Abstract

ABSTRACTThe number of workers potentially exposed to nanoparticles (NPs) in industrial processes is constantly increasing, even though the toxicological effects of these compounds have not yet been fully characterized. The hazards associated with this exposure can be assessed most relevantly by toxicology studies involving inhalation of nanoaerosols by animals. In this paper, we describe and characterize an aerosol generated in a nose-only exposure system used to study the respiratory effects of NPs in rat; this system was designed to meet the most stringent requirements for animal testing in terms of protection of operators against risks associated with NPs and biohazards and to comply with the OECD guidelines for chemical testing. The inhalation facility was fully validated by exposing Fisher 344 rats to TiO2 P25 aerosols at 10 mg m–3. Aerosol monitoring and in-depth characterization were ensured by real-time devices (condensation particle counter, optical particle sizer, scanning mobility particle sizer, aerodynamic particle sizer and electrical low pressure impactor) and samples taken for off-line analyses (gravimetric analysis, mass size distribution from cascade impactor, TEM observations). The test atmosphere was stable in terms of concentrations and distributions (mass or number) between different inhalation towers on a given day and between days (intra-experiment), as well as between inhalation campaigns (between experiments). In terms of the respiratory deposition profile, preliminary results after exposure for one month indicate that this system is relevant, and should therefore be appropriate for in vivo inhalation toxicity studies.

Highlights

  • Due to the growing use of nanoparticles (NPs) in industrial processes, the number of workers potentially exposed to these compounds is increasing even though their toxicological effects have not yet been fully characterized

  • The results presented in this paper demonstrate that our safe experimental set up can generate a nanoaerosol suitable for in vivo subacute inhalation toxicity studies in rats

  • Particular attention was paid to respecting of the criteria mentioned in the OECD inhalation guidelines TG412 and TG413 for chemical testing

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Summary

Introduction

Due to the growing use of nanoparticles (NPs) in industrial processes, the number of workers potentially exposed to these compounds is increasing even though their toxicological effects have not yet been fully characterized. Because inhalation represents the main route of occupational exposure to airborne nanoparticles, the first line of exposure is the respiratory system. For this reason, toxicology studies involving inhalation of nanoaerosols by animals appear to be the most relevant to assess the hazards associated with exposure to these particles. To obtain relevant inhalation toxicity data and ensure inter-experiment comparability, it is crucial that the nanoaerosol generation methods and physico-. Two different approaches are generally considered in experimental inhalation studies; the first corresponds to the “direct synthesis method” which uses a non-particulate substrate as a source of nanoparticles, the second involves wet or dry systems generating nanoaerosols from nanostructured powders (Morimoto et al, 2013). Since more than half of the industrial activities using nanopowders involve mixing (for the formulation of preparation) and transfer (loading, unloading, weighing) operations, dry generation methods appear better reflect industrial conditions (MDDE, 2014)

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