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FUNDAMENTALS                                 CH. 7 ENVIRONMENTAL AND SAFETY ISSUES WITH NANOPARTICLES
                  stress resulting in increased intracellular calcium and  asbestos.  A few data are available concerning the
                  gene activation; (2) transition metals released from  biological effects of carbon nanotubes. The biologi-
                  particles result in oxidative stress, increased intracel-  cal effects of carbon nanotubes are being researched.
                  lular calcium, and gene activation; (3) cell surface  Epithelioid granulomas and interstitial inflammation
                  receptors are activated by transition metals released  are induced in mice and rats following exposure to
                  from particles, resulting in subsequent gene activation;  single-walled carbon nanotubes [18–20]. Untreated
                  or (4) intracellular distribution of insoluble nanoparti-  carbon nanotubes contain the nanoparticles of tran-
                  cles to mitochondria generates oxidative stress.   sition metals such as iron and nickel, which are used
                    In the workplace, the concentration of nanoparti-  as catalysts in forming carbon nanotubes.  These
                  cles may be at a high level and most of the nanopar-  nickel-containing carbon nanotubes have been
                  ticles become agglomerates, while nanoparticles  reported to be toxic [19].
                  will form single nanoparticle at low levels in the  The concentration of airborne asbestos fibers is
                  general environment. It is a matter of debate  expressed as a number concentration, that is, fibres
                  whether agglomerates of nanoparticles react as a  per cubic centimeter or fiber per liter. When fiber
                  larger particle or a single nanoparticle in the lung or  concentrations are determined by phase contrast
                  other organs.                                  light microscopy, the fibers with a diameter of less
                    If insoluble particles are retained in the lung for a  than 3 m, a length longer than 5 m, and a length-
                  longer time without enough clearance mechanisms,  to-diameter ratio (aspect ratio) greater than 3 are
                  they can cause pulmonary inflammation or pneumo-  counted [21].  Asbestos fibers having nanosized
                  coniosis. It is of interest that nanoparticles deposited  diameter were often observed in analyses of envi-
                  in the lung can move into the blood vessel through  ronmental samples using electron microscopy.
                  alveolar epithelium and they can damage vessels or  International  Agency for Research on Cancer
                  produce blood clots [14, 15]. In a recent study,  (IARC) rated asbestos as a known human carcinogen
                  nanoparticles deposited in the nose may move directly  (group 1) [22] and the concentration of chrysotile
                  to the brain via the olfactory bulb [16].      asbestos is expressed as a risk level of 0.15
                                                                        3
                                                                 fiber/cm [9]. Health effects of vitreous fibers and
                  (2) Biological effects of fullerene            other asbestos substitutes have been assessed to
                  The biological effects of fullerene have being inves-  determine their OELs or their carcinogenicity in
                  tigated intensively. In rats dosed orally with  humans. The health effects of carbon nanotubes are
                  radioisotope-labeled C  60  fullerenes, most were  being intensively investigated now.
                  excreted in the feces and some were found in the
                  urine. A small amount of them can be absorbed via  (4) Biological effects of carbon black
                  the gastrointestinal tract. In contrast, in the same  The OEL for carbon black respirable dust is 1 mg/m 3
                  study, 90% of the same labeled fullerenes adminis-  and these for activated charcoal and graphite are 0.5
                                                                     3
                  tered intravenously were retained after 1 week, with  mg/m in each [9]. In the Ref. [23], while rats and
                  most found in the liver [17].                  mice inhaled carbon black with a particle diameter of
                                                                                                    3
                    LD50s (acute toxicity) by intraperitoneal injec-   30 nm at a concentration of 5–13 mg/m did not
                  tion in mice and rats were 1.2 and 0.6 g/kg, respec-  produce any specific changes, particles (agglomerate
                  tively. The dose of 2.5 g/kg orally in rats did not  of small particles) of  450 nm at a concentration of
                                                                         3
                  result in death.  The reproductive translocation of  2–6 mg/m produced early pulmonary changes.
                  fullerenes was also observed in mice. Fullerenes
                  have shown mutagenic activity in  Ames tests.  (5) Biological effects of metal oxides
                  Fullerenes have shown no skin irritation or allergic  Micronsized titanium dioxide particles are thought to
                  reactions [18].                                have almost no toxicity and often used as a negative
                    On the other hand, fullerenes are being tested for  control substance. The OEL for titanium dioxide is
                                                                       3
                  possible medical use. Fullerenes are basically  1 mg/m for respirable fraction [9]. However, the
                  hydrophobic but water-soluble derivatives have been  results of a series of studies by Oberdörster et al.
                  synthesized to be used as drugs or its carrier. The  [3, 11, 24, 25] on submicron- and nanosized titanium
                  derivative can be anticipated as drugs, for example,  dioxide suggested that as size decreases, inflamma-
                  anti-AIDS drug. It has been stated that the toxicity of  tory effects are intensified, and normally nontoxic
                  fullerenes changes due to slight structural changes  substances may assume  hazardous  characteristics.
                  including chemical modification [18].          Fig. 7.3.4 shows a part of the results by Oberdörster
                                                                 et al. in which rats and mice were exposed to anatase
                  (3) Biological effects of carbon nanotubes     titanium dioxide particles [25]. Their results have been
                  Carbon nanotubes are chemically stable and are sim-  frequently cited in the discussion of whether the health
                  ilar in form and size to asbestos; these characteris-  effects of fine particles should be based on its mass
                  tics have given rise to concern that carbon nanotubes  or its surface area. In Fig. 7.3.4, percentages of
                  may have the potential to cause pulmonary diseases  neutrophils in lung lavage of rats are shown as indi-
                  such as lung cancer and mesothelioma similar to  cators of inflammation after intratracheal instillation

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