Inhalation Exposure System Research Articles

Nanoparticles-containing spray can aerosol: characterization, exposure assessment, and generator design

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 TiO2 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/m3, or 1.6 × 105 particles/cm3, with a nanoparticle fraction limited to 170 µg/m3, or 1.2 × 105 particles/cm3. The results were used to estimate the pulmonary dose in an average human (0.075 µg TiO2 per m2 alveolar epithelium per minute) and rat (0.03 µg TiO2) 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.

Ferrets develop fatal influenza after inhaling small particle aerosols of highly pathogenic avian influenza virus A/Vietnam/1203/2004 (H5N1).

BackgroundThere is limited knowledge about the potential routes for H5N1 influenza virus transmission to and between humans, and it is not clear whether humans can be infected through inhalation of aerosolized H5N1 virus particles. Ferrets are often used as a animal model for humans in influenza pathogenicity and transmissibility studies. In this manuscript, a nose-only bioaerosol inhalation exposure system that was recently developed and validated was used in an inhalation exposure study of aerosolized A/Vietnam/1203/2004 (H5N1) virus in ferrets. The clinical spectrum of influenza resulting from exposure to A/Vietnam/1203/2004 (H5N1) through intranasal verses inhalation routes was analyzed.ResultsFerrets were successfully infected through intranasal instillation or through inhalation of small particle aerosols with four different doses of Influenza virus A/Vietnam/1203/2004 (H5N1). The animals developed severe influenza encephalomyelitis following intranasal or inhalation exposure to 101, 102, 103, or 104 infectious virus particles per ferret.ConclusionsAerosolized Influenza virus A/Vietnam/1203/2004 (H5N1) is highly infectious and lethal in ferrets. Clinical signs appeared earlier in animals infected through inhalation of aerosolized virus compared to those infected through intranasal instillation.

Exposing Animals to Oxidant Gases: Nose Only vs. Whole Body

Inhalation experiments using laboratory animals are performed under controlled conditions to assess the toxicity of and to investigate interventional strategies to ameliorate injury resulting from oxidant gas exposures. A variety of dynamic inhalation exposure systems that use whole-body or nose-only exposure chambers have been developed for rodents. In a whole-body exposure chamber, the animals are immersed in the test atmosphere, whereas in nose-only or head-only exposure systems, exposures are localized primarily to the head and/or nasal regions. There are advantages and disadvantages with both types of exposure approaches. Considerations such as animal number, exposure duration, end points of study, and availability of test material should influence the selection of a particular exposure system.

Characterization of a nose-only inhalation exposure system for hydrocarbon mixtures and jet fuels

A directed-flow nose-only inhalation exposure system was constructed to support development of physiologically based pharmacokinetic (PBPK) models for complex hydrocarbon mixtures, such as jet fuels. Due to the complex nature of the aerosol and vapor-phase hydrocarbon exposures, care was taken to investigate the chamber hydrocarbon stability, vapor and aerosol droplet compositions, and droplet size distribution. Two-generation systems for aerosolizing fuel and hydrocarbons were compared and characterized for use with either jet fuels or a simple mixture of eight hydrocarbons. Total hydrocarbon concentration was monitored via online gas chromatography (GC). Aerosol/vapor (A/V) ratios, and total and individual hydrocarbon concentrations, were determined using adsorbent tubes analyzed by thermal desorption–gas chromatography–mass spectrometry (TDS-GC-MS). Droplet size distribution was assessed via seven-stage cascade impactor. Droplet mass median aerodynamic diameter (MMAD) was between 1 and 3 μm, depending on the generator and mixture utilized. A/V hydrocarbon concentrations ranged from ∼200 to 1300 mg/m3, with between 20% and 80% aerosol content, depending on the mixture. The aerosolized hydrocarbon mixtures remained stable during the 4-h exposure periods, with coefficients of variation (CV) of less than 10% for the total hydrocarbon concentrations. There was greater variability in the measurement of individual hydrocarbons in the A-V phase. In conclusion, modern analytical chemistry instruments allow for improved descriptions of inhalation exposures of rodents to aerosolized fuel.

Inhalation exposure systems for the development of rodent models of sulfur mustard-induced pulmonary injury

Sulfur mustard (SM) is a chemical threat agent for which its effects have no current treatment. Due to the ease of synthesis and dispersal of this material, the need to develop therapeutics is evident. The present manuscript details the techniques used to develop SM laboratory exposure systems for the development of animal models of pulmonary injury. These models are critical for evaluating SM injury and developing therapeutics against that injury. Iterative trials were conducted to optimize a lung injury model. The resulting pathology was used as a guide, with a goal of effecting homogeneous and diffuse lung injury comparable to that of human injury. Inhalation exposures were conducted by either nose-only inhalation or intubated inhalation. The exposures were conducted to either directly vaporized SM or SM that was nebulized from an ethanol solution. Inhalation of SM by nose-only inhalation resulted in severe nasal epithelial degeneration and minimal lung injury. The reactivity of SM did not permit it to transit past the upper airways to promote lower airway injury. Intratracheal inhalation of SM vapors at a concentration of 5400 mg · min/m3 resulted in homogeneous lung injury with no nasal degeneration.

Prenatal exposure to environmental tobacco smoke alters gene expression in the developing murine hippocampus

Background Little is known about the effects of passive smoke exposures on the developing brain. Objective The purpose of the current study was to identify changes in gene expression in the murine hippocampus as a consequence of in utero exposure to sidestream cigarette smoke (an experimental equivalent of environmental tobacco smoke (ETS)) at exposure levels that do not result in fetal growth inhibition. Methods A whole body smoke inhalation exposure system was utilized to deliver ETS to pregnant C57BL/6J mice for 6 h/day from gestational days 6–17 (gd 6–17) [for microarray] or gd 6–18.5 [for fetal phenotyping]. Results There were no significant effects of ETS exposure on fetal phenotype. However, 61 “expressed” genes in the gd 18.5 fetal hippocampus were differentially regulated (up- or down-regulated by 1.5-fold or greater) by maternal exposure to ETS. Of these 61 genes, 25 genes were upregulated while 36 genes were down-regulated. A systems biology approach, including computational methodologies, identified cellular response pathways, and biological themes, underlying altered fetal programming of the embryonic hippocampus by in utero cigarette smoke exposure. Conclusions Results from the present study suggest that even in the absence of effects on fetal growth, prenatal smoke exposure can alter gene expression during the “early” period of hippocampal growth and may result in abnormal hippocampal morphology, connectivity, and function.

Role of the Serotonergic System in Reduced Pulmonary Function after Exposure to Methamphetamine

Although use of methamphetamine (MA) by smoking is the fastest growing method of administration, very limited data are available describing the effects of smoked MA. Using a murine inhalation exposure system, we explored the pulmonary effects of low-dose acute inhalation exposure to MA vapor (smoke). Inhalation of MA vapor resulted in transiently reduced pulmonary function, as measured by transpulmonary resistance, dynamic compliance, and whole-body plethysmography compared with unexposed control animals. These changes were associated with an approximately 34% reduction in serotonin (5-hydroxytryptamine [5-HT]) metabolism/inactivation to 5-hydroxyindolacetic acid, and a nearly 40% reduction in monoamine oxidase (MAO)-A activity in the lung. Pretreatment of mice with a selective 5-HT reuptake inhibitor completely ablated the MA-induced changes in pulmonary function, confirming a key role for the 5-HT transporter (serotonin transporter [SERT]) and the serotonergic system in this effect. Immunofluorescent staining of mouse lung tissue confirmed high expression of SERT in airway epithelial cells. Using mouse airway epithelial cell line, LA-4, and purified human MAO-A, it was demonstrated that MA impedes 5-HT metabolism through direct inhibition of MAO-A activity in vitro. Together, these data demonstrate that low-dose exposure to MA results in reduced pulmonary function mediated via SERT and subsequent perturbation of 5-HT metabolism in the lung. This supports a role for the serotonergic system in MA-mediated pulmonary effects.

Evaluation of a novel inhalation exposure system to determine acute respiratory responses to tobacco and polymer pyrolysate mixtures in Swiss-Webster mice

Modern cigarette production processes are highly automated and yield millions of cigarettes per day. The forming cigarette and its components contact many different materials in the production process, some of which may leave minute residues. The potential for small inclusions of non-cigarette materials such as wood, plastic, cardboard and other materials exists from the bulk handling and processing of tobacco, in spite of vigilant workers and numerous online systems designed to keep the tobacco stream clean. Currently, there are no published methods that describe an approach to evaluate the potential toxicological impact of these non-tobacco residues and inclusions on the biological activity from exposure to the complex mixture of tobacco smoke. There are, however, many methods which describe toxicological evaluation approaches for pure materials, particularly synthetic polymers. We used the Deutsche Institute fur Normung (DIN) 53-436 tube furnace and nose-only exposure chamber in combination to conduct pilot studies in Swiss-Webster mice in order to develop a standardized methodology for the evaluation of sensory irritation and other potentially useful biological endpoints for predicting any potential hazards. Sensory and/or pulmonary irritation was assessed based on respiratory function parameters using the ASTM E981-84 method described by in mice, exposed to test atmospheres of 100% tobacco pyrolysate or tobacco/polymer pyrolysate mixtures. Other biological evaluations included respiratory function parameters, clinical signs, body weights, bronchoalveolar lavage fluid analysis, carboxyhemoglobin, blood cyanide concentrations and histopathology of the respiratory tract. These pilot studies have demonstrated that such an approach can detect biological changes resulting from exposure to unique tobacco/polymer pyrolysates. Small differences were detected in the sensory irritation responses (respiratory function), activation state of pulmonary macrophages, and histopathological findings in the nose of mice exposed to 100% tobacco or tobacco/polymer pyrolysates. Analytical measurements were also performed in order to characterize the test atmospheric changes that could occur from inclusion of the polymer into the tobacco. These included DIN-generated wet total particulate matter (TPM) DIN-Generated wet TPM (DWTPM), nicotine, cyanide, formaldehyde, acetaldehyde, acrolein, carbon monoxide, carbon dioxide, and nitrogen oxides. We attempted to correlate analyte differences in the test atmospheres with the resulting biological findings in the mice. The results demonstrated that this approach could detect minimal toxicological effects in mice exposed to test atmospheres of 100% tobacco or 70%/30% tobacco/polymer pyrolysates.

Characterization of a Nose-Only Inhalation Exposure System for Ectromelia Virus Infection of Mice

A nose-only inhalation exposure system (NOIES) was evaluated for its performance in this study using test polystyrene latex spheres (PLS) and ectromelia virus (ECTV), which is a surrogate for variola virus, the causative agent of smallpox. The test aerosol sampled at the various ports of the NOIES was found to be consistent in particle size and number concentration. ECTV bio-aerosol was delivered to A/J mice strain and the lethal dose (LD50) value at which mortality was 50% was found to be 41 PFU/mL. The airborne ECTV particles were sampled and collected on TEM grids for particle size imaging using a scanning electron microscope (SEM) and structural integrity imaging using a transmission electron microscope (TEM). SEM images of ECTV after aerosolization showed the virions to be coated with the smaller size solute particles generated from the buffer solution during the aerosolization process. TEM images showed the ECTV to be structurally intact after undergoing the process of aerosolization. From the viable ECTV particle size distribution, the geometric mean diameter (GMD) of the airborne ECTV particles was calculated to be 278 nm with a geometric standard deviation (GSD) of 1.73.

Computer controlled multi-walled carbon nanotube inhalation exposure system

Inhalation exposure systems are necessary tools for determining the dose–response relationship of inhaled toxicants under a variety of exposure conditions. The objective of this project was to develop an automated computer controlled system to expose small laboratory animals to precise concentrations of airborne multi-walled carbon nanotubes (MWCNT). An aerosol generator was developed which was capable of suspending a respirable fraction of multi-walled carbon nanotubes from bulk material. The output of the generator was used to expose small laboratory animals to constant aerosol concentrations up to 12 mg/m3. Particle distribution and morphology of the MWCNT aerosol delivered to the exposure chamber were measured and compared to samples previously taken from air inside a facility that produces MWCNT. The comparison showed the MWCNT generator was producing particles similar in size and shape to those found in a work environment. The inhalation exposure system combined air flow controllers, particle monitors, data acquisition devices, and custom software with automatic feedback control to achieve constant and repeatable exposure chamber temperature, relative humidity, pressure, aerosol concentration, and particle size distribution. The automatic control algorithm was capable of maintaining the mean aerosol concentration to within 0.1 mg/m3 of the selected target value, and it could reach 95% of the target value in less than 10 minutes during the start-up of an inhalation exposure. One of the major advantages of this system was that once the exposure parameters were selected, a minimum amount of operator intervention was required over the exposure period.

Effects of rock wool on the lungs evaluated by magnetometry and biopersistence test.

BackgroundAsbestos has been reported to cause pulmonary fibrosis, and its use has been banned all over the world. The related industries are facing an urgent need to develop a safer fibrous substance. Rock wool (RW), a kind of asbestos substitute, is widely used in the construction industry. In order to evaluate the safety of RW, we performed a nose-only inhalation exposure study in rats. After one-month observation period, the potential of RW fibers to cause pulmonary toxicity was evaluated based on lung magnetometry findings, pulmonary biopersistence, and pneumopathology.MethodsUsing the nose-only inhalation exposure system, 6 male Fischer 344 rats (6 to 10 weeks old) were exposed to RW fibers at a target fiber concentration of 100 fibers/cm3 (length [L] > 20 μm) for 6 hours daily, for 5 consecutive days. As a magnetometric indicator, 3 mg of triiron tetraoxide suspended in 0.2 mL of physiological saline was intratracheally administered after RW exposure to these rats and 6 unexposed rats (controls). During one second magnetization in 50 mT external magnetic field, all magnetic particles were aligned, and immediately afterwards the strength of their remanent magnetic field in the rat lungs was measured in both groups. Magnetization and measurement of the decay (relaxation) of this remanent magnetic field was performed over 40 minutes on 1, 3, 14, and 28 days after RW exposure, and reflected cytoskeleton dependent intracellular transport within macrophages in the lung. Similarly, 24 and 12 male Fisher 344-rats were used for biopersistence test and pathologic evaluation, respectively.ResultsIn the lung magnetometric evaluation, biopersistence test and pathological evaluation, the arithmetic mean value of the total fiber concentration was 650.2, 344.7 and 390.7 fibers/cm3, respectively, and 156.6, 93.1 and 95.0 fibers/cm3 for fibers with L > 20 μm, respectively. The lung magnetometric evaluation revealed that impaired relaxation indicating cytoskeletal toxicity did not occur in the RW exposure group. In addition, clearance of the magnetic tracer particles was not significantly affected by the RW exposure. No effects on lung pathology were noted after RW exposure.ConclusionThese findings indicate that RW exposure is unlikely to cause pulmonary toxicity within four weeks period. Lung magnetometry studies involving long-term exposure and observation will be necessary to ensure the safety of RW.

Design and performance of a system for blood collection of rats under whole-body inhalation exposure

In order to obtain basic risk assessment data on human health exposure to volatile organic compound (VOC) vapor by inhalation, a whole-body inhalation exposure system which allows blood collection during the exposure period was designed. The system was tested using chloroform as a model VOC. Chloroform vapor, sampled from the supply-header, animal-chambers and exhaust-header, remained constant in this system with variations in its concentration being less than 2%; flow rate of the vapor through the system was also constant. Rats were exposed to chloroform vapor and blood collected from the tail during exposure to the chloroform vapor. The chloroform concentration in the blood increased during the initial 60 min of exposure, and afterwards its concentration remained at about 2 microg/ml from 60 to 360 min. In conclusion, our design allows blood to be collected from individual rats during exposure by inhalation to test VOCs and changes in the blood concentration of the VOC during exposure to be assessed.

Inhalation of tobacco smoke induces increased proliferation of urinary bladder epithelium and endothelium in female C57BL/6 mice

Cigarette smoking is the major environmental risk factor for bladder cancer in humans. Aromatic amines, potent DNA-reactive bladder carcinogens present in cigarette smoke, contribute significantly. However, increased cell proliferation, caused by direct mitogenesis or in response to cytotoxicity, may also play a role since urothelial hyperplasia has been observed in human cigarette smokers. We examined the urothelial effects of cigarette smoke (whole body inhalation exposure (Teague) system) in female C57BL/6 mice at various times in two studies, including reversibility evaluations. In both studies, no urothelial hyperplasia was observed by light microscopy in any group. However, in study 1, the Ki-67 labeling index (LI) of the urothelium was significantly increased in the smoke exposed group compared to controls through 3 months, but was not present at 6, 9 or 12 months even with continued exposures. In the groups that discontinued smoke exposure, it returned to the same levels as controls or lower. In study 2, the bromodeoxyuridine LI was similar to controls on day 1 but significantly increased at 5 days in the smoke exposed group. In the group that discontinued smoke exposure for 2 days, the LI was increased compared to controls but not significantly. Superficial urothelial cell cytotoxicity and necrosis were detectable by scanning electron microscopy at 5 days. Changes in LI of submucosal endothelial cells generally followed those of the urothelium and effects were reversible upon cessation of exposure. The increased urothelial proliferation appeared to be due to superficial cell cytotoxicity with consequent regeneration.

Inhalation Exposure Systems: Design, Methods and Operation

The respiratory system, the major route for entry of oxygen into the body, provides entry for external compounds, including pharmaceutic and toxic materials. These compounds (that might be inhaled under environmental, occupational, medical, or other situations) can be administered under controlled conditions during laboratory inhalation studies. Inhalation study results may be controlled or adversely affected by variability in four key factors: animal environment; exposure atmosphere; inhaled dose; and individual animal biological response. Three of these four factors can be managed through engineering processes. Variability in the animal environment is reduced by engineering control of temperature, humidity, oxygen content, waste gas content, and noise in the exposure facility. Exposure atmospheres are monitored and adjusted to assure a consistent and known exposure for each animal dose group. The inhaled dose, affected by changes in respiration physiology, may be controlled by exposure-specific monitoring of respiration. Selection of techniques and methods for the three factors affected by engineering allows the toxicologic pathologist to study the reproducibility of the fourth factor, the biological response of the animal.

Generation and Characterization of Hardwood Smoke Inhalation Exposure Atmospheres

An inhalation exposure system and operating protocol were developed that resulted in consistent achievement of targeted exposure concentrations of hardwood smoke without compromising the desire to include multiple phases of a burn cycle. A conventional, noncatalyzed stove was operated in a temperature-controlled room with a three-phase (kindling, high burn, and low burn) cycle. Equally sized wood of similar moisture content was loaded in a consistent fashion each day of the study. A stable and controllable dilution system was employed that involved simultaneous withdrawal of smoke from a primary dilution tunnel. Exposure operators utilized real-time measurements of particulate matter (PM), CO, and stove temperature, along with operational experience, to gauge when adjustments to dilution air or the firebox were necessary. Dilutions of smoke were controlled in four separate inhalation atmospheres with daily average particle mass concentrations of 30, 100, 300, and 1000 μg/m3. Each of these atmospheres was ...

Design, Construction, and Characterization of a Novel Robotic Welding Fume Generator and Inhalation Exposure System for Laboratory Animals

Respiratory effects observed in welders have included lung function changes, metal fume fever, bronchitis, and a possible increase in the incidence of lung cancer. Many questions remain unanswered regarding the causality and possible underlying mechanisms associated with the potential toxic effects of welding fume inhalation. The objective of the present study was to construct a completely automated, computer-controlled welding fume generation and inhalation exposure system to simulate real workplace exposures. The system comprised a programmable six-axis robotic welding arm, a water-cooled arc welding torch, and a wire feeder that supplied the wire to the torch at a programmed rate. For the initial studies, gas metal arc welding was performed using a stainless steel electrode. A flexible trunk was attached to the robotic arm of the welder and was used to collect and transport fume from the vicinity of the arc to the animal exposure chamber. Undiluted fume concentrations consistently ranged from 90–150 mg/m3 in the animal chamber during welding. Temperature and humidity remained constant in the chamber during the welding operation. The welding particles were composed of (from highest to lowest concentration) iron, chromium, manganese, and nickel as measured by inductively coupled plasma atomic emission spectroscopy. Size distribution analysis indicated the mass median aerodynamic diameter of the generated particles to be approximately 0.24 μm with a geometric standard deviation (σ g ) of 1.39. As determined by transmission and scanning electron microscopy, the generated aerosols were mostly arranged as chain-like agglomerates of primary particles. Characterization of the laboratory-generated welding aerosol has indicated that particle morphology, size, and chemical composition are comparable to stainless steel welding fume generated in other studies. With the development of this novel system, it will be possible to establish an animal model using controlled welding exposures from automated gas metal arc and flux-cored arc welding processes to investigate how welding fumes affect health.

Development of an animal model to study the potential neurotoxic effects associated with welding fume inhalation

Serious questions have been raised regarding a possible causal association between neurological effects in welders and the presence of manganese in welding fume. An experimental model is needed that could examine the potential neurotoxic effect of manganese after pulmonary exposure to welding fume. The National Institute for Occupational Safety and Health (NIOSH) has recently finished construction of a completely automated, computer controlled welding fume generation and inhalation exposure system for laboratory animals. The system is comprised of a programmable six-axis robotic welding arm and a water-cooled arc welding torch. A flexible trunk has been attached to the robotic arm of the welder and is used to collect and transport fume from the vicinity of the arc to the animal exposure chamber. Preliminary fume characterization studies have indicated that particle morphology, size, and chemical composition were comparable to welding fume generated in the workplace. Animal inhalation studies are currently underway. With the development of this novel system, an animal model has been established using controlled welding exposures to investigate the possible mechanisms by which welding fume may affect the central nervous system.

The automated bioaerosol exposure system: Preclinical platform development and a respiratory dosimetry application with nonhuman primates

Introduction: Well-characterized inhalation exposure systems are critical for preclinical testing and pathogenesis studies. The automated bioaerosol exposure system (ABES) provides a microprocessor-driven inhalation platform that provides exquisite data acquisition and control over all aspects of inhalation exposures. Because this represents a new technology, the development and characteristics of the ABES are thoroughly discussed. In addition to control over homeostatic and aerosol conditions, the ABES incorporates a dosimetry function based on respiratory performance of the test animal during inhalation. Methods: To test the system, rhesus macaques were initially sham-exposed using the ABES in a head-only inhalation configuration. The ABES was subsequently used under biosafety level (BSL)-III conditions in a vaccine efficacy challenge using aerosolized staphylococcal enterotoxin B (SEB) toxin, again using the real-time dosimetry function of the system. Results: Sham exposure results indicated significant departures from corresponding whole-body plethysmography (WBP) respiratory function estimates taken before the inhalation procedure. The results of the SEB exposure demonstrated the utility of using the ABES to generate consistently accurate and precise inhalation dose. Discussion: Taken together, the results of the sham and toxin challenge experiments demonstrate that the dosimetry function of the ABES improves the precision and accuracy of inhaled dose delivery and calculation as compared to predictive WBP conducted before the exposure. The ABES represents a highly adaptable platform for the design of inhalation systems to suit the requirements of a variety of animal models.

Automated Feedback Control of an Inhalation Exposure System with Discrete Sampling Intervals: Testing, Performance, and Modeling

The application of a proportional-integral-derivative (PID) control algorithm to an inhalation exposure system using a building automation system is described. Previous studies had utilized a control system in which concentration was monitored continuously and adjustments to the generator were made on a continuous basis. In this system, benzene vapor was generated into a chamber, and a gas chromatograph was used to measure the concentration in a chamber at discrete 30-min intervals. Thus only limited opportunities were available to sample and adjust the vapor generator flow rate. A series of tests were conducted in which the generator was operated without control, with control, with an additional load, and with nonoptimal settings. The results showed that the PID control loop could function effectively to restore a system back to the target set point, even with an additional load on the system. With nonoptimal control settings, the system showed oscillatory behavior. A model to simulate operation of the chamber was developed on a spreadsheet program. The model was accurate at simulating the various testing scenarios and useful for selecting the proper control settings. A PID feedback control system operating with a concentration monitoring system that sampled on a 30-min cycle was shown to produce exposures that were accurate in matching the target set point and maintaining a constant concentration.

Automated Feedback Control of an Inhalation Exposure System with Discrete Sampling Intervals: Testing, Performance, and Modeling

The application of a proportional-integral-derivative (PID) control algorithm to an inhalation exposure system using a building automation system is described. Previous studies had utilized a control system in which concentration was monitored continuously and adjustments to the generator were made on a continuous basis. In this system, benzene vapor was generated into a chamber, and a gas chromatograph was used to measure the concentration in a chamber at discrete 30-min intervals. Thus only limited opportunities were available to sample and adjust the vapor generator flow rate. A series of tests were conducted in which the generator was operated without control, with control, with an additional load, and with nonoptimal settings. The results showed that the PID control loop could function effectively to restore a system back to the target set point, even with an additional load on the system. With nonoptimal control settings, the system showed oscillatory behavior. A model to simulate operation of the chamber was developed on a spreadsheet program. The model was accurate at simulating the various testing scenarios and useful for selecting the proper control settings. A PID feedback control system operating with a concentration monitoring system that sampled on a 30-min cycle was shown to produce exposures that were accurate in matching the target set point and maintaining a constant concentration.