With advances in nanotechnology, engineered nanomaterial applications are a rapidly growing sector of the economy. Some nanomaterials can reach the brain through nose-to-brain transport. This transport creates concern for potential neurotoxicity of insoluble nanomaterials and a need for toxicity screening tests that detect nose-to-brain transport. Such tests can involve intranasal instillation of aqueous suspensions of nanomaterials in dispersion media that limit particle agglomeration. Unfortunately, protein and some elements in existing dispersion media are suboptimal for potential nose-to-brain transport of nanomaterials because olfactory transport has size- and ion-composition requirements. Therefore, we designed a protein-free dispersion media containing phospholipids and amino acids in an isotonic balanced electrolyte solution, a solution for nasal and olfactory transport (SNOT). SNOT disperses hexagonal boron nitride nanomaterials with a peak particle diameter below 100 nm. In addition, multiwalled carbon nanotubes (MWCNTs) in an established dispersion medium, when diluted with SNOT, maintain dispersion with reduced albumin concentration. Using stereomicroscopy and microscopic examination of plastic sections, dextran dyes dispersed in SNOT are demonstrated in the neuroepithelium of the nose and olfactory bulb of B6;129P2-Omp(tm3Mom)/MomJ mice after intranasal instillation in SNOT. These findings support the potential for SNOT to disperse nanomaterials in a manner permitting nose-to-brain transport for neurotoxicity studies.

RATIONALE: The reasons for resurgent coal workers' pneumoconiosis and its most severe forms, rapidly progressive pneumoconiosis and progressive massive fibrosis (PMF), in the United States (US) are not yet fully understood. OBJECTIVE: To compare the pathologic and mineralogic features of contemporary coal miners suffering severe pneumoconiosis to their historical counterparts. METHODS: Lung pathology specimens from 85 coal miners with PMF were included for evaluation and analysis. We compared the proportion of cases with pathologic and mineralogic findings in miners born between 1910 and 1930 (historical) to those born in or after 1930 (contemporary). RESULTS: We found a significantly higher proportion of silica-type PMF (57% vs. 18%, p<0.001) among contemporary miners compared to their historical counterparts. Mineral dust alveolar proteinosis (MDAP) was also more common in contemporary miners compared to their historical counterparts (70% vs. 37%, p<0.01). In situ mineralogic analysis showed the percentage (26.1% vs. 17.8%, p<0.01) and concentration (47.3 x 108 vs. 25.8 X 108 particles/cm3, p=0.036) of silica particles was significantly greater in specimens from contemporary miners compared to their historical counterparts. The concentration of silica particles was significantly greater when silica-type PMF, MDAP, silicotic nodules, or immature silicotic nodules were present (p<0.05). CONCLUSIONS: Exposure to respirable crystalline silica appears causal in the unexpected surge in severe disease in contemporary miners. Our findings underscore the importance of controlling workplace silica exposure in order to prevent the disabling and untreatable adverse health effects afflicting US coal miners. Primary Source of Funding: Alpha Foundation for the Improvement of Mine Safety and Health, Inc.

Flavorings-related lung disease is a potentially disabling and sometimes fatal lung disease of workers making or using flavorings. First identified almost 20 years ago in microwave popcorn workers exposed to butter-flavoring vapors, flavorings-related lung disease remains a concern today. In some cases, workers develop bronchiolitis obliterans, a severe form of fixed airways disease. Affected workers have been reported in microwave popcorn, flavorings, and coffee production workplaces. Volatile alpha-dicarbonyl compounds, particularly diacetyl (2,3-butanedione) and 2,3-pentanedione, are implicated in the etiology. Published studies on diacetyl and 2,3-pentanedione document their ability to cause airway epithelial necrosis, damage biological molecules, and perturb protein homeostasis. With chronic exposure in rats, they produce airway fibrosis resembling bronchiolitis obliterans. To add to this knowledge, we recently evaluated airway toxicity of the 3-carbon alpha-dicarbonyl compound, methylglyoxal. Methylglyoxal inhalation causes epithelial necrosis at even lower concentrations than diacetyl. In addition, we investigated airway toxicity of mixtures of diacetyl, acetoin, and acetic acid, common volatiles in butter flavoring. At ratios comparable to workplace scenarios, the mixtures or diacetyl alone, but not acetic acid or acetoin, cause airway epithelial necrosis. These new findings add to existing data to implicate alpha-dicarbonyl compounds in airway injury and flavorings-related lung disease.