title: Interlaboratory evaluation of in vitro cytotoxicity and inflammatory responses to engineered nanomaterials: the NIEHS Nano GO Consortium.
abstract: BACKGROUND
  Differences in interlaboratory research protocols contribute to the conflicting data in the literature regarding engineered nanomaterial (ENM) bioactivity.
  
  
  OBJECTIVE
  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.
authors: Department of Medicine, Division of NanoMedicine, Center for Environmental Implications of Nanotechnology, California Nanosystems Institute, University of California at Los Angeles, Los Angeles, California, USA.
authors: Tian
authors: T
authors: Xia
authors: Raymond F
authors: RF
authors: Hamilton
authors: James C
authors: JC
authors: Bonner
authors: Edward D
authors: ED
authors: Crandall
authors: Alison
authors: A
authors: Elder
authors: Farnoosh
authors: F
authors: Fazlollahi
authors: Teri A
authors: TA
authors: Girtsman
authors: Kwang
authors: K
authors: Kim
authors: Somenath
authors: S
authors: Mitra
authors: Susana A
authors: SA
authors: Ntim
authors: Galya
authors: G
authors: Orr
authors: Mani
authors: M
authors: Tagmount
authors: Alexia J
authors: AJ
authors: Taylor
authors: Donatello
authors: D
authors: Telesca
authors: Ana
authors: A
authors: Tolic
authors: Christopher D
authors: CD
authors: Vulpe
authors: Andrea J
authors: AJ
authors: Walker
authors: Xiang
authors: X
authors: Wang
authors: Frank A
authors: FA
authors: Witzmann
authors: Nianqiang
authors: N
authors: Wu
authors: Yumei
authors: Y
authors: Xie
authors: Jeffery I
authors: JI
authors: Zink
authors: Andre
authors: A
authors: Nel
authors: Andrij
authors: A
authors: Holian
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D007249:Inflammation / Q000139:chemically induced*; D053583:Interleukin-1beta / Q000096:biosynthesis; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D037742:Nanotubes, Carbon / Q000737:chemistry / Q000633:toxicity*; D054585:National Institute of Environmental Health Sciences (U.S.); D051381:Rats; D014025:Titanium / Q000737:chemistry / Q000633:toxicity*; D014481:United States; D015034:Zinc Oxide / Q000633:toxicity*
chemical_list: D053583:Interleukin-1beta; D037742:Nanotubes, Carbon; C009495:titanium dioxide; D014025:Titanium; D015034:Zinc Oxide
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