Abstract

BackgroundInformation on particle deposition, retention, and clearance is important when evaluating the risk of inhaled nanomaterials to human health. The revised Organization Economic Cooperation and Development (OECD) inhalation toxicity test guidelines now require lung burden measurements of nanomaterials after rodent subacute and sub-chronic inhalation exposure (OECD 412, OECD 413) to inform on lung clearance behavior and translocation after exposure and during post-exposure observation (PEO). Lung burden measurements are particularly relevant when the testing chemical is a solid poorly soluble nanomaterial. Previously, the current authors showed that total retained lung burden of inhaled soluble silver nanoparticles (AgNPs) could be effectively measured using any individual lung lobe.Methods and resultsAccordingly, the current study investigated the evenness of deposition/retention of poorly soluble gold nanoparticles (AuNPs) after 1 and 5 days of inhalation exposure. Rats were exposed nose-only for 1 or 5 days (6 h/day) to an aerosol of 11 nm well-dispersed AuNPs. Thereafter, the five lung lobes were separated and the gold concentrations measured using an inductively coupled plasma-mass spectrophotometer (ICP-MS). The results showed no statistically significant difference in the AuNP deposition/retention among the different lung lobes in terms of the gold mass per gram of lung tissue.ConclusionsThus, it would seem that any rat lung lobe can be used for the lung burden analysis after short or long-term NP inhalation, while the other lobes can be used for collecting and analyzing the bronchoalveolar lavage fluid (BALF) and for the histopathological analysis. Therefore, combining the lung burden measurement, histopathological tissue preparation, and BALF assay from one rat can minimize the number of animals used and maximize the number of endpoints measured.

Highlights

  • Information on particle deposition, retention, and clearance is important when evaluating the risk of inhaled nanomaterials to human health

  • Conclusions: it would seem that any rat lung lobe can be used for the lung burden analysis after short or long-term NP inhalation, while the other lobes can be used for collecting and analyzing the bronchoalveolar lavage fluid (BALF) and for the histopathological analysis

  • Combining the lung burden measurement, histopathological tissue preparation, and BALF assay from one rat can minimize the number of animals used and maximize the number of endpoints measured

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Summary

Introduction

Information on particle deposition, retention, and clearance is important when evaluating the risk of inhaled nanomaterials to human health. When the inhaled test nanomaterials are poorly soluble, OECD guidelines mandate that the lung burden should be measured to inform about the pulmonary-retained dose. Such lung burden measurements should be performed for all test chemicals within 24 h after exposure termination and at two or more additional post-exposure observation (PEO) intervals [1, 2]. The results showed that 20 nm inhaled well-dispersed AgNPs were evenly deposited and retained in all lung lobes in terms of the Ag mass per gram of lung tissue [3] This suggests that any lung lobe can be used to determine the total lung burden, as long as the same lobe is sampled for these measurements. The amounts retained in the lung lobes were evaluated in terms of mass and particle number

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