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Determining the kinetics of fullerenes within the body, subsequent to expo- sure (via the lungs, gut and skin) is necessary to identify potential targets of fullerene toxicity, and thereby direct relevant in vitro assessments of their tox- icity at particular target sites. However, only few studies provide evidence for the absorption of fullerenes into the blood from their exposure site.

Absorption Inhalation

In a study by Baker et al. (2008) nano and microparticulete forms of fullere- nes were not detected in blood following inhalation by rats, suggesting that they do not translocate from their exposure site. A half life of 26 days for fullerenes nanoparticles was determined which is similar to microparticles (29 days) suggesting that similar elimination processes are involved during the removal from the lungs. However, the pulmonary deposition fraction was 50 % higher for the nano form compared to the non-nano form. It is necessary to note that the preparation method and therefore the form of the fullerene dis- persion could influence this data and therefore additional studies are required before this finding can be considered universal.

In a rat study no translocation of C₆₀ to other organs was observed after intra- tracheal installation (3.3 mg/kg bw) or inhalation exposure (0.12 mg/m3_),

supporting that there is no absorption after inhalation (Shinohara et al., 2009) In contrast Naota et al. (2009) suggested that nano C₆₀ may be absorbed after installation. However, it is unclear whether the suspension induced oedema could have influenced the result.

Oral:

After oral administration to rats and mice, C₆₀ was not effectively absorbed, but instead the majority was excreted in the faeces within 48 hours. However, trace amounts of fullerene were observed in the urine, indicating that some fullerenes were able to pass through the gut wall (Yamago et al., 1995). In a study by Folkmann et al. (2009) oxidative DNA damage was observed in liver and lung after oral exposure via gavage to C₆₀ suspended in either saline or corn oil, indicating absorption via the oral route.

Dermal:

In a study by Xia et al. (2010) it was shown that pristine nanoC60 can pene- trate deep into the stratum corneum both in vivo (tape stripping an tissue bi- opsies in weanling pigs) and in vitro (diffusion cell experiment). The absorp- tion was modulated by the solvent, in which C₆₀ was dispersed. This observa- tion underlines the importance of taken the effect of the dispersion medium into account in risk assessment of C₆₀.

After administration of C₆₀ dissolved in squalane (Lipo-fullerene, LF-SQ) to human skin biopsies at concentrations as high as 223 ppm C₆₀ in LF-SQ, C₆₀ permeated into the epidermis but into the dermis, indicating that this prepara- tion of C₆₀ will not be systemically available after dermal administration (Kato et al., 2009).

Other studies:

Several in vitro studies have shown that fullerenes are taken up by different cell types often with oxidative and lethal consequences. Computer simulation has also been used to simulate uptake, but the relevance of these studies is still unknown (Stone et al., 2010).

Distribution

Inhalation, oral, dermal

There is limited information on distribution to secondary organs, probably because there is no or low absorption.

Other routes - injection

Following intraperitoneal injection into rats water soluble, polyalkylsulfonated C60 were transported via blood, accumulating in liver, spleen and kidney, with evidence of toxicity at sites of accumulation (Chen et al., 1998b). After intravenous injection water soluble fullerenes were rapidly removed from the blood and accumulated primarily in liver, but also, presumably depending on their water solubility in kidney, lungs, spleen, heart and brain (Yamago et al., 1995).

Yamago et al. (1995) investigated the distribution of 14C labelled, water solu- ble C₆₀ within rats, after intravenous injection. Subsequent to exposure, the fullerenes were rapidly removed from the blood (only 1.6% of the adminis- tered dose remained in the blood after an hour) and accumulated within the liver, which was the primary site of localisation, although some localisation was also evident within, for example the kidney, lungs spleen, heart and brain. In a similar study, Bullard-Dillard et al. (1996) also exposed rats via intrave- nous exposure to pristine (unmodified) and a water soluble quaternary am- monium salt-derivatised C₆₀. Clearance of C₆₀ from the blood was again rapid. However, the clearance of quaternary ammonium salt-derivatised C₆₀, was slower than of pristine C₆₀ due to its water soluble character. Again the major- ity of the unmodified particles were contained within the liver (over 90%) at 120 minutes post exposure, with minimal accumulation within the spleen, lung and muscle. The water-soluble C₆₀ had a wider tissue distribution, with only 50% of the administered dose evident within the liver, with the remaining dose contained in the spleen, lungs, muscle and cellular component of blood. After 120 hours, it was apparent that the majority (95%) of unmodified C₆₀ still remained within the liver, with no evidence of elimination within urine or faeces, highlighting that the liver is a potential target for fullerene accumula- tion and toxicity.

Metabolism

The metabolism of fullerenes has been suggested to occur, following their ac- cumulation within Kupffer cells in the liver of rats (Gharbi et al., 2005). The metabolites have not yet been identified.

Elimination

The elimination of fullerenes in urine (Yamago et al., 1995) and faeces (Mori et al., 2006; Yamago et al., 1995) has been demonstrated in rat and mouse, suggesting that they may be eliminated, in part, from the body following ex- posure via a number of routes.