Population Pharmacokinetic Model of Oxfendazole and Metabolites in Healthy Adults following Single Ascending Doses.

Oxfendazole is a potent veterinary benzimidazole anthelmintic under transition to humans for the treatment of multiple parasitic infectious diseases. The first-in-human study evaluating the disposition of oxfendazole and its metabolites in healthy adults following single ascending oral doses from 0.5 to 60 mg/kg of body weight shows that oxfendazole pharmacokinetics is substantially nonlinear, which complicates correlating oxfendazole dose to exposure. To quantitatively capture the relation between oxfendazole dose and exposure, a population pharmacokinetic model for oxfendazole and its metabolites, oxfendazole sulfone and fenbendazole, in humans was developed using a nonlinear mixed-effect modeling approach. Our final model incorporated mechanistic characterization of dose-limited bioavailability as well as different oxfendazole metabolic processes and provided insight into the significance of presystemic metabolism in oxfendazole and metabolite disposition. Oxfendazole clinical pharmacokinetics was best described by a one-compartment model with nonlinear absorption and linear elimination. Oxfendazole apparent clearance and apparent volume of distribution were estimated to be 2.57 liters/h and 35.2 liters, respectively, at the lowest dose (0.5 mg/kg), indicating that oxfendazole is a low extraction drug with moderate distribution. The disposition of both metabolites was adequately characterized by a one-compartment model with formation rate-limited elimination. Fenbendazole formation from oxfendazole was primarily through systemic metabolism, while both presystemic and systemic metabolism were critical to the formation of oxfendazole sulfone. Our model adequately captured the concentration-time profiles of both oxfendazole and its two metabolites in healthy adults over a wide dose range. The model can be used to predict oxfendazole disposition under new dosing regimens to support dose optimization in humans.

Pharmacokinetics, Safety, and Tolerability of Oxfendazole in Healthy Volunteers: a Randomized, Placebo-Controlled First-in-Human Single-Dose Escalation Study.

Cysticercosis is a parasitic disease that frequently involves the human central nervous system (CNS), and current treatment options are limited. Oxfendazole, a veterinary medicine belonging to the benzimidazole family of anthelmintic drugs, has demonstrated substantial activity against the tissue stages of Taenia solium and has potential to be developed as an effective therapy for neurocysticercosis. To accelerate the transition of oxfendazole from veterinary to human use, the pharmacokinetics, safety, and tolerability of oxfendazole were evaluated in healthy volunteers in this phase 1 first-in-human (FIH) study. Seventy subjects were randomly assigned to receive a single oral dose of oxfendazole (0.5, 1, 3, 7.5, 15, 30, or 60 mg oxfendazole/kg body weight) or placebo and were followed for 14 days. Blood and urine samples were collected, and the concentrations of oxfendazole were measured using a validated ultraperformance liquid chromatography mass spectrometry method. The pharmacokinetic parameters of oxfendazole were estimated using noncompartmental analysis. Oxfendazole was rapidly absorbed with a mean plasma half-life ranging from 8.5 to 11 h. The renal excretion of oxfendazole was minimal. Oxfendazole exhibited significant nonlinear pharmacokinetics with less than dose-proportional increases in exposure after single oral doses of 0.5 mg/kg to 60 mg/kg. This nonlinearity of oxfendazole is likely due to the dose-dependent decrease in bioavailability that is caused by its low solubility. Oxfendazole was found to be well tolerated in this study at different escalating doses without any serious adverse events (AEs) or deaths. There were no significant differences in the distributions of hematology, biochemistry, or urine parameters between oxfendazole and placebo recipients. (This study has been registered at ClinicalTrials.gov under identifier NCT02234570.).

Design and Evaluation of a High-Flowrate Nanoparticle Respiratory Deposition (NRD) Sampler.

A high-flow (10 L/min) nanoparticle respiratory deposition (NRD) sampler was designed and evaluated to achieve reduced limits of quantification (LOQs) for metal nanoparticles. The high-flow NRD consists of an inlet, impactor stage, diffusion stage, and a final filter. An impactor stage with 12 nozzles was designed from theory to achieve a cut-off diameter of 300 nm at 50% particle collection efficiency (d50). Various depths of 37-mm-diameter polyurethane foam cylinders were tested for the diffusion stage to obtain a collection efficiency curve similar to the deposition of nanoparticles in the human respiratory tract, known as the nanoparticulate matter (NPM) criterion. The objective for the final filter was a collection efficiency of near 100% with minimal pressure drop. The collection efficiencies by size and pressure drops were measured for all NRD sampler components. The final design of the impactor stage nozzle achieved a d50 of 305 nm. The collection efficiency for the diffusion stage with a depth of 7 cm when adjusted for presence of the impactor was the closest to the NPM curve with a R2 value of 0.96 and d50 of 43 nm. Chemical analysis of the metal content for foam affirmed that the high-flow NRD sampler required less sampling time to meet metal LOQs than the 2.5 L/min NRD sampler. The final filter with a modified support pad had a collection efficiency near 100%. The overall pressure drop of the sampler of 8.5 kPa (34 in. H2O) could not be handled by commercial personal sampling pumps. Hence the high-flow NRD sampler can be used as an area sampler or without the final filter for collection of nanoparticles.

Collection of airborne ultrafine cellulose nanocrystals by impinger with an efficiency mimicking deposition in the human respiratory system.

As cellulose nanocrystals (CNCs) are increasing in production, establishing safe workplace practices in industry will be paramount to their continued use and growth. Particles other than CNCs with similar high aspect ratios have exhibited toxicity on inhalation. Safeguards are needed to monitor concentrations of CNCs in air in industrial and laboratory settings to protect workers. However, because of their size, morphology, and chemical makeup, CNCs are difficult to characterize and differentiate from other dust and cellulose products. This work is focused on developing an effective method of characterizing the concentration of airborne ultrafine CNCs that may deposit in the respiratory tract. CNCs were tagged with rhodamine b (RhB-CNCs) for improved visualization and characterized using UV-vis spectroscopy (UV-vis), transmission electron microscopy (TEM), and dynamic light scattering (DLS), then aerosolized and collected via a novel method using plastic impingers. Concentration of RhB-CNCs was measured using UV-vis and scanning mobility particle sizer (SMPS). The plastic impinger with 3D-printed nozzle collected airborne CNCs at an efficiency that improves upon commercially available impingers for relevant particle sizes.

Sources of error and variability in particulate matter sensor network measurements.

The quality of mass concentration estimates from increasingly popular networks of low-cost particulate matter sensors depends on accurate conversion of sensor output (e.g., voltage) into gravimetric-equivalent mass concentration, typically using a calibration procedure. This study evaluates two important sources of variability that lead to error in estimating gravimetric-equivalent mass concentration: the temporal changes in sensor calibration and the spatial and temporal variability in gravimetric correction factors. A 40-node sensor network was deployed in a heavy vehicle manufacturing facility for 8 months. At a central location in the facility, particulate matter was continuously measured with three sensors of the network and a traditional, higher-cost photometer, determining the calibration slope and intercept needed to translate sensor output to photometric-equivalent mass concentration. Throughout the facility, during three intensive sampling campaigns, respirable mass concentrations were measured with gravimetric samplers and photometers to determine correction factors needed to adjust photometric-equivalent to gravimetric-equivalent mass concentration. Both field-determined sensor calibration slopes and intercepts were statistically different than those estimated in the laboratory (α = 0.05), emphasizing the importance of aerosol properties when converting voltage to photometric-equivalent mass concentration and the need for field calibration to determine slope. Evidence suggested the sensors' weekly field calibration slope decreased and intercept increased, indicating the sensors were deteriorating over time. The mean correction factor in the cutting and shot blasting area (2.9) was substantially and statistically lower than that in the machining and welding area (4.6; p = 0.01). Therefore, different correction factors should be determined near different occupational processes to accurately estimate particle mass concentrations.

Size, composition, morphology, and health implications of airborne incidental metal-containing nanoparticles.

There is great concern regarding the adverse health implications of engineered nanoparticles. However, there are many circumstances where the production of incidental nanoparticles, i.e., nanoparticles unintentionally generated as a side product of some anthropogenic process, is of even greater concern. In this study, metal-based incidental nanoparticles were measured in two occupational settings: a machining center and a foundry. On-site characterization of substrate-deposited incidental nanoparticles using a field-portable X-ray fluorescence provided some insights into the chemical characteristics of these metal-containing particles. The same substrates were then used to carry out further off-site analysis including single-particle analysis using scanning electron microscopy and energy-dispersive X-ray spectroscopy. Between the two sites, there were similarities in the size and composition of the incidental nanoparticles as well as in the agglomeration and coagulation behavior of nanoparticles. In particular, incidental nanoparticles were identified in two forms: submicrometer fractal-like agglomerates from activities such as welding and supermicrometer particles with incidental nanoparticles coagulated to their surface, herein referenced as nanoparticle collectors. These agglomerates will affect deposition and transport inside the respiratory system of the respirable incidental nanoparticles and the corresponding health implications. The studies of incidental nanoparticles generated in occupational settings lay the groundwork on which occupational health and safety protocols should be built.

Spermine oxidase maintains basal skeletal muscle gene expression and fiber size and is strongly repressed by conditions that cause skeletal muscle atrophy.

Skeletal muscle atrophy is a common and debilitating condition that remains poorly understood at the molecular level. To better understand the mechanisms of muscle atrophy, we used mouse models to search for a skeletal muscle protein that helps to maintain muscle mass and is specifically lost during muscle atrophy. We discovered that diverse causes of muscle atrophy (limb immobilization, fasting, muscle denervation, and aging) strongly reduced expression of the enzyme spermine oxidase. Importantly, a reduction in spermine oxidase was sufficient to induce muscle fiber atrophy. Conversely, forced expression of spermine oxidase increased muscle fiber size in multiple models of muscle atrophy (immobilization, fasting, and denervation). Interestingly, the reduction of spermine oxidase during muscle atrophy was mediated by p21, a protein that is highly induced during muscle atrophy and actively promotes muscle atrophy. In addition, we found that spermine oxidase decreased skeletal muscle mRNAs that promote muscle atrophy (e.g., myogenin) and increased mRNAs that help to maintain muscle mass (e.g., mitofusin-2). Thus, in healthy skeletal muscle, a relatively low level of p21 permits expression of spermine oxidase, which helps to maintain basal muscle gene expression and fiber size; conversely, during conditions that cause muscle atrophy, p21 expression rises, leading to reduced spermine oxidase expression, disruption of basal muscle gene expression, and muscle fiber atrophy. Collectively, these results identify spermine oxidase as an important positive regulator of muscle gene expression and fiber size, and elucidate p21-mediated repression of spermine oxidase as a key step in the pathogenesis of skeletal muscle atrophy.

Toxicity assessment of zinc oxide nanoparticles using sub-acute and sub-chronic murine inhalation models.

BACKGROUND: Although ZnO nanoparticles (NPs) are used in many commercial products and the potential for human exposure is increasing, few in vivo studies have addressed their possible toxic effects after inhalation. We sought to determine whether ZnO NPs induce pulmonary toxicity in mice following sub-acute or sub-chronic inhalation exposure to realistic exposure doses. METHODS: Mice (C57Bl/6) were exposed to well-characterized ZnO NPs (3.5 mg/m3, 4 hr/day) for 2 (sub-acute) or 13 (sub-chronic) weeks and necropsied immediately (0 wk) or 3 weeks (3 wks) post exposure. Toxicity was assessed by enumeration of total and differential cells, determination of total protein, lactate dehydrogenase activity and inflammatory cytokines in bronchoalveolar lavage (BAL) fluid as well as measurements of pulmonary mechanics. Generation of reactive oxygen species was assessed in the lungs. Lungs were evaluated for histopathologic changes and Zn content. Zn concentration in blood, liver, kidney, spleen, heart, brain and BAL fluid was measured. RESULTS: An elevated concentration of Zn2+ was detected in BAL fluid immediately after exposures, but returned to baseline levels 3 wks post exposure. Dissolution studies showed that ZnO NPs readily dissolved in artificial lysosomal fluid (pH 4.5), but formed aggregates and precipitates in artificial interstitial fluid (pH 7.4). Sub-acute exposure to ZnO NPs caused an increase of macrophages in BAL fluid and a moderate increase in IL-12(p40) and MIP-1α, but no other inflammatory or toxic responses were observed. Following both sub-acute and sub-chronic exposures, pulmonary mechanics were no different than sham-exposed animals. CONCLUSIONS: Our ZnO NP inhalation studies showed minimal pulmonary inflammation, cytotoxicity or lung histopathologic changes. An elevated concentration of Zn in the lung and BAL fluid indicates dissolution of ZnO NPs in the respiratory system after inhalation. Exposure concentration, exposure mode and time post exposure played an important role in the toxicity of ZnO NPs. Exposure for 13 wks with a cumulative dose of 10.9 mg/kg yielded increased lung cellularity, but other markers of toxicity did not differ from sham-exposed animals, leading to the conclusion that ZnO NPs have low sub-chronic toxicity by the inhalation route.

Induction of inflammasome-dependent pyroptosis by carbon black nanoparticles.

Inhalation of nanoparticles has been implicated in respiratory morbidity and mortality. In particular, carbon black nanoparticles are found in many different environmental exposures. Macrophages take up inhaled nanoparticles and respond via release of inflammatory mediators and in some cases cell death. Based on new data, we propose that exposure of macrophages (both a macrophage cell line and primary human alveolar macrophages) to carbon black nanoparticles induces pyroptosis, an inflammasome-dependent form of cell death. Exposure of macrophages to carbon black nanoparticles resulted in inflammasome activation as defined by cleavage of caspase 1 to its active form and downstream IL-1ß release. The cell death that occurred with carbon black nanoparticle exposure was identified as pyroptosis by the protective effect of a caspase 1 inhibitor and a pyroptosis inhibitor. These data demonstrate that carbon black nanoparticle exposure activates caspase 1, increases IL-1ß release after LPS priming, and induces the proinflammatory cell death, pyroptosis. The identification of pyroptosis as a cellular response to carbon nanoparticle exposure is novel and relates to environmental and health impacts of carbon-based particulates.

Murine pulmonary responses after sub-chronic exposure to aluminum oxide-based nanowhiskers.

BACKGROUND: Aluminum oxide-based nanowhiskers (AO nanowhiskers) have been used in manufacturing processes as catalyst supports, flame retardants, adsorbents, or in ceramic, metal and plastic composite materials. They are classified as high aspect ratio nanomaterials. Our aim was to assess in vivo toxicity of inhaled AO nanowhisker aerosols. METHODS: Primary dimensions of AO nanowhiskers specified by manufacturer were 2-4 nm x 2800 nm. The aluminum content found in this nanomaterial was 30% [mixed phase material containing Al(OH)3 and AlOOH]. Male mice (C57Bl/6 J) were exposed to AO nanowhiskers for 4 hrs/day, 5 days/wk for 2 or 4 wks in a dynamic whole body exposure chamber. The whiskers were aerosolized with an acoustical dry aerosol generator that included a grounded metal elutriator and a venturi aspirator to enhance deagglomeration. Average concentration of aerosol in the chamber was 3.3 ± 0.6 mg/m3 and the mobility diameter was 150 ± 1.6 nm. Both groups of mice (2 or 4 wks exposure) were necropsied immediately after the last exposure. Aluminum content in the lung, heart, liver, and spleen was determined. Pulmonary toxicity assessment was performed by evaluation of bronchoalveolar lavage (BAL) fluid (enumeration of total and differential cells, total protein, activity of lactate dehydrogenase [LDH] and cytokines), blood (total and differential cell counts), lung histopathology and pulmonary mechanics. RESULTS: Following exposure, mean Al content of lungs was 0.25, 8.10 and 15.37 µg/g lung (dry wt) respectively for sham, 2 wk and 4 wk exposure groups. The number of total cells and macrophages in BAL fluid was 2-times higher in animals exposed for 2 wks and 6-times higher in mice exposed for 4 wks, compared to shams (p < 0.01, p < 0.001, respectively). However no neutrophilic inflammation in BAL fluid was found and neutrophils were below 1% in all groups. No significant differences were found in total protein, activity of LDH, or cytokines levels (IL-6, IFN-γ, MIP-1α, TNF-α, and MIP-2) between shams and exposed mice. CONCLUSIONS: Sub-chronic inhalation exposures to aluminum-oxide based nanowhiskers induced increased lung macrophages, but no inflammatory or toxic responses were observed.

Nanosilver induces minimal lung toxicity or inflammation in a subacute murine inhalation model.

BACKGROUND: There is increasing interest in the environmental and health consequences of silver nanoparticles as the use of this material becomes widespread. Although human exposure to nanosilver is increasing, only a few studies address possible toxic effect of inhaled nanosilver. The objective of this study was to determine whether very small commercially available nanosilver induces pulmonary toxicity in mice following inhalation exposure. RESULTS: In this study, mice were exposed sub-acutely by inhalation to well-characterized nanosilver (3.3 mg/m³, 4 hours/day, 10 days, 5 ± 2 nm primary size). Toxicity was assessed by enumeration of total and differential cells, determination of total protein, lactate dehydrogenase activity and inflammatory cytokines in bronchoalveolar lavage fluid. Lungs were evaluated for histopathologic changes and the presence of silver. In contrast to published in vitro studies, minimal inflammatory response or toxicity was found following exposure to nanosilver in our in vivo study. The median retained dose of nanosilver in the lungs measured by inductively coupled plasma-optical emission spectroscopy (ICP-OES) was 31 µg/g lung (dry weight) immediately after the final exposure, 10 µg/g following exposure and a 3-wk rest period and zero in sham-exposed controls. Dissolution studies showed that nanosilver did not dissolve in solutions mimicking the intracellular or extracellular milieu. CONCLUSIONS: Mice exposed to nanosilver showed minimal pulmonary inflammation or cytotoxicity following sub-acute exposures. However, longer term exposures with higher lung burdens of nanosilver are needed to ensure that there are no chronic effects and to evaluate possible translocation to other organs.

Estimating personal exposures from a multi-hazard sensor network.

Occupational exposure assessment is almost exclusively accomplished with personal sampling. However, personal sampling can be burdensome and suffers from low sample sizes, resulting in inadequately characterized workplace exposures. Sensor networks offer the opportunity to measure occupational hazards with a high degree of spatiotemporal resolution. Here, we demonstrate an approach to estimate personal exposure to respirable particulate matter (PM), carbon monoxide (CO), ozone (O3), and noise using hazard data from a sensor network. We simulated stationary and mobile employees that work at the study site, a heavy-vehicle manufacturing facility. Network-derived exposure estimates compared favorably to measurements taken with a suite of personal direct-reading instruments (DRIs) deployed to mimic personal sampling but varied by hazard and type of employee. The root mean square error (RMSE) between network-derived exposure estimates and personal DRI measurements for mobile employees was 0.15 mg/m3, 1 ppm, 82 ppb, and 3 dBA for PM, CO, O3, and noise, respectively. Pearson correlation between network-derived exposure estimates and DRI measurements ranged from 0.39 (noise for mobile employees) to 0.75 (noise for stationary employees). Despite the error observed estimating personal exposure to occupational hazards it holds promise as an additional tool to be used with traditional personal sampling due to the ability to frequently and easily collect exposure information on many employees.

Evaluation of a Portable Aerosol Collector and Spectrometer to measure particle concentration by composition and size.

We evaluated a newly developed Portable Aerosol Collector and Spectrometer (PACS) in the laboratory. We developed an algorithm to estimate mass concentration by size and composition with a PACS. In laboratory experiments, we compared particle size distributions measured with the PACS to research instruments for multi-modal aerosols: two-mode generated by spark discharge, consisting of ultrafine (fresh Mn fume) and fine particles (aged Cu fume); and three-mode produced by adding coarse particles (Arizona road dust) to the two-mode. Near-real-time size distributions from the PACS compared favorably to those from a scanning mobility particle sizer and an aerodynamic particle sizer for the three-mode aerosol (number, bias=9.4% and R2=0.96; surface area, bias=17.8%, R2=0.77; mass, bias=-2.2%, R2=0.94), but less so for the two-mode aerosol (number, bias=-17.7% and R2=0.51; surface area, bias=-45.5%, R2=0; for mass, bias=-81.75%, R2=0.08). Elemental mass concentrations by size were similar to those measured with a nano micro-orifice uniform deposition impactor for coarse-mode particles, whereas agreement was considerably poorer for ultrafine- and fine-mode particles. The PACS has merit in estimating multi-metric concentrations by size and composition but requires further research to resolve discrepancies identified for two-mode aerosol.

Mapping Occupational Hazards with a Multi-sensor Network in a Heavy-Vehicle Manufacturing Facility.

Due to their small size, low-power demands, and customizability, low-cost sensors can be deployed in collections that are spatially distributed in the environment, known as sensor networks. The literature contains examples of such networks in the ambient environment; this article describes the development and deployment of a 40-node multi-hazard network, constructed with low-cost sensors for particulate matter (SHARP GP2Y1010AU0F), carbon monoxide (Alphasense CO-B4), oxidizing gases (Alphasense OX-B421), and noise (developed in-house) in a heavy-vehicle manufacturing facility. Network nodes communicated wirelessly with a central database in order to record hazard measurements at 5-min intervals. Here, we report on the temporal and spatial measurements from the network, precision of network measurements, and accuracy of network measurements with respect to field reference instruments through 8 months of continuous deployment. During typical production periods, 1-h mean hazard levels ± standard deviation across all monitors for particulate matter (PM), carbon monoxide (CO), oxidizing gases (OX), and noise were 0.62 ± 0.2 mg m-3, 7 ± 2 ppm, 155 ± 58 ppb, and 82 ± 1 dBA, respectively. We observed clear diurnal and weekly temporal patterns for all hazards and daily, hazard-specific spatial patterns attributable to general manufacturing processes in the facility. Processes associated with the highest hazard levels were machining and welding (PM and noise), staging (CO), and manual and robotic welding (OX). Network sensors exhibited varying degrees of precision with 95% of measurements among three collocated nodes within 0.21 mg m-3 for PM, 0.4 ppm for CO, 9 ppb for OX, and 1 dBA for noise of each other. The median percent bias with reference to direct-reading instruments was 27%, 11%, 45%, and 1%, for PM, CO, OX, and noise, respectively. This study demonstrates the successful long-term deployment of a multi-hazard sensor network in an industrial manufacturing setting and illustrates the high temporal and spatial resolution of hazard data that sensor and monitor networks are capable of. We show that network-derived hazard measurements offer rich datasets to comprehensively assess occupational hazards. Our network sets the stage for the characterization of occupational exposures on the individual level with wireless sensor networks.

Physicochemical properties of air discharge-generated manganese oxide nanoparticles: Comparison to welding fumes.

Exposures to high doses of manganese (Mn) via inhalation, dermal contact or direct consumption can cause adverse health effects. Welding fumes are a major source of manganese containing nanoparticles in occupational settings. Understanding the physicochemical properties of manganese-containing nanoparticles can be a first step in understanding their toxic potential following exposure. In particular, here we compare the size, morphology and Mn oxidation states of Mn oxide nanoparticles generated in the laboratory by arc discharge to those from welding collected in heavy vehicle manufacturing. Fresh nanoparticles collected at the exit of the spark discharge generation chamber consisted of individual or small aggregates of primary particles. These nanoparticles were allowed to age in a chamber to form chain-like aggregates of primary particles with morphologies very similar to welding fumes. The primary particles were a mixture of hausmannite (Mn3O4), bixbyite (Mn2O3) and manganosite (MnO) phases, whereas aged samples revealed a more amorphous structure. Both Mn2+ and Mn3+, as in double valence stoichiometry present in Mn3O4, and Mn3+, as in Mn2O3 and MnOOH, were detected by X-ray photoelectron spectroscopy on the surface of the nanoparticles in the laboratory nanoparticles and welding fumes. Dissolution studies conducted for these two Mn samples (aged and fresh fume) reveal different release kinetics of Mn ions in artificial lysosomal fluid (pH 4.5) and very limited dissolution in Gamble's solution (pH 7.4). Taken together, these data suggest several important considerations for understanding the health effects of welding fumes. First, the method of particle generation affects the crystallinity and phase of the oxide. Second, welding fumes consist of multiple oxidation states whether they are amorphous or crystalline or occur as isolated nanoparticles or agglomerates. Third, although the dissolution behavior depends on conditions used for nanoparticle generation, the dissolution of Mn oxide nanoparticles in the lysosome may promote Mn ions translocation into various organs causing toxic effects.

Particle Concentrations in Occupational Settings Measured with a Nanoparticle Respiratory Deposition (NRD) Sampler.

There is an increasing need to evaluate concentrations of nanoparticles in occupational settings due to their potential negative health effects. The Nanoparticle Respiratory Deposition (NRD) personal sampler was developed to collect nanoparticles separately from larger particles in the breathing zone of workers, while simultaneously providing a measure of respirable mass concentration. This study compared concentrations measured with the NRD sampler to those measured with a nano Micro Orifice Uniform-Deposit Impactor (nanoMOUDI) and respirable samplers in three workplaces. The NRD sampler performed well at two out of three locations, where over 90% of metal particles by mass were submicrometer particle size (a heavy vehicle machining and assembly facility and a shooting range). At the heavy vehicle facility, the mean metal mass concentration of particles collected on the diffusion stage of the NRD was 42.5 ± 10.0 µg/m3, within 5% of the nanoMOUDI concentration of 44.4 ± 7.4 µg/m3. At the shooting range, the mass concentration for the diffusion stage of the NRD was 5.9 µg/m3, 28% above the nanoMOUDI concentration of 4.6 µg/m3. In contrast, less favorable results were obtained at an iron foundry, where 95% of metal particles by mass were larger than 1 µm. The accuracy of nanoparticle collection by NRD diffusion stage may have been compromised by high concentrations of coarse particles at the iron foundry, where the NRD collected almost 5-fold more nanoparticle mass compared to the nanoMOUDI on one sampling day and was more than 40% different on other sampling days. The respirable concentrations measured by NRD samplers agreed well with concentrations measured by respirable samplers at all sampling locations. Overall, the NRD sampler accurately measured concentrations of nanoparticles in industrial environments when concentrations of large, coarse mode, particles were low.

Health and safety implications of occupational exposure to engineered nanomaterials.

The rapid growth and commercialization of nanotechnology are currently outpacing health and safety recommendations for engineered nanomaterials. As the production and use of nanomaterials increase, so does the possibility that there will be exposure of workers and the public to these materials. This review provides a summary of current research and regulatory efforts related to occupational exposure and medical surveillance for the nanotechnology workforce, focusing on the most prevalent industrial nanomaterials currently moving through the research, development, and manufacturing pipelines. Their applications and usage precedes a discussion of occupational health and safety efforts, including exposure assessment, occupational health surveillance, and regulatory considerations for these nanomaterials.