Dataset Information

Pulmonary toxicity of inhaled nano-sized cerium oxide aerosols in Sprague-Dawley rats.

ABSTRACT: 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.

SUBMITTER: Guo C

PROVIDER: S-EPMC6816500 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Pulmonary toxicity of inhaled nano-sized cerium oxide aerosols in Sprague-Dawley rats.

Guo Chang C Robertson Sarah S Weber Ralf J M RJM Buckley Alison A Warren James J Hodgson Alan A Rappoport Joshua Z JZ Ignatyev Konstantin K Meldrum Kirsty K Römer Isabella I Macchiarulo Sameirah S Chipman James Kevin JK Marczylo Tim T Leonard Martin O MO Gant Timothy W TW Viant Mark R MR Smith Rachel R

Nanotoxicology 20190201 6

Cerium oxide nanoparticles (CeO<sub>2</sub>NPs), 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 CeO<sub>2</sub>NP 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 inv ...[more]

PMID: 30704321

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Project description:The use of flavoring substances is an important element in the development of reduced-risk products for adult smokers to increase product acceptance and encourage switching from cigarettes. In a first step towards characterizing the sub-chronic inhalation toxicity of neat flavoring substances, a study was conducted using a mixture of the substances in a base solution of e-liquid, where the standard toxicological endpoints of the nebulized aerosols were supplemented with transcriptomics analysis. The flavor mixture was produced by grouping 178 flavors into 26 distinct chemical groups based on structural similarities and potential metabolic and biological effects. Flavoring substances predicted to show the highest toxicological effect from each group were selected as the flavor group representatives (FGR). Following Organization for Economic Cooperation and Development Testing Guideline 413, rats were exposed to three concentrations of the FGR mixture in an e-liquid composed of nicotine (23 µg/L), propylene glycol (1520 µg/L), and vegetable glycerin (1890 µg/L), while non-flavored and no-nicotine mixtures were included as references to identify potential additive or synergistic effects between nicotine and the flavoring substances. The results indicated that the inhalation of an e-liquid containing the mixture of FGRs caused very minimal local and systemic toxic effects. In particular, there were no remarkable clinical (in-life) observations in flavored e-liquid-exposed rats. The biological effects related to exposure to the mixture of neat FGRs were limited and mainly nicotine-mediated, including changes in hematological and blood chemistry parameters and organ weight. These results indicate no significant additive biological changes following inhalation exposure to the nebulized FGR mixture above the nicotine effects measured in this sub-chronic inhalation study. In a subsequent study, e-liquids with FGR mixtures will be aerosolized by thermal treatment and assessed for toxicity.

Dataset Information

Pulmonary toxicity of inhaled nano-sized cerium oxide aerosols in Sprague-Dawley rats.

Publications

Pulmonary toxicity of inhaled nano-sized cerium oxide aerosols in Sprague-Dawley rats.

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