Page 429 - Book Hosokawa Nanoparticle Technology Handbook

7.3 SAFETY OF NANOPARTICLES FUNDAMENTALS
and enter into the bloodstream. It is further presumed
Nanoparticle
1.0 that the mechanism of health effects of nanoparticles
Overall on cardiovascular system other than the respiratory
tract is similar to that in the airborne ultrafine particles
0.8
from DEP.
Regional deposition (−) 0.6 Alveolar (1) Biological effects of particulate matters
7.3.2.2 Biological effects of nanoparticles

In Japan, two reference values, the ‘administrative
0.4
limits’ (OELs), are used for the regulation of haz-
Tracheobronchial Nasal, Pharyngeal, control levels’ (ACL) and the ‘occupational exposure
ardous chemicals as well as dust (particle matters).
Laryngeal
0.2
OELs are recommended and revised every year by the
Japan Society for Occupational Health. OEL (OEL-
Mean) for mean concentration of a chemical sub-
0.0
0.1 1 10 100 1,000 10,000 stance is defined as the reference value to the mean
Diameter (nm) exposure concentration at or below which adverse
health effects caused by the substance do not appear
Figure 7.3.3 in most workers working for 8h a day, 40h a week
Predicted fractional deposition of inhaled particles in the under a moderate workload [9]. The ‘threshold limit
nasopharyngeal, tracheobronchial and alveolar region of value’ (TLV) has the same definition (but may not be
human respiratory tract during nose breathing based on the same values as OEL of the same substance) pro-
ICRP Publication 66 [7] (Healthy adult and breathing rate vided by the American Conference of Governmental
3
is 1.2 m /h). Industrial Hygienists (ACGIH).
ACL is an index to determine the control class to
judge the propriety of the working environment con-
deposition of nanoparticle chain-like agglomeration trol based on the results for working environment
and fibrous particles such as carbon nanotubes cannot measurement, which have been implemented for the
be estimated by this model. unit work area in accordance with the Working
Most inhaled nanoparticles are deposited on the sur- Environment Measurement Standard. The results of
face of the respiratory tract. Generally, if insoluble par- working environment measurement are evaluated by
ticles are deposited in the ciliated airspaces which are classifying the working environments concerned into
lined with a mucous layer, they are transported to the three control classes (Control Class I, II, and III).
digestive tract with the mucous flow by mucociliary These classes are used as the standards to classify the
movements. Particles deposited on nonciliated bronchi- level of the working environment concerned. Among
oles and alveoli are phagocytosed by macrophages, those subject to working environment measurement,
which is a kind of white blood cell. As a result, their these standards apply to workplace where dust, lead,
residence time is longer, however, they are usually organic solvent, and specified chemical substances
transported to the ciliated upper part of the respiratory are used. Article 65 of the Industrial Safety and
tract. Removal of deposited particles described above is Health Law stipulates that certain workplaces in
called clearance. When the amount of deposited parti- which harmful substances are involved or harmful
cles is below a certain value, no health effect is pro- work operations are performed shall be the subject to
duced. In relation to a macrophage response to working environment measurement. A 50% cut-off
particles, crystalline silica is hazardous, whereas tita- size of the dust particle is set at 4 m for both stan-
nium dioxide is not. Pneumoconiosis is a well-known dards and is far larger than nanosized particles. OEL
lung disease that is caused by exposure to dust particles or ACL [10] for particulate matters are usually based
of several micrometers in diameter. Silicosis is a typi- on mass concentration, that is, milligram per cubic
cal form of pneumoconiosis resulting from exposure to meter. Therefore, if the particulate matters have broad
crystalline silica dust and characterized by a progres- size distribution, the contribution of nanoparticles is
sive fibrosis of the lungs. The macrophage-mediated not large to in terms of mass of particles.
clearance (phagocytes) was effective for micron and Evidence from a number of toxicological studies on
submicron particles. It has been reported that only 20% insoluble particles indicates that the primary determi-
of deposited nanoparticles were removed by the clear- nant of the health effect of particles depends on the
ance mechanism [8]. It has been suggested that the surface area of particles deposited [11,12]. On the
remaining nanoparticles may pass through the alveolar basis of the results from a number of in vitro studies of
walls, penetrate into the blood or lymphatic circulation, insoluble nanoparticles, a hypothetical cellular interac-
and be transported to other organs. Many studies have tion has been proposed [13]: inflammation and oxida-
shown that the smaller the particle size the greater the tive stress can be mediated by several primary
mobility or they pass easily through the alveolar wall pathways: (1) the particle surface causes oxidative

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