Deposition of graphene nanomaterial aerosols in human upper airways.

Graphene nanomaterials have attracted wide attention in recent years on their application to state-of-the-art technology due to their outstanding physical properties. On the other hand, the nanotoxicity of graphene materials also has rapidly become a serious concern especially in occupational health. Graphene naomaterials inevitably could become airborne in the workplace during manufacturing processes. The inhalation and subsequent deposition of graphene nanomaterial aerosols in the human respiratory tract could potentially result in adverse health effects to exposed workers. Therefore, investigating the deposition of graphene nanomaterial aerosols in the human airways is an indispensable component of an integral approach to graphene occupational health. For this reason, this study carried out a series of airway replica deposition experiments to obtain original experimental data for graphene aerosol airway deposition. In this study, graphene aerosols were generated, size classified, and delivered into human airway replicas (nasal and oral-to-lung airways). The deposition fraction and deposition efficiency of graphene aerosol in the airway replicas were obtained by a novel experimental approach. The experimental results acquired showed that the fractional deposition of graphene aerosols in airway sections studied were all less than 4%, and the deposition efficiency in each airway section was generally lower than 0.03. These results indicate that the majority of the graphene nanomaterial aerosols inhaled into the human respiratory tract could easily penetrate through the head airways as well as the upper part of the tracheobronchial airways and then transit down to the lower lung airways, where undesired biological responses might be induced.

Carbon nanotubes size classification, characterization and nasal airway deposition.

Workers and researchers in the carbon nanotubes (CNT)-related industries and laboratories might be exposed to CNT aerosols while generating and handling CNT materials. From the viewpoint of occupational health, it is essential to study the deposition of CNT aerosol in the human respiratory tract to investigate the potential adverse health effects. In this study, a human nasal airway replica and two types of CNT materials were employed to conduct CNT nasal airway deposition studies. The two CNT materials were aerosolized by a nebulizer-based wet generation method, with size classified by three designated classification diameters (51, 101 and 215 nm), and then characterized individually in terms of their morphology and aerodynamic diameter. The nasal deposition experiments were carried out by delivering the size classified CNTs into the nasal airway replica in three different inspiratory flow rates. From the characterization study, it showed that the morphology of the size classified CNTs could be in a variety of complex shapes with their physical dimension much larger than their classification diameter. In addition, it was found that the aerodynamic diameters of the classified CNTs were slightly smaller than their classification diameter. The nasal deposition data acquired in this study showed that the deposition efficiency of CNTs in the nasal airway were generally less than 0.1, which implies that the majority of the CNTs inhaled into the nose could easily penetrate through the entire nasal airway and transit further down to the lower airways, possibly causing adverse health effects.

Mechanisms of pharmaceutical aerosol deposition in the respiratory tract.

Aerosol delivery is noninvasive and is effective in much lower doses than required for oral administration. Currently, there are several types of therapeutic aerosol delivery systems, including the pressurized metered-dose inhaler, the dry powder inhaler, the medical nebulizer, the solution mist inhaler, and the nasal sprays. Both oral and nasal inhalation routes are used for the delivery of therapeutic aerosols. Following inhalation therapy, only a fraction of the dose reaches the expected target area. Knowledge of the amount of drug actually deposited is essential in designing the delivery system or devices to optimize the delivery efficiency to the targeted region of the respiratory tract. Aerosol deposition mechanisms in the human respiratory tract have been well studied. Prediction of pharmaceutical aerosol deposition using established lung deposition models has limited success primarily because they underestimated oropharyngeal deposition. Recent studies of oropharyngeal deposition of several drug delivery systems identify other factors associated with the delivery system that dominates the transport and deposition of the oropharyngeal region. Computational fluid dynamic simulation of the aerosol transport and deposition in the respiratory tract has provided important insight into these processes. Investigation of nasal spray deposition mechanisms is also discussed.

Thoracic fraction of inhaled fiber aerosol.

Size-selective sampling is a health-related method to collect airborne particles based on penetration of inhaled particles into different regions of the human respiratory tract; thus, it is the most relevant sampling method to correlate health risks with occupational exposure. The current practice of sampling asbestos and other fibers is not a size-selective method. The thoracic size fraction, defined as the portion of inhaled particles that can penetrate through the larynx, has been suggested as the most relevant size-selective sampling method for fiber aerosol. The thoracic fraction is based on 1-deposition of inhaled spherical particles in the human extrathoracic airways for mouth breathing and corrected for the particle inhalability. There is no comparable information for fiber aerosols; therefore, there is no technical basis to ascertain whether the current thoracic fraction definition is suitable for fiber aerosols. No human data are available from controlled experiments of inhaled fiber aerosols for the obvious reason that most fiber materials are potentially hazardous when inhaled. Our approach was to measure penetration of fiber aerosol in realistic human oropharyngeal airway replicas and to compare that with data from spherical particles. We showed that realistic human oral airway replicas (including the oral cavity, pharynx, and larynx regions) provided useful spherical and fiber particle deposition in the human head airway. These data could be used to test the thoracic fraction curves. The spherical penetration is in agreement with human in vivo data used to establish the thoracic fraction curve. Fiber penetrations through the larynx of two human oral airway replicas were higher than those for spherical particles for the same aerodynamic diameter using the same replicas. The thoracic curve as defined for spherical particles, therefore, may not include some fibers that could penetrate to the thoracic region.

Novel active personal nanoparticle sampler for the exposure assessment of nanoparticles in workplaces.

A novel active personal nanoparticle sampler (PENS), which enables the collection of both respirable particulate mass (RPM) and nanoparticles (NPs) simultaneously, was developed to meet the critical demand for personal sampling of engineered nanomaterials (ENMs) in workplaces. The PENS consists of a respirable cyclone and a micro-orifice impactor with the cutoff aerodynamic diameter (d(pa50)) of 4 µm and 100 nm, respectively. The micro-orifice impactor has a fixed micro-orifice plate (137 nozzles of 55 µm in the inner diameter) and a rotating, silicone oil-coated Teflon filter substrate at 1 rpm to achieve a uniform particle deposition and avoid solid particle bounce. A final filter is used after the impactor to collect the NPs. Calibration results show that the d(pa50) of the respirable cyclone and the micro-orifice impactor are 3.92 ± 0.22 µm and 101.4 ± 0.1 nm, respectively. The d(pa50) at the loaded micro-Al(2)O(3) mass of 0.36-3.18 mg is shifted to 102.9-101.2 nm, respectively, while it is shifted to 98.9-97.8 nm at the loaded nano-TiO(2) mass of 0.92-1.78 mg, respectively. That is, the shift of d(pa50) due to solid particle loading is small if the PENS is not overloaded. Both NPs and RPM concentrations were found to agree well with those of the IOSH respirable cyclone and MOUDI. By using the present PENS, the collected samples can be further analyzed for chemical species concentrations besides gravimetric analysis to determine the actual exposure concentrations of ENMs in both RPM and NPs fractions in workplaces, which are often influenced by the background or incident pollution sources.

A wind tunnel test of newly developed personal bioaerosol samplers.

In this study the performance of two newly developed personal bioaerosol samplers was evaluated. The two test samplers are cyclone-based personal samplers that incorporate a recirculating liquid film. The performance evaluations focused on the physical efficiencies that a personal bioaerosol sampler could provide, including aspiration, collection, and capture efficiencies. The evaluation tests were carried out in a wind tunnel, and the test personal samplers were mounted on the chest of a full-size manikin placed in the test chamber of the wind tunnel. Monodisperse fluorescent aerosols ranging from 0.5 to 20 microm were used to challenge the samplers. Two wind speeds of 0.5 and 2.0 m/sec were employed as the test wind speeds in this study. The test results indicated that the aspiration efficiency of the two test samplers closely agreed with the ACGIH inhalable convention within the size range of the test aerosols. The aspiration efficiency was found to be independent of the sampling orientation. The collection efficiency acquired from these two samplers showed that the 50% cutoff diameters were both around 0.6 microm. However the wall loss of these two test samplers increased as the aerosol size increased, and the wall loss of PAS-4 was considerably higher than that of PAS-5, especially in the aerosol size larger than 5 microm, which resulted in PAS-4 having a relatively lower capture efficiency than PAS-5. Overall, the PAS-5 is considered a better personal bioaerosol sampler than the PAS-4.

Evaluation of physical sampling efficiency for cyclone-based personal bioaerosol samplers in moving air environments.

The need to determine occupational exposure to bioaerosols has notably increased in the past decade, especially for microbiology-related workplaces and laboratories. Recently, two new cyclone-based personal bioaerosol samplers were developed by the National Institute for Occupational Safety and Health (NIOSH) in the USA and the Research Center for Toxicology and Hygienic Regulation of Biopreparations (RCT & HRB) in Russia to monitor bioaerosol exposure in the workplace. Here, a series of wind tunnel experiments were carried out to evaluate the physical sampling performance of these two samplers in moving air conditions, which could provide information for personal biological monitoring in a moving air environment. The experiments were conducted in a small wind tunnel facility using three wind speeds (0.5, 1.0 and 2.0 m s(-1)) and three sampling orientations (0°, 90°, and 180°) with respect to the wind direction. Monodispersed particles ranging from 0.5 to 10 µm were employed as the test aerosols. The evaluation of the physical sampling performance was focused on the aspiration efficiency and capture efficiency of the two samplers. The test results showed that the orientation-averaged aspiration efficiencies of the two samplers closely agreed with the American Conference of Governmental Industrial Hygienists (ACGIH) inhalable convention within the particle sizes used in the evaluation tests, and the effect of the wind speed on the aspiration efficiency was found negligible. The capture efficiencies of these two samplers ranged from 70% to 80%. These data offer important information on the insight into the physical sampling characteristics of the two test samplers.

Aerosolized Red Tide Toxins (Brevetoxins) and Asthma: Continued health effects after 1 hour beach exposure.

Blooms of the toxic dinoflagellate, Karenia brevis, produce potent neurotoxins in marine aerosols. Recent studies have demonstrated acute changes in both symptoms and pulmonary function in asthmatics after only 1 hour of beach exposure to these aerosols. This study investigated if there were latent and/or sustained effects in asthmatics in the days following the initial beach exposure during periods with and without an active Florida red tide.Symptom data and spirometry data were collected before and after 1 hour of beach exposure. Subjects kept daily symptom diaries and measured their peak flow each morning for 5 days following beach exposure. During non-exposure periods, there were no significant changes in symptoms or pulmonary function either acutely or over 5 days of follow-up. After the beach exposure during an active Florida red tide, subjects had elevated mean symptoms which did not return to the pre-exposure baseline for at least 4 days. The peak flow measurements decreased after the initial beach exposure, decreased further within 24 hours, and continued to be suppressed even after 5 days. Asthmatics may continue to have increased symptoms and delayed respiratory function suppression for several days after 1 hour of exposure to the Florida red tide toxin aerosols.

Florida Red Tide Toxins (Brevetoxins) and Longitudinal Respiratory Effects in Asthmatics.

Having demonstrated significant and persistent adverse changes in pulmonary function for asthmatics after 1 hour exposure to brevetoxins in Florida red tide (Karenia brevis bloom) aerosols, we assessed the possible longer term health effects in asthmatics from intermittent environmental exposure to brevetoxins over 7 years. 125 asthmatic subjects were assessed for their pulmonary function and reported symptoms before and after 1 hour of environmental exposure to Florida red tide aerosols for upto 11 studies over seven years. As a group, the asthmatics came to the studies with normal standardized percent predicted pulmonary function values. The 38 asthmatics who participated in only one exposure study were more reactive compared to the 36 asthmatics who participated in ≥4 exposure studies. The 36 asthmatics participating in ≥4 exposure studies demonstrated no significant change in their standardized percent predicted pre-exposure pulmonary function over the 7 years of the study. These results indicate that stable asthmatics living in areas with intermittent Florida red tides do not exhibit chronic respiratory effects from intermittent environmental exposure to aerosolized brevetoxins over a 7 year period.

Review of Florida Red Tide and Human Health Effects.

This paper reviews the literature describing research performed over the past decade on the known and possible exposures and human health effects associated with Florida red tides. These harmful algal blooms are caused by the dinoflagellate, Karenia brevis, and similar organisms, all of which produce a suite of natural toxins known as brevetoxins. Florida red tide research has benefited from a consistently funded, long term research program, that has allowed an interdisciplinary team of researchers to focus their attention on this specific environmental issue-one that is critically important to Gulf of Mexico and other coastal communities. This long-term interdisciplinary approach has allowed the team to engage the local community, identify measures to protect public health, take emerging technologies into the field, forge advances in natural products chemistry, and develop a valuable pharmaceutical product. The Review includes a brief discussion of the Florida red tide organisms and their toxins, and then focuses on the effects of these toxins on animals and humans, including how these effects predict what we might expect to see in exposed people.

Dermal and ocular exposure systems for the development of models of sulfur mustard-induced injury.

Sulfur mustard (SM) is a chemical threat agent for which the 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 article details the techniques used to develop SM laboratory exposure systems for the development of animal models of ocular and dermal injury. These models are critical to enable evaluation of SM injury and therapeutics against that injury. Iterative trials were conducted to optimize dermal and ocular injury models in guinea pigs and rabbits respectively. The goal was a homogeneous and diffuse ocular and dermal injury that compares to the human injury. Dermal exposures were conducted by either a flow-past or static vapor cup system. Ocular exposures were conducted by a static exposure system. Ocular and dermal exposures were conducted with vaporized SM. Vapor concentrations increased with time in the dermal and ocular exposure systems but were stable with varying amounts of applied SM. A dermal deposition estimation study was also conducted. Deposited volumes increased with exposure time.

Inland Transport of Aerosolized Florida Red Tide Toxins.

Florida red tides, an annual event off the west coast of Florida, are caused by the toxic dinoflagellate, Karenia brevis. K. brevis produces a suite of potent neurotoxins, brevetoxins, which kill fish, sea birds, and marine mammals, as well as sickening humans who consume contaminated shellfish. These toxins become part of the marine aerosol, and can also be inhaled by humans and other animals. Recent studies have demonstrated a significant increase in symptoms and decrease lung function in asthmatics after only one hour of beach exposure during an onshore Florida red tide bloom.This study constructed a transect line placing high volume air samplers to measure brevetoxins at sites beginning at the beach, moving approximately 6.4 km inland. One non-exposure and 2 exposure studies, each of 5 days duration, were conducted. No toxins were measured in the air during the non-exposure period. During the 2 exposure periods, the amount of brevetoxins varied considerably by site and by date. Nevertheless, brevetoxins were measured at least 4.2 kilometers from the beach and/or 1.6 km from the coastal shoreline. Therefore, populations sensitive to brevetoxins (such as asthmatics) need to know that leaving the beach may not discontinue their environmental exposure to brevetoxin aerosols.

Evaluation of IOM personal sampler at different flow rates.

The Institute of Occupational Medicine (IOM) personal sampler is usually operated at a flow rate of 2.0 L/min, the rate at which it was designed and calibrated, for sampling the inhalable mass fraction of airborne particles in occupational environments. In an environment of low aerosol concentrations only small amounts of material are collected, and that may not be sufficient for analysis. Recently, a new sampling pump with a flow rate up to 15 L/min became available for personal samplers, with the potential of operating at higher flow rates. The flow rate of a Leland Legacy sampling pump, which operates at high flow rates, was evaluated and calibrated, and its maximum flow was found to be 10.6 L/min. IOM samplers were placed on a mannequin, and sampling was conducted in a large aerosol wind tunnel at wind speeds of 0.56 and 2.22 m/s. Monodisperse aerosols of oleic acid tagged with sodium fluorescein in the size range of 2 to 100 microm were used in the test. The IOM samplers were operated at flow rates of 2.0 and 10.6 L/min. Results showed that the IOM samplers mounted in the front of the mannequin had a higher sampling efficiency than those mounted at the side and back, regardless of the wind speed and flow rate. For the wind speed of 0.56 m/s, the direction-averaged (the average value of all orientations facing the wind direction) sampling efficiency of the samplers operated at 2.0 L/min was slightly higher than that of 10.6 L/min. For the wind speed of 2.22 m/s, the sampling efficiencies at both flow rates were similar for particles < 60 microm. The results also show that the IOM's sampling efficiency at these two different flow rates follows the inhalable mass curve for particles in the size range of 2 to 20 microm. The test results indicate that the IOM sampler can be used at higher flow rates.

Development of a personal bioaerosol sampler based on a conical cyclone with recirculating liquid film.

This article describes the development of a novel, high-performance personal aerosol sampler intended to monitor occupational air pollution, specifically, microbial constituents. This prototype sampler has a horizontally positioned conical cyclone with recirculating liquid film and an ejection supply of adsorptive liquid into the inlet nozzle. Airborne pollutants were collected in the adsorptive liquid, thus improving the survivability of microbiological aerosol samples. Experimental modules of different dimensions were first evaluated. Based on the test results, a prototype sampler was fabricated and tested. Evaluation of the collection efficiency of the prototype unit indicated a higher than 90% collection efficiency for particles > 1.0 microm. The 50% cutoff diameter was between 0.70-0.75 microm. For assessment of the sampling process effect on the collected microorganisms, Bacillus thuringiensis was tested at a concentration of about 1.0 x 10(6) cells per cm(3). The viability in the prototype sampler decreased to 78% after 60 min of operation.

Personal exposure to aerosolized red tide toxins (brevetoxins).

Florida red tides occur annually in the Gulf of Mexico from blooms of the marine dinoflagellate, Karenia brevis, which produces highly potent natural polyether toxins, brevetoxins. Several epidemiologic studies have demonstrated that human exposure to red tide aerosol could result in increased respiratory symptoms. Environmental monitoring of aerosolized brevetoxins was performed using a high-volume sampler taken hourly at fixed locations on Siesta Beach, Florida. Personal exposure was monitored using personal air samplers and taking nasal swab samples from the subjects who were instructed to spend 1 hr on Sarasota Beach during two sampling periods of an active Florida red tide event in March 2005, and in May 2008 when there was no red tide. Results showed that the aerosolized brevetoxins from the personal sampler were in modest agreement with the environmental concentration taken from a high-volume sampler. Analysis of nasal swab samples for brevetoxins demonstrated 68% positive samples in the March 2005 sampling period when air concentrations of brevetoxins were between 50 to 120 ng/m(3) measured with the high-volume sampler. No swab samples showed detectable levels of brevetoxins in the May 2008 study, when all personal samples were below the limit of detection. However, there were no statistical correlations between the amounts of brevetoxins detected in the swab samples with either the environmental or personal concentration. Results showed that the personal sample might provide an estimate of individual exposure level. Nasal swab samples showed that brevetoxins indeed were inhaled and deposited in the nasal passage during the March 2005 red tide event.

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 x min/m(3) resulted in homogeneous lung injury with no nasal degeneration.

Influence of moisture accumulation in inline spacer on delivery of aerosol using metered-dose inhaler during mechanical ventilation.

BACKGROUND: A practitioner questioned whether moisture that collected in the ventilator circuit and spacer affected the delivery of aerosol from a pressurized metered-dose inhaler (pMDI). An in vitro model was used to quantify the impact of accumulated humidity in a pMDI spacer and ventilator over time. METHODS: A ventilator with an adult heated-wire ventilator circuit and humidifier was set to deliver adult settings. An impactor was placed between the endotracheal tube and the test lung to determine drug mass and mass median aerodynamic diameter of the aerosol delivered. An AeroVent pMDI spacer was placed in the inspiratory limb of the ventilator circuit and left in an open position. Eight actuations of HFA albuterol pMDI (720 microg) was administered at 1, 2, and 3 hours after the heater had reached equilibrium at 37 degrees C, and <10 min after turning off the heater/humidifier. The spacer was dried and returned to the heated circuit for additional testing. Samples were analyzed via spectrophotometer. One-way analysis of variance was applied (P<.05). RESULTS: The delivered drug as a percent of emitted dose (mean+/-SD) was greater at hour one (23+/-2.1%) and with the dry spacer (21.8+/-3.3%) than at hours 2 and 3 or with humidifier off (11.4+/-3.8%, 12.3+/-0.8%, and 12.7+/-0.3%, respectively, P=.002). Mass median aerodynamic diameters with each comparison did not vary between conditions. Delivery efficiency was similar for the dry spacer and the spacer in the humidified circuit for one hour. However, once visible condensate occurred, drug delivery efficiency decreased by approximately 50%. CONCLUSIONS: Aerosol delivery from a pMDI with spacer during mechanical ventilation was greater with a dry spacer and unchanged for the first hour after initiating heated humidification. Turning off the heated humidifier did not increase drug delivered.

Fiber deposition in the tracheobronchial region: deposition equations.

A lung deposition model for fibrous aerosol needs accurate deposition equations for different regions of the human respiratory tract. For fiber deposition in the tracheobronchial region there are several theoretical and empirical equations to predict deposition efficiency in the impaction-dominant region. However, few were verified with experimental data. We have obtained experimental data of fiber deposition in realistic human airway replicas using carbon fibers. Comparison of experimental data and existing deposition models yield variable results, with some models performing better than other models. There was no consistent agreement found over the Stokes number range of experimental data. A generic empirical model for fiber deposition in the tracheobronchial region was developed based on all carbon fiber deposition data in human lung replicas. This model includes the size of fibers and the geometry of the tracheobronchial bifurcation. Because it is difficult to develop only one equation for all data from the trachea to the major bronchial bifurcations, the deposition patterns in the trachea and first generation were each predicted by their own equations. An additional equation was developed for the second to fourth generations. This model, combined with oral and nasal deposition predictions which will be published elsewhere, can be used to investigate the inhalation dosimetry and deposition patterns of fibers in human lungs for assessing occupational hazards and air pollutants.

Numerical simulations investigating the regional and overall deposition efficiency of the human nasal cavity.

Numerical simulations have been carried out on a model of the right passageway of an anonymous, adult male's nasal cavity, constructed from magnetic resonance imagery (MRI) scans. Steady, laminar, inspiratory flow was assumed to simulate inhalation. Analysis shows smoothly varying streamlines with a peak in velocity magnitude occurring in the nasal valves and a peak in vorticity magnitude immediately posterior. Dilute, uniform concentrations of inertial (1 microm < or = d(ae) < or = 10 microm) particles were released at the nostril and tracked via a Lagrangian tracking algorithm. Deposition efficiency is shown to increase with particle size and flow rate. Preferential deposition is seen in the anterior third of the nasal cavity for large Stokes number particles. An empirical expression for particle deposition is proposed that incorporates particle size, flow rate, and nose anatomy.

Recreational exposure to low concentrations of microcystins during an algal bloom in a small lake.

We measured microcystins in blood from people at risk for swallowing water or inhaling spray while swimming, water skiing, jet skiing, or boating during an algal bloom. We monitored water samples from a small lake as a Microcystis aeruginosa bloom developed. We recruited 97 people planning recreational activities in that lake and seven others who volunteered to recreate in a nearby bloom-free lake. We conducted our field study within a week of finding a 10-microg/L microcystin concentration. We analyzed water, air, and human blood samples for water quality, potential human pathogens, algal taxonomy, and microcystin concentrations. We interviewed study participants for demographic and current health symptom information. Water samples were assayed for potential respiratory viruses (adenoviruses and enteroviruses), but none were detected. We did find low concentrations of Escherichia coli, indicating fecal contamination. We found low levels of microcystins (2 microg/L to 5 microg/L) in the water and (<0.1 ng/m(3)) in the aerosol samples. Blood levels of microcystins for all participants were below the limit of detection (0.147 microg/L). Given this low exposure level, study participants reported no symptom increases following recreational exposure to microcystins. This is the first study to report that water-based recreational activities can expose people to very low concentrations of aerosol-borne microcystins; we recently conducted another field study to assess exposures to higher concentrations of these algal toxins.