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Immunotoxicity Assessment of Multiwalled Carbon Nanotubes Following Whole-Body Inhalation Exposure for 30 and 90 Days in B6C3F1/N Mice and 30 Days in HSD:Harlan Sprague Dawley SD® Rats

Victor J. Johnson1, Nigel J. Walker2, Michael I. Luster1, Gary R. Burleson1, Michelle Cora2, Gregory L. Baker3, Barney Sparrow4, Dori R. Germolec2,

1Burleson Research Technologies, Inc., Morrisville, NC, USA
2Division of Translational Toxicology, National Toxicology Program, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA
3Sarepta Therapeutics, Columbus, OH, USA
4Battelle Memorial Institute, Columbus, OH, USA

DOI: https://doi.org/10.22427/NTP-DATA-500-005-001-000-1

Publication

Abstract

Background: Several lines of evidence have suggested the possibility that inhalation exposure to multi-walled carbon nanotubes (MWCNT) at occupationally relevant doses can lead to systemic immunotoxicity. To test this hypothesis, we undertook in-depth examination of immune function in mice and rats exposed by inhalation to relatively low levels of 1020 Long Multiwalled Carbon Nanotubes (L-MWNT-1020).
Methods: Studies were conducted to determine the systemic and pulmonary immunotoxic effects in mice and rats exposed to L-MWNT-1020 following whole-body inhalation for 6 hours/day for 5 days/week for 30 (mice and rats) and 90 (mice) days at dose levels of 0, 0.06, 0.2 and 0.6 mg/m3. Additional groups were administered cyclophosphamide (CPS) as a positive control for each cohort. Following exposure, pulmonary macrophage activity, immunophenotypic analysis of immune cells populations in the spleen, and systemic immune function, including tests for humoral (T-dependent antibody response, TDAR), cell-mediated (cytotoxic T-lymphocyte [CTL] activity), and innate (Natural Killer [NK] cell activity) immunity were conducted.
Results: While exposure increased pulmonary macrophage activity, no major changes were observed in any of the systemic immune parameters measured in mice exposed for 30 or 90 days. In rats, there was a slight decrease in humoral immunity coinciding with an increase in the number of splenic T cell and NK cell populations.
Conclusion: Although pulmonary macrophage activity increased in mice following exposure to L-MWNT-1020, systemic immune function for the most part remained unaffected. In contrast, rats demonstrated a slight decrease in humoral immune function as well as an increase in spleen cell numbers, T cell, and NK cell populations suggesting species-specific effects on systemic immunity, however, these effects were small and their biological significance with respect to altering disease susceptibility is unclear.

Related Publications

National Toxicology Program. Toxicity studies of 1020 Long Multiwalled Carbon Nanotubes (L-MWNT-1020) administered by inhalation to Sprague Dawley (Hsd:Sprague Dawley SD) rats and B6C3F1/N mice. Toxic Rep Ser. 2019 Nov;(94):NTP-TOX-94

Study Data

Study Tables - Rat Immunotox 30-Day Study

Study Tables - Mouse Immunotox 30-Day Study

Study Tables - Mouse Immunotox 90-Day Study

Individual Animal Data - Rat Immunotox 30-Day Study

Individual Animal Data - Mouse Immunotox 30-Day Study

Individual Animal Data - Mouse Immunotox 90-Day Study

Supplemental Materials

Supplemental Information