Size-dependent deposition of inhaled nanoparticles in the rat respiratory tract using a new nose-only exposure system

Abstract

Concerns about the potential health effects of exposure to nanomaterials have led to a growing number of in vivo inhalation 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 nanosize 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. EDITORWarren H. Finlay

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

“…As a consequence, the relative discrepancies between calculated and estimated fractions could be partly explained by the uncertainties on the set of parameters retained. In line with our observations, this point has been particularly addressed by Buckley et al (2016), who highlighted that the deposition efficiencies derived from experiments obtained after iridium-192 inhalation were broadly consistent with the model prediction, although typically higher.…”

“…This confirms the homogeneity of the aerosol delivered and of the system as a whole. These data are in line with the ones recently published by Buckley et al (2016), who describe the inhalation of radioactive iridium-192 nanoparticle aerosol in a similar inhalation facility.…”

Pulmonary effects of inhalation of spark-generated silver nanoparticles in Brown-Norway and Sprague–Dawley rats

“…Aerosols of AgNPs were generated using a spark generator (DNP 4000, Palas, Karlsruhe, Germany) by the homogeneous nucleation of vapour produced between two electrodes (5 mm length and 1 mm diameter silver wire; Premion™ 99.999 % purity, Alfa Aesar™, Heysham, UK) in an inert argon atmosphere at a flow rate of 5 L min −1 , as previously described [ 24 ]. The rate of primary particle production and final size was dependent on the sparking frequency (90–300 Hz).…”

“…The particles were passed through a krypon-85 charge neutraliser (Model 3077A, TSI Incorporated, Shoreview, MN, USA) and were diluted with oxygen and nitrogen to give a total aerosol flow-rate of 9 L min −1 . This was led into a custom-built nose-only exposure manifold consisting of 4 chambers as previously described [ 24 ]. Animals were held in restraining tubes attached to the chamber ports, thus each had an individual aerosol supply directed to the nose area.…”

“…Aerosol mass concentrations were determined gravimetrically using Pallflex® emfab™ filters (Pall Life Sciences, Ann Arbor, MI, USA) with the aerosol drawn at 2 L min −1 with continuous monitoring using a TEOM™ ambient particulate monitor (Model 1400a, Thermo Scientific, Franklin, MA, USA) [ 24 ]. The AgNP aerosol was immediately diluted to prevent coagulation using a Palas® ejector dilution system (Model VKL 100, Palas GmbH, Karlsruhe, Germany).…”