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Cerium oxide nanoparticles (CeO2NPs), used in some diesel fuel additives to improve fuel combustion efficiency and exhaust filter operation, have been detected in ambient air and concerns have been raised about their potential human health impact. The majority of CeO2NP inhalation studies undertaken to date have used aerosol particles of larger sizes than the evidence suggests are emitted from vehicles using such fuel additives. Hence, the objective of this study was to investigate the effects of inhaled CeO2NP aerosols of a more environmentally relevant size, utilizing a combination of methods, including untargeted multi-omics to enable the broadest possible survey of molecular responses and synchrotron X-ray spectroscopy to investigate cerium speciation. Male Sprague–Dawley rats were exposed by nose-only inhalation to aerosolized CeO2NPs (mass concentration 1.8 mg/m3, aerosol count median diameter 40 nm) for 3 h/d for 4 d/week, for 1 or 2 weeks and sacrificed at 3 and 7 d post-exposure. Markers of inflammation changed significantly in a dose- and time-dependent manner, which, combined with results from lung histopathology and gene expression analyses suggest an inflammatory response greater than that seen in studies using micron-sized ceria aerosols. Lipidomics of lung tissue revealed changes to minor lipid species, implying specific rather than general cellular effects. Cerium speciation analysis indicated a change in Ce3+/Ce4+ ratio within lung tissue. Collectively, these results in conjunction with earlier studies emphasize the importance of aerosol particle size on toxicity determination. Furthermore, the limited effect resolution within 7 d suggested the possibility of longer-term effects. [ABSTRACT FROM AUTHOR]

Concerns about the potential health effects of exposure to nanomaterials have led to a growing number ofin vivoinhalation toxicity studies using nanoparticle aerosols. Estimates of aerosol deposition within the respiratory tract are important for these studies to enable: (a) the interpretation of the results, in particular, the evaluation of dose–response relationships; (b) comparison with the results of other related studies; and (c) the extrapolation of results from animal models to human. Unfortunately, only a limited number of studies have been undertaken to investigate respiratory tract deposition efficiencies for nano-sized aerosol particles. This is of particular importance as deposition efficiencies are predicted to vary significantly over the nano-size range for some elements of the respiratory tract. In this study, female Wistar-Kyoto rats were exposed in a new design nose-only inhalation exposure system to spark generated radioactive iridium-192 nanoparticle aerosols of four particle sizes chosen to cover the majority of the nano-size range (nominal sizes: 10, 15, 35, and 75 nm). The content of iridium-192 in the lung, head, gastrointestinal tract, and various other organs and tissues was measured. Aerosol deposition efficiencies in the whole respiratory tract and components (head airways, lung, alveolar region, and tracheobronchial region) were estimated and compared with the predictions of the Multiple Path Particle Dosimetry (MPPD) model (v2.11). The experimentally derived deposition efficiencies were broadly consistent with, but typically higher than, model predictions and the results of comparable studies in the literature. Copyright © 2016 American Association for Aerosol Research [ABSTRACT FROM AUTHOR]