiO2 and CNT NSPs in the Workplace .........................47
4.5 Voluntary Guidelines for Safe Nanomaterials Management .......................................50
4.6 Regulatory Management of Nanomaterials and Shortfalls ..........................................50
4.7 Lifecycle Management Approach ...................................................................................54
Chapter 5 Conclusions and Recommendations for Further Research ..................................58
5.1 Conclusion .........................................................................................................................58
5.2 Future Research Needs.....................................................................................................58
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Acronyms/ Abbreviations:
ACGIH American Conference of Governmental Industrial Hygienists
APR air purifying respirator
ASTM American Society of Testing and Materials
BMD benchmark dose
CAA Clean Air Act
CWA Clean Water Act
CFR Code of Federal Regulations
CNF carbon nanofiber
CNT carbon nanotube
CRT cathode ray tube
CNS central nervous system
CVD chemical vapor deposition
DOE Department of Energy
EHS environmental health and safety
ENP engineered nanoparticle
EOL end of life
EPA Environmental Protection Agency
FDA Food and Drug Administration
FIFRA Federal Insecticide Fungicide and Rodenticide Act
g/kg gram(s) per kilogram
GMO genetically modified organism
HAP hazardous air pollutant
HEPA high efficiency particulate air filter
IARC International Agency for Research on Cancer
ISO International Organization for Standardization
LOEL lowest observed effect level
LOQ limit of quantitation
MCL maximum contaminant level
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MEK methyl ethyl ketone
MSDS material safety data sheet
MnO2 manganese dioxide
MWCNT multi-walled carbon nanotube
µg/kg micrograms per kilogram
Nano-TiO2 nanoscale titanium dioxide
NEHI National Environmental Health Implications work group
NGO non-governmental organization
NIOSH National Institute for Occupational Safety and Health
NSC Nanoscience Safety Committee
NSF National Science Foundation
NSRC Nanoscale Science Research Center
Nm nanometer
NP nanoparticle
NNI National Nanotechnology Initiative
NRDC Natural Resources Defense Council
NSP nano-sized particle
OECD Organization for Economic Co-operation and Development
OEL occupational exposure limit
ORD US EPA Office of Research and Development
OSHA Occupational Safety and Health Administration
PAH polycyclic aromatic hydrocarbon
PEL permissible exposure limit
PM particulate matter
PNOR particles not otherwise regulated
PPE personal protective equipment
R & D research and development
RCRA Resource Conservation and Recovery Act
REL recommended exposure limit
RPP respiratory protection program
SAR supplied air respirator
SCBA self-contained breathing apparatus
SDWA Safe Drinking Water Act
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SEM scanning electron microscopy
SLAC Stanford Linear Accelerator Laboratory
SWCNT single-walled carbon nanotube
TEM transmission electron microscopy
TiO2 titanium dioxide
TLV threshold limit value
TSCA Toxic Substances Control Act
TWA time-weighted average
UFP ultrafine particle
UV ultraviolet
VOC volatile organic compound
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Chapter 1: Introduction
Nanomaterials have been naturally occurring on earth throughout the origins of
humanity and well before the dawn of nanotechnology and human manipulation of matter
on the nanoscale. Some of these early observations of nanoparticles in the human
environment result from volcano eruptions and resulting volcanic particulate emissions,
forest fires, viruses and mineral composites, all on the nanoscale. Dramatic increases in
exposure to ultrafine particles (UFPs) since the Industrial Revolution include
anthropogenic sources such as automobile exhaust, energy production and other
manufacturing practices. The UFPs from nanotechnology are likely to become another
exposure route to humans as the field of engineered nanoparticles manufacturing and
product integration advances significantly.
1.1 Defining Nanotechnology
To understand nanotechnology it is first important to understand the nano scale as it
relates to particle size and the sizes of other objects in our natural world. Nanoparticles or
nanomaterials are particles or objects with at least one dimension within the the range of
1-100 nanometers (nm). To put this into perspective, one nanometer is one billionth of a
meter. For a relative size comparison, the width of one human hair is approximately 200
micrometers, or three orders of magnitude larger than something on the nanoscale. The
nano scale is on the cellular/molecular scale, including bacteria and viruses (See Figure
1.1). With this in mind, the definition of nanotechnology is the manipulation of matter on
the near-atomic scale to produce new types of structures, materials, and devices with new
and unique properties not seen naturally occurring in the environment.
Figure 1.1 Nano-scale image (University of Vermont 2012)
Figure 1.1 Nano-scale size chart
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Applications using nanotechnology range widely and include medical and
pharmaceuticals, environmental remediation technologies, materials sciences and
engineering, as well as applications which enhance manufacturing and waste management
sectors. It was not until the 1980’s that this technology had even become technically
available. In 1985 the first report of manipulation of individual atoms and reports of the
first carbon fullerenes was a scientific breakthrough and resulted in a Nobel Prize in 1996
(Pelley and Saner 2009). According to (Lux Research 2007) projections indicate that new
emerging nanotechnology applications will affect nearly every type of manufactured
product through the next decade and become incorporated into 15% of global
manufacturing output by 2014.
It is important to distinguish between different types of nano materials as the structure,
chemical composition, surface area, and size are all important indicators as to how a
nanomaterial will interact with its surroundings, both chemically and biologically.
Different terminology may be used across various disciplines, however, the most common
types of nano materials are “nano-sized particles” (NSPs), which include both engineered
and ambient nano-sized spherical particles < 100 nm. Naturally occurring NSPs can
commonly be found in vehicle exhaust or welding fumes and particulates from volcanic
eruptions. Engineered or ambient particles <100 nm can be referred to as NSPs or
“Ultrafine Particles” (UFPs) interchangeably. “Engineered nano particles” (ENPs) include
only the type of NSP’s specifically engineered in a laboratory setting, differentiating them
from naturally occurring particles. Often ENPs are referred to on the basis of their shape,
including nanotubes, nanowires, nanorings, and so on. These materials are engineered
specifically in these shapes as their structure defines their properties and functionality
(Oberdorster 2005).
1.2 Unique Properties and Applications for Nanotechnology
In the case of nanomaterials, there are many uncertainties due to their unique
characteristics which may be different than those of larger particles with the identical
chemical composition (NIOSH 2009). Nanotechnology creates new materials with
enhanced properties such as catalytic efficiency, increased electric conductivity, improved
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hardness and improved strength that are all a result of the larger surface area, increased
reactivity and quantum effects that occur on the nanoscale (Moore 2012). Consumers can
find nanomaterials widely available in sunscreens, cosmetics, medical or electronic
devices, pharmaceuticals, sporting equipment, clothing and many other products.
Nanotechnology applications promise enhancements in environmental remediation,
contamination reduction, and water treatment as well.
Certain metal oxides have been known to remove contaminants from groundwater and
soil and even improve the technology utilized to detect and monitor contamination.
Ironically the unique properties that make nanomaterials useful are in fact the same
properties which would make these nanomaterials potentially toxic to humans and the
environment. It has been shown that certain nanomaterials that have entered animal tissues
have crossed through cell membranes or even crossed the blood-brain barrier and entered
the central nervous system as well as other target organs (EPA 2007). While this
mechanism is useful in targeted drug delivery, this same property can result in unintended
exposures and consequences. It has also been observed that inhaled nanoparticles can
become lodged in the lungs and exhibit specific toxicity similar to that of asbestos fiber
(EPA 2007). Many engineered NSPs have even been found to penetrate current respiratory
protection equipment and filters, proving them ineffective for occupational exposure
protection. Specifically a test on the N95 air purifying face mask, showed vulnerability
and leakage to particles on the range of 80-200 nm (Lee 2008). There is also the
unanswered question of how to manage the fate of these highly reactive and persistent
particles as waste in the environment (EPA 2007).
1.3 Hazard Assessment and Toxicology
While acknowledging the promise of enhancements to our lives through scientific
progress in the nanotechnology sector, the potential hazards and undesirable effects these
materials may have upon human health and the environment cannot be ignored. Because
these materials exhibit different properties due to their small size, surface area, shape and
reactivity, it becomes necessary to examine environmental health and safety implications
of engineered nanomaterials, human exposure routes, environmental fate and pathways, as
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well as to create policy based on the best available technology. As these materials become
more prevalent in our society and mass produced in the industrial sector it is important
that proper assessment is made of risks to both human health and the environment
utilizing current risk assessment and toxicological data, as well as studies conducted on
the newly created nanomaterials which exhibit different or enhanced properties as
compared to their macro-scale forms (EPA 2007).
1.4 Regulatory Management and Oversight
An incomplete understanding of the hazards presented by nanomaterials throughout
their life cycle creates the potential for adverse human health exposures, environmental
releases and exposures, and other unknown consequences recently being addressed by the
scientific and regulatory communities. There are numerous collaborations both
internationally, nationally, and at the inter-agency level which would like to make
responsible development of this new technology a priority by evaluating environmental
health and safety implications of nanotechnology, as well as the potential benefits of
research and development in this sector.
In the United States, the National Nanotechnology Initiative (NNI) is one inter-agency
consortium, launched in 2001 to coordinate fundamental research on new materials,
instrumentation, devices, and standards, as well as to evaluate the health and safety
implications of this new technology. The NNI is comprised of twenty-five federal
agencies including the U.S. Environmental Protection Agency (EPA), National Institute
for Occupational Safety and Health (NIOSH), Occupational Safety and Health
Administration (OSHA), National Science Foundation (NSF), and these groups complete
much of their work through the National Science, Engineering and Technology (NSET)
subcommittee and Nanotechnology Environmental Health Implications (NEHI) work
group. Funding for NNI has grown from $464 million in 2001 to $1.3 billion in 2006 (Lux
Research 2004). Another $2 billion in annual Research and Development (R&D)
investment is being spent by states, academia, and private industry on nanotechnology
sector development. The private sector has also created several workgroups including the
Nano Business Alliance, and the Nanoparticle Occupational Safety and Health
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Consortium to develop exposure and monitoring protocols. Many non-governmental
organizations (NGOs) including the National Academy of Sciences (NAS), Natural
Resources Defense Council (NRDC), and Royal Society of the United Kingdom,
Greenpeace, and International Life Sciences Institute are contributing to the research as
well (EPA 2007). Globally in 2007 $9 billion was being spent for various R & D
applications related to this sector (Lux Research 2007).
Internationally the issue of nanotechnology health and safety will require the global
cooperation and synthesis of research for science and policy makers in all regions where
this technology is emerging. European and Asian governments have acted to research
health and safety as well as environmental implications of nanotechnology by
collaborating on efforts and working with the United Kingdom Department of
Environment, and the European Union Scientific Community on Emerging and Newly
Identified Health Risks. Also, several international organizations including Organization
for Economic Co-operation and Development (OECD), and International Standards
Organization (ISO) have formed a committee to develop international standards for
nanotechnologies. The EPA’s Nanotech Research Strategy (NRS) is one component of a
major initiative in the U.S. underway currently, including the OECD and NNI, which all
perform important functions. The OECD is working to establish a testing program for
nanomaterials likely to be coming to market while the NNI coordinates inter-agency
activity while the Nanomaterial Stewardship Program (NMSP) in EPA’s Office of
Pollution Prevention has initiated a program of voluntary submission of environmental,
health and safety issues researched by both private and public sectors (NRS 2009).
Engaging the international community, with representatives from regulatory,
scientific, academic, and NGO institutions, as well as industry participation and
collaboration will ensure that as domestic and international nanotechnology products
become more readily available, the right decisions will be made to prevent significant
impacts to human health and the environment (EPA 2007). However, at this point there
are certain regulatory gaps and knowledge gaps that have been acknowledged which
correspond to the toxicology of these materials to human subjects versus animals, and the
toxicology of nanoparticles in comparison to their bulk counterparts. Many of the
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international standards are voluntary as well, including ISO and American Society for
Testing and Materials (ASTM) industry standards, creating uncertainty in the
management of the waste nanomaterials and their final fate and transport.
1.5 Human Exposure Routes and Nanomaterials Life Cycle
Historically, nanoparticles (NPs) from human origin would include airborne
particulates from cooking fires, diesel exhaust, and welding to name a few. It has in fact
been documented that many of these naturally or incidentally occurring nano-sized
particles (NSPs) cause adverse human health effects due to their particle size and ability to
enter the body through inhalation as a primary exposure route (Oberdorster 2005). This
documented link between natural nanoparticles and human health effects leads us to
believe that engineered nanomaterials as well would be associated with possible human
exposure risks and unique environmental health effects.
Throughout a nanoproduct’s life cycle there are many opportunities for both
occupational exposures in the workplace as well as releases into the environment. Bio-
kinetic toxicology studies on ambient NSPs already present and measurable in the
atmosphere have created a basis for understanding how engineered nanoparticles are
creating unique and often unknown hazards. These materials can enter environmental
pathways and create human exposure routes throughout their life cycle, from research and
development, manufacturing, consumer application, to post consumer waste management.
Understanding and controlling hazards resulting from nanotechnology poses many
technical challenges for regulatory agencies, international standards organizations,
scientists, doctors and toxicologists (Oberdorster 2005). In an effort to allow the safe
development of nanotechnology and the broad spectrum of benefits offered across
industrial and medical sectors, it is important that there is investment in proper research
and development of these promising new materials.
It remains clear that additional research is required in the field of nanotoxicology for
human exposure assessments and life cycle analysis of nanomaterials with consideration
of their often unique properties to ensure that appropriate precautionary measures and
regulatory requirements can be established. Documented examples of adverse health
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effects from ambient ultra fine particles (UFPs) are documented by the California Air
Resources Board Freeway studies of UFPs comprised of diesel exhaust and particulate
matter (PM) (CARB 2011).
1.6 Environmental Fate and Transport
It is not only direct human exposure routes that are of concern for regulators and
industrial hygienists as nanotechnology products venture into all facets of commercial,
medical, and industrial markets. Concerns exist that nanomaterials could be released into
air, water, and soil, causing unknown and unwanted environmental effects. According to
the EPA (2007), the potential exists for nanomaterials to enter our environment through
various pathways including direct/ indirect releases from manufacturing or refining
processes, such as chemical manufacturing processes, and releases from environmental
remediation processes utilizing nanomaterials as a clean-up mechanism. The consumer
product side of nanoproducts also creates exposure pathways as the materials begin to
break down at their end of life (EOL) stage. These products include spent or expired
pharmaceuticals, cosmetics, computer screens, tires, and even clothing integrated with
nanomaterials. Current understanding of the fate and environmental transport of these
materials is limited and full of uncertainty, according to the European Commission (2004)
as there has been a lack of studies conducted on new materials utilized by nanotechnology
applications.
Some of the hazardous characteristics of nanomaterials known by the EPA (2007) as
these materials reach the environment are bioavailability, bioaccumulation, and
biodegradation, the potential for these materials to break down into more toxic
metabolites. Further concerns include reactivity with other environmental contaminants, as
well as how applicable current environmental fate and transport models are to predict the
presence of nanomaterials in the natural environment. It is not guaranteed that
nanomaterials will behave the same way as their bulk counterparts, and there is no
established history of nanoparticle exposure on a large scale so it would be prudent to
develop a precautionary strategy in evaluating nanoparticle mechanisms before they come
to market and end up in landfills and beyond (EPA 2007).
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1.7 Descriptions and Background for Nano-sized TiO2 and CNTs
Given that the field of nanotechnology encompasses a broad range of materials and
products, the focus of this research will be to conduct occupational exposure hazard
assessments, and present a life cycle management approach for nano-sized titanium
dioxide (TiO2) and various forms of carbon nanotubes (CNTs) on the market and in the
workplace. Given the different types of applications as well as the possible environmental
health and safety exposure pathways created by these unique materials, it is beneficial to
examine these two materials in concert as they represent different levels of risk based on
their application, physical and chemical properties, as well as their final fate and transport
in the environment. This section presents a brief overview of Ti02 and CNTs in order to
provide a better understanding of these materials, known and unknown hazards, as well as
applications which promise to enhance our lives.
1.7.1 Titanium Dioxide (TiO2)
Titanium Dioxide or Ti02 is a white, crystalline, non-combustible solid and odorless
powder already being used extensively as a commercial product found in paints,
cosmetics, paper, plastics, and food products. Other uses for Ti02 are as a catalyst for
environmental remediation, and removal of toxins and heavy metals from soil and
groundwater including Arsenic, Chromium (III), pesticides, benzene, and toluene (Shan et
al 2009). In 2007, production of Ti02 was estimated at 1.45 tons from eight factories over
seven states and employing 4,300 workers (DOI 2008). Currently it is unknown how many
workers may be exposed to Ti02 dust (NIOSH 2007). Ti02 can be found in the
occupational workplace during various phases of production in particle sizes ranging from
fine particles, (>.1 micrometer), to UFPs ranging from (0-100 nanometers). In 1991, Ti02
was the 43rd
highest volume chemical produced in the US (NIOSH 2007), and paints/
coatings were found to be 95% of the Ti02 used in the US in 2004. The number of workers
in this industry is estimated at 68,000 nationally. The main occupational exposure
pathway is inhalation, and OSHA has set a PEL (Permissible Exposure Limit) to TiO2 at
15mg/m3
for the workplace. NIOSH recommended that TiO2 be classified as a carcinogen
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in 1988, based on early animal tumor studies on rats utilizing fine particles (>100 nm) at
250 mg/m3
.
More studies utilizing the UFP size particles showed a strong correlation between
exposure at 10mg/m3
and significant increase in lung cancer rates for rats indicating the
UFPs had a more detrimental effect based on surface area reactivity (NIOSH 2007). (See
Figure 1.2) Currently the IARC classified Ti02 as Group 2B, with sufficient evidence
showing carcinogenicity in lab animals, however lack of evidence for human
carcinogenicity and overall rates as 2B, “possibly carcinogenic” to humans (IARC 2010).
This lack of evidence leads to different PEL permissible exposure limits for fine particles
than those for ultrafine particles of Ti02. While studies have not confirmed the
carcinogenicity of Ti02 in rats and extrapolated data for human exposure, there is a strong
correlation of dose-response data indicating the particle surface area is a major factor in
relation to the tumor response in animals.(NIOSH 2011) Being that the nano-sized Ti02
particles exhibit this more potent effect due to their increased surface area reactivity and
Ti02 is found in a multitude of products ranging across industries, it is warranted that
further studies and a life cycle management approach be taken in order to understand and
mitigate risks associated with Ti02 nanomaterials. While it is unknown exactly how many
workers are at risk for occupational exposures to Ti02, equally important are end users of
the products including consumers as the materials are purchased, utilized, and disposed of
in landfills. So, it also becomes important to look at the final disposition of these materials
being released into the air, soil, and water through their use or being discarded and
breaking down in the environment. It is currently unknown how these materials will react
once incinerated as hazardous waste or placed into a landfill.
Figure 1.2 TiO2 Mass Dose in Rat Lungs After 2 Year Inhalation. Lung Tumor Proportion
to Fine vs. Ultrafine TiO2 Particles (NIOSH 2011)
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1.7.2 Carbon Nanotubes (CNTs) and Nanofibers
Carbon nanotubes (CNTs) are one of the more commonly found nanomaterials in the
emerging market and promise to deliver a multitude of industrial and commercial
applications through their extraordinary chemical and physical properties. The CNTs are
essentially engineered nanoscale cylinders of carbon which can be produced in a variety of
shapes, forms, and aspect ratios. The functionality for CNTs is derived from their shape,
dimensions, physical characteristics, coatings, as well as chemical composition. There are
single-walled carbon nanotubes (SWCNTs) which have a diameter as small as 1
nanometer (nm), however the length of these materials can be in the range of multiple
micrometers. Multi-walled carbon nanotubes (MWCNTs) consist of many single-walled
tubes stacked along-side each other, resulting in dimensions from 2-100 nm. The CNTs
and MWCNTs exhibit unique characteristics including mechanical strength, flexibility,
lightweight design, heat resistance, and electrical conductivity, opening the door to a wide
range of applications. Some applications include advanced solar cells, enhanced battery
technology, reinforced plastics, biosensors and other enhanced imaging/sensing devices,
biomedical devices, bone grafting mechanisms, tissue repair and targeted drug delivery
systems (NIOSH 2010).
Figure 1.2 Lung Tumor proportion
from exposure to fine vs. nano-
sized TiO2
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Carbon nanotubes have shown promise in remediation of contaminated groundwater
and soil including the adsorption of benzene, methanol, lead, and polycyclic aromatic
hydrocarbons (PAHs) due to their structure, size and surface reactivity (Shan et al. 2009).
Advanced carbon nanomaterials also promise additional benefits of reduced
environmental burden by controlling pollution, replacing existing toxic materials, and
utilizing less material in various processes due to their enhanced properties (Shan et al.
2009). While CNTs promise benefits of green processes, treatment of agricultural and
industrial wastes, industrial enhancements, as well as potentially improving air and water
quality, these materials must be introduced in a responsible way by analyzing the life
cycle of the materials.
Beginning with occupational exposure pathways at research and development
laboratories, to manufacturing, consumer use, and final disposal there exists potential for
multiple exposure routes to human health and the environment along the way. The extent
of the exposures have not been fully characterized, however occupational exposure to
MWCNTs and SWCNTs have been compared to exposure to asbestos fibers, as CNTs
have been observed to exhibit similar toxicity to asbestos based on their similar size,
shape, and design. Similar observed exposure mechanisms during inhalation of asbestos
fibers and CNTS have shown that these NSPs become lodged deeply in the lungs when
inhaled and can result in cancer and adverse pulmonary effects (Kolosnjaj 2007).
Experiments have shown a dose-response relationship between inhalation exposures and
cell toxicity, formulation of tumors and granulomas within different animal species and
extrapolation of data for humans would show that these CNT species pose a human health
risk for exposure (Kolosnjaj 2007). It is also necessary to take an international approach
across industry, regulatory agencies and academic institutions so that the beneficial
applications of these new materials can be enjoyed, while avoiding the adverse health and
environmental effects.
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Chapter 2: Applications and Potential Exposure Pathways
This chapter will outline the various technological applications in which
nanotechnology can be applied including environmental remediation, medical
applications, and advanced materials development, and will identify potential exposure
pathways associated with these applications.
2.1 Applications for Nano-sized Titanium Dioxide and Carbon Nanotubes
While the unique properties of engineered nanomaterials account for their application
in many modern technologies, these same properties are posing hazards to human health
and the environment if not controlled properly or not thoroughly understood. By outlining
some of the various applications for nanomaterials across the broad spectrum of modern
industry, it will be demonstrated the expansive range of nanotechnology which promises
to enhance our lives in virtually every sector of the economy. However with this broad
new exposure to nanotechnologies integrated into every aspect of daily life, it makes sense
for regulatory agencies, academic institutions, the medical community, and other national
and international groups to ensure this technology is applied safely and appropriately in
order to prevent unknown or unwanted effects on public health or environment.
2.1.2 Materials Sciences and Applications
As the unique properties of nanomaterials begin to be understood, it is clear that a
wide range of applications can be introduced in materials sciences, which is a foundation
for many other related technologies. While it has been shown the carbon nanotubes
(CNTs) have semiconducting properties, CNTs also show unique mechanical, electrical
and thermal advantages. While examining mechanical properties, it has been shown that
the stiffness, strength and flexibility of CNTs rival that of other modern materials
including carbon fiber (Treacy Ebbesen et al. 1996; Salvetat, Bonard et al. 1999). It has
been shown that CNTs are five times stiffer and up to 50 times stronger than steel. CNTs
also have a high density up to 1000 times greater than copper, making them desirable in a
variety of commercial applications (Berber, Kwon et al. 2000).
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Based on their enhanced physical and chemical properties, CNTs can be utilized in
advanced photovoltaics, enhanced battery technology, structural polymers, and many of
these products have already come to market. According to The Project on Emerging
Nanotechnologies (PEN), there are already numerous consumer products on the market
which contain CNTs in the sporting goods industry, visual display units, electronic
devices, and aircraft parts. There are 26 known consumer products including tennis
rackets, golf clubs, baseball bats, bicycles, aircraft engine parts, and electronics, currently
integrating CNTs to reinforce and develop superior materials (PEN 2010). According to
the National Nanotechnology Initiative (NNI), funding for U.S. research and development
has more than tripled from $464 million in 2001 to $1.7 billion (NNI 2010). It has also
been shown that nanotechnology was utilized in over $147 billion in products in 2007 and
projected to reach $3 trillion worth of products by 2015 (Lux Research 2008).
With this market growing exponentially, evaluating the safety and assessing the risks
of these materials as they enter commerce and human ecosystems is a crucial and daunting
task at the same time. Also, we must truly understand the human health effects and
environmental fate of these materials as they become prevalent in daily life.
2.1.3 Medical Applications and Cosmetics
Applications for nanomaterials in the medical field include advanced drug delivery
systems, sensor technology, and utilizing nanomaterials as a coating for drugs to target
specific cells that are causing cancer. Advanced nanosensors can also locate cancer cells in
real-time without requiring laboratory analysis. In one such application utilizing a
nanoshell of silicon dioxide (Si02) and a thin coat of gold, nano shells are specifically
engineered to adhere to the surface of a specific type of breast cancer cell known by
researchers as HER2+ (Bickford 2010). Utilizing this mechanism, as well as the optical
properties of engineered silicon and titanium dioxide allow doctors to view existing cancer
cells by illuminating them to be more easily detected. This type of detector can be highly
useful to a surgeon while performing a procedure as they would have the ability to see if
all cancerous tissue has been removed while the patient is still in surgery. The implication
here is that this application would increase the efficiency of treatment, detection and
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potentially increase success rates and survival rates for earlier detection of cancer cells in
patients (Bickford 2010). As interesting as this application of nanomaterials might be with
the obvious benefits to cancer patients, effects of these materials and their intentional
insertion into the human body may have potential health effects worth investigating. One
aspect worth considering is that if NSPs have a therapeutic value on a nanoscale for
delivering medications, this use might translate to cytotoxicity on the cellular level if other
NSPs become bio-available from un-intended release into the human body.
Another common use for nano-sized titanium dioxide (TiO2) is cosmetics and
sunscreens, primarily for ultraviolet radiation (UV) protection and nearly invisible
physical appearance. Nano-sized TiO2 has the unique property that it will appear
transparent on the skin, as compared to the conventional TiO2 which can appear visible as
white streaks on the skin due to its ability to scatter light rather than reflect it (EPA 2010).
Aside from aesthetic benefits, nano-sized TiO2 has the unique ability to absorb UV-A and
UV-B wavelengths on the scale from 290-400 nanometers making it an effective physical
blocker of UV radiation (EPA 2010).
The Food and Drug Administration (FDA), that is responsible for regulating food and
cosmetic products, requires additional requirements for NSP containing cosmetic products
which will be directly applied to the skin or may enter the body through other exposure
routes. The FDA recognizes the unique physicochemical properties that can alter toxicity
of compounds, and requires additional safety assessments for nanoproducts. Some areas
for safety testing include increased absorption, transport to cells, crossing the blood-brain
barrier, altered bioavailability, and biological half-life (FDA 2012). Many cosmetic
nanoproducts such as sunscreen can have spray on application, therefore inhalation and
ingestion may become viable human exposure routes as the NSPs become airborne in the
customer breathing zone. Due to the observations that nanomaterials can cross cell barriers
and enter the central nervous system (CNS), it is also recommended that toxicity testing be
conducted on secondary and target organs resulting from primary exposure (FDA 2012).
2.1.4 Environmental Remediation Applications and Ecological Benefits
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Utilizing the unique properties of engineered nanomaterials has applications for
environmental remediation techniques including groundwater and soil remediation, the
cleanup of halogenated light bulbs, wastewater treatment, and drinking water purification.
Due to their high specific surface area to volume ratio, nanomaterials can alter physical
properties on the nanoscale, making them effective catalysts, adsorbents, and membranes
which are useful properties in water treatment and environmental clean-ups. Titanium
dioxide nanomaterials have been shown to be useful in drinking water treatment
applications through the removal of arsenic, copper and polycyclic aromatic
hydrocarbons (PAHs) (Gwinn 2011). One concern is that the nano-sized TiO2 used in the
treatment process would have to be dispersed into the water supply and while it promises
to remove toxic contaminants, the TiO2 may not be destroyed or reclaimed during the
process, rendering the final fate of the nano-sized TiO2 uncertain (Gwinn 2011). This
uncertainty would pose a concern that residual nano-sized TiO2 remaining in the drinking
water could reach potential human exposure routes cause health effects and even deliver
adhered contaminants such as arsenic to new exposure pathways making them bio-
available on a nanoscale (EPA 2010). While the original application for the treatment of
drinking water is a viable one, it is unclear how much of this material may pass through
the filter matrix and reaches the public. Currently this purification technique is in the
development phase and there is further research needed in order to determine both the
efficacy and potential for environmental release.
Another application for air and groundwater remediation with toxic contaminant
adsorption involves the usage of carbon nanotubes (CNTs) anchored onto substrates in
order to adsorb organic materials, as well as heavy metals. Activated carbon has been
utilized for some time as an adsorbent to reduce nonpoint source pollution as well as
remove toxic contaminants. Nano-sized carbon adsorbents utilizing single-walled carbon
nanotubes (SWCNTs), and multi-walled carbon nanotubes (MWCNTs) observations
indicate potential for the removal of benzene, toluene, methyl ethyl ketone (MEK), PAHs
and many other toxic contaminants found in air and water (Yang et al. 2006). The CNTs
have also been found to adsorb lead, atrazine, and other hazardous constituents, including
trihalomethanes, using an MWCNT with modified pH (Wang and Zhou 2007). The CNT
22. 22
absorptive effectiveness is based on morphological and structural factors which can be
engineered on the nanoscale for each specific application and contaminant of concern.
Currently this type of research is in its infancy to understand all of the potential
applications for environmental remediation utilizing nanotechnology. While the utilization
of NSPs in removing contaminants from the environment is promising, it must also be
demonstrated that these same nanomaterials involved in the removal do not end up
becoming contaminants throughout any phase of their life cycle. Therefore, it makes sense
to complete proper testing throughout the life cycle of the product and its application
before being widely distributed so as to prevent unintentional contamination through
landfill deposition, groundwater intrusion, or air pollution resulting from toxic clean-ups.
Further ecological benefits can be seen by the utilization of nanotechnology sensor
development designed to detect chemical and biological contaminants on the nanoscale.
Utilizing nanotechnology provides science with the ability to improve exposure
assessments, allowing collection of large numbers of samples at a lower cost and
improved specificity. Most research is currently focused on the defense and biomedical
communities for these applications which are capable of detecting harmful chemical
warfare agents or biological materials at very low concentrations, enhancing security, and
detection of pathogens both in our food/water supply and in a medical environment (EPA
2007). There is also viable application for real-time detection of pathogens in dairy, meat,
as well as agricultural products for the FDA, further protecting the health of the public
(FDA 2012). As the process of enhancement and changes to the types of products develop
begins through integration of nanotechnology, it also becomes necessary to modify the
way we detect chemical and biological contaminants in our environment which would
otherwise remain undetectable by conventional instrumentation. Nanotechnology offers
new risks and exposure potential, yet at the same time provides potential for more
advanced detection technology for protection of public health and the environment.
2.1.5 Energy Efficiency and Less Toxic Materials Usage
With the new availability of nanoscale materials, there is much potential to offset or
eliminate the usage of hazardous materials in production of materials as well as
23. 23
dramatically increase the energy efficiency of current industrial processes. One such
example is the application of CNTs and quantum dots of various metal oxides in the solar
panel industry. This new technology utilizing a nanomaterials process results in high-
efficiency non-silicon panels with efficiency in the range of 42% energy conversion
(Shabaev and Nozrik 2006). While this process dramatically increases the efficiency of
current advanced solar photovoltaics on the market, it also limits the dependence on
silicon as the primary component of these panels and limiting resource.
Carbon nanotubes and other integrated nanomaterials are also contributing to the
reduction of toxic materials utilized in conventional manufacturing methods. For example,
traditional cathode ray tubes (CRTs) contain heavy metals such as lead and mercury which
create serious environmental impacts and toxic human exposures throughout their life
cycle and end of life disposal. Utilizing CNTs for computer and television monitors
eliminates the usage of heavy metals while enhancing the performance, quality, and even
increasing energy efficiency (USEPA 2001). Removing toxic materials from the
manufacturing process will result in downstream pollution prevention as these toxic
contaminants will not be available for exposure by workers during the manufacturing
process or through the deposition of hazardous materials into landfills. And while the
conventional toxic materials known to cause detrimental human health and environmental
effects are replaced, it is also important to consider the life cycle management of products
integrated with nanomaterials to ensure that through proper management a new
classification of pollution is not introduced into the environment.
2.2 Life Cycle of Nanomaterials and End of Life
A life cycle approach to nanomaterials and nanowaste management allows effective
assessment of the environmental benefits from utilizing nanotechnology as well as
determination of what risks and exposure routes may be present throughout the life cycle
of the material. The end of life (EOL) of a product can be understood as the specific point
at which the product no longer satisfies the owner or purchaser’s needs (Asmatalu 2012).
At this point the product has a fate or final destination which can range from recycling to
disposal in the environment. All products, if not recycled, will end up in landfills or even
24. 24
be incinerated if deemed to be hazardous waste. The EOL of nanoproducts is critical
because significant impacts or benefits for the environment may arise at this phase. One
approach to the nanowaste problem is to ensure that there is a high recyclability for
products containing NSPs by attaching some type of rebate or incentive to the proper
disposal. This incentive would lead to sustainability of nanoproducts and effectively
reduce the chance of these materials ending up in landfills (Asmatalu 2012) (See Figure
1.2). Another approach would involve new regulations mandating specific waste profiles
to be completed and “cradle to grave” management as hazardous waste if these materials
are found in a waste determination to exhibit hazardous characteristics. However, nano-
sized materials are currently and often regulated the same as their bulk counterparts
regardless of whether they exhibit different toxicity or increased surface reactivity (EPA
2010).
Figure 1.2 Nanoproduct Distribution Based on the End-of-Life, Total PEN CPI List (1,014
products). (Asmatalu 2012)
Figure 1.2 Nanoproduct EOL
distribution
25. 25
Chapter 3: Human Health Hazard Assessment to Nanomaterials: TiO2 and
CNTs
3.1 Introduction and Hazards Identification
In performing a hazard assessment on human exposure to nanomaterials it is important
to address multiple factors. First of all it is necessary to identify the potential hazards and
their properties which will help to identify exposure pathways and probable exposure
routes. In this chapter, occupational exposures to nano-sized titanium dioxide (TiO2) and
carbon nanotubes (CNTs) will be examined. The physical and chemical properties of these
materials as well as their size and surface reactivity will play a part in their relative
toxicity. In order to properly assess risks to human health and classify potential exposure
routes, a dose-response assessment study involving in vitro and in vivo animal testing
results will be evaluated in order to demonstrate the dose response relationship between
animal and human exposures. Once the relationship between exposure to nanomaterials
and the dose response relationship from exposures to toxic nanomaterials is shown, an
exposure assessment can be completed for those materials. Also, safe and recommended
exposure limits and guidelines are assigned by government and industry groups as the data
is properly evaluated.
Given what we know about the potential for human toxicity based on exposure to
nano-sized TiO2 and CNTs, a risk characterization can be performed which indicates the
probability of human exposures throughout the product life cycle and to what degree these
risks exist. As the potential degree of risks through occupational and EOL product
exposures to nano-sized TiO2 and carbon nanotubes are evaluated, strategies to mitigate
these risks can be identified which eliminate exposure pathways and recommend utilizing
a life cycle management approach with new regulatory requirements. Some of the
challenges that present themselves in nanotechnology risk assessments are the diversity
and complexity of the types of materials being manufactured, as well as the seemingly
limitless potential applications for TiO2 and CNT’s (EPA 2007). Furthermore it can be
said that there are a limited amount of research available on the subject as the technology
is relatively new.
26. 26
3.2 Hazard Identification: Source, Fate, Transport and Exposure Routes
While CNT research and development is relatively new, and though there is a growing
number of CNT integrated products reaching the market every day, there is not a large
amount of data available on toxicity of carbon nanotubes, which is cause for concern and
further analysis. There are many factors which will affect the relative toxicity of CNTs
including the structure, size distribution, surface area, surface chemistry, and surface
charge (Kolosnjaj 2012). The CNTs can be engineered in a variety of shapes, structures,
sizes and processes which will result in a variety of toxicological properties as well as
physical-chemical properties, creating a challenge in conducting a hazard assessment. As
more nanoproducts are developed and CNTs are integrated into products within virtually
every sector of the economy, the potential for release into the environment is increased. It
is not unreasonable to assume that the presence of nanomaterials in the environment will
increase as well as the potential for human and environmental exposure (EPA 2007).
Potential human exposures to nanomaterials, including CNTs and TiO2 NSPs can occur
through a variety of exposure pathways throughout the life cycle of the nanoproduct.
Some exposure pathways include direct occupational exposures to workers during R & D,
manufacture, use, packaging, transport or recycling and disposal of nanomaterials, not to
mention the unintended exposure to humans or populations from releases to the
environment during all phases of the product life cycle.
3.3 Dose Response Assessment: Toxicity of CNT Exposure
While many types of carbon nanotubes (CNTs) and variations thereof are being
produced and utilized within a broad range of products available to the public, there is
evidence for potential toxic effects from occupational exposure to CNTs in the workplace
and even throughout the product life cycle. The dose-response data for carbon nanotubes
in animal experiments provide a scientific basis for developing recommended exposure
limits (RELs) in an effort to protect worker health and safety. While additional research is
needed to further understand biological responses for human exposures to CNTs, findings
of adverse respiratory effects in animals indicate the need for a precautionary approach to
management of CNTs in the workplace in an effort to limit risk of occupational lung
27. 27
diseases to workers handling carbon nanotubes (NIOSH 2010 CIB). While there are some
concerns, albeit not fully understood, about CNTs fate and transport in the environment,
evidence is limited. Therefore, the scope of this research will focus primarily on
occupational exposures to CNTS. Proper life cycle management of these nanomaterials
and a precautionary approach to their management is advocated due to lack of full
understanding of the fate and transport of these materials in the environment.
In laboratory settings, some types of multi-walled carbon nanotubes (MWCNTs) have
been found to induce fibrosis symptoms similar to mesothelioma when exposed to rodent
lungs (Nature Technology 2008). The effect was observed for longer, stiffer nanotubes,
which have been compared to the shape of asbestos, of which the respiratory hazards are
well known and documented over the past thirty years. The researchers concluded that the
mechanism of injury was similar to asbestos because of the fibrous nature of stiff
nanotubes and ability of these small fibers to become lodged in the lung (Nature
Technology 2008). Studies like this are rather alarming as they begin to trigger a whole
new range of issues related to the proper management of CNTs both in the workplace and
as products in commerce.
Human exposures include the workers exposed to the dust after the collapse of the
World Trade Center in 2001 who were exposed to CNTs as a result of high temperatures
and the combustion of fuel and metals. These workers were found to have severe lung
impairment including small airways disease, granuloma formation, and parynchema
disease (Wu et al. 2010). Utilizing a transmission electron microscope (TEM), it was
observed that patients’ lungs showed CNTs of various sizes, along with asbestos fibers,
shards of glass, and other silicates and ultra fine particles (UFPs) generated and made
airborne after the collapse. However it is unclear how significant the CNTs were in this
situation (Wu et al. 2010).
If in fact CNTs can exhibit equivalent toxicity to asbestos fibers when inhalation is the
primary exposure route, it would be practical to manage them as a hazardous waste or
hazardous material. If CNTs can exhibit toxicity throughout their product life cycle we
must ensure environmental release and exposure pathways are eliminated by all practical
28. 28
means and a proper hazard assessment is conducted on each new product coming to
market. It will be important to establish if the CNTs can become bio-available through
inhalation, as their primary exposure route for humans. While the comparative risks of
inhalation of CNTs and asbestos are serious, some studies have also demonstrated CNTs
crossing the membrane barriers in the body and reaching target organs, which can induce
adverse effects such as inflammatory or fibrotic reactions (Kolosnjaj 2012).
At this point in the research on toxicity of CNTs and human exposure there are still
uncertainties and contradictions within the scientific community including some research
indicating CNTs as highly toxic, while others assert that toxicity is low (Kolosnjaj 2012).
This discrepancy provides more of a reason to perform adequate hazard assessments and
an exhaustive study of the multitude of configurations of CNTs, manufactured to meet
varying chemical and biological reactivity, shape and properties throughout their range of
applications. According to the International Agency for Research on Cancer (IARC),
toxicological studies of naturally occurring materials such as asbestos and manmade “bio-
persistent fibers” like CNTS associate these materials with increased risks of pulmonary
fibrosis and cancer after prolonged exposures (IARC 2002).
3.4 Physical and Chemical Composition and Manufacturing Methods
In order to understand the specific properties and hazards associated with each type of
CNT, it is important to understand the differences between specific structural variations
and how this structure affects relative toxicity. Carbon nanotubes can generally be
classified into two separate headings, single-walled carbon nanotubes (SWCNTs), which
are composed of a single layered “graphite-like” sheet, and multi-walled carbon nanotubes
(MWCNTs) which are composed of several layers of graphite materials. The diameter
ranges from 0.7 to 20 nanometers (nm) for SWCNT, and between 1.4 nm to 100 nm for
MWCNT of which the length can reach up to several micrometers (NIOSH 2010). The
CNTs will form themselves and re-align into what s referred to as “ropes”. These ropes
are held together by van der Waals forces and this can actually make them less bio-
available (Kolosnjaj 2012). Oftentimes the van der Waals effect is also a limiting factor to
their toxicity if they are bound together.
29. 29
Based on structure, CNTs will exhibit different thermal properties as well as
conductive characteristics. Their chemical reactivity is also dependent on their structure
and they have been found to be insoluble in solvents of any type (O’Driscoll et al. 2009).
There are three different manufacturing approaches to CNTs as well which is important as
each type of manufacturing method will present unique hazards and potentially different
exposure routes. The three main processes utilized for manufacturing CNTs include
carbon arc-discharge (CAD), laser ablation (LA), and chemical vapor deposition (CVD)
(NIOSH 2010). The most easily scaled up process available for industrial application is
among the CVD process, a high-pressure carbon monoxide process (HiPCO) which allows
the user to control both diameter and length of CNT at high purity rates. Oftentimes the
CNTs will utilize surfactants to assist with dispersion in biological environment
(O’Driscoll et al. 2009 and Kolsnjaj 2009). The CNTs may also contain up to 30% metals
used as a catalyst, commonly iron or nickel is used (Kolosnjaj 2012). Manufacture or
materials handling can present a variety of exposure routes, and the integration of metals
or other coatings may also affect relative toxicity of CNTs through inhalation exposure,
warranting the need for proper air monitoring and dust control in this environment.
3.5 Toxicology and Primary Exposure Route: Inhalation
While hazard assessments have been conducted on various exposure routes including
dermal contact and ingestion, unprocessed single-walled carbon nanotubes (SWCNTs) are
very light and can become airborne with agitation. Based on their size, physical
composition, and product life cycle, inhalation is the most probable exposure route. In the
studies by Stoeger et al. (2006), Lam et al. (2004) the toxic pulmonary effects on mice of
three types of CNTs including, raw, pure, and those with impurities were examined. These
studies were conducted in comparison to the effects of carbon black and quartz particles
for negative and positive controls, both of which are known to exhibit pulmonary toxicity
to varying degrees. The mice were instilled intratracheally with a solution and after a
single treatment there was a lung examination after seven and 90 days to see the
toxicological effects. All CNT exposed animals showed dose-dependent epithelioid
granulomas (tumors), and some effects after only seven days post exposure (Stoeger et al.
2006). The lungs of the mice exposed to carbon black were normal, and those treated with
30. 30
high-doses of quartz were moderately inflamed. What these results demonstrate is that if
able to reach the lungs, CNTs were found to be much more toxic than carbon black and
quartz, which are considered to be serious occupational inhalation exposure hazards (Lam
and James 2004). Comparative studies with ultrafine particles (UFPs) that are currently
known to cause adverse health effects when inhaled can serve as an exposure model and
indication of the relative toxicity of CNTs through inhalation.
Additional toxicology studies conducted using intra-tracheal doses of CNTs showed
significant acute pulmonary effects which subsided in rats (Warheit et al. 2007), and were
persistent in mice, as in Lam et al. (2004) and Shvedova et al. (2004). While there were
differences in the studies possibly due to difference in species (rats versus mice), also
criticized was the intra-tracheal exposure design of the experiment as not realistic.
However, it has been shown that granuloma formation was observed in all the studies as a
foreign body response of the lungs from a high dose of persistent particulates (Oberdorster
2005). Furthermore, it was shown that while acute effects may have been due simply to
pulmonary blockages by the large doses of CNTS exhibited, it has also not been ruled out
that residual metals in the CNT samples are exhibiting toxicity (Warheit et al. 2004).
Critics of these studies will argue against the methodology of experimentation in that
intra-tracheal insertion of the dosage of CNTS is not consistent with the typical effects of
actual inhalation, dosage concentration, as well as the difference between animal and
human exposure and bioavailability. While there are some inconsistencies in results across
species boundaries as well as obvious constraints with using an intra-tracheal dosing
method versus actual inhalation, implications of carcinogenicity, pulmonary toxicity, and
potential crossing of the blood brain barrier for CNTs and adhered toxic metals indicate
that further analysis is warranted.
Another study on CNT exposures demonstrates the possible translocation of inhaled
nano-sized particles (NSPs) to the central nervous system (CNS) and other target organ
systems (Oberdorster 2005). Results from an inhalation study on solid nano-sized carbon
particles 35 nanometers (nm) and manganese oxide (MnO2) particles resulted in a
significant increase of carbon in the olfactory bulb, which continued to increase after Day
7 of post exposure. This result demonstrates the slow migration or translocation
31. 31
mechanism for NSPs that can occur through inhalation exposure and indicates a
translocation mechanism is possible.
3.6 Dose Response Assessment: Toxicity of Nano-sized TiO2 Exposure
As the use of nanotechnology and its broad spectrum of applications are growing
exponentially, new products and materials are being introduced into the commercial
markets in rapidly increasing numbers. Conventional (non nano-sized) titanium dioxide
(TiO2) is being replaced by the nanoparticles compound, with an exceptional range of
applications and wide use in cosmetics, pigments, toners, coating and cleaning materials,
and even as an anti-microbial agent (Lepannen 2010). Conventional titanium dioxide has
been used for commercial and industrial purposes for decades and has even been utilized
as a negative control in dust inhalation studies due to it exhibiting little or no risk to
respiratory health (Lepannen 2010). However because nano-sized TiO2 particles exhibit
different chemical and physical properties they have been observed to cause adverse
effects after inhalation exposure.
In several recent studies, exposure to nano-sized TiO2 has been shown to cause
inflammation in rodent lungs after inhalation (Li et al. 2007) and also adverse pulmonary
effects and emphysema-like symptoms. Furthermore, toxicity of nano-sized TiO2 has been
shown to cause pulmonary lesions in rats, however this effect was not observed as
obviously in hamsters and mice (Li et al 2007). TiO2 in its nano form has also been
categorized as a potential carcinogen in human subjects according to International Agency
for Research on Cancer (Lepannen 2010). Animal and human data relevant to determining
carcinogenicity and adverse health effects from nano-sized TiO2 exposures, and dose-
response data modeling for rats and human lung exposure assessments are further
evaluated.
The National Institute for Occupational Safety and Health (NIOSH) (2011) has set exposure
limits for fine ( >100 nm) particles TiO2 at 2.4 mg/m3 and 0.3 mg/m3 for ultrafine (<100 nm) or
engineered nano-sized TiO2 as TWA (Time Weighted Average) for a 10 hours per day, over a 40
hour work week. Further, it has been determined that ultrafine nano-sized TiO2 is a potential
carcinogen based on occupational exposures (NIOSH 2011). The NIOSH states that the
32. 32
recommended exposure limits (RELs) will reduce the risks of lung cancer from occupational
exposures below 1 in 1000. Two years after NIOSH classified TiO2 as a potential carcinogen after
observation of lung tumor formation in a chronic inhalation study on rats (1998), it found that
there was a significantly higher increase in lung cancer rates for rats exposed to ultrafine TiO2
nano-sized particles (NIOSH 2011). Furthermore, the International Agency for Research on
Cancer (IARC) concluded that TiO2 showed sufficient evidence to be a human carcinogen Group
2B “possibly carcinogenic to humans” (IARC 2010).
It has been demonstrated that there is a significant dose-response relationship to nano-
sized TiO2 exposure as compared to the larger particles (>100nm) that correlates with
increased particle surface area reactivity. The ultrafine particles have a higher mass-based
potency as they have greater surface area relative to their size (See figures 1. 5, 1.6, and
1.7). The NIOSH has come to the conclusion that while TiO2 is not directly acting as a
carcinogen, there is a secondary genotoxicity mechanism related to the particle size and
surface area (NIOSH 2011). Several types of nano-sized metals and metal oxides
including titanium dioxide have been shown to reach a pathway along the olfactory nerve
in the nasal cavity through a modeled transport mechanism and get can eventually get into
the brain (NIOSH 2011). This pathway becomes a point of concern especially for TiO2
consumer products with spray applications, rendering inhalation the primary exposure
route. These secondary transport mechanisms must also be considered when examining
the toxicity.
Figure 1.5 Fractional Disposition of Inhaled Particles Into Different Respiratory Regions
Based on Particle Size Distribution.(Obserdorster 2005)
34. 34
Figure 1.6 In vivo retention or inhaled nano-sized and larger particles in alveolar
macrophages and in exhaustively lagged lungs (Oberdorster 2005)
Figure 1.7 Surface molecules as a function of particle size. Oberdorster 2005
Figure 1.6 Total Lung Burden Based of Particle Size for
Inhaled NSPs vs. larger size particles
Figure 1.7 Surface molecules and particle
size effect
35. 35
While some of the test and experimental methods on animals have resulted in
discrepancies over the accuracy or efficacy of these experiments when translating to
human exposure, it cannot be denied that the decreased size and consequently increased
surface area of nano-sized particles and fibers exhibit increased toxicity. Some
nanomaterials have been shown to exhibit carcinogenicity and cross cell barriers as well,
resulting in unknown and unpredictable toxic effects on humans and animals. While
current research is still being conducted in these areas, the implications for serious human
health effects from occupational exposures to nano-sized TiO2 and CNTs must be taken
seriously, and methods to detect, prevent, measure and mitigate exposures must be
implemented as a precautionary approach as further applications and technologies
utilizing these materials are developed.
Furthermore, it has been observed that single walled carbon nanotubes (SWCNTs) and
TiO2 nanoparticles have been implicated in the creation of plaque in the arteries which can
result in heart disease (Takagi et al. 2008). Through imaging techniques the medical
community can show CNTs penetrating into the inner layers of tissue in the lungs, known
as the alveolar epithelium. The particularly alarming implication is that multi-walled
CNTs that get respired deeply into the lungs have the negative potential to cross the
epithelial barrier and get into the space where mesothelioma originates (See Image 1.1)
(Takagi et al. 2008). Mesothelioma has in fact been produced in mice with direct
inhalation exposure to multi-walled carbon nanotubes (MWCNTs). Specifically this result
was demonstrated with MWCNT fibers with long aspect ratios, fibers that have nano-sized
diameters and a significantly longer length, creating more of a pulmonary response due to
their size (Takagi 2008; Poland 2008). Historically, mesothelioma occurrence has shown a
direct correlation with occupational exposures to asbestos, and to suggest that the same
mechanisms for asbestos exposure into the epithelium barrier can be observed in CNTs
would offer a model for how to prevent CNTs from becoming bio-available. (See Figure
1.4) Completing proper assessments, implementing administrative and mechanical
engineering controls, and workplace monitoring are techniques used to manage asbestos
exposures currently. Utilizing learned methods for NSP inhalation hazard in managing
asbestos mitigation can prevent releases or worker exposures to CNTs as well.
36. 36
Image 1.1 MWCNT Penetrates Lung Pleura (NIOSH 2010)
Image 1.2 TEM image showing SWNT ropes and bundles (arrows) inside a rat
macrophage (Kolosnjaj 2007)
Image 1.1 MWCNT penetrates
lung pleura
Image 1.2 Transmission Electronic Microscope
image SWNTs inside rat macrophage
37. 37
3.7 Toxicity for Dermal and Ingestion Exposure routes
While not primary exposure routes for TiO2 or CNTs there exist a several studies
which examine the toxicity of various nanoparticles to human skin cells in laboratory
settings. Titanium oxides, metals, quantum dots and other carbon based nanoparticles such
as CNTs have all demonstrated the ability to damage skin cells through a variety of
mechanisms, most notably as a result of oxidative stress and DNA damage. While it is
unlikely that these exposure routes will exist on the occupational level, there lies the
possibility of cross contamination or the release of nanomaterials into the environment
which could potentially lead to skin contact or ingestion (EPA 2010). Since nano-sized
TiO2 NSPs are used in many consumer products it is expected that some of this material
will end up in the environment, such as from sunscreen in swimming pools and natural
water bodies as it comes off of users over time. While this material will most likely be in
small concentrations, if it reached drinking water sources there could be potential for
ingestion and dermal contact (EPA 2010).
Unintended ingestion of nanoparticles can occur as a response to inhalation when
mucus moves material up out of the respiratory system and it is eventually swallowed in a
lung clearance mechanism known as the mucociliary escalator (Oberdorster 2005). Also,
through smoking, eating, and cross contamination, accidental ingestion could occur. This
exposure is not well researched and is considered the least possible exposure route, with
inhalation the primary exposure route for nanomaterials. However, one medical
application using nanoparticles as an ingested drug delivery mechanism is currently being
assessed.
Many of the nanotechnology integrated drug agents are designed for ingestion to get
the substance in the body and the medicine is then trans-located to other areas of the body,
including target organs. This functional mechanism itself demonstrates that ingested
nanomedicines will migrate out of the digestive tract and into other biological systems of
the body. One study has demonstrated this mechanism recently single-walled carbon
nanotubes (SWCNTs) were ingested by rodents and entered their stomachs, with
38. 38
pathological results showing that the same SWCNTs were later found to affect the, liver,
heart, brain and other parts of the digestive tract (Fadeel 2010). This translocation is
important because although inhalation is the primary exposure route for both CNTs and
nano-sized TiO2, understanding these transport mechanisms within the central nervous
system and target organs will allow models to be developed for exposure pathways for
other potential nanomaterials.
39. 39
Chapter 4: Nanotechnology Risk Management: Current Management
Techniques and Regulatory Approaches
4.1 Exposure Monitoring Practices and Methods
Toxicological studies are still in development for the vast range of new nanomaterials
entering the marketplace, all with unique properties and characteristics. Based on adverse
health implications from existing toxicological research it would seem a prudent approach
that mass production and introduction of nanomaterials into commerce be halted until a
proper risk assessment can be performed for each material. While this precautionary
approach would ensure that the risks of nanomaterials are mitigated before causing
adverse human health effects from occupational and environmental exposure routes, it can
also be argued that developing guidelines and regulations specifically targeting
nanomaterials can allow for safe development of these materials while not halting
scientific progress. However, this is no simple task. Due to the wide range of applications
and new developments within a broad spectrum of international manufacturing,
coordination would be needed between academic institutions, international standards
organizations, regulatory agencies, as well as competing multi-national corporations
striving to utilize nanotechnology to create the next technological breakthrough and
successful product. With the promise of new environmental remediation technology, as
well as advancements in materials sciences, medicine, energy efficiency, and other
technologies that can benefit humanity, a balance must be achieved between further
development and conducting thorough risk assessments on these nanomaterials. In order
to achieve this balance, proper knowledge about animal and eco-toxicological profiles as
well as commitment from governmental agencies and industry to perform scientific risk
assessment is necessary.
Through completion of a thorough risk assessment on nanotechnology development
risk management procedures, permissible occupational exposure limits, and regulatory
guidelines for all of industry can be established. Currently, it is not possible to develop
new regulations due to the lack of information that is widely accepted in the scientific
community (Oberdorster 2005). One major shortfall within regulatory agency oversight is
40. 40
the fact that nano-sized particles (NSPs) are classified the same as their bulk counterparts,
according to parts of regulation by the EPA (2008) unless they meet the definition of a
new chemical. This exclusion for new classification ignores the fact that NSPs have new
and unique chemical and biological risks due to their size, structure, and surface reactivity.
Much of the lack of regulatory action is due to the fact that there is inadequate data on the
materials and the sheer volume of new engineered NSPs coming to market (Oberdorster
2005). One idea would be to require separate registration of nano-sized particles from that
required for their bulk counterparts.
The NSPs, as compared to their bulk material, may have different exposure routes and
threshold limits, exhibit more potent toxicity at a lesser exposure due to their size, and
even exhibit carcinogenicity or cyto-toxicity in mammals upon inhalation. Currently,
many NSPs are treated the same as the bulk material and therefore do not require a
separate registration process. This similar treatment results in potential occupational
exposures occurring with the nano-sized form of a material which is not toxic in its bulk
form, un-regulated as a toxic material in the nano form. At a minimum there must be
different recommended exposure limits for bulk materials as compared to the nano-sized
counterparts, as the exposure to one does not result in the same toxicity. A good example
would be TiO2 which is considered as carcinogenic by the IARC in its nano-sized form
due to smaller size and the increased ability to be inhaled deeply into the lungs. Yet the
particles in the larger micro range, (> than 100 nanometers) would not exhibit this same
pulmonary effect of carcinogenicity due to their larger size keeping them from entering
this part of the lung (IARC 2010). Many regulatory exposure guidelines are developed
utilizing toxicological tests and profiles, the resulting database of Material Safety Data
Sheets (MSDS) and permissible exposure limits (PELs) for devising the standards.
Therefore, it would make sense that separate profiles and data sheets be developed for
nano-sized materials.
It is likely that the nano-sized materials once properly profiled would require new
standards and stricter regulation for manufacturing and life cycle management of these
materials from “cradle to grave”, possibly even classification of certain waste containing
toxic NSPs as hazardous waste. According to Title 22 of the Code of Federal Regulations
41. 41
(CFR) a waste determination must be conducted on waste that is potentially hazardous. If
the waste meets any of the specific hazard characteristics including ignitability, reactivity,
corrosivity, or toxicity, then that material must meet special regulatory disposal
requirements as a hazardous waste. As was demonstrated for TiO2 in its bulk form, this
powder may not exhibit specific toxic characteristics and therefore can be thrown in a
landfill. However, nanoscale Ti02 upon inhalation exposure can cause adverse pulmonary
effects as well as internal health effects, making a case for a separate toxicology profile or
classification.
The primary reason that NSPs are engineered from the parent substance is because the
NSP will exhibit new properties from that substance, including enhanced mechanical,
biological, or chemical properties due to smaller size, increased surface area and
reactivity. While the toxicity level of the bulk or parent material (>100 nanometers) may
be well understood and profiled, even classified as “non-toxic” there may be new
characteristics exhibited in the toxicological profile of the engineered NSPs. Since the
entire reason for the specific NSP design is due to the material exhibiting unique
properties, re-evaluation of the materials on the nanoscale is necessary in order to
accurately profile the hazards associated with exposure to NSPs (Oberdorster 2005).
Not only have certain nano-materials been found to exhibit potent toxicity as
compared to their parent material, NSPs have been shown to create new health exposure
routes than before. For example, it has been shown that inhaled NSPs have actually been
able to enter the Central Nervous System (CNS) through absorption through the upper
respiratory tract; reaching other target organs, creating new exposure routes altogether
(Oberdorster 2005). This fact should motivate regulatory agencies and industry to act
proactively and from a precautionary stance, as proper toxicology assessments have not
been performed on the nano versus larger form of every material that workers are
potentially getting exposed to because it is not legally required. The information to make
such determinations on every type of nano-sized particle is still being compiled. While it
is a daunting task to profile all nanomaterials, there may be predictable models that can be
generated once we understand some of the basic mechanisms of how nanomaterials
interact with the human body and the environment that will help with both assessing the
42. 42
long-term effects of nanotechnology and planning accordingly. One way this relationship
has been shown in research is through the observed toxicological effects associated with
ambient ultrafine particles in the past.
There remain a number of unanswered questions when it comes to the potential human
and environmental toxicity for nanomaterials, such as what the environmental effects are
if nanomaterials are released into the food chain and ecosystems, what the long-term
exposure hazards are for NSPs in human exposure, and which target organs may be
affected. As exponential growth in development of new products and technologies
containing NSPs occurs it becomes necessary to create a system for properly profiling
hazards of NSPs and hopefully identifying some common modes of behavior between
NSPs at large, allowing us to clearly understand the mechanisms of toxicity at a broader
level. Much of the future cause and effect relationships with nanotechnology interactions
and exposure are unknown because they have yet to occur, so it can only be hypothesized
about potential adverse ecological or environmental health effects based on existing data,
and attempts to model and predict these behaviors in order to prevent them.
As with nanotechnology, genetic engineering and genetically modified organisms are
having a similar effect on the regulatory and public community, as there were many
unknown factors and risks associated with the application of genetically modified
organisms (GMOs) and how these new organisms might affect existing ecosystems.
Currently the issue of whether GMOs are a good idea and if there are any risks associated
with cultivating and consuming GMOS is still hotly debated. This uncertainty leads to
public distrust if a GMO or NSP is released into the environment with potentially adverse
effects and lacks proper hazard assessments demonstrating their safety (Oberdorster
2005). During the life cycle of a product containing NSPs, it is probable that
nanomaterials will enter the environment either during manufacture, use, or disposal and
since there is no mechanism to evaluate the eco-toxicological effects of these materials,
there is great associated risk (EPA 2010).
4.2 Hazard Management: Occupational Exposures to CNTs and TiO2
43. 43
In the occupational setting, there can be a variety of exposure pathways in which a
worker will come into contact with nano-sized particles (NSPs) throughout the product
life cycle. This process begins with research and development of NSPs in a laboratory
setting, leading to the larger scale manufacturing and production including distribution,
shipping, packaging and eventually to the customer who could face potential exposure if
the material is made bio-available. (See Figure 1.8) The potential exposure pathways do
not end with the consumer. Many products containing engineered NSPs will be disposed
of in landfills or incinerated, making the environmental fate of discarded nanowaste
improperly evaluated or regulated.
It has been suggested that nanowaste materials, once they are disposed of, could
potentially leach into groundwater to create an ingestion hazard, or if incinerated create an
inhalation exposure once airborne (EPA 2010). These end of product life (EOL)
environmental pathways for human exposures are currently hypothesized but there is
more research needed in order to make this final waste determination. Workers in the
occupational setting will be exposed to free nano-TiO2 or CNTs airborne at significant
concentrations, while the consumer will receive the product containing NSPs embedded
within (EPA 2010). These pathways should result in a much lower risk of exposure to the
end user of the products and public, compared to the employee who is subject to airborne
occupational exposures of nanomaterials in the workplace for 40 hours a week.
44. 44
Figure 1.8 Life cycle Exposure Routes for Nanomaterials in the Environment
(Oberdorster 2005)
While considering the life cycle of a nanoproduct it is clear that many exposure
pathways exist throughout the life phases of the product, from product development to the
final disposal/waste management stage, yet clearly the highest occupational exposure risk
comes to the workers who are in direct contact with the raw nanomaterials. It was
determined in an epidemiological study throughout four manufacturing facilities that the
greatest exposure risk to nano-sized TiO2 occurred during several processes including
bagging, milling, micronizing, or shoveling of spilled material, referred to as internal
recycling (Lee et al. 2011). In order to maintain a high standard of workplace safety,
hazards are generally engineered out if possible, utilizing engineering methods such as
ventilation, administrative controls, hazard monitoring, and personal protective equipment
(PPE). In conjunction with these controls to minimize hazards, permissible exposure limits
(PELs) have been established by National Institute of Occupational Safety and Health
(NIOSH) to ensure that workers in these environments do not exceed exposure limits over
a time weighted average (TWA), typically the 40-hour work week. In 2005 NIOSH
Figure 1.8 Exposure pathways for
NSPs in the environment
45. 45
established draft occupational exposure limits of 1.5 mg/m3
for fine particles (<10
microns) of TiO2, and 0.1 mg/m3
for ultrafine (<100 nanometers) particles of TiO2.
Exposures to carbon nanotubes (CNTs) are also evaluated in a life cycle management
approach throughout this paper, and exposure pathways present themselves throughout
each phase of the product life cycle, yet occupational exposures to the worker during
research and development, production, and manufacturing processes present the greatest
hazards to the public at this time. The CNTs are encountered in a variety of facilities from
laboratories and production and manufacturing plants, to disposal and recycling facilities
where CNTs are disposed of or recycled. Based on evidence evaluating adverse
pulmonary effects on animal exposures to inhaled CNTs, this information provides
guidance for industry and regulatory bodies on setting exposure limits and
recommendations for safe handling of nanomaterials throughout the product life cycle
(EPA 2010).
Recommended exposure limits (RELs) proposed by the National Institute for
Occupational Safety and Health (NIOSH) for carbon nanotubes (CNTs) and carbon
nanofibers (CNFs), were set at 7 micrograms per cubic meter (µg/m3
) which also happens
to be the upper limit of quantitation (LOQ), which translates as the lowest level that the
analytical method can detect (NIOSH Sampling Method 5040). The RELs were
determined based on animal dose-response relationships to inhalation, and instillation of
CNTs in rodents, then extrapolating the exposure data to develop safe human exposure
limits from the dosage in mg/kg.
According to NIOSH some of the tasks that resulted in a high risk for exposure
included working with liquid nanomaterials without personal protective equipment (PPE),
any activity that results in aerosolization of nanoparticles, handling of powders in the nano
form, cleaning up spills or waste materials, and cleaning of dust collection and filter
systems. While skin absorption is mentioned in the list of hazardous activities, generally
the hazards of CNTs result from inhalation of respirable particles that can deposit
themselves in the alveolar region of the lung, causing adverse pulmonary effects.
Therefore, much of the occupational safety focus on CNT exposure routes is geared
46. 46
towards inhalation as primary route of entry rather than working with these materials in a
liquid mixture, or solid matrix. Therefore mechanical and ventilation controls, closed
reactors, ventilation and dust control systems, respiratory protection, and active
monitoring are the basis for health and safety programs revolving around safe
management of CNTs and CNFs in the workplace (NIOSH 2009).
4.3 Administrative Controls, Engineering Controls and Personal Protective
Equipment
While not always possible, it is desirable that an environmental health and safety
(EHS) approach be used that can engineer out a specific hazard from the workplace, either
by utilizing administrative controls such as alternating processes and safer work practices,
or mechanical controls, primarily ventilation and dust collection systems within the
nanomaterials risk framework, and not simply reliance on personal protective equipment
(PPE) (NIOSH 2009). In order to determine the specific types of controls to put in place, it
is necessary to perform a hazard assessment of each workplace, monitoring for specific
exposure hazards, determining exposure routes, evaluate the processes and tasks of
workers, and assigning appropriate PPE for each specific hazard in conjunction with
proper training and a respiratory protection program (RPP).
The NIOSH has specifically stated that “Until further information on the possible
health risks and extent of occupational exposure to nanomaterials becomes available,
interim protective measures should be developed and implemented” (NIOSH 2009).
Specific engineering controls such as source enclosures and local exhaust ventilation units
can typically be adequate for controlling airborne NSPs in the laboratory setting. The type
of engineering controls will be designed according to the types of materials present and
what specific hazards or exposure routes they create. For inhalation exposure, higher risk
of exposure is expected when handling loose dry powders that can become airborne rather
than solutions in a liquid or embedded within a solid aggregate material (NIOSH 2009).
Further, the types of high risk activities that have been identified within the realm of
occupational exposures include the actual cleaning and maintenance of ventilation and
dust-collection systems designed to capture airborne NSPs, as these activities can result in
47. 47
deposited nanomaterials becoming airborne. A similar mechinism also would account for
hazards created while managing waste streams containing dry-powder nanomaterials
which can easily become agitated or airborne. Typically the materials labeled as low-risk
would be the nanomaterials suspended within liquid solution or embedded in a solid
matrix form, making inhalation unlikely due to lack of airborne particulates.
Stanford Linear Accelerator Center (SLAC), a Department of Energy (DOE) facility
completes research and development within nanomaterials science and is an example of an
institution that has created their own nanomaterial safety plan (SLAC 2010) to reduce
occupational exposures to engineered NSPs. The SLAC’s nanomaterial safety plan hazard
controls consist of engineering controls, design reviews, use of PPE, formal training,
waste analysis and expert assessments using industrial hygienists. When designing
exposure controls, SLAC utilizes a grading system which effectively rates the highest
hazard compounds, dry-loose powder material which can easily become airborne as red,
extremely hazardous, while NSPs in liquid solution are yellow, and those embedded
within a solid matrix are determined to be green, or lowest likely exposure hazard. In
SLAC’s plan, work areas are specifically designed to ensure worker protection in areas
where engineered nanoparticles will be handled, with special care taken to ensure that
nanomaterials are not taken out of work areas by establishing buffer areas for
decontamination, step-off pads which remove materials from shoes, and disposable
clothing and PPE (SLAC 2010).
Proper design of projects can ensure that hazards can be engineered out of the process
before an exposure can take place. When designing ventilation controls, SLAC’s process
ensures that work which could generate engineered NSPs within an enclosure must
operate at negative pressures as compared to the employee breathing zone. Examples of
negative pressure enclosures include glove boxes, glove bags, and laboratory bench-
mounted fume hoods. These types of systems effectively eliminate any direct contact
between the worker and the nanomaterials, as they are separated by an impermeable
barrier and the negative pressure will effectively control the NSPs from leaving the
ventilation unit. Currently the DOE requires that “enclosed systems under positive
pressure must be used in a negative pressure enclosure and exhausted prior to opening
48. 48
(DOE 456.1)”. These types of negative pressure systems can control any airborne NSPs
generated in the experiment, reducing inhalation exposure to workers and eliminating the
need for PPE during the experimental process. Most commonly high-efficiency particulate
air (HEPA) filtration devices will be used to remove nanoparticles from the air, and these
have shown effectiveness down to 2 nanometers in particle size diameter (SLAC 2010).
While personal protective equipment (PPE) is typically considered the last line of
defense in protection from occupational exposures, it represents an important tool in
eliminating human exposure risks from nanomaterials. When safer work practices and
engineering controls cannot effectively reduce the exposure below a safe recommended
exposure limit (REL), or completely eliminate inhalation hazards, respiratory protection
should be utilized. Some form of PPE, specifically respiratory protection, becomes
necessary when performing high-risk tasks such as maintenance of equipment or filtration
systems, cleaning up debris or spills of engineered NSPs, and nanomaterial waste
management (NIOSH 2010). While there are many types of respirators designed for
different types of hazards, respirator selection must be specifically designed for the
hazard. According to OSHA respiratory protection standards, there are specific
requirements in designing and implementing a respiratory protection program (RPP).
These standards include medical evaluation for personnel using respirators, regular
training, periodic exposure monitoring, as well as annual fit-testing and a respirator
cleaning and maintenance plan (OSHA 29 CFR 1910).
For specific selection of a respirator for a hazard such as carbon nanotubes (CNTs)
there is guidance available from NIOSH on which type of unit is appropriate. Based on
workplace monitoring information, it has been suggested that a half-face particulate air-
purifying respirator (APR) utilizing a 95 or 100 series filter will be acceptable to provide
adequate worker protection when mechanical ventilation mechanisms cannot remove
100% of the hazard and have been shown to offer protection up to 10 times the REL
(NIOSH 2010). It must be considered in respirator selection that due to the nature of
CNTs and other airborne NSPs, that nanoparticles can clog filter matrixes, overloading
filters, so proper change out schedules for filters and maintenance must be adjusted based
on exposure levels.
49. 49
The safest bet is to choose the respirator with the highest assigned protection factor
(APF) which will result in the most protection, however, these fine mesh filters can be
more cumbersome for the worker by making breathing more strained. Some studies on the
N-95 series APR have shown that penetration levels for 40 nanometer sized particles
range from 1.4% to 5.2%, which would indicate that N-95 or N-100 series, are effective at
minimizing exposures to CNTs (NIOSH 2010). To ensure 100% protection from
extremely hazardous airborne particulates, there exist supplied air respirators (SARs) and
self-contained breathing apparatus (SCBA) commonly used by Fire Departments and
other first responders when dealing with unknown inhalation hazards. For the purpose of
this research however, it has been determined that APRs provide adequate protection for
occupational exposures to nanoparticles in conjunction with mechanical ventilation
controls and safely designed processes.
In managing the occupational exposure to nano-sized titanium dioxide (TiO2), a
similar approach is taken to that of managing carbon nanotubes (CNTs), specifically that
the hazards are eliminated through administrative and mechanical controls and personal
protective equipment (PPE) is to be utilized as the last line of defense. It is important to
assess potential exposure pathways and high-risk activities for exposure risks throughout
each phase of production in the occupational setting. Hazard assessments can evaluate
methods for engineering the hazards out of the workplace utilizing the life cycle
management approach once exposure pathways or suggested exposure pathways are
known.
4.4 Detection and Monitoring of TiO2 and CNT NSPs in Workplace
While eliminating exposures from nano-sized TiO2 and CNTs in the workplace
through mechanical controls, administrative controls and personal protective equipment is
a challenge, measurement and detection methods for NSPs are not adequate for low
detection levels at this time. This lack of analytical methodology and equipment creates
uncertainty and requires innovation and adaptation of the application of currently available
detection methods. As is known from hazard analysis of both TiO2 and CNTs, the size
and surface area of the NSP creates unique hazards to workers upon exposure, however
50. 50
there is currently no device available which can measure particle surface area in the
worker breathing zone (NIOSH 2010). Currently, NIOSH has specified NIOSH Method
0600 and NIOSH Method 7300 for sampling protocols to detect occupational exposures of
TiO2 in the workplace, however there are challenges associated with their use. NIOSH
Method 0600 detects the overall respirable exposure concentration in the workplace,
however does not distinguish the particle size, by specifying whether the particles are fine
( >100 nanometers), or ultrafine ( <100 nanometers) in size. The failure to be able to
identify the particle size is a problem because the fine and the ultrafine (nano-sized)
particles have different recommended exposure limits (RELS) of 2.4 mg/m3
for fine
particles and 0.3 mg/m3
for ultrafine NSPs (NIOSH 2010).
If NIOSH Method 0600 shows detection limits below 0.3 milligrams per cubic meter
(mg/m3
) for respirable Ti02, then being lower than the nano-sized TiO2 particles would be
deemed a safe exposure level. However if the test indicates that airborne concentrations of
ultrafine/fine TiO2 exceed 0.3mg/m3
then further analysis must be done in order to
determine particle size of the concentration. The NIOSH Method 7300 can help to
differentiate between different types of particles, by utilizing technology including
transmission electron microscopy (TEM) and X-ray dispersive spectroscopy (EDS). In
order to ensure accurate results, it is recommended that both analyses are performed
simultaneously for respirable TiO2 dust using a hydrophobic filter for NIOSH Method
0600, and mixed cellulose ester filter (MCEF) for Method 7300. If the sample exceeds the
0.3mg/m3
REL for NSPs of TiO2, the MCEF sample can be measured using TEM which
can differentiate between nano-sized particles and fine particles. At this point, the
industrial hygienist can determine based on analytical results whether the RELs have been
exceeded (NIOSH 2011).
In order to successfully reduce dangerous occupational exposure to hazardous
concentrations of carbon nanotubes (CNTs) and carbon nanofibers (CNFs), first their
concentrations must be successfully detected through a reliable method. Currently CNTs
are detected utilizing a method known as NIOSH Method 5040, which can effectively
measure the airborne concentration over an 8- hour time-weighted average (TWA) for
CNTs. Currently the safe recommended exposure limit for CNTs is 7 µg/m3
