Page 414 - Environmental Nanotechnology Applications and Impacts of Nanomaterials

Toxicological Impacts of Nanomaterials 397

excreted in the feces. Intravenously administered fullerenes were
14
distributed to various tissues in the body after one week. C-labeled
fullerene even penetrated the blood-brain barrier although acute toxicity
was low (Yamago et al., 1995). Apharmacokinetic study used intravenous
administration of another water-soluble fullerene, the bis (monosuccin-
imide) derivative of p,p’-bis(2-amino-ethyl)-diphenyl-C (MSAD-C ), in
60
60
rats. The concentration of fullerenes in blood plasma was observed to
decrease over time in a fashion that was described by a polyexponential
model with a terminal half-life of 6.8 hours. Fullerenes were extensively
bound by proteins (99%) and fullerenes were not detected in the urine at
24 hours. These data confirm extensive tissue distribution and minimal
clearance from the body. A 15-mg/kg dose of this fullerene derivative was
tolerated by the rats, but a 25-mg/kg dose resulted in death after five min-
utes (Rajagopalan et al., 1996). Biodistribution was also studied with
99m
radio-labeled Tc-labeling of C (OH) fullerenes in mice and rabbits,
60
x
which showed a wide distribution in all tissues, with a significant per-
centage in the kidneys, bone, spleen, and liver by 48 hours (Qingnuan
et al., 2002). These studies have demonstrated that “water-soluble”
fullerenes can be distributed after nonoral routes of administration. Very
little is known regarding fullerene metabolism or systemic elimination.
One study has shown that fullerenol-1 can suppress levels of cytochrome
P450–dependent monooxygenase in vivo in mice and mitochondrial oxida-
tive phosphorylation in vitro liver microsomes (Ueng et al., 1997).
Carboxy fullerenes are potent free radical scavengers and have been
both effective in reducing neuronal cell death and suggested to act as
neuroprotective agents in mice and in mouse neocortical cultures. At
100 M of a water-soluble carboxylic acid derivative fullerene fully
blocked an N-methyl-D-aspartate receptor–mediated toxicity and reduced
apoptotic neuronal death induced by serum deprivation or exposure to
the Alzheimer’s disease amyloid peptide Aβ 1-42 (Dugan et al., 1997).
Other studies have shown that the immune system can process a water-
soluble fullerene derivative conjugated to bovine and rabbit serum
albumin and present the processed peptides for recognition by T cells
to yield IgG antibodies (Chen et al., 1998).
A water-soluble carboxylic acid derivative fullerene (carboxyfullerene)
has been shown to possess antioxidative properties that can suppress
iron-induced lipid peroxidation in rat brains (Lin et al., 1999). Uncoated
fullerenes have also been shown to induce oxidative stress in juvenile
largemouth bass at 0.5 ppm and cause a significant increase in lipid
peroxidation of the brain and glutathione depletion in the gills after
48 hours (Oberdorster, 2004). In addition, they also assessed the toxicity
) on fresh water crustaceans, a marine
of stable fullerene suspension (nC 60
copepod, fathead minnow, and Japanese medaka fishes. It was noted
that after 21 days of exposure, the daphnia had a delay in molting and