Joseph A Fisher
H 546 – Assigned Paper
Oregon State University
Nanoparticles: A Public Health Review
30 May 2008
INTRODUCTION
Nanoparticles are the end products of physical, chemical, and biological processes from natural and
anthropogenic sources. Natural sources include particles from volcanic eruptions, large forest fires, and other
specific combustions. Anthropogenic production of nanoparticles is a recent phenomena that is accelerating
and new products are currently being manufactured and sold. This brief article reviews nanoparticles from a
public health perspective and the scope includes both exposures to the general public as well as the
occupational worker. Public Health professionals, Toxicologists, Hygienists, and other preventative health
professionals are expected to be busy dealing with nanoparticle hazards as the introduction of nanoparticles
proliferates into everyday life.
The basic unit of measurement for nanoparticles is the nanometer (nm or 10-9 meters), which is one billionth of
a meter or 10 angstroms. The nanometer scale is just one factor of 10 (10-10 meters) from what we regard as
the atomic scale. Nanoparticles have by definition at least one dimension that is less than 100 nm. They can
be thought of as "a very small piece of something". Putting this size into perspective is sometimes difficult. For
example; the average sheet of paper is 100,000 nm thick, viruses have a maximum dimension of 10 to 100
nm, and the DNA molecule has a diameter of 2 to 12 nm. Thus, the dimension or size of a single nanoparticle
is equivalent to the diameter of a DNA molecule or a virus.
There is tremendous interest in nanoparticles because of their unique properties. As particles approach the
nanoscale, they exhibit different chemical, physical, and/or biological effects versus bulk scale elements. This
is because particles this small often exhibit quantum or atomic effects versus classical effects. Another feature
includes a very high surface area to volume and mass ratio. These unique properties have allowed the creation
of some very interesting products. Common examples of nanoparticle products range from single nanoparticles
such as titanium dioxide and zinc oxide which can be found in sunscreens and cosmetics to assemblies of
nanoparticles such as carbon which can be used to produce automobiles and airplanes.
The U.S. National Nanotechnology Initiative (NNI) was launched in 2001 [1]. The NNI 2007 budget supporting
research in nanotechnology is $1,445 million. NNI estimates that there are currently 20,000 researchers
working on nanotechnology. The National Science Foundation estimates that in 15 years, nanotechnology will
become a trillion dollar global industry employing an estimated 2 million workers. Current and future products
of nanotechnology include many different chemical, physical, and biological applications.
The U.S. Food and Drug Administration (FDA) and U.S. Environmental Protection Agency (EPA) have begun
research into the safety and health aspects of nanoparticles [2, 3]. FDA is examining the skin absorption and
phototoxicity of nano-sized titanium dioxide and zinc oxide preparations used in sunscreens. EPA as well has
begun looking at different nanoparticles in an effort to determine potential human and environmental risks.
PHYSICAL CHARACTERISTICS / PROPERTIES
Nanoscience includes research on materials with dimensions at the nanoscale or generally from 1 to 100 nm.
These elements or materials have unique behaviors and properties that distinguish them from their bulk
counterparts. The most unique aspect of nanoparticles is a large surface area compared to their volume and
mass. Other features include the ability to conduct electricity, heat, light, and the ability to assemble individual
particles into large well connected chains. Nanoparticles have the potential of revolutionary benefit much like
the impact of the information age. Perhaps the near future will be called the nano age.
The NanoRoadMap (NRM) project, co-funded by the European Commission (EC), is aimed at roadmapping
nanotechnology related applications in three different areas; Materials, Health and Medical Systems, and
Energy [4]. Materials most commonly utilized for nanomaterials include metal oxide ceramics, metals, silicates
and non-oxide ceramics, polymers, and compound semiconductors. Applications for nanomaterials in materials
science will only be limited by the imagination. Health and medical systems are looking at numerous
applications of nanomaterials including hygienic nano surfaces, drug delivery, and nano films. Energy
applications with nanoparticles promises great breakthroughs in photovoltaic solar energy.
Nanoparticles exhibit different and often improved properties based on specific characteristics (size,
distribution, morphology, phase, etc.), when compared with larger particles from bulk materials. Some of the
most potentially exploitable properties include; mechanical, chemical properties (e.g. reactivity), thermal,
electrical, optical (e.g. transparency), magnetic, and surface area. Though many of these properties are
important, their large surface area to volume and mass is unique and incredible beneficial.
The small size and low mass of nanoparticles allows them to be easily aerosolized when in a raw form. Particle
size is the primary parameter governing aerosols. While small particles in aerosol form are constrained by
inertia, gravitational, and diffusional forces, very small particles (nanoparticles) tend to be only limited by
diffusional forces. Nanoparticles behave more like a gas or vapor and their charge will impact their tendency to
diffuse into substrates. This effect is well explained by the UK Institute of Occupational Medicine [5].
Devices such as scanning (SEM) or transmission electron microscope (TEM) and Electron Dispersive
Spectrometer (EDS) are used to characterize nanoparticles. Information obtained usually includes size, shape,
structure, and compositional information. This type of work is currently being done for natural and
anthropogenic nanoparticles. For example, the University of Oregon (UO) department of Vulconology regularly
analyzes nano-sized particles obtained from volcanic eruptions. Other groups (CAMCOR) at UO are analyzing
anthropogenic nanoparticles using electron microscopes [6]. These nanoparticles include nanotubes,
nanowires, nanocrystals, quantum dots, etc. Researchers across the country and around the world are
investigating, building, and characterizing nanoparticles using high precision measurement instruments.
RISKS
Although nanoparticles exhibit outstanding characteristics and properties, their potential hazardous health
impact is a topic of great concern. Research and development in nanotechnology has boomed in the last
several years. Nanoparticles in the Materials, Health & Medical Systems, and Energy industries are rapidly
being developed. Recently, there is a greater interest and research in nanoparticle safety and health.
Nanoparticles exhibit unique characteristics and properties that present a challenge to safety and health.
Paracelsus is often cited as coining the phrase "the dose makes the poison". Every substance is toxic in
sufficient quantity. Water, salt, and sugar all have their levels of lethal dose or lethal concentration. Some
substance are toxic at one molecule while others require substantially larger doses. Toxicologists, hygienists,
public health professionals, and to a small extent the general public are cognizant of traditional chemical,
physical, and biological hazardous substances. Yet most people including professional don't have good
understanding of nanoparticle hazards. Toxicological risks from nanoparticles are thought to be associated
with their size, shape, and chemical composition. The FDA, EPA, and other safety and health organizations
have begun developing models to better understand the risks, pathways, toxicokinetics, toxicodynamics, and
controls for nanoparticles. Defining the risk in perspective of human hazard, exposure, and dose is a
complexity in itself. Defining the breakdown and release of nanoparticles into the environment is another.
Risk to human and environmental health with nanoparticles can be similarly defined as it is with other toxins.
Every risk requires some hazard, some exposure, and some absorbed dose. Common exposure routes include
inhalation (lungs), ingestion (gut), and contact (skin and eye). A simple scenario helps illustrate this point. For
example, a sealed vile of nanocarbon is a hazardous substance. If someone or something opens the vile we
have an exposure. A human located in this environment has potential exposure routes including the lungs, gut,
skin and eyes. Once an absorbed dose of a hazardous substance is obtained, pathways lead to endpoint
toxicity. The combination of all three elements are required in order to have some risk or endpoint toxicity.
Endpoint toxicity types are wide and varied but include; death, cancer, acute effects, chronic effects, and other
negative health related events.
The risk of nanoparticle hazards has not been well defined and work continues in this fascinating field of
research. Toxicologists, hygienists, public health and medical professionals have great opportunities to help
define the risks from nanoparticle hazards. Although great progress has been made defining the interaction of
xenobiotics with biological systems, there are many unknown details about the interaction of nanoparticles and
biological systems. Animal experiments have demonstrated the ability of nanoparticles to pass the blood brain
barrier, placenta barrier, and virtually every human barrier including the nucleus of cells. On one hand the
ability to pass through natural human barriers may be beneficial (i.e., brain cancer treatment) whereas on the
other hand it could prove to be a tremendous hazard [7].
CONTROL
The National Institute of Occupational Safety and Health (NIOSH) is one of the lead agencies conducting
research into the control of nanoparticle hazards. NIOSH is asking questions such as: "How might workers be
exposed to nano-sized particles in the manufacturing or industrial use of nanomaterials?, How do
nanoparticles interact with the body’s systems?, What effects might nanoparticles have on the body’s
systems?" [8]. Workers and the general public can be exposed to nanoparticles through several entry points.
The most commonly understood entry points include the Respiratory Tract (inhalation), Gastrointestinal Tract
(ingestion), and Skin and Eyes (contact). Current occupational protections from bulk hazards include
replacement, administrative, engineering, and PPE controls. Nanoparticles present a great challenge due to
their unique properties and characteristics. Protecting the human body from 1 to 100 nm sized nanoparticles
will be a great challenge. New particle detectors, samplers, and methods to analyze concentrations and
particle counts of nanomaterials need to be developed. Controls and PPE for nanomaterials need to be
developed and more clearly defined. The ability to measure nanoparticle concentration and dynamics in air has
not been well modeled nor routinely implemented in an occupational setting. Also, it is not even know if
nanoparticle exposures are best measured with mass-concentration or number-surface area.
Strategies to control exposure to nanoparticles would still include the traditional elements of administrative,
engineering, and PPE controls. These elements include; total enclosure of a process, partial enclosure with
local exhaust ventilation, general ventilation, limitations within the work area, reduction of exposures, cleaning,
prohibition of eating - drinking - chewing gum - smoking in the work area, and PPE. Unfortunately, controls for
nanoparticle exposures are currently in their infancy.
Researchers have shown that there is a tremendous difference between nanoparticle mass (concentration)
and both particle numbers and particle surface area [9]. In 2005, Oberdorster showed 5 nm nanoparticles with
an airborne concentration of 153 million particles per cubic centimeter. Current particulate matter standards
such as the EPA PM10 and PM2.5 measure concentrations in ug/m3, and not in particles per volume.
Researchers will need to determine what is the appropriate way to measure nanoparticle concentrations.
Since airborne nanoparticles behave more like a gas, particles not constrained will remain airborne for a long
time. Workplace engineering controls such as ventilation systems need to be designed to higher specifications
to properly control these particles. Current HEPA filter standards do not test particles less than 300 nm in size.
Though little work has been done to quantify the efficiency of nanofilters, it is widely accepted that the
properties and characteristics (shape, charge, diffusion) of nanoparticles will allow their capture. Implementing
a sophisticated ventilation system or sealed process is a surmountable engineering challenge, creating
nanoparticle gloves, suits, and respirators (PPE) will be difficult. Ultimately, the biggest control issue facing
researchers is controlling some hazard that is not clearly defined.
TOXICOKINETICS
Xenobiotics enter the human body and undergo a toxicokinetic process. This process is often defined as the
ADME cycle. This cycle is Absorption, Distribution, Metabolism and/or Storage, and Excretion (ADME).
Typically xenobiotics are absorbed through the lungs, gut, and skin. After a xenobiotic absorbs, it primarily
diffuses into the bloodstream. Once a xenobiotic enters the bloodstream, it is widely distributed throughout the
body. If a xenobiotic is not immediately drawn to some target organ, it usually ends up in the liver where a
factory of enzymes continue the metabolism process. Some xenobiotics or elements like lead have little to no
metabolism and are either stored in the body or excreted. Eventually, most xenobiotics are metabolized to
metabolite forms and excreted primarily through the feces and urine.
While many researchers believe that nanoparticles are just another xenobiotic, others have concerns. Will
nanoparticles that exhibit unique properties and characteristics behave like xenobiotics that don't exhibit these
properties and characteristics? Do nanoparticles present different and more dangerous toxicokinetics
challenges? Unfortunately, at this time, the answers are not clear. It is generally agreed that the size of a
nanoparticle is one reason why they are dangerous, but others factors such as surface area and charge are
thought to be equally important.
Large scale epidemiological studies have found that particulate matter (PM) found in the air from dust, dirt,
soot, smoke, and liquid droplets cause pulmonary diseases [10]. The EPA notes that particles less than 10,000
nm (PM10 - microns) pose a health concern because they can be inhaled and accumulate in the respiratory
system. Particles less than 2,500 nm (PM2.5 - microns) are referred to as fine particles and are believed to
poses the greatest health risks due to their small size and ability to lodge deeply into the lungs. Nanoparticle
animal studies to date have focused on airborne particles delivered to the lung, yet information on the
biological fate of nanoparticles including ADME and target organs is still minimal.
CONCLUSION
While nanotechnology promises great benefits to humankind, it also presents great risks. Other anthropogenic
substances such as lead in fuel and paint, asbestos, DDT, dioxins, and antibiotics where once regarded as the
saviors for some human ill or inconvenience. Today our bodies are filled with hazardous xenobiotics and
cancer incidence rates are risen to 50% in males and 33% in females. Nobody can predict the benefits and ills
associated with nanoparticles. Public Health epidemiological studies will undoubtedly provide valuable and
perhaps causal information on nanoparticle exposures and outcomes. Research and work in the area of
nanoparticle toxicology and risk aversion will have a long and busy future. The old saying "the genie is out of
the bottle" is appropriate here. Nothing will stop the development and manufacturing of nanoparticles. All we
can do from a Public Health perspective is work to minimize the risk.
REFERENCES
[1] U.S. National Nanotech Initiative (NNI). [Accessed 10 May 2008, http://www.nano.gov/]
[2] U.S. Food and Drug Administration (FDA), [Accessed 10 May 2008, http://www.fda.gov/nanotechnology/]
[3] U.S. Environmental Protection Agency (EPA), [Accessed 10 May 2008, http://es.epa.gov/ncer/nano/]
[4] Willems & van den Wildenberg (W&W). Roadmaps At 2015 On Nanotechnology Application in the Sectors
of: Materials, Health & Medical Systems, Energy. November 2005. [Accessed 10 May 2008,
http://www.nanoroadmap.it/roadmaps/NRM_Nanoparticles.pdf]
[5] RJ Aitken, KS Creely, CL Tran. Institute of Occupational Medicine. Nanoparticles: An occupational hygiene
review. 2004. [Accessed 20 May 2008. http://www.hse.gov.uk/research/rrpdf/rr274.pdf]
[6] CAMCOR. University of Oregon, Eugene, OR. [Accessed 20 May 2008. http://www.epmalab.uoregon.edu/]
[7] Kumar, Challa. Nanomaterials -- Toxicity, Health and Environmental Issues. Wiley-VHH. 2006. Pages 5372.
[8] National Institute for Occupational Safety and Health (NIOSH). [Accessed 10 May 2008.
http://www.cdc.gov/niosh/topics/nanotech/]
[9] Oberdorster G, Sharp Z, Atudorei V, Elder A, Gelein R, Kreyling W, Cox C. (2004). Translocation of inhaled
ultrafine particles to the brain. Inhalation Toxicology; 16: 437-445.
[10] R Harrison, D Smith, and A Kibble. What is responsible for the carcinogenicity of PM2.5? Occup Environ
Med. 2004 October; 61(10): 799–805. [Accessed 20 May 2008,
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1740668]