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
Environ Health Perspect 2013 May; :[Epub ahead of print]
Background: Engineered nanomaterials (ENMs) have potential benefits, but also present safety concerns for human health. Inter-laboratory studies in rodents using standardized protocols are needed for ENM toxicity assessment. Methods: Four labs evaluated lung responses in C57BL/6 mice to ENMs delivered by oropharyngeal aspiration (OPA). Three labs evaluated Sprague-Dawley (SD) or Fisher (F)344 rats following intratracheal instillation (IT). ENMs tested were three forms of titanium dioxide (TiO2); anatase/rutile spheres (TiO2-P25), anatase spheres (TiO2-A), anatase nanobelts (TiO2-NB), and three forms of multiwalled carbon nanotubes (MWCNT); original (O), purified (P), and carboxylic acid "functionalized" (F). Bronchoalveolar lavage fluid was collected after 1 day for differential cell counts, lactate dehydrogenase (LDH), and protein. Lungs were fixed for histopathology. Responses were also examined at 7 days (TiO2) and 21 days (MWCNTs). Results: TiO2-A, TiO2-P25, and TiO2-NB caused significant neutrophilia in mice at 1 day in 3 out of 4 labs, respectively. TiO2-NB caused neutrophilia in rats at 1 day in 2 out of 3 labs, while TiO2-P25 or 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 3 out of 4 mouse labs and all rat labs. Three out of 4 labs observed similar histopathology to O-MWCNT or TiO2-NB in mice. Conclusions: ENMs produced similar patterns of neutrophilia and pathology in rats and mice. Although inter-laboratory 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 inter-laboratory comparisons.
Nanotechnology; Animal-studies; Laboratory-animals; Laboratory-testing; Respiratory-system-disorders; Pulmonary-system-disorders; Lung-disorders; Lung-function; Carboxylic-acids; Alveolar-cells; Proteins; Cellular-reactions; Histopathology; Neutrophils; Immune-reaction; Dose-response; Dioxides;
Author Keywords: carbon nanotubes; inflammation; lung; nanoparticles; titanium dioxide
James C. Bonner, Department of Environmental and Molecular Toxicology, North Carolina State University, Raleigh, NC 27606 USA
Environmental Health Perspectives
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