Interlaboratory evaluation of rodent pulmonary responses to engineered nanomaterials: The NIEHS nano GO consortium

James C. Bonner, Rona M. Silva, Alexia J. Taylor, Jared M. Brown, Susana C. Hilderbrand, Vincent Castranova, Dale Porter, Alison Elder, Günter Oberdörster, Jack R. Harkema, Lori A. Bramble, Terrance J. Kavanagh, Dianne Botta, Andre Nel, Kent E Pinkerton

Research output: Contribution to journalArticle

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Abstract

Background: Engineered nanomaterials (ENMs) have potential benefits, but they also present safety concerns for human health. Interlaboratory studies in rodents using standardized protocols are needed to assess ENM toxicity. Methods: Four laboratories evaluated lung responses in C57BL/6 mice to ENMs delivered by oropharyngeal aspiration (OPA), and three labs evaluated Sprague-Dawley (SD) or Fisher 344 (F344) rats following intratracheal instillation (IT). ENMs tested included three forms of titanium dioxide (TiO2) [anatase/rutile spheres (TiO2-P25), anatase spheres (TiO2-A), and anatase nanobelts (TiO2-NBs)] and three forms of multiwalled carbon nanotubes (MWCNTs) [original (O), purified (P), and carboxylic acid "functionalized" (F)]. One day after treatment, bronchoalveolar lavage fluid was collected to determine differential cell counts, lactate dehydrogenase (LDH), and protein. Lungs were fixed for histopathology. Responses were also examined at 7 days (TiO2 forms) and 21 days (MWCNTs) after treatment. Results: TiO2-A, TiO2-P25, and TiO2-NB caused significant neutrophilia in mice at 1 day in three of four labs. TiO2-NB caused neutrophilia in rats at 1 day in two of three labs, and TiO2-P25 and TiO2-A had no significant effect in any of the labs. Inflammation induced by TiO2 in mice and rats resolved by day 7. All MWCNT types caused neutrophilia at 1 day in three of four mouse labs and in all rat labs. Three of four labs observed similar histopathology to O-MWCNTs and TiO2-NBs in mice. Conclusions: ENMs produced similar patterns of neutrophilia and pathology in rats and mice. Although interlaboratory variability was found in the degree of neutrophilia caused by the three types of TiO2 nanoparticles, similar findings of relative potency for the three types of MWCNTs were found across all laboratories, thus providing greater confidence in these interlaboratory comparisons.

Original languageEnglish (US)
Pages (from-to)676-682
Number of pages7
JournalEnvironmental Health Perspectives
Volume121
Issue number6
DOIs
StatePublished - Jun 2013

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National Institute of Environmental Health Sciences (U.S.)
Nanostructures
Carbon Nanotubes
Rodentia
Lung
Bronchoalveolar Lavage Fluid
Carboxylic Acids
titanium dioxide
Inbred C57BL Mouse
L-Lactate Dehydrogenase
Nanoparticles
Cell Count
Pathology
Inflammation
Safety

Keywords

  • Carbon nanotubes
  • Inflammation
  • Lung
  • Nanoparticles
  • Titanium dioxide

ASJC Scopus subject areas

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

Cite this

Interlaboratory evaluation of rodent pulmonary responses to engineered nanomaterials : The NIEHS nano GO consortium. / Bonner, James C.; Silva, Rona M.; Taylor, Alexia J.; Brown, Jared M.; Hilderbrand, Susana C.; Castranova, Vincent; Porter, Dale; Elder, Alison; Oberdörster, Günter; Harkema, Jack R.; Bramble, Lori A.; Kavanagh, Terrance J.; Botta, Dianne; Nel, Andre; Pinkerton, Kent E.

In: Environmental Health Perspectives, Vol. 121, No. 6, 06.2013, p. 676-682.

Research output: Contribution to journalArticle

Bonner, JC, Silva, RM, Taylor, AJ, Brown, JM, Hilderbrand, SC, Castranova, V, Porter, D, Elder, A, Oberdörster, G, Harkema, JR, Bramble, LA, Kavanagh, TJ, Botta, D, Nel, A & Pinkerton, KE 2013, 'Interlaboratory evaluation of rodent pulmonary responses to engineered nanomaterials: The NIEHS nano GO consortium', Environmental Health Perspectives, vol. 121, no. 6, pp. 676-682. https://doi.org/10.1289/ehp.1205693
Bonner, James C. ; Silva, Rona M. ; Taylor, Alexia J. ; Brown, Jared M. ; Hilderbrand, Susana C. ; Castranova, Vincent ; Porter, Dale ; Elder, Alison ; Oberdörster, Günter ; Harkema, Jack R. ; Bramble, Lori A. ; Kavanagh, Terrance J. ; Botta, Dianne ; Nel, Andre ; Pinkerton, Kent E. / Interlaboratory evaluation of rodent pulmonary responses to engineered nanomaterials : The NIEHS nano GO consortium. In: Environmental Health Perspectives. 2013 ; Vol. 121, No. 6. pp. 676-682.
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T1 - Interlaboratory evaluation of rodent pulmonary responses to engineered nanomaterials

T2 - The NIEHS nano GO consortium

AU - Bonner, James C.

AU - Silva, Rona M.

AU - Taylor, Alexia J.

AU - Brown, Jared M.

AU - Hilderbrand, Susana C.

AU - Castranova, Vincent

AU - Porter, Dale

AU - Elder, Alison

AU - Oberdörster, Günter

AU - Harkema, Jack R.

AU - Bramble, Lori A.

AU - Kavanagh, Terrance J.

AU - Botta, Dianne

AU - Nel, Andre

AU - Pinkerton, Kent E

PY - 2013/6

Y1 - 2013/6

N2 - Background: Engineered nanomaterials (ENMs) have potential benefits, but they also present safety concerns for human health. Interlaboratory studies in rodents using standardized protocols are needed to assess ENM toxicity. Methods: Four laboratories evaluated lung responses in C57BL/6 mice to ENMs delivered by oropharyngeal aspiration (OPA), and three labs evaluated Sprague-Dawley (SD) or Fisher 344 (F344) rats following intratracheal instillation (IT). ENMs tested included three forms of titanium dioxide (TiO2) [anatase/rutile spheres (TiO2-P25), anatase spheres (TiO2-A), and anatase nanobelts (TiO2-NBs)] and three forms of multiwalled carbon nanotubes (MWCNTs) [original (O), purified (P), and carboxylic acid "functionalized" (F)]. One day after treatment, bronchoalveolar lavage fluid was collected to determine differential cell counts, lactate dehydrogenase (LDH), and protein. Lungs were fixed for histopathology. Responses were also examined at 7 days (TiO2 forms) and 21 days (MWCNTs) after treatment. Results: TiO2-A, TiO2-P25, and TiO2-NB caused significant neutrophilia in mice at 1 day in three of four labs. TiO2-NB caused neutrophilia in rats at 1 day in two of three labs, and TiO2-P25 and TiO2-A had no significant effect in any of the labs. Inflammation induced by TiO2 in mice and rats resolved by day 7. All MWCNT types caused neutrophilia at 1 day in three of four mouse labs and in all rat labs. Three of four labs observed similar histopathology to O-MWCNTs and TiO2-NBs in mice. Conclusions: ENMs produced similar patterns of neutrophilia and pathology in rats and mice. Although interlaboratory variability was found in the degree of neutrophilia caused by the three types of TiO2 nanoparticles, similar findings of relative potency for the three types of MWCNTs were found across all laboratories, thus providing greater confidence in these interlaboratory comparisons.

AB - Background: Engineered nanomaterials (ENMs) have potential benefits, but they also present safety concerns for human health. Interlaboratory studies in rodents using standardized protocols are needed to assess ENM toxicity. Methods: Four laboratories evaluated lung responses in C57BL/6 mice to ENMs delivered by oropharyngeal aspiration (OPA), and three labs evaluated Sprague-Dawley (SD) or Fisher 344 (F344) rats following intratracheal instillation (IT). ENMs tested included three forms of titanium dioxide (TiO2) [anatase/rutile spheres (TiO2-P25), anatase spheres (TiO2-A), and anatase nanobelts (TiO2-NBs)] and three forms of multiwalled carbon nanotubes (MWCNTs) [original (O), purified (P), and carboxylic acid "functionalized" (F)]. One day after treatment, bronchoalveolar lavage fluid was collected to determine differential cell counts, lactate dehydrogenase (LDH), and protein. Lungs were fixed for histopathology. Responses were also examined at 7 days (TiO2 forms) and 21 days (MWCNTs) after treatment. Results: TiO2-A, TiO2-P25, and TiO2-NB caused significant neutrophilia in mice at 1 day in three of four labs. TiO2-NB caused neutrophilia in rats at 1 day in two of three labs, and TiO2-P25 and TiO2-A had no significant effect in any of the labs. Inflammation induced by TiO2 in mice and rats resolved by day 7. All MWCNT types caused neutrophilia at 1 day in three of four mouse labs and in all rat labs. Three of four labs observed similar histopathology to O-MWCNTs and TiO2-NBs in mice. Conclusions: ENMs produced similar patterns of neutrophilia and pathology in rats and mice. Although interlaboratory variability was found in the degree of neutrophilia caused by the three types of TiO2 nanoparticles, similar findings of relative potency for the three types of MWCNTs were found across all laboratories, thus providing greater confidence in these interlaboratory comparisons.

KW - Carbon nanotubes

KW - Inflammation

KW - Lung

KW - Nanoparticles

KW - Titanium dioxide

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