A current overview of health effect research on nanoparticles
Environ Health Prev Med
A current overview of health effect research on nanoparticles
Seishiro Hirano 0
0 S. Hirano (&) Environmental Nanotoxicology Section, RCER, National Institute for Environmental Studies , 16-2 Onogawa, Tsukuba, Ibaraki 305-8506 , Japan
Nanotoxicology and nano-risk have been attracting increasing attention of toxicologists and regulatory scientists as the production of nanomaterials increases worldwide (Oberdorster et al. in Environ Health Perspect 113:823-839, 2005). In general, nanotoxicology is associated with manufactured nanomaterials. In atmospheric science and environmental health science, however, very small particles that exist transiently at high count concentrations near road intersections and roadsides are called environmental nanoparticles, and most of these have originated from automobiles. Accordingly there are two types of nanoparticle in toxicology and health science-environmental nanoparticles and manufactured or engineered nanoparticles. In this minireview I would like to address the following issues: (1) What is a nanoparticle? (2) Why is the nanoparticle currently a significant health issue? (3) How has ''testing manufactured nanoparticles'' been discussed worldwide? (4) What problems have scientists encountered in assessing the health hazard of nanoparticles? and (5) What research is required in the future in nanotoxicology? ultrafine particles and most atmospheric nanoparticles are usually 50 nm. It has been shown that the particlecount distribution peaks at 20-30 nm at roadsides with heavy traffic . The differences between environmental and manufactured nanoparticles are summarized in Table 1. Environmental or atmospheric nanoparticles contain semivolatile alkanes that originate from fuels and lubricants  whereas components of manufactured or engineered nanoparticles vary, depending on the type of product. It should be noted that nanoparticles are also used in drug-delivery systems (DDS), because nanoparticles can evade phagocytosis and efficiently reach the target points.
Nanomaterial; Nanoparticle; Carbon nanotubes
Diesel-exhaust particles (DEP) are usually black
carbonaceous soots with particle dimensions 200–300 nm. They
are major components of fine particles or PM2.5
(particulate substances less than 2.5 lm). Installing a
dieselparticle filter (DPF) can reduce the number of larger
particles in the exhaust. However, nanoparticles, which
account for a much greater particle number concentration
in the atmosphere than the larger particles, are produced
during regeneration of the DPF. It has not been well
investigated whether nanoparticles are responsible for
pulmonary and extrapulmonary health effects of PM2.5,
although the fine particles are reportedly associated with
mortality from cardiovascular diseases [
can permeate through tissue walls, translocate to other
tissues from the deposition sites, and cause cardiovascular
dysfunction. However, we do not have a clear answer as to
whether nanoparticles have a distinctive toxicological
aspect and are more toxic than larger particles.
1–100 nm (biomedical nanoparticles can
be larger than 100 nm)
Three dimensions are on the nanoscale
(nano-objects with one and two
nanoscale dimensions are called
nanoplates and nanofibers, respectively)
Nanoparticles, nanospheres, nanotubes,
nanorods, nanofibers, nanowires,
nanoropes, nanosheets, nanoeggs,
nanoliposomes, dendrimers, etc.
Carbon (fullerene, nanotube), metal oxide
(TiO2, ZnO), CdSe, metalloids,
transition metals, polymers
Production of nanomaterials, cosmetics,
How has ‘‘testing manufactured nanoparticles’’
been discussed worldwide?
Two major international organizations have discussed
guidelines for testing nanoparticles. The Organization for
Economic Co-operation and Development (OECD) has
published a series of guidelines for testing chemicals and
those guidelines are generally accepted by many developed
countries. The OECD has been struggling to decide
whether current OECD test guidelines are applicable to human
health and environmental aspects of nanoparticles or
nanomaterials. The International Organization for
Standardization (ISO) also has an Environment/Safety Working
Group for nanomaterials. It may not be easy to apply
current test methods to nanoparticles or nanomaterials,
because most of these particles are insoluble and current
guidelines are primarily designed for water-soluble
substances or the water accommodated fraction (WAF) of
poorly water-soluble substances.
What problems have scientists encountered in assessing the health hazard of nanoparticles?
There are many debates about the metric which best
describes the toxicity of nanoparticles. The most
commonly accepted dose metric is probably the surface area.
Particle shape (e.g. fibrous or spherical), chemical
composition, and the physico-chemistry of the particle surface,
including the zeta-potential, are also important factors that
determine the toxicity of nanoparticles. Also, impurities
and the degree of agglomeration in the nanoparticle
suspension in test media may affect the toxicity. An
appropriate endotoxin-free medium should be chosen to
prepare the suspension of nanoparticles [
]. In nature the
nanoparticle has a large surface area which may function as
adsorption or even catalytic sites and interfere in various
What research is required in the future in nanotoxicology?
Exposure to nanomaterials should be assessed as soon as
possible, because most nanomaterials are about to be
produced on a large scale and some of these materials (e.g.,
nano-silver and nanosize titanium dioxide) are already
present in commercial products. The environmental fate of
nanoparticles should also be studied as a matter of urgency.
Reference substances are required to evaluate the toxicity
of nanoparticles and to prepare a proper test procedure. It
has been reported that the carcinogenic potency and
toxicity of asbestos [
] and the toxicity of MWCNTs 
largely depend on fiber length. Fibrous titanium dioxide
particles have been shown to be much more cytotoxic than
spherical nanosize titanium dioxide particles to alveolar
]. Special attention should be paid to
fibrous nanoparticles, because fiber length may be
predominant metric determining the toxicity of biopersistent
fibrous nanoparticles. An inhalation study, rather than
intratracheal instillation, is needed to evaluate the toxicity
of airborne nanoparticles, because nanoparticles
agglomerate easily in suspension and toxicological outcomes from
bolus injections of nanoparticles may differ significantly
from those of dispersed nanoparticles.
The overall physico-chemical properties of
nanoparticles/nanomaterials are important factors determining their
toxicity. Nanotoxicology is a new research field and
appropriate reference methods are required for assay of the
toxicity of nanoparticles either in vitro or in vivo.
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