title: Interlaboratory evaluation of rodent pulmonary responses to engineered nanomaterials: the NIEHS Nano GO Consortium.
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.
authors: Department of Environmental and Molecular Toxicology, North Carolina State University, Raleigh, North Carolina, USA.
authors: James C
authors: JC
authors: Bonner
authors: Rona M
authors: RM
authors: Silva
authors: Alexia J
authors: AJ
authors: Taylor
authors: Jared M
authors: JM
authors: Brown
authors: Susana C
authors: SC
authors: Hilderbrand
authors: Vincent
authors: V
authors: Castranova
authors: Dale
authors: D
authors: Porter
authors: Alison
authors: A
authors: Elder
authors: Günter
authors: G
authors: Oberdörster
authors: Jack R
authors: JR
authors: Harkema
authors: Lori A
authors: LA
authors: Bramble
authors: Terrance J
authors: TJ
authors: Kavanagh
authors: Dianne
authors: D
authors: Botta
authors: Andre
authors: A
authors: Nel
authors: Kent E
authors: KE
authors: Pinkerton
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000633:toxicity*; D037742:Nanotubes, Carbon / Q000633:toxicity*; D054585:National Institute of Environmental Health Sciences (U.S.); D009504:Neutrophils / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D014025:Titanium / Q000633:toxicity*; D014481:United States
chemical_list: D037742:Nanotubes, Carbon; C009495:titanium dioxide; D014025:Titanium
references: Part Fibre Toxicol. 2011 Jul 22;8:21
references: 21781304
references: Toxicology. 2010 Mar 10;269(2-3):136-47
references: 19857541
references: Science. 2006 Feb 3;311(5761):622-7
references: 16456071
references: Nanomedicine (Lond). 2011 Jan;6(1):143-56
references: 21182425
references: Annu Rev Public Health. 2009;30:137-50
references: 19705557
references: Nanotoxicology. 2011 Dec;5(4):711-29
references: 21073401
references: Toxicol Sci. 2007 Nov;100(1):203-14
references: 17660506
references: Am J Physiol Lung Cell Mol Physiol. 2008 Sep;295(3):L400-11
references: 18641236
references: Nat Nanotechnol. 2009 Nov;4(11):747-51
references: 19893520
references: J Toxicol Environ Health A. 2002 Oct 25;65(20):1513-30
references: 12396866
references: Environ Health Perspect. 2005 Jul;113(7):823-39
references: 16002369
references: J Toxicol Sci. 2008 Feb;33(1):105-16
references: 18303189
references: Toxicol Sci. 2009 Dec;112(2):468-81
references: 19584127
references: Am J Respir Cell Mol Biol. 2009 Mar;40(3):349-58
references: 18787175
references: Environ Health Perspect. 2013 Jun;121(6):683-90
references: 23649538
references: Toxicol Sci. 2009 Aug;110(2):442-8
references: 19429663
references: Proc Am Thorac Soc. 2010 May;7(2):138-41
references: 20427587
references: Nanotoxicology. 2013 Jun;7(4):389-401
references: 22397515
references: Ind Health. 2011;49(2):215-20
references: 21173528
references: ACS Nano. 2011 Dec 27;5(12):9772-87
references: 22047207
references: Environ Sci Technol. 2009 Jun 15;43(12):4227-33
references: 19603627
references: Part Fibre Toxicol. 2009 Dec 31;6:35
references: 20043844
references: Inhal Toxicol. 2009 Jul;21 Suppl 1:55-60
references: 19558234
references: Inhal Toxicol. 2010 Mar;22(4):340-7
references: 20064106
references: Nat Biotechnol. 2010 Dec;28(12):1275-6
references: 21139613
references: Am J Physiol Lung Cell Mol Physiol. 2008 Oct;295(4):L552-65
references: 18658273
references: Part Fibre Toxicol. 2006 Aug 14;3:11
references: 16907977
references: Nat Mater. 2009 Jul;8(7):543-57
references: 19525947
references: Toxicol Sci. 2010 Jan;113(1):226-42
references: 19822600