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 Witzmann, Nianqiang Wu & 4 others Yumei Xie, Jeffery I. Zink, Andre Nel, Andrij Holian

Research output: Contribution to journalArticle

108 Citations (Scopus)

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

Fingerprint

Nanostructures
National Institutes of Health (U.S.)
Interleukin-1
Carbon Nanotubes
Zinc Oxide
Epithelial Cells
Inflammasomes
Alveolar Epithelial Cells
In Vitro Techniques
Biological Assay
Macrophages
Cell Line
Lung
Research

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

Cite this

Interlaboratory evaluation of in vitro cytotoxicity and inflammatory responses to engineered nanomaterials : The NIEHS Nano go consortium. / Xia, Tian; Hamilton, Raymond F.; Bonner, James C.; Crandall, Edward D.; Elder, Alison; Fazlollahi, Farnoosh; Girtsman, Teri A.; Kim, Kwang; Mitra, Somenath; Ntim, Susana A.; Orr, Galya; Tagmount, Mani; Taylor, Alexia J.; Telesca, Donatello; Tolic, Ana; Vulpe, Christopher D.; Walker, Andrea J.; Wang, Xiang; Witzmann, Frank; Wu, Nianqiang; Xie, Yumei; Zink, Jeffery I.; Nel, Andre; Holian, Andrij.

In: Environmental Health Perspectives, Vol. 121, No. 6, 06.2013, p. 683-690.

Research output: Contribution to journalArticle

Xia, T, Hamilton, RF, Bonner, JC, Crandall, ED, Elder, A, Fazlollahi, F, Girtsman, TA, Kim, K, Mitra, S, Ntim, SA, Orr, G, Tagmount, M, Taylor, AJ, Telesca, D, Tolic, A, Vulpe, CD, Walker, AJ, Wang, X, Witzmann, F, Wu, N, Xie, Y, Zink, JI, Nel, A & Holian, A 2013, 'Interlaboratory evaluation of in vitro cytotoxicity and inflammatory responses to engineered nanomaterials: The NIEHS Nano go consortium', Environmental Health Perspectives, vol. 121, no. 6, pp. 683-690. https://doi.org/10.1289/ehp.1306561
Xia, Tian ; Hamilton, Raymond F. ; Bonner, James C. ; Crandall, Edward D. ; Elder, Alison ; Fazlollahi, Farnoosh ; Girtsman, Teri A. ; Kim, Kwang ; Mitra, Somenath ; Ntim, Susana A. ; Orr, Galya ; Tagmount, Mani ; Taylor, Alexia J. ; Telesca, Donatello ; Tolic, Ana ; Vulpe, Christopher D. ; Walker, Andrea J. ; Wang, Xiang ; Witzmann, Frank ; Wu, Nianqiang ; Xie, Yumei ; Zink, Jeffery I. ; Nel, Andre ; Holian, Andrij. / Interlaboratory evaluation of in vitro cytotoxicity and inflammatory responses to engineered nanomaterials : The NIEHS Nano go consortium. In: Environmental Health Perspectives. 2013 ; Vol. 121, No. 6. pp. 683-690.
@article{64ffdb48f4ba45e898c565e1fe399b31,
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. 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.",
keywords = "Cell viability, In vitro, Inflammation, MWCNT, Nanotoxicology, Round-robin testing, TiO, ZnO",
author = "Tian Xia and Hamilton, {Raymond F.} and Bonner, {James C.} and Crandall, {Edward D.} and Alison Elder and Farnoosh Fazlollahi and Girtsman, {Teri A.} and Kwang Kim and Somenath Mitra and Ntim, {Susana A.} and Galya Orr and Mani Tagmount and Taylor, {Alexia J.} and Donatello Telesca and Ana Tolic and Vulpe, {Christopher D.} and Walker, {Andrea J.} and Xiang Wang and Frank Witzmann and Nianqiang Wu and Yumei Xie and Zink, {Jeffery I.} and Andre Nel and Andrij Holian",
year = "2013",
month = "6",
doi = "10.1289/ehp.1306561",
language = "English",
volume = "121",
pages = "683--690",
journal = "Environmental Health Perspectives",
issn = "0091-6765",
publisher = "Public Health Services, US Dept of Health and Human Services",
number = "6",

}

TY - JOUR

T1 - Interlaboratory evaluation of in vitro cytotoxicity and inflammatory responses to engineered nanomaterials

T2 - The NIEHS Nano go consortium

AU - Xia, Tian

AU - Hamilton, Raymond F.

AU - Bonner, James C.

AU - Crandall, Edward D.

AU - Elder, Alison

AU - Fazlollahi, Farnoosh

AU - Girtsman, Teri A.

AU - Kim, Kwang

AU - Mitra, Somenath

AU - Ntim, Susana A.

AU - Orr, Galya

AU - Tagmount, Mani

AU - Taylor, Alexia J.

AU - Telesca, Donatello

AU - Tolic, Ana

AU - Vulpe, Christopher D.

AU - Walker, Andrea J.

AU - Wang, Xiang

AU - Witzmann, Frank

AU - Wu, Nianqiang

AU - Xie, Yumei

AU - Zink, Jeffery I.

AU - Nel, Andre

AU - Holian, Andrij

PY - 2013/6

Y1 - 2013/6

N2 - 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.

AB - 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.

KW - Cell viability

KW - In vitro

KW - Inflammation

KW - MWCNT

KW - Nanotoxicology

KW - Round-robin testing

KW - TiO

KW - ZnO

UR - http://www.scopus.com/inward/record.url?scp=84878457573&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878457573&partnerID=8YFLogxK

U2 - 10.1289/ehp.1306561

DO - 10.1289/ehp.1306561

M3 - Article

VL - 121

SP - 683

EP - 690

JO - Environmental Health Perspectives

JF - Environmental Health Perspectives

SN - 0091-6765

IS - 6

ER -