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398   Potential Impacts of Nanomaterials

        a significant decrease in offspring production at 2.5 and 5.0 ppm of nC .
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        They showed that the peroxisomal lipid transport protein PMP70 was
        reduced in the fathead minnow but not in the medaka, indicating alter-
        ations in the acyl-CoA pathways (Oberdörster et al., 2006).
          Some C  60  fullerene derivatives can interact with the active site of
        HIV-1 protease, suggesting antiviral activity (Friedman et al., 1993). C 60
        can also protect quiescent human peripheral blood mononuclear cells
        from apoptosis induced by 2-deoxy-D-ribose or tumor necrosis factor
        alpha plus cycloheximide (Monti et al., 2000). Studies with C 60  solubi-
        lized by polyvinyl-pyrrolidone (PVP) coating in water and applied to
        the mouse midbrain cell differentiation system found inhibition of cell
        differentiation and proliferation. Harmful effects with C 60  on mam-
        malian embryos have also been noted (Tsuchiya et al., 1995, 1996;
        Friedman et al., 1993). Under some conditions, C can convert oxygen
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        from the triplet to the singlet state (see Chapter 5 ), creating some con-
        cern for potential health risks through this mechanism.
          Since skin is the largest organ of the body and most probably will
        come into contact with fullerenes, especially during the manufacturing
        process, the dermal toxicity of fullerenes has been the focus of some
        studies. Topical administration of 200 µg of fullerenes to mouse skin
        over a 72-hour period found no effect on either DNA synthesis or
        ornithine decarboxylase activity. The ability of fullerenes to act as tumor
        promoters has also been investigated. Repeated application to mouse
        skin after initiation with dimethlybenzanthracene (DMBA) for 24 weeks
        did not result in benign or malignant skin tumor formation. But pro-
        motion was observed with 12-0-tetradecanoylphorbol-13-acetate (TPA)
        resulting in benign skin tumors (Nelson et al., 1993). In vitro studies
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        using  C-labeled underivatized C exposed to immortalized human ker-
                                       60
        atinocytes depicted cellular incorporation of the label uptake at various
        times. Approximately 50 percent of the radio-labeled C was taken up
                                                           60
        within six hours, but it was unclear whether particles actually entered
        the cell or were associated with the cell surface. They also found no effect
        on the proliferation of immortalized keratinocytes and fibroblast
        (Scrivens and Tour, 1994).
          There are conflicting reports as to the potential toxicity of fullerenes
        such as C . While C itself has essentially no solubility in water, it does
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                 60
        have the ability to form aggregates, referred to as nC , through either
                                                         60
        organic solvent inclusion or after partial hydrolysis, that are stable col-
        loidal suspensions in water (see Chapter 7). One hypothesis that has
        been put forward is that functionalizing a fullerene with carboxyl or
        hydroxyl groups should decrease the cytotoxic response in cells by alter-
        ing membrane solubility and interactions with cellular membrane bind-
        ing sites. In one study, four types of water-soluble fullerenes were
        assessed with respect to their toxicity to human carcinoma cells and
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