Nose-only inhalation exposures to alumina nanoparticles / hydrogen chloride gas mixtures induce strong pulmonary pro-inflammatory response

Abstract Background: Combustion processes, especially in aerospace and defense fields, can lead to complex aerosols emission containing gases and nanoparticles (NPs). Alumina (Al2O3) NPs and hydrogen chloride gas (HClg) are for instance present in high concentrations after solid composite propellants use. Exposure to these pollutants mixtures by inhalation is thus possible but literature data towards their pulmonary toxicity are missing. To specify hazards resulting from these combustion aerosols, an inhalation study was implemented.Male Wistar rats were exposed by nose-only to Al2O3 NPs (13 nm) and/or HClg aerosols for 4h (unique exposures ; UE) or 4h a day for 4 days (iterative exposures ; IE). Bronchoalveolar lavage fluids (BALF) content and lungs histopathology were analyzed 24h after exposures.Results: Iterative co-exposures (IE) increased total proteins and lactate dehydrogenases (LDH) concentrations in BALF indicating alveolar-capillary barrier permeabilization and cytolysis. Early pulmonary inflammation was induced after IE to Al2O3 NPs ± HClg resulting in polymorphonuclear neutrophils (PMN) and pro-inflammatory cytokines increases (TNF-α, IL-1β, GRO/KC) in BALF. Moreover, after exposure to Al2O3 NPs ± HClg aerosols, both exposure scenarios induced early pulmonary histopathological lesions, among which vascular congestions, bronchial pre-exfoliations, vascular and interalveolar septum edemas. Lung oxidative damages (8-hydroxy-2'-deoxyguanosine ; 8-OHdG) were observed in situ following UE in each experimental condition, suggesting early oxidative stress induction by aerosols inhalation. However, no 8-isoprostane concentration increase was simultaneously found in animals BALF.Conclusions: Biological effects of the studied aerosols are dependent on both aerosol content and exposure scenario. Results showed an important early pro-inflammatory effect of Al2O3 NPs/HClg mixtures on rats lungs following iterative inhalations (IE). Taken together these data raise concerns towards potential long term pulmonary toxicity of combustion mixtures aerosols, and highlight the importance for workers to wear individual protections.