Environmental Risks of Nanomaterials - Nanotechnologies for Water Environment Applications - page 597

explain the toxic effects of inhaled NPs (Bell, 2003; Shvedova et al., 2005). Physical
characteristics of NMs, together with in vitro assays for ROS and oxidative stress (phase
II responses, inflammation, and mitochodrionmediated apoptosis) plus in vivo markers
of oxidative stress, is an example of a predictive paradigm for toxicity screening (Nel et
al., 2006). Under conditions of excess ROS production, ROS may occur in the lung and
possibly the circulatory system during NMs exposures (Nel, 2005); the natural
antioxidant defenses may be overwhelmed (Halliwell and Gutteridge, 1999). Moderately
low levels of oxygen radicals may result in initiating the normal inflammation responses
to environmental toxins and attracting immune cells to the site of injury. Pulmonary
toxicology is a well-developed area of medical research. Many occupational diseases
(e.g., asbestosis) are caused by the inhalation of inorganic particles (Borm, 2002). In
vitro and in vivo toxicological studies of NMs have been developed by pulmonary
toxicologists (Warheit and Hartsky, 1997; Yang, 2002). There is a tendency for
pulmonary toxicity to increase as the particle size decreases. Recently, most reports find
that NMs are more toxic than equivalent bulk materials at similar doses per gram of
body weight (Donaldson et al., 2000). Earlier work on toxicity was performed in
conjunction with studies for possible use of NMs in tumor treatment, drug delivery, and
medical imaging. Many specific information concerning NM health effects can be
gleaned from studies aiming to develop nanobiotechnology (Colvin, 2003).
The cytotoxicity of NMs, such as photosensitive fullerenes and inorganic NMs
(e.g., SiO 2 , TiO 2 , ZnO), associated with oxidative stress, could be stimulated in the
presence of light to cause high toxicity. For examples, Fullerenes (C 60 ) water suspension
is cytotoxic to human cell lines taken up by human keratinocytes (Sayes et al., 2004).
C 60 encapsulated in poly(vinyl- pyrrolidone), cyclodextrins, or poly(ethylene glycol)
damaged eukaryotic cell lines (Nakajima et al., 1996; Sakai et al., 1999; Kamat et al.,
2000). Fullerene derivatives with pyrrolidine groups caused the deletion of plasmid
DNA (Mashino et al., 2003). Other alkane derivatives of C 60 induced DNA damage in
plasmids, inhibited protein folding as a result of their accumulation in rat livers
(Tokuyama et al., 1993). In cultured mammalian cells, the cytotoxicity of fullerenes was
related to their lipophilicity (Colvin, 2003), since fullerenes bind strongly with cell
membranes due to their hydrophobic nature (Foley, 2002). Modification of the surface
of fullerenes reduced their lipophilicity, by introducing aliphatic and hydroxyl groups,
and thus, reduced the cytotoxicity. Poly(ethylene glycol)-C 60 having a terminal primary
amino group or carboxyl groups resulted in formation of C 60 conjugates in water. These
conjugates showed strong cytotoxicity to cells upon visible light irradiation, likely
because of the superoxide production (Nakajima et al., 1996); the cytotoxicity of C 60
derivatives appeared to be irradiation- and dose-dependent (Yang et al., 2002). Other
animal studies of fullerenes have found minimal dermal and oral toxicity, but more
pronounced acute toxicity was observed upon intravenous administration (Rajagopalan
et al., 1996). For instance, metallofullerene may accumulate in rat livers (Cagle et al.,
1999). Barlow et al. (2005) exposed bovine serum to carbon NPs and demonstrated that