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Purpose: To investigate the molecular mechanisms underlying the pulmonary toxicity induced by exposure to one form of multi-walled carbon nanotubes (MWCNT-7). Materials and methods: Rats were exposed, by whole-body inhalation, to air or an aerosol containing MWCNT-7 particles at target cumulative doses (concentration x time) ranging from 22.5 to 180 (mg/m 3 )h over a three-day (6 hours/day) period and toxicity and global gene expression profiles were determined in the lungs. Results: MWCNT-7 particles, associated with alveolar macrophages (AMs), were detected in rat lungs following the exposure. Mild to moderate lung pathological changes consisting of increased cellularity, thickening of the alveolar wall, alveolitis, fibrosis, and granuloma formation were detected. Bronchoalveolar lavage (BAL) toxicity parameters such as lactate dehydrogenase activity, number of AMs and polymorphonuclear leukocytes (PMNs), intracellular oxidant generation by phagocytes, and levels of cytokines were significantly ( p  < 0.05) increased in response to exposure to MWCNT-7. Global gene expression profiling identified several significantly differentially expressed genes (fold change >1.5 and FDR p value <0.05) in all the MWCNT-7 exposed rats. Bioinformatic analysis of the gene expression data identified significant enrichment of several diseases/biological function categories (for example, cancer, leukocyte migration, inflammatory response, mitosis, and movement of phagocytes) and canonical pathways (for example, kinetochore metaphase signaling pathway, granulocyte and agranulocyte adhesion and diapedesis, acute phase response, and LXR/RXR activation). The alterations in the lung toxicity parameters and gene expression changes exhibited a dose-response to the MWCNT exposure. Conclusions: Taken together, the data provided insights into the molecular mechanisms underlying the pulmonary toxicity induced by inhalation exposure of rats to MWCNT-7.

Face masks reduce the expulsion of respiratory aerosols produced during coughs and exhalations ("source control"). Factors such as the directions in which people are facing (orientation) and separation distance also affect aerosol dispersion. However, it is not clear how the combined effects of masking, orientation, and distance affect the exposure of individuals to respiratory aerosols in indoor spaces. We placed a respiratory aerosol simulator ("source") and a breathing simulator ("recipient") in a 3 m × 3 m chamber and measured aerosol concentrations for different combinations of masking, orientation, and separation distance. When the simulators were front-to-front during coughing, masks reduced the 15-min mean aerosol concentration at the recipient by 92% at 0.9 and 1.8 m separation. When the simulators were side-by-side, masks reduced the concentration by 81% at 0.9 m and 78% at 1.8 m. During breathing, masks reduced the aerosol concentration by 66% when front-to-front and 76% when side-by-side at 0.9 m. Similar results were seen at 1.8 m. When the simulators were unmasked, changing the orientations from front-to-front to side-by-side reduced the cough aerosol concentration by 59% at 0.9 m and 60% at 1.8 m. When both simulators were masked, changing the orientations did not significantly change the concentration at either distance during coughing or breathing. Increasing the distance between the simulators from 0.9 m to 1.8 m during coughing reduced the aerosol concentration by 25% when no masks were worn but had little effect when both simulators were masked. During breathing, when neither simulator was masked, increasing the separation reduced the concentration by 13%, which approached significance, while the change was not significant when both source and recipient were masked. Our results show that universal masking reduces exposure to respiratory aerosol particles regardless of the orientation and separation distance between the source and recipient.

Objective: Human exposure to cellulose nanocrystal (CNC) is possible during the production and/or use of products containing CNC. The objectives of the current study were to determine the lung toxicity of CNC and the underlying molecular mechanisms of the toxicity., Methods: Rats were exposed to air or CNC (20 mg/m 3 , six hours/day, 14 d) by whole-body inhalation and lung toxicity and global gene expression profile were determined., Results: Significant increases in lactate dehydrogenase activity, pro-inflammatory cytokine levels, phagocyte oxidant production, and macrophage and neutrophil counts were detected in the bronchoalveolar lavage cells or fluid from the CNC exposed rats. Mild lung histological changes, such as the accumulation of macrophages and neutrophils, were detected in the CNC exposed rats. Gene expression profiling by next generation sequencing identified 531 genes whose expressions were significantly different in the lungs of the CNC exposed rats, compared with the controls. Bioinformatic analysis of the lung gene expression data identified significant enrichment in several biological functions and canonical pathways including those related to inflammation (cellular movement, immune cell trafficking, inflammatory diseases and response, respiratory disease, complement system, acute phase response, leukocyte extravasation signaling, granulocyte and agranulocyte adhesion and diapedesis, IL-10 signaling, and phagosome formation and maturation) and oxidative stress (NRF2-mediated oxidative stress response, production of nitric oxide and reactive oxygen species in macrophages, and free radical scavenging)., Conclusion: Our data demonstrated that inhalation exposure of rats to CNC resulted in lung toxicity mediated mainly through the induction of inflammation and oxidative stress.