NTP technical report on the toxicity studies of fullerene C60 (1\sμm and 50\snm) (CASRN 99685-96-8) administered by nose-only inhalation to Wistar Han [Crl:WI (Han)] rats and B6C3F1/N mice
Mice exposed to micro-C60 demonstrated a significant increase in MIP-1α levels in the BALF, while those exposed to nano-C60 demonstrated no such effect. Alterations in BALF cell phenotype were observed in female Wistar Han rats at all exposure levels. Levels of specific cytokines in the BALF were al...
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| Format: | eBook |
| Language: | English |
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Research Triangle Park, North Carolina, USA
National Toxicology Program, Public Health Service, U.S. Department of Health and Human Services
2020, July 2020
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| Series: | NTP TOX
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| Online Access: | |
| Collection: | National Center for Biotechnology Information - Collection details see MPG.ReNa |
| Summary: | Mice exposed to micro-C60 demonstrated a significant increase in MIP-1α levels in the BALF, while those exposed to nano-C60 demonstrated no such effect. Alterations in BALF cell phenotype were observed in female Wistar Han rats at all exposure levels. Levels of specific cytokines in the BALF were altered following exposure to micro- or nano-C60 in both rats and mice. Shifts in spleen cell phenotype were noted in B6C3F1/N female mice exposed to either micro- (15 and 30\smg/m3) or nano- (0.5 and 2\smg/m3) C60. Neither micro- nor nano-C60 increased the frequencies of micronucleated reticulocytes or erythrocytes in peripheral blood of male or female Wistar Han rats or B6C3F1/N mice. Neither size particle affected the percentage of reticulocytes in peripheral blood, suggesting no exposure-related bone marrow toxicity. In conclusion, C60 fullerene nose-only inhalation in both rats and mice for 13\sweeks had little effect on systemic immune function. In male rats, the t1/2 of micro-C60 was shorter than that of nano-C60 particles at the same mass-based exposure concentration (2\smg/m3). In the micro-C60 study in rats no exposure-related effects on body weights or clinical pathology were found in male or female rats. Liver weights of 30\smg/m3 males were significantly greater than those of the control males. Histologically, exposure-related increases in the lung (chronic active inflammation and histiocyte infiltration) of both male and female rats occurred. Exposure-related increases in pigmentation (presumably test article) were seen in the lung and the bronchial (male) and mediastinal (females) lymph nodes. Micro-C60 exposure exhibited the potential to be a reproductive toxicant in male rats on the basis of decreased sperm motility and low incidences of histopathological findings in the testes (germinal epithelium degeneration). In the micro-C60 study in mice, mean body weights of exposed groups of males and females were similar to those of the control groups. Lung weights of 30\smg/m3 exposed females were significantly higher than those of the control females. There were no exposure-related effects on hematology in male or female mice. Histologically, exposure-related lesions occurred in the lung (chronic active inflammation and histiocyte infiltration) and larynx (squamous metaplasia). Exposure-related increases in pigmentation were seen in the lung and bronchial lymph nodes (males). Micro-C60 exposure also exhibited the potential to be a reproductive toxicant in female mice on the basis of increased probability of extended estrus and in male mice on the basis of decreased sperm motility. In the nano-C60 study in rats, no effects were observed on body weights, clinical pathology, or organ weights, and no exposure-related increases were found in chronic active inflammation and histiocyte infiltration in the lung. Exposure-related increases in pigmentation were seen in the lung (females) and bronchial lymph nodes. Low incidences of germinal epithelium degeneration in the testis and hypospermia were observed in male rats in the 2\smg/m3 group compared to none in control males. Sperm motility was significantly reduced in all exposed groups. Nano-C60 exposure exhibited the potential to be a reproductive toxicant in male rats, but not in male mice, on the basis of lower sperm motility and low incidences of histopathological findings in the testis (germinal epithelium degeneration) and epididymis (hypospermia). Fullerene C60 (C60), a primary allotrope of carbon, is used in a variety of consumer applications including microelectronics, photovoltaics, batteries and fuel cells, and water treatment methods. Human exposure to engineered C60 due to industrial applications may occur via inhalation, oral, dermal, or parenteral routes. In these toxicity and tissue burden studies, male and female Wistar Han rats and B6C3F1/N mice were exposed to fullerene C60 (at least 95% pure) via nose-only inhalation for 3\smonths. Two different C60 fullerene aggregate sizes, 1\sµm diameter (micro-C60) and 50\snm diameter (nano-C60) were studied to assess the potential for differential effects based on particle size. In the nano-C60 study in mice, there were no exposure-related effects on body weights, organ weights, and clinical pathology and no exposure-related increase in chronic active inflammation as seen with micro-C60. Exposure-related increases in histiocyte infiltration were seen in the lungs of male mice. Exposure-related increases in pigmentation were seen in the lung and bronchial lymph nodes (males). Nano-C60 exposure exhibited the potential to be a reproductive toxicant in female mice on the basis of increased probability of extended estrus compared to control females. Micro- and nano-C60 exposure had minimal effects on the components of the immune system examined, including innate, humoral, and cell-mediated immunity, in female rats and mice. Bronchoalveolar lavage fluid (BALF) macrophages from female rats and mice exposed to nano-C60 and micro-C60 contained intracytoplasmic, brown to black, granular to globular pigment. Locally, lung inflammatory responses were observed, primarily at the higher exposure concentrations. Inflammatory effects of nano-C60 exposure were, in general, more severe than micro-C60 exposure at the same mass-based atmospheric exposure concentrations. Synonyms: Buckminsterfullerene; Buckminsterfullerene (C60); Buckyball, C60 fullerenecarbon (C60); carbon cluster (C60); carbon C60 fullerene; carbon (C60) mol.; carbon, mol. (C60); follene-60, footballene; footballene (C60); [60]fullerene; [5,6]fullerene C60; fullerene-60, fullerene-C60; fullerene C60 cluster; icosahedral C60; soccerballene Groups of 10\smale and 10\sfemale core study rats and mice were exposed to atmospheres of the two fullerene C60 particle sizes via nose-only inhalation at concentrations of 0, 2, 15, or 30\smg/m3 (micro-C60 studies) or 0, 0.5, or 2\smg/m3 (nano-C60 studies), 3\shours per day, 5\sdays per week for 13\sweeks. Additional groups of rats and mice were analyzed for tissue burden and studied for clearance studies and immunotoxicity. Lung tissue weights were significantly increased at multiple timepoints in male rats and mice exposed to micro- or nano-C60 particles. Lung tissue burden increased with exposure concentration following exposure to either micro- or nano-C60 particles and was greater in rats and mice exposed to the same concentration (2\smg/m3) of nano-C60 relative to micro-C60 particles. The calculated lung clearance half-life (t1/2) for both particle sizes was, in general, longer in male rats than in male mice. |
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| Physical Description: | 1 PDF file (various pagings) illustrations |