Physicochemical characterization and genotoxicity of the broad class of carbon nanotubes and nanofibers used or produced in US facilities

Background Carbon nanotubes and nanofibers (CNT/F) have known toxicity but simultaneous comparative studies of the broad material class, especially those with a larger diameter, with computational analyses linking toxicity to their fundamental material characteristics was lacking. It was unclear if all CNT/F confer similar toxicity, in particular, genotoxicity. Nine CNT/F (MW #1-7 and CNF #1-2), commonly found in exposure assessment studies of U.S. facilities, were evaluated with reported diameters ranging from 6 to 150 nm. All materials were extensively characterized to include distributions of physical dimensions and prevalence of bundled agglomerates. Human bronchial epithelial cells were exposed to the nine CNT/F (0-24 mu g/ml) to determine cell viability, inflammation, cellular oxidative stress, micronuclei formation, and DNA double-strand breakage. Computational modeling was used to understand various permutations of physicochemical characteristics and toxicity outcomes. Results Analyses of the CNT/F physicochemical characteristics illustrate that using detailed distributions of physical dimensions provided a more consistent grouping of CNT/F compared to using particle dimension means alone. In fact, analysis of binning of nominal tube physical dimensions alone produced a similar grouping as all characterization parameters together. All materials induced epithelial cell toxicity and micronuclei formation within the dose range tested. Cellular oxidative stress, DNA double strand breaks, and micronuclei formation consistently clustered together and with larger physical CNT/F dimensions and agglomerate characteristics but were distinct from inflammatory protein changes. Larger nominal tube diameters, greater lengths, and bundled agglomerate characteristics were associated with greater severity of effect. The portion of tubes with greater nominal length and larger diameters within a sample was not the majority in number, meaning a smaller percentage of tubes with these characteristics was sufficient to increase toxicity. Many of the traditional physicochemical characteristics including surface area, density, impurities, and dustiness did not cluster with the toxicity outcomes. Conclusion Distributions of physical dimensions provided more consistent grouping of CNT/F with respect to toxicity outcomes compared to means only. All CNT/F induced some level of genotoxicity in human epithelial cells. The severity of toxicity was dependent on the sample containing a proportion of tubes with greater nominal lengths and diameters

Metabolomic signatures associated with weight gain and psychosis spectrum diagnoses: A pilot study

Psychosis spectrum disorders (PSDs), as well as other severe mental illnesses where psychotic features may be present, like bipolar disorder, are associated with intrinsic metabolic abnormalities. Antipsychotics (APs), the cornerstone of treatment for PSDs, incur additional metabolic adversities including weight gain. Currently, major gaps exist in understanding psychosis illness biomarkers, as well as risk factors and mechanisms for AP-induced weight gain. Metabolomic profiles may identify biomarkers and provide insight into the mechanistic underpinnings of PSDs and antipsychotic-induced weight gain. In this 12-week prospective naturalistic study, we compared serum metabolomic profiles of 25 cases within approximately 1 week of starting an AP to 6 healthy controls at baseline to examine biomarkers of intrinsic metabolic dysfunction in PSDs. In 17 of the case participants with baseline and week 12 samples, we then examined changes in metabolomic profiles over 12 weeks of AP treatment to identify metabolites that may associate with AP-induced weight gain. In the cohort with pre-post data (n = 17), we also compared baseline metabolomes of participants who gained ≥5% baseline body weight to those who gained <5% to identify potential biomarkers of antipsychotic-induced weight gain. Minimally AP-exposed cases were distinguished from controls by six fatty acids when compared at baseline, namely reduced levels of palmitoleic acid, lauric acid, and heneicosylic acid, as well as elevated levels of behenic acid, arachidonic acid, and myristoleic acid (FDR < 0.05). Baseline levels of the fatty acid adrenic acid was increased in 11 individuals who experienced a clinically significant body weight gain (≥5%) following 12 weeks of AP exposure as compared to those who did not (FDR = 0.0408). Fatty acids may represent illness biomarkers of PSDs and early predictors of AP-induced weight gain. The findings may hold important clinical implications for early identification of individuals who could benefit from prevention strategies to reduce future cardiometabolic risk, and may lead to novel, targeted treatments to counteract metabolic dysfunction in PSDs

Passive sampling to capture the spatial variability of coarse particles by composition in Cleveland, OH

Passive samplers deployed at 25 sites for three, week-long intervals were used to characterize spatial variability in the mass and composition of coarse particulate matter (PM10-2.5) in Cleveland, OH in summer 2008. The size and composition of individual particles determined using computer-controlled scanning electron microscopy with energy-dispersive X-ray spectroscopy (CCSEM-EDS) was then used to estimate PM10-2.5 concentrations (μg m−3) and its components in 13 particle classes. The highest PM10-2.5 mean mass concentrations were observed at three central industrial sites (35 μg m−3, 43 μg m−3, and 48 μg m−3), whereas substantially lower mean concentrations were observed to the west and east of this area at suburban background sites (13 μg m−3 and 15 μg m−3). PM10-2.5 mass and components associated with steel and cement production (Fe-oxide and Ca-rich) exhibited substantial heterogeneity with elevated concentrations observed in the river valley, stretching from Lake Erie south through the central industrial area and in the case of Fe-oxide to a suburban valley site. Other components (e.g., Si/Al-rich typical of crustal material) were considerably less heterogeneous. This work shows that some species of coarse particles are considerably more spatially heterogeneous than others in an urban area with a strong industrial core. It also demonstrates that passive sampling coupled with analysis by CCSEM-EDS is a useful tool to assess the spatial variability of particulate pollutants by composition. [Display omitted] •Examined spatial variability of PM10-2.5 and components in Cleveland, OH.•Used passive samplers with automated microscopy to classify particles.•Components associated with steel and cement production highest in industrial area.•Components associated with crustal material more uniformly distributed.•Method may be useful to reduce exposure misclassification in epidemiological studies

Single-Particle SEM-EDX Analysis of Iron-Containing Coarse Particulate Matter in an Urban Environment: Sources and Distribution of Iron within Cleveland, Ohio

The physicochemical properties of coarse-mode, iron-containing particles and their temporal and spatial distributions are poorly understood. Single-particle analysis combining X-ray elemental mapping and computer-controlled scanning electron microscopy (CCSEM-EDX) of passively collected particles was used to investigate the physicochemical properties of iron-containing particles in Cleveland, OH, in summer 2008 (Aug–Sept), summer 2009 (July–Aug), and winter 2010 (Feb–March). The most abundant classes of iron-containing particles were iron oxide fly ash, mineral dust, NaCl-containing agglomerates (likely from road salt), and Ca–S containing agglomerates (likely from slag, a byproduct of steel production, or gypsum in road salt). The mass concentrations of anthropogenic fly ash particles were highest in the Flats region (downtown) and decreased with distance away from this region. The concentrations of fly ash in the Flats region were consistent with interannual changes in steel production. These particles were observed to be highly spherical in the Flats region, but less so after transport away from downtown. This change in morphology may be attributed to atmospheric processing. Overall, this work demonstrates that the method of passive collection with single-particle analysis by electron microscopy is a powerful tool to study spatial and temporal gradients in components of coarse particles. These gradients may correlate with human health effects associated with exposure to coarse-mode particulate matter

Elevated Concentrations of Lead in Particulate Matter on the Neighborhood-Scale in Delhi, India As Determined by Single Particle Analysis

High mass concentrations of atmospheric lead particles are frequently observed in the Delhi, India metropolitan area, although the sources of lead particles are poorly understood. In this study, particles sampled across Delhi (August - December 2008) were analyzed by computer-controlled scanning electron microscopy with energy dispersive X-ray spectroscopy (CCSEM-EDX) to improve our understanding of the spatial and physicochemical variability of lead-rich particles (>90% lead). The mean mass concentration of lead-rich particles smaller than 10 μm (PM10) was 0.7 μg/m(3) (1.5 μg/m(3) std. dev.) with high variability (range: 0-6.2 μg/m(3)). Four samples (16% of 25 samples) with PM10 lead-rich particle concentrations >1.4 μg/m(3) were defined as lead events and studied further. The temporal characteristics, heterogeneous spatial distribution, and wind patterns of events, excluded regional monsoon conditions or common anthropogenic sources from being the major causes of the lead events. Individual particle composition, size, and morphology analysis indicate informal recycling operations of used lead-acid batteries as the likely source of the lead events. This source is not typically included in emission inventories, and the observed isolated hotspots with high lead concentrations could represent an elevated exposure risk in certain neighborhoods of Delhi