Lung Cell Toxicity of Metal-Containing Nanoparticles

Among the various nanomaterials present in society, many contain metals or metal compounds [...

Bioaccessibility, bioavailability and toxicity of commercially relevant iron- and chromium-based particles: in vitro studies with an inhalation perspective

<p>Abstract</p> <p>Background</p> <p>Production of ferrochromium alloys (FeCr), master alloys for stainless steel manufacture, involves casting and crushing processes where particles inevitably become airborne and potentially inhaled. The aim of this study was to assess potential health hazards induced by inhalation of different well-characterized iron- and chromium-based particles, i.e. ferrochromium (FeCr), ferrosiliconchromium (FeSiCr), stainless steel (316L), iron (Fe), chromium (Cr), and chromium(III)oxide (Cr₂O₃), in different size fractions using in vitro methods. This was done by assessing the extent and speciation of released metals in synthetic biological medium and by analyzing particle reactivity and toxicity towards cultured human lung cells (A549).</p> <p>Results</p> <p>The amount of released metals normalized to the particle surface area increased with decreasing particle size for all alloy particles, whereas the opposite situation was valid for particles of the pure metals. These effects were evident in artificial lysosomal fluid (ALF) of pH 4.5 containing complexing agents, but not in neutral or weakly alkaline biological media. Chromium, iron and nickel were released to very low extent from all alloy particles, and from particles of Cr due to the presence of a Cr(III)-rich protective surface oxide. Released elements were neither proportional to the bulk nor to the surface composition after the investigated 168 hours of exposure. Due to a surface oxide with less protective properties, significantly more iron was released from pure iron particles compared with the alloys. Cr was predominantly released as Cr(III) from all particles investigated and was strongly complexed by organic species of ALF. Cr₂O₃particles showed hemolytic activity, but none of the alloy particles did. Fine-sized particles of stainless steel caused however DNA damage, measured with the comet assay after 4 h exposure. None of the particles revealed any significant cytotoxicity in terms of cell death after 24 h exposure.</p> <p>Conclusion</p> <p>It is evident that particle and alloy characteristics such as particle size and surface composition are important aspects to consider when assessing particle toxicity and metal release from alloy particles compared to pure metal particles. Generated results clearly elucidate that neither the low released concentrations of metals primarily as a result of protective and poorly soluble surface oxides, nor non-bioavailable chromium complexes, nor the particles themselves of occupational relevance induced significant acute toxic response, with exception of DNA damage from stainless steel.</p

Genotoxicity and inflammatory potential of stainless steel welding fume particles: an in vitro study on standard vs Cr(VI)-reduced flux-cored wires and the role of released metals.

Welders are daily exposed to various levels of welding fumes containing several metals. This exposure can lead to an increased risk for different health effects which serves as a driving force to develop new methods that generate less toxic fumes. The aim of this study was to explore the role of released metals for welding particle-induced toxicity and to test the hypothesis that a reduction of Cr(VI) in welding fumes results in less toxicity by comparing the welding fume particles of optimized Cr(VI)-reduced flux-cored wires (FCWs) to standard FCWs. The welding particles were thoroughly characterized, and toxicity (cell viability, DNA damage and inflammation) was assessed following exposure to welding particles as well as their released metal fraction using cultured human bronchial epithelial cells (HBEC-3kt, 5-100 µg/mL) and human monocyte-derived macrophages (THP-1, 10-50 µg/mL). The results showed that all Cr was released as Cr(VI) for welding particles generated using standard FCWs whereas only minor levels (\u3c 3% of total Cr) were released from the newly developed FCWs. Furthermore, the new FCWs were considerably less cytotoxic and did not cause any DNA damage in the doses tested. For the standard FCWs, the Cr(VI) released in cell media seemed to explain a large part of the cytotoxicity and DNA damage. In contrast, all particles caused rather similar inflammatory effects suggesting different underlying mechanisms. Taken together, this study suggests a potential benefit of substituting standard FCWs with Cr(VI)-reduced wires to achieve less toxic welding fumes and thus reduced risks for welders

Presenting features and long-term effects of growth hormone treatment of children with optic nerve hypoplasia/septo-optic dysplasia

<p>Abstract</p> <p>Background</p> <p>Optic nerve hypoplasia (ONH) with/or without septo-optic dysplasia (SOD) is a known concomitant of congenital growth hormone deficiency (CGHD).</p> <p>Methods</p> <p>Demographic and longitudinal data from KIGS, the Pfizer International Growth Database, were compared between 395 subjects with ONH/SOD and CGHD and 158 controls with CGHD without midline pathology.</p> <p>Results</p> <p>ONH/SOD subjects had higher birth length/weight, and mid-parental height SDS. At GH start, height, weight, and BMI SDS were higher in the ONH/SOD group. After 1 year of GH, both groups showed similar changes in height SDS, while weight and BMI SDS remained higher in the ONH/SOD group. The initial height responses of the two groups were similar to those predicted using the KIGS-derived prediction model for children with idiopathic GHD. At near-adult height, ONH/SOD and controls had similar height, weight, and BMI SDS.</p> <p>Conclusions</p> <p>Compared to children with CGHD without midline defects, those with ONH/SOD presented with greater height, weight, and BMI SDS. These differences persisted at 1 year of GH therapy, but appeared to be overcome by long-term GH treatment.</p

Early development of negative and positive affect: Implications for ADHD symptomatology across three birth cohorts

High levels of early emotionality (of either negative or positive valence) are hypothesized to be important precursors to early psychopathology, with attention-deficit/hyperactivity disorder (ADHD) a prime early target. The positive and negative affect domains are prime examples of Research Domain Criteria (RDoC) concepts that may enrich a multilevel mechanistic map of psychopathology risk. Utilizing both variable-centered and person-centered approaches, the current study examined whether levels and trajectories of infant negative and positive emotionality, considered either in isolation or together, predicted children's ADHD symptoms at 4 to 8 years of age. In variable-centered analyses, higher levels of infant negative affect (at as early as 3 months of age) were associated with childhood ADHD symptoms. Findings for positive affect failed to reach statistical threshold. Results from person-centered trajectory analyses suggest that additional information is gained by simultaneously considering the trajectories of positive and negative emotionality. Specifically, only when exhibiting moderate, stable or low levels of positive affect did negative affect and its trajectory relate to child ADHD symptoms. These findings add to a growing literature that suggests that infant negative emotionality is a promising early life marker of future ADHD risk and suggest secondarily that moderation by positive affectivity warrants more consideration.</p

VERITAS Observations of the BL Lac Object 1ES 1218+304

The VERITAS collaboration reports the detection of very-high-energy (VHE) gamma-ray emission from the high-frequency-peaked BL Lac object 1ES 1218+304 located at a redshift of z=0.182. A gamma-ray signal was detected with high statistical significance for the observations taken during several months in the 2006-2007 observing season. The photon spectrum between ~160 GeV and ~1.8 TeV is well described by a power law with an index of Gamma = 3.08 +/- 0.34(stat) +/- 0.2(sys). The integral flux above 200 GeV corresponds to ~6% of that of the Crab Nebula. The light curve does not show any evidence for VHE flux variability. Using lower limits on the density of the extragalactic background light (EBL) in the near-IR to mid-IR we are able to limit the range of intrinsic energy spectra for 1ES 1218+304. We show that the intrinsic photon spectrum is harder than a power law with an index of Gamma = 2.32 +/- 0.37. When including constraints from the spectra of 1ES 1101-232 and 1ES 0229+200, the spectrum of 1ES 1218+304 is likely to be harder than Gamma = 1.86 +/- 0.37.Comment: Submitted to Proceedings of "4th Heidelberg International Symposium on High Energy Gamma-Ray Astronomy 2008

Status of the VERITAS Observatory

VERITAS, an Imaging Atmospheric Cherenkov Telescope (IACT) system for gammma-ray astronomy in the GeV-TeV range, has recently completed its first season of observations with a full array of four telescopes. A number of astrophysical gamma-ray sources have been detected, both galactic and extragalactic, including sources previously unknown at TeV energies. We describe the status of the array and some highlight results, and assess the technical performance, sensitivity and shower reconstruction capabilities.Comment: Submitted to Proceedings of "4th Heidelberg International Symposium on High Energy Gamma-Ray Astronomy 2008

Evidence for long-term Gamma-ray and X-ray variability from the unidentified TeV source HESS J0632+057

HESS J0632+057 is one of only two unidentified very-high-energy gamma-ray sources which appear to be point-like within experimental resolution. It is possibly associated with the massive Be star MWC 148 and has been suggested to resemble known TeV binary systems like LS I +61 303 or LS 5039. HESS J0632+057 was observed by VERITAS for 31 hours in 2006, 2008 and 2009. During these observations, no significant signal in gamma rays with energies above 1 TeV was detected from the direction of HESS J0632+057. A flux upper limit corresponding to 1.1% of the flux of the Crab Nebula has been derived from the VERITAS data. The non-detection by VERITAS excludes with a probability of 99.993% that HESS J0632+057 is a steady gamma-ray emitter. Contemporaneous X-ray observations with Swift XRT reveal a factor of 1.8+-0.4 higher flux in the 1-10 keV range than earlier X-ray observations of HESS J0632+057. The variability in the gamma-ray and X-ray fluxes supports interpretation of the ob ject as a gamma-ray emitting binary.Comment: 8 pages, 3 figures, Accepted for publication in The Astrophysical Journa

A connection between star formation activity and cosmic rays in the starburst galaxy M 82

Although Galactic cosmic rays (protons and nuclei) are widely believed to be dominantly accelerated by the winds and supernovae of massive stars, definitive evidence of this origin remains elusive nearly a century after their discovery [1]. The active regions of starburst galaxies have exceptionally high rates of star formation, and their large size, more than 50 times the diameter of similar Galactic regions, uniquely enables reliable calorimetric measurements of their potentially high cosmic-ray density [2]. The cosmic rays produced in the formation, life, and death of their massive stars are expected to eventually produce diffuse gamma-ray emission via their interactions with interstellar gas and radiation. M 82, the prototype small starburst galaxy, is predicted to be the brightest starburst galaxy in gamma rays [3, 4]. Here we report the detection of >700 GeV gamma rays from M 82. From these data we determine a cosmic-ray density of 250 eV cm-3 in the starburst core of M 82, or about 500 times the average Galactic density. This result strongly supports that cosmic-ray acceleration is tied to star formation activity, and that supernovae and massive-star winds are the dominant accelerators.Comment: 18 pages, 4 figures; published in Nature; Version is prior to Nature's in-house style editing (differences are minimal