Design and Characterization of an Inhalation System to Expose Rodents to Nanoaerosols

Abstract

The 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 TiO 2 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.

Retained particle surface area dose drives inflammation in rat lungs following acute, subacute, and subchronic inhalation of nanomaterials

“…In addition, double-chamber plethysmographs were used the week preceding the exposures or the day preceding the necropsy of the animals to measure nasal and thoracic flows allowing evaluation of the Specific Airway Resistance. TiO 2 aerosols were produced from powder using a rotating brush aerosol generator (RBG1000, PALAS, Karlsruhe, Germany) [32] or from a suspension (100 mg/L) in ultrapure water using two nebulizers operated in parallel (AGK2000, PALAS, Karlsruhe, Germany). Printex-90 aerosol was generated using an SAG410/U solid aerosol generator (TOPAS, Dresden, Germany); and MWNT-7 aerosol was produced by an upgraded (high-pressure version) of an acoustic generator (IEStechno, Morgantown, USA) [14,33] (Supplemental 1 and 2).…”

“…Details of the inhalation exposure set-up and the strategy used to characterize and monitor aerosols have been previously described [32]. Briefly, aerosol monitoring relied on the use of (1) a condensation particle counter (CPC) (TSI, model 3007, Shoreview, Minnesota, USA) for the on-line measurement of total submicron particle concentrations, (2) an optical particle counter (OPC) (FIDAS mobile, PALAS, Karlsruhe, Germany) to monitor the airborne particle number size distribution, and (3) systematic closed-face cassette samplers (CFC equipped with PVC or PTFE membranes filters, Millipore, Molsheim France) changed two to four times per day to measure the average mass concentration of the aerosol by gravimetry (XP6U, Mettler-Toledo, Viroflay, France -0.1 μg resolution).…”

“…Briefly, aerosol monitoring relied on the use of (1) a condensation particle counter (CPC) (TSI, model 3007, Shoreview, Minnesota, USA) for the on-line measurement of total submicron particle concentrations, (2) an optical particle counter (OPC) (FIDAS mobile, PALAS, Karlsruhe, Germany) to monitor the airborne particle number size distribution, and (3) systematic closed-face cassette samplers (CFC equipped with PVC or PTFE membranes filters, Millipore, Molsheim France) changed two to four times per day to measure the average mass concentration of the aerosol by gravimetry (XP6U, Mettler-Toledo, Viroflay, France -0.1 μg resolution). The in-depth characterization of relevant aerosol parameters is described in the same reference [32]. Briefly, it was achieved using time-resolved instruments such as scanning mobility particle sizer (SMPS) (Differential Mobility Analyzer TSI 3082 + Water-based CPC TSI 3787, Shoreview, Minnesota, USA), aerodynamic particle sizer (APS) (TSI 3321, Shoreview, Minnesota, USA), or electrical low-pressure impactor (ELPI, Dekati, Finland).…”

Preclinical evaluation of aerosol administration systems using Positron Emission Tomography

“…Two major disadvantages of this method are the potential induction of lesions due to the introduction of the insufflators and the need to maintain the animals under anaesthesia during the administration, which can cause some problems in certain scenarios (Guillon et al 2012). Alternatively to endo/intratracheal insufflations, nose-only exposure inhalation towers can be used for pulmonary administration of aerosols to small rodents (Asgharain et al 2003;Cosnier et al 2016). In this case, the aerosol reaches the lungs through natural respiration, and hence this method is perceived to result in a homogeneous distribution of the aerosol within the lungs.…”

Determination of the Concentration of Ultrafine Aerosol Using an Ionization Sensor

“…Nanomaterials are a very diverse group of chemicals; it is thus difficult to make general statements about their potentially adverse health effects. Over the years, studies have been conducted on the effects of NOAA impact on human health using the in vitro models [ 10 , 11 , 12 , 13 ]. Besides direct exposure, NOAA can also be accumulated in soil and plants, causing a risk not only to people directly involved in their production or processing [ 14 ].…”