Inhaled diesel emissions generated with cerium oxide nanoparticle fuel additive induce adverse pulmonary and systemic effects

Samantha J. Snow, John McGee, Desinia B. Miller, Virginia Bass, Mette C. Schladweiler, Ronald F. Thomas, Todd Krantz, Charly King, Allen D. Ledbetter, Judy Richards, Jason P. Weinstein, Teri Conner, Robert Willis, William P. Linak, David Nash, Charles E. Wood, Susan A. Elmore, James P. Morrison, Crystal L. Johnson, Matthew Ian GilmourUrmila P. Kodavanti

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56 Citations (Scopus)


Diesel exhaust (DE) exposure induces adverse cardiopulmonary effects. Cerium oxide nanoparticles added to diesel fuel (DECe) increases fuel burning efficiency but leads to altered emission characteristics and potentially altered health effects. Here, we evaluated whether DECe results in greater adverse pulmonary effects compared with DE. Male Sprague Dawley rats were exposed to filtered air, DE, or DECe for 5 h/day for 2 days. N-acetyl glucosaminidase activity was increased in bronchial alveolar lavage fluid (BALF) of rats exposed to DECe but not DE. There were also marginal but insignificant increases in several other lung injury biomarkers in both exposure groups (DECe > DE for all). To further characterize DECe toxicity, rats in a second study were exposed to filtered air or DECe for 5 h/day for 2 days or 4 weeks. Tissue analysis indicated a concentration- and time-dependent accumulation of lung and liver cerium followed by a delayed clearance. The gas-phase and high concentration of DECe increased lung inflammation at the 2-day time point, indicating that gas-phase components, in addition to particles, contribute to pulmonary toxicity. This effect was reduced at 4 weeks except for a sustained increase in BALF γ-glutamyl transferase activity. Histopathology and transmission electron microscopy revealed increased alveolar septa thickness due to edema and increased numbers of pigmented macrophages after DECe exposure. Collectively, these findings indicate that DECe induces more adverse pulmonary effects on a mass basis than DE. In addition, lung accumulation of cerium, systemic translocation to the liver, and delayed clearance are added concerns to existing health effects of DECe.

Original languageEnglish
Pages (from-to)403-417
Number of pages15
JournalToxicological Sciences
Issue number2
Early online date19 Sep 2014
Publication statusPublished - Dec 2014


  • Acetylglucosaminidase/metabolism
  • Animals
  • Aorta/drug effects
  • Bronchoalveolar Lavage Fluid/chemistry
  • Cerium/chemistry
  • Dose-Response Relationship, Drug
  • Gasoline/analysis
  • Liver/drug effects
  • Lung/drug effects
  • Lung Injury/chemically induced
  • Male
  • Microscopy, Electron, Transmission
  • Nanoparticles/chemistry
  • Particle Size
  • Rats, Sprague-Dawley
  • Time Factors
  • Vasoconstriction/drug effects
  • Vehicle Emissions/toxicity

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