Interlaboratory evaluation of in vitro cytotoxicity and inflammatory responses to engineered nanomaterials: The NIEHS Nano go consortium

Tian Xia, Raymond F. Hamilton, James C. Bonner, Edward D. Crandall, Alison Elder, Farnoosh Fazlollahi, Teri A. Girtsman, Kwang Kim, Somenath Mitra, Susana A. Ntim, Galya Orr, Mani Tagmount, Alexia J. Taylor, Donatello Telesca, Ana Tolic, Christopher D. Vulpe, Andrea J. Walker, Xiang Wang, Frank A. Witzmann, Nianqiang WuYumei Xie, Jeffery I. Zink, Andre Nel, Andrij Holian

Research output: Contribution to journalArticle

124 Scopus citations

Abstract

Background: Differences in interlaboratory research protocols contribute to the conflicting data in the literature regarding engineered nanomaterial (ENM) bioactivity. Objectives: Grantees of a National Institute of Health Sciences (NIEHS)-funded consortium program performed two phases of in vitro testing with selected ENMs in an effort to identify and minimize sources of variability. Methods: Consortium program participants (CPPs) conducted ENM bioactivity evaluations on zinc oxide (ZnO), three forms of titanium dioxide (TiO2), and three forms of multiwalled carbon nanotubes (MWCNTs). In addition, CPPs performed bioassays using three mammalian cell lines (BEAS-2B, RLE-6TN, and THP-1) selected in order to cover two different species (rat and human), two different lung epithelial cells (alveolar type II and bronchial epithelial cells), and two different cell types (epithelial cells and macrophages). CPPs also measured cytotoxicity in all cell types while measuring inflammasome activation [interleukin-1β (IL-1β) release] using only THP-1 cells. Results: The overall in vitro toxicity profiles of ENM were as follows: ZnO was cytotoxic to all cell types at ≥ 50 μg/mL, but did not induce IL-1β. TiO2 was not cytotoxic except for the nanobelt form, which was cytotoxic and induced significant IL-1β production in THP-1 cells. MWCNTs did not produce cytotoxicity, but stimulated lower levels of IL-1β production in THP-1 cells, with the original MWCNT producing the most IL-1β. Conclusions: The results provide justification for the inclusion of mechanism-linked bioactivity assays along with traditional cytotoxicity assays for in vitro screening. In addition, the results suggest that conducting studies with multiple relevant cell types to avoid false-negative outcomes is critical for accurate evaluation of ENM bioactivity.

Original languageEnglish (US)
Pages (from-to)683-690
Number of pages8
JournalEnvironmental Health Perspectives
Volume121
Issue number6
DOIs
StatePublished - Jun 1 2013

Keywords

  • Cell viability
  • In vitro
  • Inflammation
  • MWCNT
  • Nanotoxicology
  • Round-robin testing
  • TiO
  • ZnO

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Public Health, Environmental and Occupational Health

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    Xia, T., Hamilton, R. F., Bonner, J. C., Crandall, E. D., Elder, A., Fazlollahi, F., Girtsman, T. A., Kim, K., Mitra, S., Ntim, S. A., Orr, G., Tagmount, M., Taylor, A. J., Telesca, D., Tolic, A., Vulpe, C. D., Walker, A. J., Wang, X., Witzmann, F. A., ... Holian, A. (2013). Interlaboratory evaluation of in vitro cytotoxicity and inflammatory responses to engineered nanomaterials: The NIEHS Nano go consortium. Environmental Health Perspectives, 121(6), 683-690. https://doi.org/10.1289/ehp.1306561