Flavorings-related lung disease is a potentially disabling disease of food industry workers associated with exposure to the α-diketone butter flavoring, diacetyl (2,3-butanedione). To investigate the hypothesis that another α-diketone flavoring, 2,3-pentanedione, would cause airway damage, rats that inhaled air, 2,3-pentanedione (112, 241, 318, or 354 ppm), or diacetyl (240 ppm) for 6 hours were sacrificed the following day. Rats inhaling 2,3-pentanedione developed necrotizing rhinitis, tracheitis, and bronchitis comparable to diacetyl-induced injury. To investigate delayed toxicity, additional rats inhaled 318 (range, 317.9-318.9) ppm 2,3-pentanedione for 6 hours and were sacrificed 0 to 2, 12 to 14, or 18 to 20 hours after exposure. Respiratory epithelial injury in the upper nose involved both apoptosis and necrosis, which progressed through 12 to 14 hours after exposure. Olfactory neuroepithelial injury included loss of olfactory neurons that showed reduced expression of the 2,3-pentanedione-metabolizing enzyme, dicarbonyl/L-xylulose reductase, relative to sustentacular cells. Caspase 3 activation occasionally involved olfactory nerve bundles that synapse in the olfactory bulb (OB). An additional group of rats inhaling 270 ppm 2,3-pentanedione for 6 hours 41 minutes showed increased expression of IL-6 and nitric oxide synthase-2 and decreased expression of vascular endothelial growth factor A in the OB, striatum, hippocampus, and cerebellum using real-time PCR. Claudin-1 expression increased in the OB and striatum. We conclude that 2,3-pentanedione is a respiratory hazard that can also alter gene expression in the brain.
This is the first report demonstrating that a commercially available household consumer product produces nanoparticles in a respirable range. This report describes a method developed to characterize nanoparticles that were produced under typical exposure conditions when using a consumer spray product. A well-controlled indoor environment was simulated for conducting spray applications approximating a human exposure scenario. Results indicated that, while aerosol droplets were large with a count median diameter of 22 µm during spraying, the final aerosol contained primarily solid TiO(2) particles with a diameter of 75 nm. This size reduction was due to the surface deposition of the droplets and the rapid evaporation of the aerosol propellant. In the breathing zone, the aerosol, containing primarily individual particles (>90%), had a mass concentration of 3.4 mg/m(3), or 1.6 × 10(5) particles/cm(3), with a nanoparticle fraction limited to 170 µg/m(3), or 1.2 × 10(5) particles/cm(3). The results were used to estimate the pulmonary dose in an average human (0.075 µg TiO(2) per m(2) alveolar epithelium per minute) and rat (0.03 µg TiO(2)) and, consequently, this information was used to design an inhalation exposure system. The system consisted of a computer-controlled solenoid ''finger'' for generating constant concentrations of spray can aerosols inside a chamber. Test results demonstrated great similarity between the solenoid ''finger''-dispersed aerosol compared to human-generated aerosol. Future investigations will include an inhalation study to obtain information on dose-response relationships in rats and to use it to establish a No Effect Exposure Level for setting guidelines for this consumer product.
The first inertial confinement fusion implosion experiments with equimolar deuterium-tritium thermonuclear fuel have been performed on the National Ignition Facility. These experiments use 0.17 mg of fuel with the potential for ignition and significant fusion yield conditions. The thermonuclear fuel has been fielded as a cryogenic layer on the inside of a spherical plastic capsule that is mounted in the center of a cylindrical gold hohlraum. Heating the hohlraum with 192 laser beams for a total laser energy of 1.6 mega joules produces a soft x-ray field with 300 eV temperature. The ablation pressure produced by the radiation field compresses the initially 2.2-mm diameter capsule by a factor of 30 to a spherical dense fuel shell that surrounds a central hot-spot plasma of 50 µm diameter. While an extensive set of x-ray and neutron diagnostics has been applied to characterize hot spot formation from the x-ray emission and 14.1 MeV deuterium-tritium primary fusion neutrons, thermonuclear fuel assembly is studied by measuring the down-scattered neutrons with energies in the range of 10 to 12 MeV. X-ray and neutron imaging of the compressed core and fuel indicate a fuel thickness of (14 ± 3) µm, which combined with magnetic recoil spectrometer measurements of the fuel areal density of (1 ± 0.09) g cm −2 result in fuel densities approaching 600 g cm −3 . The fuel surrounds a hot-spot plasma with average ion temperatures of (3.5 ± 0.1) keV that is measured with neutron time of flight spectra. Absolute neutron yields of (7.5 ± 0.1) × 10 14 have been recorded from the magnetic recoil spectrometer and nuclear activation diagnostics while gamma ray measurements provide the duration of nuclear activity of (170 ± 30) ps. These indirect-drive implosions result in the highest areal densities and neutron yields achieved on laser facilities to date. This achievement is the result of the first hohlraum and capsule tuning experiments where the stagnation pressures have been systematically increased by more than a factor of 10 by fielding low-entropy implosions through the control of radiation symmetry, small hot electron production, and proper shock timing. The stagnation pressure is above 100 Gbar resulting in high Lawson confinement parameters of P τ 10 atm s. Comparisons with radiation-hydrodynamic simulations indicate that the pressure is within a factor of three required for reaching ignition and high yield. This will be the focus of future higher-velocity implosions that will employ additional optimizations of hohlraum, capsule and laser pulse shape conditions.
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