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At least 37 records · Page 2

Olfactory bulb units - Activity correlated with inhalation cycles and odor quality.

Single olfactory bulb units were studied in two macrosmatic species of rodents under conditions intended to preserve the cyclical stimulation which normally accompanies nasal breathing. Patterns of unit activity related to the inhalation cycle were observed in all animals, often in the absence of specific stimuli, and could not be explained in simple mechanical terms. Distinctive changes in these patterns occurred in response to certain odors, and were generally independent of changes in the overall firing frequency. These findings indicate that a change in the overall firing frequency of unit discharges is neither a necessary nor sufficient measure of responsiveness to odors in the rodent olfactory bulb, and that stimulus-specific temporal distributions of unit firing may be involved in olfacto-endocrine activities.

Macrides, F.↗

Improved inhalation technology for setting safe exposure levels for workplace chemicals

Threshold Limit Values recommended as allowable air concentrations of a chemical in the workplace are often based upon a no-observable-effect-level (NOEL) determined by experimental inhalation studies using rodents. A 'safe level' for human exposure must then be estimated by the use of generalized safety factors in attempts to extrapolate from experimental rodents to man. The recent development of chemical-specific physiologically-based toxicokinetics makes use of measured physiological, biochemical, and metabolic parameters to construct a validated model that is able to 'scale-up' rodent response data to predict the behavior of the chemical in man. This procedure is made possible by recent advances in personal computer software and the emergence of appropriate biological data, and provides an analytical tool for much more reliable risk evaluation and airborne chemical exposure level setting for humans.

Stuart, Bruce O.↗

Toxicokinetics of inhaled bromotrifluoromethane (Halon 1301) in human subjects

Bromotrifluoromethane (Halon 1301, CBrF3), is used as a fire extinguishant in the Space Shuttle, where several scenarios, such as a fire or a faulty alarm, could lead to its discharge resulting in a Halon 1301 concentration of up to 1 percent in the cabin atmosphere. The effect of Halon 1301 on mental performance and physiologic function was investigated in a NASA-sponsored human inhalation study in which four pairs of male subjects were each exposed in a double-blind fashion for 24 hr to 1 percent Halon 1301 and to air in two exposures about 1 week apart. Blood and breath samples from the exposed subjects were collected to provide dosimetric and toxicokinetic information. Halon 1301 blood levels increased rapidly and approached a steady state within 2 hr of the beginning the exposure; the steady-state concentration was approximately 3-4.5 microg/ml. Breath samples collected during exposures closely reflected chamber concentrations. Analysis of postexposure blood samples revealed that Halon 1301 was eliminated biphasically with an average t(1/2) alpha and t(1/2) beta of 4.5 min and 200 min, respectively.

Lam, C. W.↗

Inhalation Toxicity of Ground Lunar Dust Prepared from Apollo-14 Soil

Within the decade one or more space-faring nations intend to return humans to the moon for more in depth exploration of the lunar surface and subsurface than was conducted during the Apollo days. The lunar surface is blanketed with fine dust, much of it in the respirable size range (<10 micron). Eventually, there is likely to be a habitable base and rovers available to reach distant targets for sample acquisition. Despite designs that could minimize the entry of dust into habitats and rovers, it is reasonable to expect lunar dust to pollute both as operations progress. Apollo astronauts were exposed briefly to dust at nuisance levels, but stays of up to 6 months on the lunar surface are envisioned. Will repeated episodic exposures to lunar dust present a health hazard to those engaged in lunar exploration? Using rats exposed to lunar dust by nose-only inhalation, we set out to investigate that question.

James, John T.↗

Tank 11H Low Temperature Aluminum Dissolution and Inhalation Dose Potential Analyses at Savannah River Site – 26018

Currently, there is approximately 34 million gallons of high-level radioactive tank waste in the Tank Farm at the Savannah River Site (SRS). The ultimate goal of operations at the Tank Farm is to remove the high level waste (HLW) from the tanks followed by stabilization of the waste through vitrification of the HLW into glass or grouting the decontaminated waste into saltstone. After bulk removal of the HLW consisting of sludge, saltcake, and supernatant, further efforts are made to reduce the residual waste present in the tank in order to declare preliminary cease waste removal (PCWR) signifying completion of HLW removal. These reduction efforts can include tank washing to remove soluble salts and radioisotopes and dissolution of solids including aluminum. Aluminum in the form of gibbsite and boehmite is relatively insoluble in water. Through addition of aqueous sodium hydroxide, the aluminum can be dissolved at mild temperatures. In order for the waste tank to meet closure mode requirements of the Concentration, Storage, and Transfer Facilities (CSTF), which includes the Tank Farm, Documented Safety Analysis (DSA), a component of the safety basis, the inhalation dose potential (IDP) and the radiolytic hydrogen generation rate of the stored waste must be demonstrated to be lower than their respective designated limits. These parameters are calculated from measured radiochemical analyses of isotopes that emit a high amount of radioactivity including Cs-137, Sr-90, Pu-238, Pu-239, Pu-240, Pu-241, Am-241, and Cm-244. Following the low temperature aluminum dissolution (LTAD) process, Tank 11H slurry samples were pulled from the tank and sent to Savannah River National Laboratory (SRNL) to measure the extent of aluminum dissolution, hydroxide concentration, densities of slurry and supernatant, weight percent solids analyses, and radionuclide activities. The analyses of the composite sample found that approximately 90% of the total aluminum in the slurry was dissolved, indicating successful reduction of the insoluble aluminum in the waste tank. Additionally, the weight percent insoluble solids (slurry basis) measurement of the composite sample was found to be approximately 1%, demonstrating that minimal solids still remain in the tank. Finally, the radiochemical analyses of the composite sample determined that the waste contents of the tank met the IDP and radiolytic hydrogen generation rate requirements of the CSTF DSA. These measurements have shown that the LTAD process in Tank 11H was successful in waste reduction efforts and a positive step towards declaring PCWR and tank closure at SRS.

Dekarske, John [Savannah River National Laboratory↗

ECAR-5127 Rev 1 Evaluation of the MARVEL Reactor Inhalation Dose Consequences

The following dose consequence analysis is performed to support the preliminary Microreactor Applications Research Validation and Evaluation Project (MARVEL) design effort. The purpose of the MARVEL project is to develop a nuclear microreactor applications test bed at Idaho National Laboratory (INL) to perform research and development on various operational features of microreactors to ultimately improve integration of microreactors to end-user applications. The MARVEL concept is a 100 kilowatt (kW) thermal (kWth) and approximately 20-kW electric (kWe) generating microreactor. The MARVEL system will be located in the INL TREAT facility in the north high-bay equipment pit. This ECAR considers the bounding release fractions of the MARVEL reactor concept and documents the dose consequences to the public and collocated worker.

21 - SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLAN↗

Systemic immunological responses are dependent on sex and ovarian hormone presence following acute inhaled woodsmoke exposure

Background: Rural regions of the western United States have experienced a noticeable surge in both the frequency and severity of acute wildfire events, which brings significant challenges to both public safety and environmental conservation efforts, with impacts felt globally. Identifying factors contributing to immune dysfunction, including endocrinological phenotypes, is essential to understanding how hormones may influence toxicological susceptibility. Methods: This exploratory study utilized male and female C57BL/6 mice as in vivo models to investigate distinct responses to acute woodsmoke (WS) exposure with a focus on sex-based differences. In a second set of investigations, two groups were established within the female mouse cohort. In one group, mice experienced ovariectomy (OVX) to simulate an ovarian hormone-deficient state similar to surgical menopause, while the other group received Sham surgery as controls, to investigate the mechanistic role of ovarian hormone presence in driving immune dysregulation following acute WS exposure. Each experimental cohort followed a consecutive 2-day protocol with daily 4-h exposure intervals under two conditions: control HEPA-filtered air (FA) and acute WS to simulate an acute wildfire episode. Results: Metals analysis of WS particulate matter (PM) revealed significantly increased levels of 63 Cu, 182 W, 208 Pb, and 238 U, compared to filtered air (FA) controls, providing insights into the specific metal components most impacted by the changing dynamics of wildfire occurrences in the region. Male and female mice exhibited diverse patterns in lung mRNA cytokine expression following WS exposure, with males showing downregulation and females displaying upregulation, notably for IL-1β, TNF-α, CXCL-1, CCL-5, TGF-β, and IL-6. After acute WS exposure, there were notable differences in the responses of macrophages, neutrophils, and bronchoalveolar lavage (BAL) cytokines IL-10, IL-6, IL-1β, and TNF-α. Significant diverse alterations were observed in BAL cytokines, specifically IL-1β, IL-10, IL-6, and TNF-α, as well as in the populations of immune cells, such as macrophages and polymorphonuclear leukocytes, in both Sham and OVX mice, following acute WS exposure. These findings elucidated the profound influence of hormonal changes on inflammatory outcomes, delineating substantial sex-related differences in immune activation and revealing altered immune responses in OVX mice due to ovarian hormone deficiency. In addition, the flow cytometry analysis highlighted the complex interaction between OVX surgery, acute WS exposure, and their collective impact on immune cell populations within the hematopoietic bone marrow niche. Conclusions: In summary, both male and female mice, alongside females subjected to OVX and those who had sham surgery, exhibit significant variations in the expression of proinflammatory cytokines, chemokines, lung mRNA gene expression, and related functional networks linked to signaling pathways. These differences potentially act as mediators of sex-specific and hormonal influences in the systemic inflammatory response to acute WS exposure during a wildfire event. Understanding the regulatory roles of genes expressed differentially under environmental stressors holds considerable implications, aiding in identifying sex-specific therapeutic targets for addressing acute lung inflammation and injury.

59 BASIC BIOLOGICAL SCIENCES↗

Systemic immunological responses are dependent on sex and ovarian hormone presence following acute inhaled woodsmoke exposure

Rural regions of the western United States have experienced a noticeable surge in both the frequency and severity of acute wildfire events, which brings significant challenges to both public safety and environmental conservation efforts, with impacts felt globally. Identifying factors contributing to immune dysfunction, including endocrinological phenotypes, is essential to understanding how hormones may influence toxicological susceptibility.

59 BASIC BIOLOGICAL SCIENCES↗

Effects of inhalation of Freon 113 on laboratory animals

Four monkeys, 8 dogs, 40 mice, and 50 rats were exposed continuously to 2000 ppm Freon 113 in a Thomas Dome for 14 days. This exposure produced no mortalities nor adverse symptomology. There were no significant alterations in hematological values, clinical chemistries, electroencephalographic findings, body weights, or organ to body weight ratios. The effect of 2% Freon 113 on nicotinic transmission through the stellate ganglion of the spinal dog was also evaluated. The exposure induced a reduction in nicotinic transmission comparable to 2% halothane.

Carter, V. L.↗

Inhaled ozone as a mutagen. II - Effect on the frequency of chromosome aberrations observed in irradiated Chinese hamsters.

Exposure-adjusted break frequencies for chromosome aberrations produced in Chinese hamster circulating blood lymphocytes were the quantitative indicator of damage from 5 hrs of exposure to X-radiation and/or to ozone. Radiation produced 5.51 x 0.0001 breaks/cell rad for cells withdrawn 2 weeks after exposure, a reasonable value when compared with data from in vivo exposure of human lymphocytes and Chinese hamster bone marrow cells. Animals exposed to the two agents simultaneously exhibited more than 70% of the total breaks anticipated assuming the expected equal contributions to be additive. Extending to humans, at presently permitted levels, exposure to ozone would be much more detrimental than exposure to radiati*n.

Zelac, R. E.↗

Development and fabrication of heat-sterilizable inhalation therapy equipment

The development of a completely heat sterilizable intermittent positive pressure breathing (IPPB) ventilator in an effort to reduce the number of hospital acquired infections is reported. After appropriate changes in materials and design were made, six prototype units were fabricated and were successfully field tested in local hospitals. Most components of the modified ventilators are compatible with existing machines. In all but a few instances, such as installation of bacteria-retentive filters and a modified venturi, the change over from non-heat-sterilizable to sterilizable units was accomplished by replacement of heat labile materials with heat stable materials.

Irons, A. S.↗

A study of the biological effect of continuous inhalation exposure of 1, 1, 1-trichloroethene (methyl chloroform) on animals

The effects of continuous exposure to 1,1,1-trichloroethane on hepatic morphology and function are evaluated and compared with those produced by methylene chloride (dichloromethane) to determine environmental concentrations of each compound that would produce a similar biological response, i.e., a comparable increase in liver triglycerides over control levels. Experimental findings on mice, rats, dogs, and monkeys indicate that the pathological alternations observed with 1,1,1-trichloroethane are similar to those observed with dichloromethane except for different time courses of the effects and different degrees of recovery. A ten fold greater atmospheric concentration of 1,1,1-trichloroethane is required to produce the minimal liver changes found at 100 ppm dichloromethane.

Macewen, J. D.↗

Hepatic pathology in mice after continuous inhalation exposure to 1, 1, 1-trichloroethane

Mice exposed to either 250ppm or 1,000ppm 1,1,1-trichloroethane in air continuously for 14 weeks demonstrated significant changes in the centrilobular hepatocytes for the 1,000ppm group. Moderate liver triglyceride accumulation was evident in the 1,000ppm group and peaked at 40mg/gm of tissue after 7 weeks of exposure. Focal hepatocyte necrosis occurred in 40% of the mice exposed to 1,000ppm for 12 weeks. This necrosis was associated with an acute inflammatory infiltrate and hypertrophy of Kupffer cells. These findings indicate that the pathological alternations observed with 1,1,1-trichloroethane are similar to those observed with dichloromethane except for different time courses of the effects and different degrees of recovery. The toxic effects of 1,1,1-trichloroethane are of a similar type to those produced by carbon tetrachloride but appear much less severe.

Mcnutt, N. S.↗

The Acute Inhalation Toxicity in Rats from the Pyrolysis Products of Four Fluoropolymers

Male Sprague-Dawley rats (225?250 g) were exposed to the thermal degradation products from four fluoropolymers. The three polymers containing vinylidene fluoride and hexafluoropropene (VF2/HFP) were pyrolyzed at 550? and 800?C, whereas polytetrafluoroethylene (PTFE) was pyrolyzed at 625 and 800?C. At the lower temperatures, the pyrolysate from the copolymer of vinylidene fluoride and hexafluoropropene (VF2/HFP) was less toxic than the pyrolysates from either the terpolymer of vinyidene fluoride, hexafluoropropene, and tetrafluoroethylene (VF2/HFP/TFE) or the copolymer of vinylidene fluoride and hexafluoropropene with ?additives? (VF2/HFP-A). However, the pyrolysates from the VF2/HFP-containing materials produced less toxic products than the pyrolysate from PTFE at 625?C. When the pyrolysis temperature was increased to 800?C, very little difference was noted between the pyrolysis toxicity for any of the VF2/HFP-containing polymers with the most toxic pyrolysate again produced by PTFE. Carbon monoxide levels were all sublethal. No correlation could be established between hydrolyzable fluoride levels and the lethality of the pyrolysates. Death following exposure occurred within 48 hr due to acute pulmonary edema and hemorrhage. Survival of this acute phase was followed by alveolar lymphocytic infiltration and peribronchial tissue proliferation.

Carter, V. L., Jr.↗