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In practice, workers often handle the same chemical(s) of interest under different control measures (e.g. local ventilation, enclosed system) during a full shift. Stoffenmanager® allows users to predict either task-based or full-shift exposures. However, most previous studies evaluated the tool by comparing task-based exposures with measured exposures. Also, limited evaluation studies of the Advanced REACH Tool (ART) with the Bayesian approach (ART+B) are available, requiring additional evaluation studies. The performance of Stoffenmanager® and ART with and without the Bayesian approach was evaluated with measured full-shift exposures to volatile liquids in terms of accuracy, precision, and conservatism. Forty-two exposure situation scenarios (including 251 exposures), developed based on job tasks and chemicals handled during tasks from workplaces, were used to generate full-shift estimates. The estimates were then compared with measured exposures using various comparison methods. Overall, Stoffenmanager® appeared to be the most accurate among the testing tools, while ART+B was the most precise. The percentage of measured exposures exceeding the tools’ 90th percentile estimates (%M>T) demonstrated that Stoffenmanager® (16%M>T) and ART+B (13%M>T) were more conservative than ART (41%M>T). When the 90% upper confidence limit of the 90th percentile estimate was considered, the level of conservatism changed from low (41%M>T) to medium (17%M>T) for ART and from medium (13%M>T) to high (0.8%M>T) for ART+B. The findings of this study indicate that no single tool would work for all ESs. Thus, it is recommended that users select a tool based on the performance results of three components (i.e. accuracy, precision, and conservatism), not depending on one or two components. The strength of this study is that the required tools’ input parameters were obtained during the sample collection to minimize assumptions for many input parameters. In addition, unlike other previous studies, multiple subtasks, which happen often in workplaces, were incorporated in this study. Nevertheless, the present study did not cover all activities listed in the tools and was limited to volatile liquids, suggesting further studies cover other exposure categories (e.g. solid, metal) and diverse activities.

The Apolipoprotein E (APOE) locus has garnered significant clinical interest because of its association with Alzheimer’s disease (AD) and longevity. This genetic association appears across multiple genes in the APOE locus. Despite the apparent differences between AD and longevity, both conditions share a commonality of aging-related changes in mitochondrial function. This commonality is likely due to accumulative biological effects partly exerted by the APOE locus. In this study, we investigated changes in mitochondrial structure/function-related markers using oxidative stress-induced human cellular models and postmortem brains (PMBs) from individuals with AD and normal controls. Our results reveal a range of expressional alterations, either upregulated or downregulated, in these genes in response to oxidative stress. In contrast, we consistently observed an upregulation of multiple APOE locus genes in all cellular models and AD PMBs. Additionally, the effects of AD status on mitochondrial DNA copy number (mtDNA CN) varied depending on APOE genotype. Our findings imply a potential coregulation of APOE locus genes possibly occurring within the same topologically associating domain (TAD) of the 3D chromosome conformation. The coordinated expression of APOE locus genes could impact mitochondrial function, contributing to the development of AD or longevity. Our study underscores the significant role of the APOE locus in modulating mitochondrial function and provides valuable insights into the underlying mechanisms of AD and aging, emphasizing the importance of this locus in clinical research.

Thermal spray coating is an industrial process in which molten metal is sprayed at high velocity onto a surface as a protective coating. An automated electric arc wire thermal spray coating aerosol generator and inhalation exposure system was developed to simulate an occupational exposure and, using this system, male Sprague-Dawley rats were exposed to stainless steel PMET720 aerosols at 25 mg/msup3/sup × 4 h/day × 9 day. Lung injury, inflammation, and cytokine alteration were determined. Resolution was assessed by evaluating these parameters at 1, 7, 14 and 28 d after exposure. The aerosols generated were also collected and characterized. Macrophages were exposed in vitro over a wide dose range (0-200 µg/ml) to determine cytotoxicity and to screen for known mechanisms of toxicity. Welding fumes were used as comparative particulate controls. In vivo lung damage, inflammation and alteration in cytokines were observed 1 day post exposure and this response resolved by day 7. Alveolar macrophages retained the particulates even after 28 day post-exposure. In line with the pulmonary toxicity findings, in vitro cytotoxicity and membrane damage in macrophages were observed only at the higher doses. Electron paramagnetic resonance showed in an acellular environment the particulate generated free radicals and a dose-dependent increase in intracellular oxidative stress and NF-kB/AP-1 activity was observed. PMET720 particles were internalized via clathrin and caveolar mediated endocytosis as well as actin-dependent pinocytosis/phagocytosis. The results suggest that compared to stainless steel welding fumes, the PMET 720 aerosols were not as overtly toxic, and the animals recovered from the acute pulmonary injury by 7 days.

The APOE locus has garnered significant clinical interest because of its association with Alzheimer's disease (AD) and longevity. This genetic association appears across multiple genes in the APOE locus. Despite the apparent differences between AD and longevity, both conditions share a commonality of aging-related changes in mitochondrial function. This commonality is likely due to accumulative biological effects, partly exerted by the APOE locus. In this study, we investigated changes in mitochondrial structure/function-related markers using oxidative stress-induced human cellular models and postmortem brains (PMBs) from individuals with AD and normal controls. Our results reveal a range of expressional alterations, either up- or down-regulated, in these genes in response to oxidative stress. In contrast, we consistently observed an upregulation of multiple APOE locus genes in all cellular models and AD PMBs. Additionally, the effects of AD status on mitochondrial DNA copy number (mtDNA CN) varied depending on APOE genotype. Our findings imply a potential coregulation of APOE locus genes, possibly occurring within the same topologically associating domain (TAD) of the 3D chromosome conformation. The coordinated expression of APOE locus genes could impact mitochondrial function, contributing to the development of AD or longevity. Our study underscores the significant role of the APOE locus in modulating mitochondrial function and provides valuable insights into the underlying mechanisms of AD and aging, emphasizing the importance of this locus in clinical research.

Thermal spray coating (TSC) is a surface treatment process whereby feedstock material is sprayed onto surfaces under pressure where it solidifies and forms a solid coating. In metal TSC processes, large quantities of aerosols, including fine and ultrafine metal particles are generated. However, exposure assessment for TSC is lacking. The goal of this study was to construct a TSC aerosol generation system and to characterize the physicochemical properties of aerosols generated during coating processes. A computer-controlled, automated electric arc wire-TSC aerosol generator system was built in an enclosed room, where a rotary motor rotates a metal feedstock pipe in circular and up-and-down directions to allow even deposition of coating material on the pipe surface. The characteristics of aerosolized particles during spray coating using a stainless-steel wire (PMET 720) showed that: 1) respirable mass concentrations ranged from 142–218 mg/m3 (3 spray shots with each shot of 1-sec during 20-min sampling), 2) diameter of peak particle number concentrations was between 360 nm and 400 nm, 3) mass median aerodynamic diameter determined by an impactor ranged from 290–370 nm, 4) particle morphology was observed to be diverse including chain-like agglomerates and spherical and cylinder-like shapes, and 5) metal composition was 80% iron, 17% chromium, and 3% manganese with trace amounts of nickel and copper. These findings are limited to one wire type and suggests the need for further investigations evaluating various parameters (e.g., wire/powder types, high/low energy, ventilation on/off) to obtain emission rates and recommend control measures.

Carbon nanotube (CNT) as a reinforcement enhances durability and performance of concrete composites. Exposure to some forms of CNT is known to cause adverse pathological outcomes. To understand potential toxicity arising from use of CNT-enabled concrete composites as it goes through various occupational life cycle stages, we evaluated 1) the physicochemical characteristics and toxicity of the as-produced CNT and 2) how particulate release during concrete manipulation (e.g., cutting) is altered by CNT incorporation. Physical dimensional profiling indicated a geometric mean length of 0.72 µm and 32 nm in diameter. The toxicity of the as-produced CNT was similar to an agglomerated CNT studied in our previous research, lacking the more severe toxicity associated with longer length and diameter CNT. Four concrete test samples, three different formulations with CNT and one without, were cut in a specialized chamber to simulate an occupational scenario. The mass median aerodynamic diameters from varying CNT incorporated composites did not change and was 5.23 µm in diameter. No free CNT was captured in the aerosols or was visible on the surface of the concrete. The toxicity of the released particulate is currently being investigate using in vitro screening tests designed to investigate mechanisms of potential toxicity. There were minimal changes in the particulate size distribution profiles after cutting, suggesting adding CNT to concrete may have subtle effects on the toxicity of the generated particulate.

Engineered nanomaterials are revolutionizing many industries, but little is known about potential exposures during the life cycle of nano-enabled composites. This study was conducted to characterize aerosolized particles using direct-reading instruments and integrated air samplers during cutting multi-walled carbon nanotubes (MWCNT)-embedded concrete cylinder blocks. Three types of blocks, 0% (reference), low%, and high% MWCNT, were tested in a specially designed enclosure housing an apparatus for the cutting of a block with an automated computer-controlled process. The highest particle number concentration (163,821 particles/cm3) was measured for the reference cylinder, while others showed similar concentrations (131,689 particles/cm3 and 140,954 particles/cm3 for the low% and high% blocks, respectively). Regardless of the cylinder type, the size-selected particle number concentrations revealed one main mode with a peak at 0.72 µm indicating no shift in the size distribution from addition(s) of MWCNT. Respirable mass concentrations were 342 mg/m3, 405 mg/m3, and 432 mg/m3 for the reference, low%, and high% blocks, respectively. The mass median aerodynamic diameters were similar, 5.23 µm for the reference and 5.05 µm for both low% and high% blocks, indicating a predominant respirable fraction. Respirable particles (quartz, feldspar, paste, etc.) often appeared to be agglomerated materials that included both paste and aggregate minerals. No free MWCNT were observed by electron microscopy from low% and high% samples. These initial studies found no evidence of free MWCNT by cutting concrete test blocks and only minor differences in the particulate aerosol generated, which included a general increase in respirable mass with increasing % CNT.

OBJECTIVES. To assess the exposure of surgical personnel to known carcinogens during pediatric tonsillectomy and adenoidectomy (T&A) and compare the efficacy of surgical smoke evacuation systems during T&A. STUDY DESIGN. Prospective, case series. SETTING. Tertiary children’s hospital. SUBJECTS AND METHODS. The present study assessed operating room workers’ exposure to chemical compounds and aerosolized particulates generated during T&A. We also investigated the effect of 3 different smoke-controlling methods: smoke-evacuator pencil cautery (SE), cautery with suction held by an assistant (SA), and cautery without suction (NS). RESULTS. Thirty cases were included: 12 in the SE group, 9 in SA, and 9 in NS. The chemical exposure levels were lower than or similar to baseline background concentrations, with the exception of methylene chloride and acetaldehyde. Within the surgical plume, none of the chemical compounds exceeded the corresponding occupational exposure limit (OEL). The mean particulate number concentration in the breathing zone during tonsillectomy was 508 particles/cm(3) for SE compared to 1661 particles/cm(3) for SA and 8208 particles/cm(3) for NS cases. NS was significantly different compared to the other two methods (P = .0009). CONCLUSIONS. Although the exposure levels to chemicals were considerably lower than the OELs, continuous exposures to these chemicals could cause adverse health effects to surgical personnel. These findings suggest that the use of a smoke-evacuator pencil cautery or an attentive assistant with handheld suction would reduce exposure levels to the aerosolized particles during routine T&A, compared to the use of cautery without suction.

Selecting a proper respirator requires determining the ratio of an employee’s maximum use concentration (MUC) divided by the occupational exposure limit of a chemical. Current industrial hygiene practice often is to obtain a percentile estimate (e.g. 95th) of the measured exposure distribution to apply as the MUC. However, practitioners who are not yet familiar with statistical or mathematical approaches may choose the highest exposure data point as the MUC, a method that is still considered appropriate by the Occupational Safety and Health Administration. Nonetheless, choosing a respirator using the highest exposure data point when only limited data are available may result in not always providing the most adequate respirator. Because some practitioners are not familiar with exposure assessment tools, our primary goal in this study was to demonstrate the best process when selecting respiratory protection by using a combination of exposure data and assessment tools. Three user-friendly tools, IHDataAnalyst, Advanced REACH Tool, and IHSTAT, were selected to demonstrate how to use different types of tool outputs when choosing a respirator. A decision logic was developed to help users navigate the combining of different data inputs. Personal full-shift exposure data collected in four different workplaces were used to describe four different outcomes generated when the maximum exposure data point and the tool’s output are compared with the exposure limit of the chemical. Outcomes varied, from determinations of ‘high confidence’ (or final decision) to ‘low confidence’ (or indicating more data are needed) in the selection of a respirator recommendation. In conclusion, systematically adopting the combination of exposure data and assessment tools could increase practitioners’ confidence in decision-making when choosing respirators from a limited exposure data set. These suggested guidelines will lead practitioners toward good industrial hygiene practices.

In Europe, several occupational exposure models have been developed and are recommended for regulatory exposure assessment. Only some information on the substance of interest (e.g., vapor pressure) and the workplace conditions (e.g., ventilation rate) is required in these models to predict an exposure value that will be later used to characterize the risk. However, it has been shown that models may differ in their predictions and that usually, one of the models best fits a given set of exposure conditions. Unfortunately, there are no clear rules on how to select the best model. In this study, we developed a new modeling approach that together uses the three most popular models, Advanced REACH Tool, Stoffenmanger, and ECETOC TRAv3, to obtain a unique exposure prediction. This approach is an extension of the TREXMO tool, and is called TREXMO+. TREXMO+ applies a machine-learning technique on a set of exposure data with the measured values to split them into smaller subsets, corresponding to exposure conditions sharing similar characteristics. For each subset, TREXMO+ then establishes a regression model with the three REACH tools used as the exposure predictors. The performance of the new model was tested and a comparison was made between the results obtained by TREXMO+ and those obtained by conventional tools. TREXMO+ model was found to be less biased and more accurate than the REACH models. Its prediction differs generally from measurements by a factor of 2-3 from measurements, whereas conventional models were found to differ by a factor 2-14. However, as the available test dataset is limited, its results will need to be confirmed by larger-scale tests.

This study experimentally evaluates the performance of different sorbent tubes for sampling acetone vapor in workplace air. A dynamic atmosphere system produced an acetone alone and a mixture with other analytes containing ~73, 483, and 1898 µg acetone mass loading at 25, 50, and 75% relative humidity (RH) at 25°C. Sorbent samples were analyzed in accordance with OSHA Method 69 (Carbosieve S-III) and NMAM 1501, modified to use Anasorb 747 sorbent. Both methods were modified to include the additional analytes. Additional extraction procedures with and without 1% dimethylformamide and anhydrous magnesium sulfate were included in the modified NMAM 1501 using Anasorb 747. Silica gel sorbent tubes analyzed according to NMAM 2027 were included. There were significant reductions in the recovery of acetone from both Anasorb 747 and Carbosieve S-III collected from air at 75% RH, relative to collection at 25 or 50% RH at very low loading compared with that of samples collected at mid to high loading. Silica gel provided a consistent recovery of acetone at all RHs and in the presence of other chemical interferences at 75% RH. The likely cause of mass dependence may arise from the humidity effect on acetone adsorption onto both beaded active carbon and carbon molecular sieve either in sampling or in analysis. The present study confirms not only previous observations but also adds to the literature showing carbonaceous sorbents are not well suited for sampling ketones at high humidity and low concentration.

Graphical abstract, Highlights • An automated thermal spray coating generator and inhalation exposure system was designed and developed. • The system can generate a consistent concentration of particles during thermal spray coating for an extended period. • The aerosols were complex metal oxides and arranged as chain-like agglomerates. • A short-term exposure study indicated that thermal spray coating stainless-steel aerosols significantly increased lung toxicity. • With the development of this thermal spray coating system, dose-response animal toxicology studies can be performed., Thermal spray coating involves spraying a product (oftentimes metal) that is melted by extremely high temperatures and then applied under pressure onto a surface. Large amounts of a complex metal aerosol (e.g., Fe, Cr, Ni, Zn) are formed during the process, presenting a potentially serious risk to the operator. Information about the health effects associated with exposure to these aerosols is lacking. Even less is known about the chemical and physical properties of these aerosols. The goal was to develop and test an automated thermal spray coating aerosol generator and inhalation exposure system that would simulate workplace exposures. An electric arc wire-thermal spray coating aerosol generator and exposure system was designed and separated into two areas: (1) an enclosed room where the spray coating occurs; (2) an exposure chamber with different measurement devices and controllers. The physicochemical properties of aerosols generated during electric arc wire-thermal spray coating using five different consumable wires were examined. The metal composition of each was determined by inductively coupled plasma-atomic emission spectroscopy (ICP-AES), including two stainless-steel wires [PMET720 (82 % Fe, 13 % Cr); PMET731(66 % Fe, 26 % Cr)], two Ni-based wires [PMET876 (55 % Ni, 17 % Cr); PMET885 (97 % Ni)], and one Zn-based wire [PMET540 (99 % Zn)]. The particles generated regardless of composition were poorly soluble, complex metal oxides and mostly arranged as chain-like agglomerates and similar in size distribution as determined by micro-orifice uniform deposit impactor (MOUDI) and electrical low-pressure impactor (ELPI). To allow for continuous, sequential spray coating during a 4-hr exposure period, a motor rotated the metal pipe to be coated in a circular and up-and-down direction. In a pilot animal study, male Sprague-Dawley rats were exposed to aerosols (25 mg/m3 × 4 h/d × 9 d) generated from electric arc wire- thermal spray coating using the stainless-steel PMET720 consumable wire. The targeted exposure chamber concentration was achieved and maintained during a 4-hr period. At 1 d after exposure, lung injury and inflammation were significantly elevated in the group exposed to the thermal spray coating aerosol compared to the air control group. The system was designed and constructed for future animal exposure studies to generate continuous metal spray coating aerosols at a targeted concentration for extended periods of time without interruption.

This study investigated the effects of particle transfer to the covers of aerosol samplers during transportation of wood dust and welding fume samples. Wood dust samples were collected in a sanding chamber using four sampler types: closed-face cassettes (CFC), CFC with Accu-CAP inserts, disposable inhalable samplers (DIS), and Institute of Occupational Medicine (IOM). Welding fumes were collected in a walk-in chamber using the same samplers, with Solu-Sert replacing Accu-CAP. The samples were divided into two groups, with one group transported by air and the other by land. They were returned in the same manner and analyzed gravimetrically for wood dust and chemically for welding fumes. For wood dust, IOM showed a significantly higher percentage of particles transferred to the covers compared with the other samplers regardless of the transportation mode (p < 0.0001; 64% by air and 15% by land), while other samplers showed less than or close to 10% (3.5–12%). When the percentages of particle transfer to the covers were compared between the air and land transportation, both IOM and CFC samples showed differences between modes of transportation, while others did not. For welding fumes, most samples (61% of samples for copper [Cu] and 76% of samples for manganese [Mn]) showed nondetectable amounts of the analyte on the covers. For all samplers, the particle transfer to the covers for both transportation modes ranged from 0.2–33% for Cu and less than 4.5% for Mn. Overall, this study confirms that particle transfer to sampler covers during transport highly depends upon the transportation mode and sampler type for wood dust, whereas particle transfer seems minimal for welding fumes. The findings of this study are based on two materials and limited sample sizes. Further investigation considering different industry types and tasks, particle size ranges, and materials might be necessary. Nevertheless, occupational professionals should account for this transfer when handling and analyzing samples in practice.

Perchloroethylene (PERC) is the most common solvent used for dry cleaning in the United States. PERC is a reproductive toxicant, neurotoxicant, potential human carcinogen, and a persistent environmental pollutant. The Environmental Protection Agency is evaluating PERC under the Frank R. Lautenberg Chemical Safety for the 21st Century Act, which amended the Toxic Substances Control Act (amended TSCA), and has mandated that PERC dry cleaning machines be removed from residential buildings. Some local and state programs are also requiring or facilitating transitions to alternative cleaning technologies. However, the potential for these alternatives to harm human health and the environment is not well-understood. This review describes the issues surrounding the use of PERC and alternative solvents for dry cleaning while highlighting the lessons learned from a local government program that transitioned PERC dry cleaners to the safest current alternative: professional wet cleaning. Implications for future public health research and policy are discussed: (1) we must move away from PERC, (2) any transition must account for the economic instability and cultural aspects of the people who work in the industry, (3) legacy contamination must be addressed even after safer alternatives are adopted, and (4) evaluations of PERC alternatives are needed to determine their implications for the long-term health and sustainability of the people who work in the industry.

Thermal spray coating is a process that applies a molten metal product under pressure onto a surface. Although thermal spray processes have been used for decades, exposure to aerosols formed during thermal spray coating is an emerging risk. Reports indicate that high concentrations of aerosols composed of toxic metals (e.g. chromium) are generated in the workplace. A knowledge gap exists related to the physicochemical properties of thermal spray coating aerosols as well as any potential associated health effects. The objective of this manuscript was to review thermal spray coating and previous studies that have examined the aerosols produced from this process. A thermal spray coating generator and exposure system is also described that has recently been developed to further evaluate the physical and chemical properties of aerosols formed during thermal spray coating as well as to assess the possible health effects of this process in an effort to mitigate potential occupational health hazards related to the industry.

Manufacturing, processing, use, and disposal of nanoclay-enabled composites potentially lead to the release of nanoclay particles from the polymer matrix in which they are embedded; however, exposures to airborne particles are poorly understood. The present study was conducted to characterize airborne particles released during sanding of nanoclay-enabled thermoplastic composites. Two types of nanoclay, Cloisite® 25A and Cloisite® 93A, were dispersed in polypropylene at 0%, 1%, and 4% loading by weight. Zirconium aluminum oxide (P100/P180 grits) and silicon carbide (P120/P320 grits) sandpapers were used to abrade composites in controlled experiments followed by real-time and offline particle analyses. Overall, sanding the virgin polypropylene with zirconium aluminum oxide sandpaper released more particles compared to silicon carbide sandpaper, with the later exhibiting similar or lower concentrations than that of polypropylene. Thus, a further investigation was performed for the samples collected using the zirconium aluminum oxide sandpaper. The 1% 25A, 1% 93A, and 4% 93A composites generated substantially higher particle number concentrations (1.3–2.6 times) and respirable mass concentrations (1.2–2.3 times) relative to the virgin polypropylene, while the 4% 25A composite produced comparable results, regardless of sandpaper type. It was observed that the majority of the inhalable particles were originated from composite materials with a significant number of protrusions of nanoclay (18–59%). These findings indicate that the percent loading and dispersion of nanoclay in the polypropylene modified the mechanical properties and thus, along with sandpaper type, affected the number of particles released during sanding, implicating the cause of potential adverse health effects.

OBJECTIVES. To describe the effect of monopolar electrocautery (EC) settings on surgical plume particulate concentration during pediatric tonsillectomy. STUDY DESIGN. Cross-sectional study. SETTING. Tertiary medical center. SUBJECTS AND METHODS. During total tonsillectomy exclusively performed with EC, air was sampled with a surgeon-worn portable particle counter. The airborne mean and maximum particle concentrations were compared for tonsillectomy performed with EC at 12 W vs 20 W, with smoke evacuation system (SES) and no smoke evacuation (NS). RESULTS. A total of 36 children were included in this analysis: 9 cases with EC at 12 W and SES (12SES), 9 cases with EC at 20 W and SES (20SES), 9 cases with EC at 12 W without SES (12NS), and 9 cases with EC at 20 W without SES (20NS). Mean particle number concentration in the breathing zone during tonsillectomy was 1661 particles/cm(3) for 12SES, 5515 particles/cm(3) for 20SES, 8208 particles/cm(3) for 12NS, and 78,506 particles/cm(3) for 20NS. There was a statistically significant difference in the particle number concentrations among the 4 groups. The correlation between the particle number concentration and EC time was either moderate (for 12SES) or negative (for remaining groups). CONCLUSION. Airborne particle concentrations during tonsillectomy are over 9.5 times higher when EC is set at 20 W vs 12 W with NS, which is mitigated to 3.3 times with SES. Applying lower EC settings with SES during pediatric tonsillectomy significantly reduces surgical plume exposure for patients, surgeons, and operating room personnel, which is a well-known occupational health hazard.

The apolipoprotein E gene (APOE) is the strongest genetic risk factor for developing Alzheimer's disease (AD). Our recent identification of altered APOE DNA methylation in AD postmortem brain (PMB) prompted this follow-up study. Our goals were to (i) validate the AD-differential methylation of APOE in an independent PMB study cohort and (ii) determine the cellular populations (i.e., neuronal vs. non-neuronal) of AD PMB that contribute to this differential methylation. Here, we obtained an independent cohort of 57 PMB (42 AD and 15 controls) and quantified their APOE methylation levels from frontal lobe and cerebellar tissue. We also applied fluorescence-activated nuclei sorting (FANS) to separate neuronal nuclei from non-neuronal nuclei within the tissue of 15 AD and 14 control subjects. Bisulfite pyrosequencing was used to generate DNA methylation profiles of APOE from both bulk PMB and FANS nuclei. Our results provide independent validation that the APOE CGI holds lower DNA methylation levels in AD compared to control in frontal lobe but not cerebellar tissue. Our data also indicate that the non-neuronal cells of the AD brain, which are mainly composed of glia, are the main contributors to the lower APOE DNA methylation observed in AD PMB. Given that astrocytes are the primary producers of ApoE in the brain our results suggest that alteration of epigenetically regulated APOE expression in glia could be an important part of APOE's strong effect on AD risk.

Increasing evidence suggests that the Translocase of Outer Mitochondria Membrane 40 (TOMM40) gene may contribute to the risk of Alzheimer’s disease (AD). Currently, there is no consensus as to whether TOMM40 expression is up- or down-regulated in AD brains, hindering a clear interpretation of TOMM40’s role in this disease. The aim of this study was to determine if TOMM40 RNA levels differ between AD and control brains. We applied RT-qPCR to study TOMM40 transcription in human postmortem brain (PMB) and assessed associations of these RNA levels with genetic variants in APOE and TOMM40. We also compared TOMM40 RNA levels with mitochondrial functions in human cell lines. Initially, we found that the human genome carries multiple TOMM40 pseudogenes capable of producing highly homologous RNAs that can obscure precise TOMM40 RNA measurements. To circumvent this obstacle, we developed a novel RNA expression assay targeting the primary transcript of TOMM40. Using this assay, we showed that TOMM40 RNA was upregulated in AD PMB. Additionally, elevated TOMM40 RNA levels were associated with decreases in mitochondrial DNA copy number and mitochondrial membrane potential in oxidative stress-challenged cells. Overall, differential transcription of TOMM40 RNA in the brain is associated with AD and could be an indicator of mitochondrial dysfunction.

The performance of the disposable inhalable aerosol sampler (DIAS), newly developed to be cost-effective and comparable to the inhalable particle sampling convention, was evaluated. Forty-eight sets of copper exposure measurements (23 personal and 25 area) with pairs of the DIAS prototypes and the IOM inhalable samplers were collected at an electrorefinery facility. For the combined data (personal and area), the geometric mean (GM) concentrations of copper were 36.1 μg m(−3) (range of 0.8 – 337.7 μg m(−3)) for the DIAS prototype and 26.5 μg m(−3) (range of 5.1 – 760.8 μg m(−3)) for the IOM sampler. The GM ratio of exposure measurements (DIAS/IOM) was 1.4 revealing ~ 81% of the ratios greater than the unit ratio. The concordance correlation coefficient tests revealed significant disagreement between the two types of samplers and suggested precision as the source of the disagreement. For the personal, area and combined data, no linear relationships were observed between the DIAS and IOM (all p-values < 0.05). In addition, the estimated average concentrations were always higher for the DIAS compared to the IOM for the combined and area exposure data (p-values < 0.05) and comparable for the personal exposure data (p-value = 0.487). Overall, regardless of the sampling method (i.e., personal and area), the DIAS generated higher exposure measurements compared to the IOM sampler. The present study is limited to one metal component (copper) of the dust at a worksite. As far as we are concerned, this is only the second field evaluation of the DIAS. Thus, it is too early to draw a firm conclusion about the performance of the DIAS vis-à-vis the inhalable convention. Additional field evaluations covering various chemicals and worksites will be necessary. In addition, particle losses on the cap during transportation of collected samples to a laboratory were observed for both sampler types. Occupational professionals should be aware of potential errors caused from transferring samples from a field to a laboratory and should be careful not to exclude particles collected on the caps.

Tier 1 occupational exposure assessment tools recommended for use under the Registration, Evaluation, Authorization, and restriction of CHemicals (REACH) were evaluated using newly collected measurement data. Evaluated tools included the ECETOC TRAv2 and TRAv3, MEASEv1.02.01, and EMKG-EXPO-TOOL. Fifty-three exposure situations (ESs) based on tasks/chemicals were developed from National Institute for Occupational Safety and Health field surveys. During the field surveys, high quality contextual information required for evaluating the tools was also collected. For each ES, applicable tools were then used to generate exposure estimates using a consensus approach. Among 53 ESs, only those related to an exposure category of liquids with vapor pressure (VP) > 10 Pa had sufficient numbers of exposure measurements (42 ESs with n = 251 for TRAv2 and TRAv3 and 40 ESs with n = 243 for EMKG-EXPO-TOOL) to be considered in detail. The results for other exposure categories (aqueous solutions, liquids with VP ≤ 10 Pa, metal processing, powders, and solid objects) had insufficient measurement to allow detailed analyses (results listed in the Supplementary File). Overall, EMKG-EXPO-TOOL generated more conservative results than TRAv2 and TRAv3 for liquids with high VP. This finding is at least partly due to the fact that the EMKG-EXPO-TOOL only considers pure substances and not mixtures of chemical agents. For 34 out of 40 ESs available for chemicals with VP > 10 Pa, the liquid was a mixture rather than a pure substance. TRAv3 was less conservative than TRAv2, probably due to additional refinement of some input parameters. The percentages of exposure measurement results exceeding the corresponding tool estimates for liquids with VP > 10 Pa by process category and by input parameters were always higher for TRAv3 compared to those for TRAv2. Although the conclusions of this study are limited to liquids with VP > 10 Pa and few process categories, this study utilized the most transparent contextual information compared to previous studies, reducing uncertainty from assumptions for unknown input parameters. A further validation is recommended by collecting sufficient exposure data covering other exposure categories and all process categories under REACH.

Stoffenmanager®v4.5 and Advanced REACH Tool (ART) v1.5, two higher tier exposure assessment tools for use under REACH, were evaluated by determining accuracy and robustness. A total of 282 exposure measurements from 51 exposure situations (ESs) were collected and categorized by exposure category. In this study, only the results of liquids with vapor pressure (VP) > 10 Pa category having a sufficient number of exposure measurements (n = 251 with 42 ESs) were utilized. In addition, the results were presented by handling/activity description and input parameters for the same exposure category. It should be noted that the performance results of Stoffenmanager and ART in this study cannot be directly compared for some ESs because ART allows a combination of up to four subtasks (and nonexposed periods) to be included, whereas the database for Stoffenmanager, separately developed under the permission of the legal owner of Stoffenmanager, permits the use of only one task to predict exposure estimates. Thus, it would be most appropriate to compare full-shift measurements against ART predictions (full shift including nonexposed periods) and task-based measurements against task-based Stoffenmanager predictions. For liquids with VP > 10 Pa category, Stoffenmanager®v4.5 appeared to be reasonably accurate and robust when predicting exposures [percentage of measurements exceeding the tool’s 90th percentile estimate (%M > T) was 15%]. Areas that could potentially be improved include ESs involving the task of handling of liquids on large surfaces or large work pieces, allocation of high and medium VP inputs, and absence of local exhaust ventilation input. Although the ART’s median predictions appeared to be reasonably accurate for liquids with VP > 10 Pa, the %M > T for the 90th percentile estimates was 41%, indicating that variance in exposure levels is underestimated by ART. The %M > T using the estimates of the upper value of 90% confidence interval (CI) of the 90th percentile estimate (UCI90) was considerably reduced to 18% for liquids with VP > 10 Pa. On the basis of this observation, users might be to consider using the upper limit value of 90% CI of the 90th percentile estimate for predicting reasonable worst case situations. Nevertheless, for some activities and input parameters, ART still shows areas to be improved. Hence, it is suggested that ART developers review the assumptions in relation to exposure variability within the tool, toward improving the tool performance in estimating percentile exposure levels. In addition, for both tools, only some handling/activity descriptions and input parameters were considered. Thus, further validation studies are still necessary.

Within the framework of Registration, Evaluation, Authorization, and restriction of CHemicals (REACH), occupational exposure models are often used to predict the levels of exposure at a workplace. Poor inter-assessor agreement with their use poses a concern that may lead to different and dangerous risk conclusions. TREXMO (v1, 2016), a web tool providing parameter translations between six exposure models under REACH, is expected to improve the inter-assessor agreement. In this study, 18 assessors performed exposure assessment for six exposure situations within and outside the framework of this translation tool. In more than half of the evaluated cases, the results showed better agreement between assessors selecting the exposure parameters within the framework of TREXMO than when manually coding. The most affected were the parameters related to activity (such as “handling types” of Stoffenmanager) and exposure control (such as local controls). Furthermore, the agreement between the estimates calculated by different assessors was also improved when performing the translations between the models. For Stoffenmanager, for example, the relative standard deviation of 70–121%, obtained for vapors without applying the translation system, was 29–94% with the translations from ART. These findings showed a potential of TREXMO to impact the inter-assessor agreement. Because the study was limited to 18 assessors and only six exposure situations were assessed, further investigations are suggested.

This study was to determine occupational exposures to formaldehyde and to compare concentrations of formaldehyde obtained by active and passive sampling methods. In one pathology and one histology laboratories, exposure measurements were collected with sets of active air samplers (Supelco LpDNPH tubes) and passive badges (ChemDisk Aldehyde Monitor 571). Sixty-six sample pairs (49 personal and 17 area) were collected and analyzed by NIOSH NMAM 2016 for active samples and OSHA Method 1007 (using the manufacturer’s updated uptake rate) for passive samples. All active and passive 8-hour time-weighted average (TWA) measurements showed compliance with the OSHA permissible exposure limit (PEL-0.75 ppm) except for one passive measurement, whereas 78% for the active and 88% for the passive samples exceeded the NIOSH recommended exposure limit (REL-0.016 ppm). Overall, 73% of the passive samples showed higher concentrations than the active samples and a statistical test indicated disagreement between two methods for all data and for data without outliers. The OSHA Method cautions that passive samplers should not be used for sampling situations involving formalin solutions because of low concentration estimates in the presence of reaction products of formaldehyde and methanol (a formalin additive). However, this situation was not observed, perhaps because the formalin solutions used in these laboratories included much less methanol (3%) than those tested in the OSHA Method (up to 15%). The passive samplers in general overestimated concentrations compared to the active method, which is prudent for demonstrating compliance with an occupational exposure limit, but occasional large differences may be a result of collecting aerosolized droplets or splashes on the face of the samplers. In the situations examined in this study the passive sampler generally produces higher results than the active sampler so that a body of results from passive samplers demonstrating compliance with the OSHA PEL would be a valid conclusion. However, individual passive samples can show lower results than a paired active sampler so that a single result should be treated with caution.

The apolipoprotein E gene (APOE) is the strongest genetic risk factor for late-onset Alzheimer’s disease (AD), yet the expression of APOE is not clearly understood. For example, it is unclear whether AD patients have elevated or decreased APOE expression or why the correlation levels of APOE RNA and the ApoE protein differ across studies. Likewise, APOE has a single CpG island (CGI) that overlaps with its 3’-exon, and this CGI’s effect is unknown. We previously reported that the APOE CGI is highly methylated in human postmortem brain (PMB) and that this methylation is altered in AD frontal lobe. In this study, we comprehensively characterized APOE RNA transcripts and correlated levels of RNA expression with DNA methylation levels across the APOE CGI. We discovered the presence of APOE circular RNA (circRNA) and found that circRNA and full-length mRNA each constitute approximately one third of the total APOE RNA, with truncated mRNAs likely constituting some of the missing fraction. All APOE RNA species demonstrated significantly higher expression in AD frontal lobe than in control frontal lobe. Furthermore, we observed a negative correlation between the levels of total APOE RNA and DNA methylation at the APOE CGI in the frontal lobe. When stratified by disease status, this correlation was strengthened in controls but not in AD. Our findings suggest a possible modified mechanism of gene action for APOE in AD that involves not only the protein isoforms but also an epigenetically regulated transcriptional program driven by DNA methylation in the APOE CGI.

Correction for ‘Characterization of aerosolized particles from nanoclay-enabled composites during manipulation processes’ by Eun Gyung Lee et al., Environ. Sci.: Nano, 2020, DOI: 10.1039/c9en01211g.

The objective of this present study was to evaluate the performance of a portable gas chromatograph-photoionization detector (GC-PID), under various test conditions to determine if it could be used in occupational settings. A mixture of 7 volatile organic compounds (VOCs)—acetone, ethylbenzene, methyl isobutyl ketone, toluene, m-xylene, p-xylene, and o-xylene—was selected because its components are commonly present in paint manufacturing industries. A full-factorial combination of 4 concentration levels (exposure scenarios) of VOC mixtures, 3 different temperatures (25°C, 30°C, and 35°C), and 3 relative humidities (RHs; 25%, 50%, and 75%) was conducted in a full-size controlled environmental chamber. Three repetitions were conducted for each test condition allowing for estimation of accuracy. Time-weighted average exposure data were collected using solid sorbent tubes (Anasorb 747, SKC Inc.) as the reference sampling medium. Calibration curves of Frog-4000 using the dry gases showed R(2) > 0.99 for all analytes except for toluene (R(2) = 0.97). Frog-4000 estimates within a test condition showed good consistency for the performance of repeated measurement. However, there was ~41–64% reduction in the analysis of polar acetone with 75% RH relative to collection at 25% RH. Although Frog-4000 results correlated well with solid sorbent tubes (r = 0.808–0.993, except for toluene) most of the combinations regardless of analyte did not meet the

The chemical compound 1-Chloro-4-(trifluoromethyl) benzene (CAS No: 98-56-6)—also known as PCBTF, Oxsol 100, or Parachlorobenzotrifluoride—was nominated to the National Toxicology Program (NTP) for toxicity and carcinogenicity studies (http://ntp.niehs.nih.gov/ntp/noms/support_docs/pcbtf06-0409.pdf). The nomination was based on the increasing use of PCBTF by industries and consumers, since it was exempted by the Environmental Protection Agency (EPA) as a volatile organic compound in emissions reporting on the basis of not reacting in a manner that would contribute to the formation of tropospheric ozone.(1) Although PCBTF is no longer manufactured in the United States, approximately 29 million lbs. were imported in 2012(2) and used in various applications to replace other chlorinated solvents with known environmental or human health hazards. Those applications include the automotive industry as industry-wide applications in coatings, thinners, and cleaning solvents, and repair and maintenance cleaning and as a consumer product for cosmetic stain removal and aerosol rust prevention.(3) The toxicity information on PCBTF is available from various resources(4,5) including the NTP website.(6) These studies, however, are limited to short-term toxicity, and chronic inhalation toxicity and carcinogenicity studies are unavailable. There are no Occupational Safety and Health Administration (OSHA) regulations specific to limiting occupational exposures to PCBTF. The National Institute for Occupational Safety and Health (NIOSH) has not established a time-weighted average (TWA) recommended exposure level, and the American Conference of Governmental Industrial Hygienists (ACGIH®) has not established a TWA-threshold limit value (TLV®) for PCBTF. The Occidental Chemical Corporation, which used to manufacture PCBTF in the United States, established a corporate exposure limit (CEL), which was a TWA limit of 25 ppm (185 mg/m3) for an 8-hr work-shift. The toxicological basis for setting this limit is not known to us. However, Occidental Chemical Corporation no longer manufactures or imports PCBTF into the United States. The purpose of this case study is to determine industry-wide occupational inhalation exposures using available industrial hygiene sampling methods. This information can be used to benchmark exposure concentrations that may be applied in future studies of inhalation toxicity in animal models. In addition, side-by-side samples of a pumped (active) and diffusive (passive) sorbent tubes were taken to compare concentration ratios between the active and passive sampling methods. Workplace Description Vehicle manufacturing plants Four vehicle manufacturing plants—helicopter (Plant A), aircraft (Plants B and C), and automobile (Plant C)—were recruited through personal contacts. All manufacturing plants were identified by code for confidentiality. At Plant A, PCBTF was used as a cleaning solvent to remove residual glue after upholstery removal during interior refurbishment. The cleaning work was done manually under a slotted back-draft ventilation hood. PCBTF was used during primer application prior to coating of an airplane at Plants B and C and plastic adhesive promoter application at Plant D. All painters wore airline respirators and applied the PCBTF-containing substances using spray guns under downdraft ventilation. The mixing worker at Plant C combined base (23 L with 0% PCBTF), activator (23 L with 30–60% PCBTF), and thinner (6 L with 60–90% PCBTF) to make primer. The mixing task was done under a canopy hood and the mixer wore a full facepiece air-purifying respirator. The amount of PCBTF per worker used during the specific tasks varied ranging from 0.3 to 18.5 L. Table I shows a summary of workplace description including tasks, PCBTF usage, room ventilation, local exhaust ventilation, respirator type, and the amount of PCBTF used during each task. Detailed information about job tasks and personal protective equipment was described in a supplementary file. TABLE I Summary of Workplace Description (Vehicle Manufacturing Plants) Paint manufacturing plants Three paint manufacturing plants were recruited via contacting American Coatings Association. Four tasks—pre-batch making, batch making, filling, and miscellaneous—were observed. In the pre-batch making area (Plants E and G), workers transferred PCBTF-containing materials to other containers using either a pumping system or a mechanized pouring system. Containers were partially opened to place a pumping system. No respirator was required for this task at both plants. In the batch-making area (Plants E, F, and G), each batch-maker added various chemicals in a batch container, mixed the chemicals, transferred the chemicals to other containers, and cleaned the emptied batches. The batch-making task was done in a closed system for all plants except for cleaning or partially opened to add or transfer materials. The batch-makers wore no respirators during mixing but wore dust masks (Plants E and G) and half facepiece respirators (Plant F) when manually adding materials. The filling operators (Plants E, F, and G) filled containers with final product from an automated dispenser and placed lids. No respirator was required for the filling task. Other miscellaneous tasks included lab quality control testing, cleaning, batch adjusting, color mixing, and pilot working. The workplaces for all tasks were controlled by general ventilation in addition to any local exhaust ventilation systems. Table II shows a summary of workplace description and detailed information for each task was described in a supplementary file. TABLE II Summary of Workplace Description (Paint Manufacturing Plants) METHODS Sample Monitoring At the four vehicle manufacturing plants, 28 personal and 8 area sample pairs were collected using actively pumped coconut-shell charcoal tubes (SKC 226-01, SKC Inc., Eighty Four, PA) and diffusive charcoal badges (SKC 575-001, SKC Inc.). The former represents an active sampling method (i.e., drawing air throughout the media using a pump) and the latter represents a passive sampling method (i.e., air intake by chemical diffusion). All workers sampled at the vehicle manufacturing plants handled the PCBTF-containing materials. At the three paint manufacturing plants, 64 personal and 26 area sample pairs were collected. Participants were workers who handled PCBTF and workers who did not but were in close proximity to the workers handling PCBTF. The sample size and sampling time for each task are listed in Table III. The sampling times ranged from 15 to 407 min for the vehicle manufacturing plants and 70 to 535 min for the paint manufacturing plants. Two types of sampling pumps, Pocket Pump (SKC Inc.) and Gilian LFS-113 (Sensidyne, Clearwater, FL), were used at sampling flow rates between 20 and 200 ml/min for the active sampling method. The sampling flow rates were adjusted based on anticipated concentrations, previously collected from similar workplaces. Each pump was calibrated before and after sample collection with a DryCal DC-Lite device (BIOS International Corporation, Butler, NJ) to assure the difference between pre- and post-sampling flow rates was within ±5%. The position of passive and active samplers for the personal sampling method was randomized to minimize bias from workers’ handiness (i.e., not always on the left or right of worker’s collar). All field surveys were performed between 2010 and 2012. TABLE III Air Sampling Results Using Active Sampling Method All active and passive samples were analyzed with gas chromatography/flame ionization detector according to the NIOSH Manual of Analytical Methods (NMAM) 1026(7) by the NIOSH contract laboratory. The NIOSH method has suggested a maximum of 25 ppm for a 10 L air sample with a working range between 0.024 and 9.15 ppm (0.178 to 67.8 mg/m3). Yost and Harper(8) tested passive badges at various loadings in a standard atmosphere chamber in which the test concentrations of the standard atmosphere were confirmed by means of coconut charcoal tubes for time period up to 8 hr. Those loadings were 0.012 mg (0.01×CEL), 0.123 mg (0.1×CEL), 0.505 mg (0.5×CEL), 1.10 mg (1.0×CEL), and 2.09 mg (2.0×CEL). Yost and Harper(8) showed charcoal tubes and passive badges to have a large capacity covering up to 2 times the CEL and the maximum concentration suggested by the NIOSH method. The mass concentrations of passive badges were calculated using the average sampling rate of 11.8 ml/min.(8) From each sampling site, 1–10 field blank samples were collected. In this study, sample results were not adjusted by field blank samples because almost all field blank samples (96% of 56 field blank samples) showed non-detectable masses. The limit of detection was 0.1 – 0.7 μg for both diffusive badge and charcoal tube. The limit of quantitation ranged between 0.5 – 2.5 μg for the diffusive charcoal badge and 0.5 – 3.4 μg for the charcoal tube. Three sample pairs showing at least one of each pair resulted in less than the limit of detection were excluded. None of the samples except for the three sample pairs showed less than the limit of quantitation.

A polyvinyl chloride (PVC) cassette insert with PVC filter (ACCU-CAP) in a 37-mm closed-face cassette (CFC) was designed for gravimetric analysis. A customized version of the ACCU-CAP, also to be used in the CFC, was manufactured from an acid-digestible cellulose-acetate cassette insert joined to a mixed cellulose ester (MCE) filter for wet chemical analysis. The aim of this study was to compare metal particle concentrations as sampled by the customized insert (CI) in a CFC sampler with the traditional sampling method using only a MCE filter in the CFC. Thirty-nine personal and 13 area samples were taken using paired filter-based CFC and the CI in CFC samplers at a solder manufacturing plant. The CI was removed from its CFC, and digested and analyzed as a whole. The MCE filter from the typical CFC was removed for analysis and then the interior of the cassette was wiped with Ghost Wipe for a separate analysis. The MCE filter only, Ghost Wipe, and CI were separately dissolved in heated nitric acid for ICP-MS analysis. Overall, the geometric mean concentration of the filter-only (FO) samples was considerably lower than that of the CI samples, by 53% for lead and 32% for tin. However, if the FO analysis was added to the corresponding Ghost Wipe analysis, i.e., filter+interior wipe (FW), the geometric mean concentrations of the FW results were similar to those of the CI results (by 113% for lead and 98% for tin). For both lead and tin the comparison of (log-transformed) metal concentrations between the FW and CI results showed no statistically significant difference (p-value = 0.3009 for lead and 0.800 for tin), while the comparison between the FO and CI results shows statistically significant differences (all p-values < 0.05). In conclusion, incorporating the sampler internal non-filter deposits by wiping or use of an internal filter capsule gave higher results than analyzing only the filter. Close agreement between the two methods of including non-filter deposits is an indication of general equivalency.

Simian foamy viruses (SFV) are complex retroviruses that are ubiquitous in nonhuman primates (NHP) and are zoonotically transmitted to humans, presumably through NHP saliva, by licking, biting, and other behaviors. We have studied SFV in free-ranging rhesus macaques in Bangladesh. It has been previously shown that SFV in immunocompetent animals replicates to detectable levels only in superficial epithelial cells of the oral mucosa, although latent proviruses are found in most, if not all, tissues. In this study, we compare DNA sequences from latent SFV proviruses found in blood cells of 30 Bangladesh rhesus macaques to RNA sequences of transcriptionally active SFV from buccal swabs obtained from the same animals. Viral strains, defined by differences in SFV gag sequences, from buccal mucosal specimens overlapped with those from blood samples in 90% of animals. Thus, latent proviruses in peripheral blood mononuclear cells (PBMC) are, to a great extent, representative of viruses likely to be transmitted to other hosts. The level of SFV RNA in buccal swabs varied greatly between macaques, with increasing amounts of viral RNA in older animals. Evidence of APOBEC3-induced mutations was found in gag sequences derived from the blood and oral mucosa.

Foamy viruses (FVs) differ from all other genera of retroviruses (orthoretroviruses) in many aspects of viral replication. In this review, we discuss FV assembly, with special emphasis on Pol incorporation. FV assembly takes place intracellularly, near the pericentriolar region, at a site similar to that used by betaretroviruses. The regions of Gag, Pol and genomic RNA required for viral assembly are described. In contrast to orthoretroviral Pol, which is synthesized as a Gag-Pol fusion protein and packaged through Gag-Gag interactions, FV Pol is synthesized from a spliced mRNA lacking all Gag sequences. Thus, encapsidation of FV Pol requires a different mechanism. We detail how WT Pol lacking Gag sequences is incorporated into virus particles. In addition, a mutant in which Pol is expressed as an orthoretroviral-like Gag-Pol fusion protein is discussed. We also discuss temporal regulation of the protease, reverse transcriptase and integrase activities of WT FV Pol.

Standardization is essential to fostering the use of harmonized methods for exposure assessment in occupational hygiene nationally and internationally. A standardized method for sampling and analys...

The dry cleaning industry is moving away from using perchloroethylene. Occupational exposures to two alternative dry cleaning solvents, butylal and high-flashpoint hydrocarbons, have not been well characterized. We evaluated four dry cleaning shops that used these alternative solvents. The shops were staffed by Korean- and Cantonese-speaking owners, and Korean-, Cantonese-, and Spanish-speaking employees. Because most workers had limited English proficiency we used language services in our evaluations. In two shops we collected personal and area air samples for butylal. We also collected air samples for formaldehyde and butanol, potential hydrolysis products of butylal. Because there are no occupational exposure limits for butylal, we assessed employee health risks using control banding tools. In the remaining two shops we collected personal and area air samples for high-flashpoint hydrocarbon solvents. In all shops the highest personal airborne exposures occurred when workers loaded and unloaded the dry cleaning machines and pressed dry cleaned fabrics. The air concentrations of formaldehyde and butanol in the butylal shops were well below occupational exposure limits. Likewise, the air concentrations of high-flashpoint hydrocarbons were also well below occupational exposure limits. However, we saw potential skin exposures to these chemicals. We provided recommendations on appropriate work practices and the selection and use of personal protective equipment. These recommendations were consistent with those derived using control banding tools for butylal. However, there is insufficient toxicological and health information to determine the safety of butylal in occupational settings. Independent evaluation of the toxicological properties of these alternative dry cleaning solvents, especially butylal, is urgently needed.

Foamy viruses (FV) synthesize Pol from a spliced pol mRNA independently of Gag, unlike orthoretroviruses, which synthesize Pol as a Gag-Pol protein that coassembles with Gag. We found that prototype FV (PFV) mutants expressing Gag and Pol only as a Gag-Pol protein without the spliced Pol contain protease activity equivalent to that of wild-type (WT) Pol. Regardless of the presence or absence of the spliced Pol, the PFV Gag-Pol proteins can assemble into virus-like particles (VLPs), in contrast to the orthoretroviral Gag-Pol proteins, which cannot form VLPs. However, the PFV Gag-Pol VLPs have aberrant morphologies and are not infectious. In the absence of the spliced Pol, coexpression of a PFV Gag-Pol protein with Gag can produce infectious virions. Our results suggest that enzymes encoded by PFV pol (protease, reverse transcriptase, and integrase) are enzymatically active if they are synthesized as part of a Gag-Pol protein.

The objective of this study was to assess the potential for using artificial neural networks (ANN) to predict inspired minute ventilation $$ \left( {\dot{V}_{I} } \right) $$ during exercise activities. Six physiological/kinematic measurements obtained from a portable ambulatory monitoring system, along with individual’s anthropometric and demographic characteristics, were employed as input variables to develop and optimize the ANN configuration with respect to reference values simultaneously measured using a pneumotachograph (PT). The generalization ability of the resulting two-hidden-layer ANN model was compared with a linear predictive model developed through partial least squares (PLS) regression, as well as other $$ \dot{V}_{I} $$ predictive models proposed in the literature. Using an independent dataset recorded from nine 80-min step tests, the results showed that the ANN-estimated $$ \dot{V}_{I} $$ was highly correlated (R 2 = 0.88) with $$ \dot{V}_{I} $$ measured by the PT, with a mean difference of approximately 0.9%. In contrast, the PLS and other regression-based models resulted in larger average errors ranging from 7 to 34%. In addition, the ANN model yielded estimates of cumulative total volume that were on average within 1% of reference PT measurements. Compared with established statistical methods, the proposed ANN model demonstrates the potential to provide improved prediction of respiratory ventilation in workplace applications for which the use of traditional laboratory-based instruments is not feasible. Further research should be conducted to investigate the performance of ANNs for different types of physical activity in larger and more varied worker populations.

Unlike orthoretroviruses, foamy retroviruses (FV) synthesize Pol independently of Gag. The FV Pol precursor is cleaved only once between reverse transcriptase (RT) and integrase (IN) by the protease (PR), resulting in a PR-RT and an IN protein. Only the Pol precursor, not the cleaved subunits, is packaged into virions. Like orthoretroviral PRs, FV PR needs to dimerize to be active. Previously, we showed that a Pol mutant lacking IN has defects in PR activity and Pol packaging into virions. We now show that introduction of a leucine zipper (zip) dimerization motif in an IN truncation mutant can restore PR activity, leading to Pol processing in cells. However, these zip mutants neither cleave Gag nor incorporate Pol into virions. We propose that IN is required for Pol dimerization, which is necessary for the creation of a functional PR active site.

The current study evaluated the Control of Substances Hazardous to Health (COSHH) Essentials model for short-term task-based exposures and full-shift exposures using measured concentrations of three volatile organic chemicals at a small printing plant. A total of 188 exposure measurements of isopropanol and 187 measurements of acetone were collected and each measurement took approximately 60 min. Historically, collected time-weighted average concentrations (seven results) were evaluated for methylene chloride. The COSHH Essentials model recommended general ventilation control for both isopropanol and acetone. There was good agreement between the task-based exposure measurements and the COSHH Essentials predicted exposure range (PER) for cleaning and print preparation with isopropanol and for cleaning with acetone. For the other tasks and for full-shift exposures, agreement between the exposure measurements and the PER was either moderate or poor. However, for both isopropanol and acetone, our findings suggested that the COSHH Essentials model worked reasonably well because the probabilities of short-term exposure measurements exceeding short-term occupational exposure limits (OELs) or full-shift exposures exceeding the corresponding full-shift OELs were

A Japanese round-robin study revealed that analysts who used a dark-medium (DM) objective lens reported higher fiber counts from American Industrial Hygiene Association (AIHA) Proficiency Analytical Testing (PAT) chrysotile samples than those using a standard objective lens, but the cause of this difference was not investigated at that time. The purpose of this study is to determine any major source of this difference by performing two sets of round-robin studies. For the first round-robin study, 15 AIHA PAT samples (five each of chrysotile and amosite generated by water-suspended method, and five chrysotile generated by aerosolization method) were prepared with relocatable cover slips and examined by nine laboratories. A second round-robin study was then performed with six chrysotile field sample slides by six out of nine laboratories who participated in the first round-robin study. In addition, two phase-shift test slides to check analysts’ visibility and an eight-form diatom test plate to compare resolution between the two objectives were examined. For the AIHA PAT chrysotile reference slides, use of the DM objective resulted in consistently higher fiber counts (1.45 times for all data) than the standard objective (P-value < 0.05), regardless of the filter generation (water-suspension or aerosol) method. For the AIHA PAT amosite reference and chrysotile field sample slides, the fiber counts between the two objectives were not significantly different. No statistically significant differences were observed in the visibility of blocks of the test slides between the two objectives. Also, the DM and standard objectives showed no pattern of differences in viewing the fine lines and/or dots of each species images on the eight-form diatom test plate. Among various potential factors that might affect the analysts’ performance of fiber counts, this study supports the greater contrast caused by the different phase plate absorptions as the main cause of high counts for the AIHA PAT chrysotile slides using the DM objective. The comparison of fiber count ratios (DM/standard) between the AIHA PAT chrysotile samples and chrysotile field samples indicates that there is a fraction of fibers in the PAT samples approaching the theoretical limit of visibility of the phase-contrast microscope with 3-degree phase-shift. These fibers become more clearly visible through the greater contrast from the phase plate absorption of the DM objective. However, as such fibers are not present in field samples, no difference in counts between the two objectives was observed in this study. The DM objective, therefore, could be allowed for routine fiber counting as it will maintain continuity with risk assessments based on earlier phase-contrast microscopy fiber counts from field samples. Published standard methods would need to be modified to allow a higher aperture specification for the objective.

The Rous sarcoma virus (RSV) Gag polyprotein is the only protein required for virus assembly and release. We previously found that deletion of either one of the two Cys–His (CH) motifs in the RSV nucleocapsid (NC) protein did not abrogate Gag–Gag interactions, RNA binding, or packaging but greatly reduced virus production (E-G. Lee, A. Alidina et al., J. Virol. 77: 2010–2020, 2003). In this report, we have further investigated the effects of mutations in the CH motifs on virus assembly and release. Precise deletion of either CH motif, without affecting surrounding basic residues, reduced virus production by approximately 10-fold, similar to levels seen for late (L) domain mutants. Strikingly, transmission electron microscopy revealed that virions of both ΔCH1 and ΔCH2 mutants were assembled normally at the plasma membrane but were arrested in budding. Virus particles remained tethered to the membrane or to each other, reminiscent of L domain mutants, although the release defect appears to be independent of the L domain functions. Therefore, two CH motifs are likely to be required for budding independent of a requirement for either Gag–Gag interactions or RNA packaging.

The Orthoretrovirus Gag interaction (I) domain maps to the nucleocapsid (NC) domain in the Gag polyprotein. We used the yeast two-hybrid system to analyze the role of Alpharetrovirus NC in Gag-Gag interactions and also examined the efficiency of viral assembly and release in vivo. We could delete either or both of the two Cys-His (CH) boxes without abrogating Gag-Gag interactions. We found that as few as eight clustered basic residues, attached to the C terminus of the spacer peptide separating the capsid (CA) and NC domains in the absence of NC, was sufficient for Gag-Gag interactions. Our results support the idea that a sufficient number of basic residues, rather than the CH boxes, play the important role in Gag multimerization. We also examined the requirement for basic residues in Gag for packaging of specific packaging signal (Ψ)-containing RNA. Using a yeast three-hybrid RNA-protein interaction assay, second-site suppressors of a packaging-defective Gag mutant were isolated, which restored Ψ RNA binding. These suppressors mapped to the p10 or CA domains in Gag and resulted in either introduction of a positively charged residue or elimination of a negatively charged one. These results imply that the structural interactions of NC with other domains of Gag are necessary for Ψ RNA binding. Taken together, our results show that while Gag assembly only requires a certain number of positively charged amino acids, Gag binding to genomic RNA for packaging requires more complex interactions inherent in the protein tertiary structure.

In the context of the Rous sarcoma virus Gag polyprotein, only the nucleocapsid (NC) domain is required to mediate the specificity of genomic RNA packaging. We have previously showed that the Saccharomyces cerevisiae three-hybrid system provides a rapid genetic assay to analyze the RNA and protein components of the avian retroviral RNA-Gag interactions necessary for specific encapsidation. In this study, using both site-directed mutagenesis and in vivo random screening in the yeast three-hybrid binding assay, we have examined the amino acids in NC required for genomic RNA binding. We found that we could delete either of the two Cys-His boxes without greatly abrogating either RNA binding or packaging, although the two Cys-His boxes are likely to be required for efficient viral assembly and release. In contrast, substitutions for the Zn-coordinating residues within the boxes did prevent RNA binding, suggesting changes in the overall conformation of the protein. In the basic region between the two Cys-His boxes, three positively charged residues, as well as basic residues flanking the two boxes, were necessary for both binding and packaging. Our results suggest that the stretches of positively charged residues within NC that need to be in a proper conformation appear to be responsible for selective recognition and binding to the packaging signal (Ψ)-containing RNAs.

Lee et al. (Evaluation of pump pulsation in respirable size-selective sampling: part I. Pulsation measurements. Ann Occup Hyg 2014a;58:60–73) introduced an approach to measure pump pulsation (PP) using a real-world sampling train, while the European Standards (EN) (EN 1232-1997 and EN 12919-1999) suggest measuring PP using a resistor in place of the sampler. The goal of this study is to characterize PP according to both EN methods and to determine the relationship of PP between the published method (Lee et al., 2014a) and the EN methods. Additional test parameters were investigated to determine whether the test conditions suggested by the EN methods were appropriate for measuring pulsations. Experiments were conducted using a factorial combination of personal sampling pumps (six medium- and two high-volumetric flow rate pumps), back pressures (six medium- and seven high-flow rate pumps), resistors (two types), tubing lengths between a pump and resistor (60 and 90 cm), and different flow rates (2 and 2.5 l min−1 for the medium- and 4.4, 10, and 11.2 l min−1 for the high-flow rate pumps). The selection of sampling pumps and the ranges of back pressure were based on measurements obtained in the previous study (Lee et al., 2014a). Among six medium-flow rate pumps, only the Gilian5000 and the Apex IS conformed to the 10% criterion specified in EN 1232-1997. Although the AirChek XR5000 exceeded the 10% limit, the average PP (10.9%) was close to the criterion. One high-flow rate pump, the Legacy (PP = 8.1%), conformed to the 10% criterion in EN 12919-1999, while the Elite12 did not (PP = 18.3%). Conducting supplemental tests with additional test parameters beyond those used in the two subject EN standards did not strengthen the characterization of PPs. For the selected test conditions, a linear regression model [PPEN = 0.014 + 0.375 × PPNIOSH (adjusted R2 = 0.871)] was developed to determine the PP relationship between the published method (Lee et al., 2014a) and the EN methods. The 25% PP criterion recommended by Lee et al. (2014a), average value derived from repetitive measurements, corresponds to 11% PPEN. The 10% pass/fail criterion in the EN Standards is not based on extensive laboratory evaluation and would unreasonably exclude at least one pump (i.e. AirChek XR5000 in this study) and, therefore, the more accurate criterion of average 11% from repetitive measurements should be substituted. This study suggests that users can measure PP using either a real-world sampling train or a resistor setup and obtain equivalent findings by applying the model herein derived. The findings of this study will be delivered to the consensus committees to be considered when those standards, including the EN 1232-1997, EN 12919-1999, and ISO 13137-2013, are revised.

Phase distribution of airborne chemicals is important because intake and uptake mechanisms of each phase are different. The phase distribution and concentrations are needed to determine strategies of exposure assessment, hazard control, and worker protection. However, procedures for establishing phase distribution and concentration have not been standardized. The objective of this study was to compare measurements of an airborne semivolatile pesticide (chlorpyrifos) by phase using two different procedures. Six pesticide applications in two facilities were studied and at each site, samples were collected for three time slots: T1, the first 1 or 2 hr after the commencement of application; T2, a 6-hr period immediately following T1; and T3, a 6-hr period after the required re-entry interval (24 hr for chlorpyrifos).Two phase-separating devices were co-located at the center of each greenhouse: semivolatile aerosol dichotomous sampler (SADS) using flow rates of 1.8 l x min(-1) and 0.2 l x min(-1), corresponding to a total inlet flow rate of 2.0 l x min(-1) with a vapor phase flow fraction of 0.1; and an electrostatic precipitator (ESP), along with a standard OVS XAD-2 tube. Chlorpyrifos in vapor and particulate form in a SADS sampling train and that in vapor form in an ESP sampling train were collected in OVS tubes. Chlorpyrifos in particulate form in the ESP setting would have been collected on aluminum substrate. However, no chlorpyrifos in particulate form was recovered from the ESP. Overall (vapor plus particle) concentrations measured by OVS ranged 11.7-186.6 μg/m(3) at T1 and decreased on average 77.1% and 98.9% at T2 and T3, respectively. Overall concentrations measured by SADS were 66.6%, 72.7%, and 102% of those measured by OVS on average at T1, T2, and T3, respectively. Particle fractions from the overall concentrations measured by SADS were 60.0%, 49.2%, and 13.8%, respectively, for T1, T2, and T3. SADS gives better guidance on the distribution of chlorpyrifos than does the ESP, although the accuracy of the concentration distribution cannot be verified in the absence of a standardized procedure for determining phase division.

The Rous sarcoma virus (RSV) Gag precursor polyprotein is the only viral protein which is necessary for specific packaging of genomic RNA. To map domains within Gag which are important for packaging, we constructed a series of Gag mutations in conjunction with a protease (PR) active-site point mutation in a full-length viral construct. We found that deletion of either the matrix (MA), the capsid (CA), or the protease (PR) domain did not abrogate packaging, although the MA domain is likely to be required for proper assembly. A previously characterized deletion of both Cys-His motifs in RSV nucleocapsid protein (NC) reduced both the efficiency of particle release and specific RNA packaging by 6- to 10-fold, consistent with previous observations that the NC Cys-His motifs played a role in assembly and RNA packaging. Most strikingly, when amino acid changes at Arg 549 and 551 immediately downstream of the distal NC Cys-His box were made, RNA packaging was reduced by more than 25-fold with no defect in particle release, demonstrating the importance of this basic amino acid region in packaging. We also used the yeast three-hybrid system to study avian retroviral RNA-Gag interactions. Using this assay, we found that the interactions of the minimal packaging region (Mψ) with Gag are of high affinity and specificity. Using a number of Mψ and Gag mutants, we have found a clear correlation between a reporter gene activation in a yeast three-hybrid binding system and an in vivo packaging assay. Our results showed that the binding assay provides a rapid genetic assay of both RNA and protein components for specific encapsidation.