Inhalation Exposure System Research Articles

A Nose-Only Inhalation Exposure System for Generation, Treatment and Characterization of Formaldehyde Vapor

A description of a novel symmetrical nose-only inhalation chamber for small animals is presented. The chamber utilizes a circular design and a round baffle plate around which the test atmosphere is evenly drawn in order to expose each symmetrically placed animal port to equivalent gas concentrations without exposing animals to each other's expired gases. The nose-only mode may be more suitable for inhalation exposures as compared to whole-body exposures which allow skin contamination and possible aerosol ingestion through preening habits. Evidence is presented that nose-only exposure which requires animal restraint is no more stressful than freely-caged exposure as measured by total peripheral white blood cell counts and the ease of animal entry into the restraining tubes. Applications of the exposure system are described for the case of pure formaldehyde vapor generation. The method of formaldehyde generation entails heating solid paraformaldehyde polymer in a mineral oil bath and diluting with filtered ...

A Nose-Only Inhalation Exposure System for Generation, Treatment and Characterization of Formaldehyde Vapor

A description of a novel symmetrical nose-only inhalation chamber for small animals is presented. The chamber utilizes a circular design and a round baffle plate around which the test atmosphere is evenly drawn in order to expose each symmetrically placed animal port to equivalent gas concentrations without exposing animals to each other's expired gases. The nose-only mode may be more suitable for inhalation exposures as compared to whole-body exposures which allow skin contamination and possible aerosol ingestion through preening habits. Evidence is presented that nose-only exposure which requires animal restraint is no more stressful than freely-caged exposure as measured by total peripheral white blood cell counts and the ease of animal entry into the restraining tubes. Applications of the exposure system are described for the case of pure formaldehyde vapor generation. The method of formaldehyde generation entails heating solid paraformaldehyde polymer in a mineral oil bath and diluting with filtered room air. The temperature of the paraformaldehyde is exponentially related to the concentration of formaldehyde generated. The standard NIOSH method of chromatropic acid analysis for formaldehyde requires modification for higher formaldehyde concentrations and system flow rates. A 2-liter impinger collects >95% of the formaldehyde generated at concentrations up to 100 ppm and flowrates of 15 liters per minute. Efficacy of the overall system in terms of maintenance of desired concentrations is described. A comparison of desired concentrations and measured concentrations is presented for four groups of rats exposed to formaldehyde vapor from 2 to 100 ppm.

Effect of cigarette smoking on experimental microvascular anastomoses.

Cigarette smoking has been shown to cause cutaneous vasoconstriction, a decrease in digital blood flow, impaired wound healing, and it was implicated as a cause of failure of microvascular anastomoses in replanted digits. The subject of the following study was to assess the effect of cigarette smoking on experimental microvascular anastomoses. Twenty Sprague-Dawley male rats weighting 200 to 250 grams were divided into groups of ten. Both the experimental and the control groups were acclimatized to a Maddox/ORNL rat smoke inhalation exposure system for six days prior to operation. At this time they were anesthetized and bilateral femoral artery end to end anastomoses were performed by two surgeons, using standard microsurgical techniques. After a recovery period of 24 hours, both groups were started on a smoking/sham-smoking regime for 12 to 13 days. After this time they were anesthetized again, the femoral artery anastomoses were checked for patency in vivo and excised for histological evaluation. Five cm3 of blood was drawn from each animal to be analyzed for the presence of nicotine and its metabolites, and the rats were sacrificed. All the anastomoses in both groups were patent at the time of exploration and no histological difference could be demonstrated between the two groups. The radioimmunoassay of nicotine and cotinine showed large amounts in the smokers, and none in the nonsmokers.

Effect of Equilibration Zones on Stability, Uniformity, and Homogeneity Profiles of Vapors and Aerosols in the ADG Nose-Only Inhalation Exposure System

Effect of Equilibration Zones on Stability, Uniformity, and Homogeneity Profiles of Vapors and Aerosols in the ADG Nose-Only Inhalation Exposure System

Retention and dosimetry of 106Ru inhaled along with inert particles by Fischer-344 rats.

This study was done to provide data useful for predicting the deposition, retention and radiation dose patterns for humans who might be exposed to an aerosol containing 106RuO4 and respirable particles. Ruthenium-106 tetroxide was introduced into air containing inert particles. The inert particles were monodisperse. 0.69 micrometer diameter fused aluminosilicate and very small residue particles from nebulized droplets. A complex exposure atmosphere resulted. In addition to condensation of 106RuO4 on pre-existing particles, self-nucleation occurred, presumably resulting from the formation of RuO2. It appears there was a significant amount of 106RuO4 present in the inhalation exposure system. When a group of Fischer-344 rats inhaled this exposure atmosphere, approx. 12% of the initial body burden reached the pulmonary region of the respiratory tract. Of the remaining 88% of the initial burden, 60% was deposited in the upper respiratory tract, 10% in the tracheobronchial region and 18% was external contamination, primarily on the nares and head skin. Most of the initial body burden was cleared via the gastrointestinal system and excreted via feces. Clearance of 106Ru from the pulmonary region had an effective half-time of approx. 30 days and was predominantly by dissolution. Relative radiation doses accumulated to 100 days after inhalation exposure, normalized to a lung dose of 1.0, were nasopharyngeal mucosa, 11; trachea and larynx, 5; lower large intestine, 5; upper large intestine, 2; liver, 0.9; and kidneys, 0.9. Other tissues and organs received lesser relative doses. Comparable results are predicted for man inhaling a similar exposure atmosphere, which could be encountered under certain circumstances in nuclear industry operations.

Time-varying concentration profile as a determinant of the inhalation toxicity of carbon tetrachloride.

Certain limitations on the flexibility of small-animal inhalation exposure systems are overcome by the machine control and monitoring of the concentration of the gas or vapor of interest. Computer assistance of chamber operation allows the user to simulate time-varying concentration profiles accurately and repeatedly. We exposed rats to seven different profiles in which the maximum concentration of carbon tetrachloride (CCl4) was 1500 ppm and the product of concentration times time (C X T) was 4500 ppm X h. The purpose was to determine the effects of systematically varying the shape of the concentration profile on the expression of hepatotoxicity of a chemical about which much was already known. All of the exposures were conducted within a span of 6 h. Examination of the severity of vacuolation and pattern of necrosis could be used to distinguish some of the exposure profiles from others. For example, vacuolation was less severe when two equal pulses were presented with an interval of 60 min, rather than 180-240 min. The indexes of necrosis varied in a more complex way, and the differences among the profiles that accounted for the differences in the patterns of the histopathological changes were not immediately apparent. We concluded that the characteristic of a time-related variation in concentration is one of the determinants of the inhalation hepatotoxicity of CCl4 and that the simple, time-weighted, average concentration may not always fairly represent the best model for the study of problems in inhalation toxicology.

Fate of inhaled hexachlorocyclopentadiene in albino rats and comparison to the oral and IV routes of administration

Hexachlorocyclopentadiene (C56) is extremely toxic when inhaled by rats, but only moderately toxic when administered orally. The difference in toxicity as a function of route of exposure was studied by determining the absorption, distribution, and ultimate fate of C56 following acute oral, inhalation, and iv exposure. For rats treated with a single oral dose (5 μg/kg) of 14C-C56, radiocarbon was primarily excreted in the 0–72 hr feces (68.2%). Animals treated with equivalent inhaled and iv doses eliminated 23.1 and 31.4% of the dose in the 0–72 hr feces, respectively. Urinary radiocarbon was equivalent to 24.4, 23.1, and 31.4% of the dose for oral, inhalation and iv treatments, respectively. Biliary excretion following all exposure routes was between 9 and 18% of the dose, indicating that the large amount of radiocarbon in the feces of orally treated rats was due to poor absorption of C56 from the gastrointestinal tract. For all exposure routes, the lungs appeared to be a major site of C56 toxicity upon post-mortem examination. This study suggests that the direct damage to lung tissue by inhaled C56 and low bioavailability of orally administered C56 contribute substantially to the difference in toxicity between oral and inhalation exposure to C56. A recently developed inhalation exposure system which allows quantitative administration of toxicant vapors to rats is also described in this report.

Design, construction and operation of a simple inhalation exposure system

An inhalation exposure system was designed from an all glass aquarium with a volume of 391 liters. A top for the chamber was fabricated from acrylic plastic and Teflon ê (surface in contact with the test atmosphere) with an inlet, outlet, 5 sampling ports, and handles. Supply air to the chamber was charcoal and HEPA filtered. Air flow through the chamber is horizontal and can range from 50 to 200 liters/minute. Air flow is measured by a glass tube rotameter and regulated by polyvinyl chloride valves. Chamber air was HEPA and charcoal filtered prior to exhausting it to ambient air. The operating characteristics of this exposure system were assessed using test atmospheres of formaldehyde, chlorine, n-hexane and an aerosol of propylene glycol. Expressed as percent of a central sampling point the chamber concentrations of formaldehyde, chlorine and n-hexane ranged from 91.6% to 103.3% with an average of 97.9%. No differences in chamber distribution were noted at 78 or 130 liters/minute (corresponding to 12 and 20 chamber volumes/hour). For propylene glycol, the mass median aerodynamic diameter (MMAD) at a chamber air flow of 79 L/minute varied from 1.37 to 1.63 μm (σg range 1.34 to 1.43). Similar results were found at 130 liters/minute. During mass sampling a concentration gradient was found from the inlet to the outlet of the chamber and ranged from 55 to 99% (¯x = 78.5%) of the inlet concentration. This inhalation exposure system is very suitable for acute or sub-acute inhalation studies of gases or vapors but is only satisfactory for aerosols under certain operating conditions. It should prove to be particularly useful for laboratories wishing to set up a modest inhalation toxicology facility.

Design, Construction and Operation of a Simple Inhalation Exposure System

Design, Construction and Operation of a Simple Inhalation Exposure System. Barrow, Craig S. and Steinhagen, William H. (1982). Fundam. Appl. Toxicol. 2:33–37. An inhalation exposure system was designed from an all glass aquarium with a volume of 391 liters. A top for the chamber was fabricated from acrylic plastic and Teflon® (surface in contact with the test atmosphere) with an inlet, outlet, 5 sampling ports, and handles. Supply air to the chamber was charcoal and HEPA filtered. Air flow through the chamber is horizontal and can range from 50 to 200 liters/minute. Air flow is measured by a glass tube rotameter and regulated by polyvinyl chloride valves. Chamber air was HEPA and charcoal filtered prior to exhausting it to ambient air. The operating characteristics of this exposure system were assessed using test atmospheres of formaldehyde, chlorine, n-hexane and an aerosol of propylene glycol. Expressed as percent of a central sampling point the chamber concentrations of formaldehyde, chlorine and n-hexane ranged from 91.6% to 103.3% with an average of 97.9%. No differences in chamber distribution were noted at 78 or 130 liters/minute (corresponding to 12 and 20 chamber volumes/hour). For propylene glycol, the mass median aerodynamic diameter (MMAD) at a chamber air flow of 79 L/minute varied from 1.37 to 1.63 μm(σg range 1.34 to 1.43). Similar results were found at 130 liters/minute. During mass sampling a concentration gradient was found from the inlet to the outlet of the chamber and ranged from 55 to 99% (⁠x¯ = 78.5%) of the inlet concentration. This inhalation exposure system is very suitable for acute or sub-acute inhalation studies of gases or vapors but is only satisfactory for aerosols under certain operating conditions. It should prove to be particularly useful for laboratories wishing to set up a modest inhalation toxicology facility.

Fate of Inhaled Hexachlorocyclopentadiene in Albino Rats and Comparison to the Oral and IV Routes of Administration

Fate of Inhaled Hexachlorocyclopentadiene in Albino Rats and Comparison to Oral and IV Routes of Administration. Lawrence, L. Jeffrey and Dorough, H. Wyman (1982). Fundam. Appl. Toxicol. 2:235-240. Hexachlorocyclopentadiene (C56) is extremely toxic when inhaled by rats, but only moderately toxic when administered orally. The difference in toxicity as a function of route of exposure was studied by determining the absorption, distribution, and ultimate fate of C56 following acute oral, inhalation, and iv exposure. For rats treated with a single oral dose (5 μg/kg) of 14C-C56, radiocarbon was primarily excreted in the 0-72 hr feces (68.2%). Animals treated with equivalent inhaled and iv doses eliminated 23.1 and 31.4% of the dose in the 0-72 hr feces, respectively. Urinary radiocarbon was equivalent to 24.4, 23.1, and 31.4% of the dose for oral, inhalation and iv treatments, respectively. Biliary excretion following all exposure routes was between 9 and 18% of the dose, indicating that the large amount of radiocarbon in the feces of orally treated rats was due to poor absorption of C56 from the gastrointestinal tract. For all exposure routes, the lungs appeared to be a major site of C56 toxicity upon postmortem examination. This study suggests that the direct damage to lung tissue by inhaled C56 and low bioavailability of orally administered C56 contribute substantially to the difference in toxicity between oral and inhalation exposure to CS6. A recently developed inhalation exposure system which allows quantitative administration of toxicant vapors to rats is also described in this report.

A system for nose-only inhalation exposures of small animals to 106RuO 4

Ruthenium-106 and 103Ru are major fission products with high probability of release as RuO 4. Ruthenium tetroxide exists as a vapor, diffuses rapidly through air and porous barriers, and is rapidly reduced to the dioxide form by an organic material. It was necessary to design production and animal inhalation exposure systems that would minimize reduction of RuO 4 during the production and the exposures. Ruthenium-106 tetroxide was produced in an all-glass generating system by oxidizing 106RuCl 3 to 106RuO 4. This was collected in glass flasks cooled by dry ice. The crystalline 106RuO 4 was subsequently sublimated and passed into an all-glass exposure system for the nose-only inhalation exposure of rats to the 106 RuO 4 vapor. The 106RuO 4 inhaled by rats was deposited mainly on the external nares and in the upper respiratory tract. The initial body burdens ranged from 4.1 to 15 μCi and the initial lung burdens ranged from 0.05 to 0.4 μCi when 250 μCi of 106Ru were sublimated. No releases of 106RuO 4 to the laboratory environment occurred during the use of this system.

Microprocessor-controlled inhalation system for repeated exposure of animals to aerosols

A microprocessor-controlled inhalation exposure system (MCIES) has been built to automate aerosol generation and sampling while controlling exposure time for animal toxicity studies. The system has a time resolution of 0.1 s and automatically sequences the exposure events from initiation to temination of the exposure. The operator is required to preset all airflows, read in a paper tape containing the time sequence of events, and initiate the automatic sequence by closing a switch.

Sensor for Detection of Tobacco Smoke Particulates in Inhalation Exposure Systems

AbstractA commercially available light emitting diode/phototransistor array was investigated for detection and analysis of tobacco smoke in the Walton Horizontal Smoking Machine (WHSM) animal inhalation exposure system. The diode element of the device emits light into the smoke aerosol, and light back-scattered by the smoke particles is detected by the phototransistor element. The sensor provides a continuous, nearly instantaneous graphicaI visualization of smoke particulates in the immediate vicinity of the array. Experimental studies showed that sensor readout is Iinearly related to smoke particulate concentration of the smoke and is independent of the composition of the smoke. Smoke particle agglomeration associated with aging of smoke causes observable but minor changes in sensor response.

Principles for inhalation exposure systems using concurrent flow spirometry

Principles are given for the design and operation of a new class of inhalation exposure systems using concurrent flow spirometry (CFS), a simple method for providing realtime measurement of respiratory volumes and rates during inhalation exposure by mouth or nose of individual experimental animals or man to known concentrations of aerosols or gases. No reciprocating valves are required because the rate of flow of gas or aerosol that is offered to the animal exceeds its maximum exhalation flow rate by a sufficient margin. This technique is especially useful for inhalation exposure of larger experimental animals, such as horses, where whole body plethysmography is usually impractical. Difficulties encountered with conventional exposure systems in maintenance of uniform aerosol or gas concentrations and in prevention of large pressure excursions in the exposure chamber during breathing of subject are obviated by systems using CFS. Deposition of inhaled material in the animal must be determined by in vivo measurements of radioactive labels rather than by comparing inhaled and exhaled concentrations. Two exposure units with CFS are described: one for Beagle dogs and one for ponies.