National Study of Nanomaterial Toxicity Sets Stage for Policies to Address Health Risks

For the first time, researchers from institutions around the country have conducted an identical series of toxicology tests evaluating lung-related health impacts associated with widely used engineered nanomaterials (ENMs). The study provides comparable health risk data from multiple labs, which should help regulators develop policies to protect workers and consumers who come into contact with ENMs.

Researchers have done a great deal of toxicological research on ENMs over the past 10 years, but the results have often been difficult to interpret. This is because ENMs from different sources had different chemical and physical properties, and because investigators used different protocols to conduct the experiments.

“The goal of creating this multicenter consortium was to have multiple labs recreate key studies using the same materials and protocols, so that policy-makers have access to consistent, comparable results from multiple institutions,” says Dr. James Bonner, an associate professor of environmental and molecular toxicology at NC State and lead author of a paper describing the work.

For this study, researchers from eight institutions used mouse and rat models to look at pulmonary health effects related to exposure to titanium dioxide nanoparticles and carbon nanotubes.

The researchers found that carbon nanotubes, which are used in everything from bicycle frames to high performance electronics, produced inflammation and inflammatory lesions in the lower portions of the lung. However, the researchers found that the nanotubes could be made less hazardous if treated to remove excess metal catalysts used in the manufacturing process or modified by adding carboxyl groups to the outer shell of the tubes to make them more easily dispersed in biological fluids.

The researchers also found that titanium dioxide nanoparticles also caused inflammation in the lower regions of the lung. Belt-shaped titanium nanoparticles caused more cellular damage in the lungs, and more pronounced lesions, than spherical nanoparticles.

“The findings are significant, but the real take-away message here is that the multicenter consortium concept works – and that means this is a starting point for assessing nanomaterials using this approach,” Bonner says. “I’m optimistic that this will serve as a blueprint for similar efforts, which will give regulators comparable data across institutions that will be easier for them to interpret.”

The paper, “Inter-laboratory Evaluation of Rodent Pulmonary Responses to Engineered Nanomaterials,” was published May 6 in Environmental Health Perspectives. Corresponding authors on the paper are Bonner and Dr. Kent Pinkerton of UC Davis. The research was funded by the National Institute of Environmental Health Sciences. The institutions were North Carolina State University, University of California Davis, East Carolina University, the National Institute for Occupational Safety and Health, University of Rochester, Michigan State University, University of Washington and the Center for Environmental Implications of Nanotechnology.

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Note to Editors: The study abstract follows.

“Inter-laboratory Evaluation of Rodent Pulmonary Responses to Engineered Nanomaterials”

Authors: James C. Bonner and Alexia J. Taylor, North Carolina State University; Kent E. Pinkerton and Rona M. Silva, University of California Davis; Jared M. Brown and Susana C. Hilderbrand, East Carolina University; Vincent Castranova and Dale Porter, National Institute for Occupational Safety and Health; Alison Elder and Günter Oberdörster, University of Rochester; Jack Harkema and Lori A. Bramble, Michigan State University; Terrance J. Kavanagh and Dianne Botta, University of Washington; Andre Nel, Center for Environmental Implications of Nanotechnology

Published: May 6, Environmental Health Perspectives

Abstract: BACKGROUND: Engineered nanomaterials (ENMs) have potential benefits, but also present safety concerns for human health. Interlaboratory 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 SpragueDawley (SD) or Fisher (F)344 rats following intratracheal instillation (IT). ENMs tested were three forms of titanium dioxide (TiO2); anatase/rutile spheres (TiO2P25), anatase spheres (TiO2A), anatase nanobelts (TiO2NB), 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: TiO2A, TiO2P25, and TiO2NB caused significant neutrophilia in mice at 1 day in 3 out of 4 labs, respectively. TiO2NB caused neutrophilia in rats at 1 day in 2 out of 3 labs, while TiO2P25 or TiO2A 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 OMWCNT or TiO2NB 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.