End-stage renal disease incidence in a cohort of US firefighters from San Francisco, Chicago, and Philadelphia.

BACKGROUND: Firefighters perform strenuous work in hot environments, which may increase their risk of chronic kidney disease. The purpose of this study was to evaluate the risk of end-stage renal disease (ESRD) and types of ESRD among a cohort of US firefighters compared to the US general population, and to examine exposure-response relationships. METHODS: ESRD from 1977 through 2014 was identified through linkage with Medicare data. ESRD incidence in the cohort compared to the US population was evaluated using life table analyses. Associations of all ESRD, systemic ESRD, hypertensive ESRD, and diabetic ESRD with exposure surrogates (exposed days, fire runs, and fire hours) were examined in Cox proportional hazards models adjusted for attained age (the time scale), race, birth date, fire department, and employment duration. RESULTS: The incidence of all ESRD was less than expected (standardized incidence ratio (SIR) = 0.79; 95% confidence interval = 0.69-0.89, observed = 247). SIRs for ESRD types were not significantly increased. Positive associations of all ESRD, systemic ESRD, and hypertensive ESRD with exposed days were observed: however, 95% confidence intervals included one. CONCLUSIONS: We found little evidence of increased risk of ESRD among this cohort of firefighters. Limitations included the inability to evaluate exposure-response relationships for some ESRD types due to small observed numbers, the limitations of the surrogates of exposure, and the lack of information on more sensitive outcome measures for potential kidney effects.

Histopathology of the broad class of carbon nanotubes and nanofibers used or produced in U.S. facilities in a murine model.

BACKGROUND: Multi-walled carbon nanotubes and nanofibers (CNT/F) have been previously investigated for their potential toxicities; however, comparative studies of the broad material class are lacking, especially those with a larger diameter. Additionally, computational modeling correlating physicochemical characteristics and toxicity outcomes have been infrequently employed, and it is unclear if all CNT/F confer similar toxicity, including histopathology changes such as pulmonary fibrosis. Male C57BL/6 mice were exposed to 40 µg of one of nine CNT/F (MW #1-7 and CNF #1-2) commonly found in exposure assessment studies of U.S. facilities with diameters ranging from 6 to 150 nm. Human fibroblasts (0-20 µg/ml) were used to assess the predictive value of in vitro to in vivo modeling systems. RESULTS: All materials induced histopathology changes, although the types and magnitude of the changes varied. In general, the larger diameter MWs (MW #5-7, including Mitsui-7) and CNF #1 induced greater histopathology changes compared to MW #1 and #3 while MW #4 and CNF #2 were intermediate in effect. Differences in individual alveolar or bronchiolar outcomes and severity correlated with physical dimensions and how the materials agglomerated. Human fibroblast monocultures were found to be insufficient to fully replicate in vivo fibrosis outcomes suggesting in vitro predictive potential depends upon more advanced cell culture in vitro models. Pleural penetrations were observed more consistently in CNT/F with larger lengths and diameters. CONCLUSION: Physicochemical characteristics, notably nominal CNT/F dimension and agglomerate size, predicted histopathologic changes and enabled grouping of materials by their toxicity profiles. Particles of greater nominal tube length were generally associated with increased severity of histopathology outcomes. Larger particle lengths and agglomerates were associated with more severe bronchi/bronchiolar outcomes. Spherical agglomerated particles of smaller nominal tube dimension were linked to granulomatous inflammation while a mixture of smaller and larger dimensional CNT/F resulted in more severe alveolar injury.

Serum peptidome: diagnostic window into pathogenic processes following occupational exposure to carbon nanomaterials.

BACKGROUND: Growing industrial use of carbon nanotubes and nanofibers (CNT/F) warrants consideration of human health outcomes. CNT/F produces pulmonary, cardiovascular, and other toxic effects in animals along with a significant release of bioactive peptides into the circulation, the augmented serum peptidome. While epidemiology among CNT/F workers reports on few acute symptoms, there remains concern over sub-clinical CNT/F effects that may prime for chronic disease, necessitating sensitive health outcome diagnostic markers for longitudinal follow-up. METHODS: Here, the serum peptidome was assessed for its biomarker potential in detecting sub-symptomatic pathobiology among CNT/F workers using label-free data-independent mass spectrometry. Studies employed a stratified design between High (> 0.5 µg/m3) and Low (< 0.1 µg/m3) inhalable CNT/F exposures in the industrial setting. Peptide biomarker model building and refinement employed linear regression and partial least squared discriminant analyses. Top-ranked peptides were then sequence identified and evaluated for pathological-relevance. RESULTS: In total, 41 peptides were found to be highly discriminatory after model building with a strong linear correlation to personal CNT/F exposure. The top-five peptide model offered ideal prediction with high accuracy (Q2 = 0.99916). Unsupervised validation affirmed 43.5% of the serum peptidomic variance was attributable to CNT/F exposure. Peptide sequence identification reveals a predominant association with vascular pathology. ARHGAP21, ADAM15 and PLPP3 peptides suggest heightened cardiovasculature permeability and F13A1, FBN1 and VWDE peptides infer a pro-thrombotic state among High CNT/F workers. CONCLUSIONS: The serum peptidome affords a diagnostic window into sub-symptomatic pathology among CNT/F exposed workers for longitudinal monitoring of systemic health risks.

Occupational Exposures to Engineered Nanomaterials: a Review of Workplace Exposure Assessment Methods.

PURPOSE OF REVIEW: The purpose of this review is to consolidate exposure assessment methods for occupational research on engineered nanomaterials (ENMs) published within the past 5 years (2015-2020). RECENT FINDINGS: The three ENMs that generated the highest volume of new research include titanium dioxide, graphene, and aluminum oxide. A multi-metric approach, using both online and offline instruments and analyses, has been found to be a useful method to characterize ENM workplace exposures and was commonly used in the recently published literature. Particle number concentration was the most common online exposure metric used, followed by the metrics of mass and surface area. There are currently no consensus methods for offline analyses of most ENMs. Researchers generally used gravimetric or elemental analyses for carbonaceous nanomaterials, titanium dioxide, and other nanometals, but there was little overlap between other ENM materials reviewed. Using biological markers of exposure, such as urinary oxidative stress biomarkers, as an indication of chronic exposure may also be useful for some ENMs and should be further researched. Generally, similar online instrumentation and offline electron microscopy methods were used for all ENMs. However, this consistency was not observed for offline mass analysis methods within specific ENMs. Consolidation of the most recent methods and results of exposure assessments within this broad material category can guide researchers toward future areas of study. Establishing consensus methods of exposure assessment for each individual ENM is crucial to characterizing workplace exposures, pooling data to fully understand their associated risks, and developing useful occupational exposure limits.

Physicochemical characterization and genotoxicity of the broad class of carbon nanotubes and nanofibers used or produced in U.S. facilities.

BACKGROUND: Carbon nanotubes and nanofibers (CNT/F) have known toxicity but simultaneous comparative studies of the broad material class, especially those with a larger diameter, with computational analyses linking toxicity to their fundamental material characteristics was lacking. It was unclear if all CNT/F confer similar toxicity, in particular, genotoxicity. Nine CNT/F (MW #1-7 and CNF #1-2), commonly found in exposure assessment studies of U.S. facilities, were evaluated with reported diameters ranging from 6 to 150 nm. All materials were extensively characterized to include distributions of physical dimensions and prevalence of bundled agglomerates. Human bronchial epithelial cells were exposed to the nine CNT/F (0-24 µg/ml) to determine cell viability, inflammation, cellular oxidative stress, micronuclei formation, and DNA double-strand breakage. Computational modeling was used to understand various permutations of physicochemical characteristics and toxicity outcomes. RESULTS: Analyses of the CNT/F physicochemical characteristics illustrate that using detailed distributions of physical dimensions provided a more consistent grouping of CNT/F compared to using particle dimension means alone. In fact, analysis of binning of nominal tube physical dimensions alone produced a similar grouping as all characterization parameters together. All materials induced epithelial cell toxicity and micronuclei formation within the dose range tested. Cellular oxidative stress, DNA double strand breaks, and micronuclei formation consistently clustered together and with larger physical CNT/F dimensions and agglomerate characteristics but were distinct from inflammatory protein changes. Larger nominal tube diameters, greater lengths, and bundled agglomerate characteristics were associated with greater severity of effect. The portion of tubes with greater nominal length and larger diameters within a sample was not the majority in number, meaning a smaller percentage of tubes with these characteristics was sufficient to increase toxicity. Many of the traditional physicochemical characteristics including surface area, density, impurities, and dustiness did not cluster with the toxicity outcomes. CONCLUSION: Distributions of physical dimensions provided more consistent grouping of CNT/F with respect to toxicity outcomes compared to means only. All CNT/F induced some level of genotoxicity in human epithelial cells. The severity of toxicity was dependent on the sample containing a proportion of tubes with greater nominal lengths and diameters.

Planning for Epidemics and Pandemics: Assessing the Potential Impact of Extended Use and Reuse Strategies on Respirator Usage Rates to Support Supply-and-Demand Planning Efforts.

During epidemics and pandemics healthcare personnel (HCP) are on the front line of disease containment and mitigation. Personal protective equipment (PPE), such as NIOSH-approved N95 filtering facepiece respirators (FFRs), serve an important role in minimizing HCP risks and are in high demand during public health emergencies. Because PPE demand can exceed supply, various public health strategies have been developed to reduce the rate of PPE consumption as supply dwindles. Extended use and limited reuse of N95 FFRs are strategies advocated by many governmental agencies used to increase the number of times a device can be used. Increased use of respirators designed for reuse-such as powered air-purifying respirators (PAPRs) and elastomeric half-mask and full facepiece air-purifying respirators- is another option designed to reduce the continuous need for new devices as the daily need for respirator use increases. Together, these strategies are designed to reduce the number of PPE units that must be discarded daily and, therefore, extend the longevity of available supply. The purpose of this paper is to theoretically estimate the impact of extended use and limited reuse strategies for N95 FFRs and the increased use of reusable respirator options on PPE consumed. The results suggest that a considerable reduction in PPE consumption would result from extended use and limited reuse of N95 FFRs and the increased use of respirators designed for reuse; however, the practical benefits must be balanced with the risks and economic costs. In addition, extended use and reuse strategies must be accompanied by proper procedures to reduce risk. The study is designed to support epidemic and pandemic PPE supply and demand planning efforts.

Association of occupational exposures with ex vivo functional immune response in workers handling carbon nanotubes and nanofibers.

The objective of this study was to evaluate the association between carbon nanotube and nanofiber (CNT/F) exposure and ex vivo responses of whole blood challenged with secondary stimulants, adjusting for potential confounders, in a cross-sectional study of 102 workers. Multi-day exposure was measured by CNT/F structure count (SC) and elemental carbon (EC) air concentrations. Demographic, lifestyle and other occupational covariate data were obtained via questionnaire. Whole blood collected from each participant was incubated for 18 hours with and without two microbial stimulants (lipopolysaccharide/LPS and staphylococcal enterotoxin type B/SEB) using TruCulture technology to evaluate immune cell activity. Following incubation, supernatants were preserved and analyzed for protein concentrations. The stimulant:null response ratio for each individual protein was analyzed using multiple linear regression, followed by principal component (PC) analysis to determine whether patterns of protein response were related to CNT/F exposure. Adjusting for confounders, CNT/F metrics (most strongly, the SC-based) were significantly (p < 0.05) inversely associated with stimulant:null ratios of several individual biomarkers: GM-CSF, IFN-γ, interleukin (IL)-2, IL-4, IL-5, IL-10, IL-17, and IL-23. CNT/F metrics were significantly inversely associated with PC1 (a weighted mean of most biomarkers, explaining 25% of the variance in the protein ratios) and PC2 (a biomarker contrast, explaining 14%). Among other occupational exposures, only solvent exposure was significant (inversely related to PC2). CNT/F exposure metrics were uniquely related to stimulant responses in challenged whole blood, illustrating reduced responsiveness to a secondary stimulus. This approach, if replicated in other exposed populations, may present a relatively sensitive method to evaluate human response to CNT/F or other occupational exposures.

Mortality in a cohort of US firefighters from San Francisco, Chicago and Philadelphia: an update.

OBJECTIVES: To update the mortality experience of a previously studied cohort of 29 992 US urban career firefighters compared with the US general population and examine exposure-response relationships within the cohort. METHODS: Vital status was updated through 2016 adding 7 years of follow-up. Cohort mortality compared with the US population was evaluated via life table analyses. Full risk-sets, matched on attained age, race, birthdate and fire department were created and analysed using the Cox proportional hazards regression to examine exposure-response associations between select mortality outcomes and exposure surrogates (exposed-days, fire-runs and fire-hours). Models were adjusted for a potential bias from healthy worker survivor effects by including a categorical variable for employment duration. RESULTS: Compared with the US population, mortality from all cancers, mesothelioma, non-Hodgkin's lymphoma (NHL) and cancers of the oesophagus, intestine, rectum, lung and kidney were modestly elevated. Positive exposure-response relationships were observed for deaths from lung cancer, leukaemia and chronic obstructive pulmonary disease (COPD). CONCLUSIONS: This update confirms previous findings of excess mortality from all cancers and several site-specific cancers as well as positive exposure-response relations for lung cancer and leukaemia. New findings include excess NHL mortality compared with the general population and a positive exposure-response relationship for COPD. However, there was no evidence of an association between any quantitative exposure measure and NHL.

Work-related injuries within a large urban public school system in the Mid-Western United States.

BACKGROUND: More than 13 million employees are working in the public education sector which includes more than just teachers in the United States. This industry sector also employs custodians, maintenance, and administration. To date, there is very limited information about the type and frequency of injuries for these employees. OBJECTIVE: To identify injury trends related to frequency and severity for different occupational injuries in a large urban school district. METHODS: Between 2014-2015, school district employees reported a total of 598 occupational injuries. Initial analysis of the data provided the frequency of injuries overall and for individual occupational categories. The Severity Index provides a score for job category and injury type based on severity and frequency. RESULTS: Overall, the Slip, Trip and Fall category had the highest frequency, followed by Combative Situations, and Over-exertion. Teacher and Para-professional workers experienced the greatest number of injuries with violence being the most frequent cause. Based on the Severity Index, Over-exertion was identified as the primary exposure concern for Custodians, while Slip, Trip and Fall category had the greatest impact on Building Engineers. CONCLUSIONS: With the diversity of negative outcomes, the administration will need targeted interventions for the various professions represented in the school systems. The injury severity profile indicates non-teachers should be a high priority for interventions with over-exertion and slips, trips and falls leading the risk.

Predicting Occupational Exposures to Carbon Nanotubes and Nanofibers Based on Workplace Determinants Modeling.

BACKGROUND: Recent cross-sectional epidemiologic studies have examined the association between human health effects and carbon nanotube and nanofiber (CNT/F) workplace exposures. However, due to the latency of many health effects of interest, cohort studies with sufficient follow-up will likely be needed. The objective of this study was to identify workplace determinants that contribute to exposure and develop predictive models to estimate CNT/F exposures for future use in epidemiologic studies. METHODS: Exposure measurements were compiled from 15 unique facilities for the metrics of elemental carbon (EC) mass at both the respirable and inhalable aerosol size fractions as well as a quantitative analysis performed by transmission electron microscopy (TEM). These metrics served as the dependent variables in model development. Repeated personal samples were collected from most of the 127 CNT/F worker participants for 252 total observations. Determinants were categorized as company-level or worker-level and used to describe the exposure relationship within the dependent variables. The influence of determinants on variance components was explored using mixed linear models that utilized a backwards stepwise selection process with a lowering of the AIC for model determinant selection. Additional ridge regression models were created that examined predictive performance with and without all two-way interactions. Cross-validation was performed on each model to evaluate the generalizability of its predictive capabilities while predictive performance was evaluated according to the corresponding R2 value and root mean square error (RMSE). RESULTS: Determinants at the company-level that increased exposure included an inadequate or semi-adequate engineering control rating, increasing average CNT/F diameter/length, daily quantities of material handled from 101 g to >1 kg and >1 kg, the use of CNF materials, the industry type of hybrid producer/user, and the expert assessment of a high exposure potential. Worker-level determinants associated with higher exposure included handling the dry-powdered form of CNT/F, handling daily quantities of material >1 kg, direct/indirect exposure, having the job title of engineer, using a respirator, using a ventilated or unventilated enclosure, and the job task of powder handling. The mixed linear models explained >60% of the total variance when using all company- and worker-level determinants to create the three exposure models. The cross-validated RMSE values for each of the three mixed models ranged from 2.50 to 4.23. Meanwhile, the ridge regression models, without all two-way interactions, estimated cross-validated RMSE values of 2.85, 2.23, and 2.76 for the predictive models of inhalable EC, respirable EC, and TEM, respectively. CONCLUSIONS: The ridge regression models demonstrated the best performance for predicting exposures to CNT/F for each exposure metric, although they only provided a modest predictive capability. Therefore, it was concluded that the models alone would not be adequate in predicting workplace exposures and would need to be integrated with other methods.

Evaluation of total and inhalable samplers for the collection of carbon nanotube and carbon nanofiber aerosols.

A growing number of carbon nanotubes and nanofibers (CNT/F) exposure and epidemiologic studies have utilized 25-mm and 37-mm open-faced cassettes (OFC) to assess the inhalable aerosol fraction. It has been previously established that the 37-mm OFC under-samples particles greater than 20 µm in diameter, but the size-selective characteristics of the 25-mm OFC have not yet been fully evaluated. This article describes an experimental study conducted to determine if the 25- and 37-mm OFCs performed with relative equivalence to a reference inhalable aerosol sampler when challenged with CNT/F particles. Side-by-side paired samples were collected within a small Venturi chamber using a 25-mm styrene OFC, 37-mm styrene OFC, 25-mm aluminum OFC, and Button Inhalable Aerosol Sampler. Three types of CNT/F materials and an Arizona road dust were used as challenge aerosols for the various sampler configurations. Repeated experiments were conducted for each sampler configuration and material. The OFC samplers operated at flow rates of 2 and 5 liters per minute. Results showed that the 25-mm OFC performed comparably to the Button Sampler when challenged with CNT/F aerosols, which was demonstrated in five of the six experimental scenarios with an average error of 20%. Overall, the results of this study indicate that the sampling efficiency of the 25- and 37-mm OFCs adequately followed the ISO/ACGIH/CEN inhalable sampling convention when challenged with CNT/F aerosols. Past exposure and epidemiologic studies that used these OFC samplers can directly compare their results to studies that have used other validated inhalable aerosol samplers.

Association of pulmonary, cardiovascular, and hematologic metrics with carbon nanotube and nanofiber exposure among U.S. workers: a cross-sectional study.

BACKGROUND: Commercial use of carbon nanotubes and nanofibers (CNT/F) in composites and electronics is increasing; however, little is known about health effects among workers. We conducted a cross-sectional study among 108 workers at 12 U.S. CNT/F facilities. We evaluated chest symptoms or respiratory allergies since starting work with CNT/F, lung function, resting blood pressure (BP), resting heart rate (RHR), and complete blood count (CBC) components. METHODS: We conducted multi-day, full-shift sampling to measure background-corrected elemental carbon (EC) and CNT/F structure count concentrations, and collected induced sputum to measure CNT/F in the respiratory tract. We measured (nonspecific) fine and ultrafine particulate matter mass and count concentrations. Concurrently, we conducted physical examinations, BP measurement, and spirometry, and collected whole blood. We evaluated associations between exposures and health measures, adjusting for confounders related to lifestyle and other occupational exposures. RESULTS: CNT/F air concentrations were generally low, while 18% of participants had evidence of CNT/F in sputum. Respiratory allergy development was positively associated with inhalable EC (p=0.040) and number of years worked with CNT/F (p=0.008). No exposures were associated with spirometry-based metrics or pulmonary symptoms, nor were CNT/F-specific metrics related to BP or most CBC components. Systolic BP was positively associated with fine particulate matter (p-values: 0.015-0.054). RHR was positively associated with EC, at both the respirable (p=0.0074) and inhalable (p=0.0026) size fractions. Hematocrit was positively associated with the log of CNT/F structure counts (p=0.043). CONCLUSIONS: Most health measures were not associated with CNT/F. The positive associations between CNT/F exposure and respiratory allergies, RHR, and hematocrit counts may not be causal and require examination in other studies.

Carbon nanotube and nanofiber exposure and sputum and blood biomarkers of early effect among U.S. workers.

BACKGROUND: Carbon nanotubes and nanofibers (CNT/F) are increasingly used for diverse applications. Although animal studies suggest CNT/F exposure may cause deleterious health effects, human epidemiological studies have typically been small, confined to single workplaces, and limited in exposure assessment. OBJECTIVES: We conducted an industrywide cross-sectional epidemiological study of 108 workers from 12 U.S. sites to evaluate associations between occupational CNT/F exposure and sputum and blood biomarkers of early effect. METHODS: We assessed CNT/F exposure via personal breathing zone, filter-based air sampling to measure background-corrected elemental carbon (EC) (a CNT/F marker) mass and microscopy-based CNT/F structure count concentrations. We measured 36 sputum and 37 blood biomarkers. We used factor analyses with varimax rotation to derive factors among sputum and blood biomarkers separately. We used linear, Tobit, and unconditional logistic regression models to adjust for potential confounders and evaluate associations between CNT/F exposure and individual biomarkers and derived factors. RESULTS: We derived three sputum and nine blood biomarker factors that explained 78% and 67%, respectively, of the variation. After adjusting for potential confounders, inhalable EC and total inhalable CNT/F structures were associated with the most sputum and blood biomarkers, respectively. Biomarkers associated with at least three CNT/F metrics were 72 kDa type IV collagenase/matrix metalloproteinase-2 (MMP-2), interleukin-18, glutathione peroxidase (GPx), myeloperoxidase, and superoxide dismutase (SOD) in sputum and MMP-2, matrix metalloproteinase-9, metalloproteinase inhibitor 1/tissue inhibitor of metalloproteinases 1, 8-hydroxy-2'-deoxyguanosine, GPx, SOD, endothelin-1, fibrinogen, intercellular adhesion molecule 1, vascular cell adhesion protein 1, and von Willebrand factor in blood, although directions of associations were not always as expected. CONCLUSIONS: Inhalable rather than respirable CNT/F was more consistently associated with fibrosis, inflammation, oxidative stress, and cardiovascular biomarkers.

Exposure assessments for a cross-sectional epidemiologic study of US carbon nanotube and nanofiber workers.

BACKGROUND: Recent animal studies have suggested the potential for wide-ranging health effects resulting from exposure to carbon nanotubes and nanofibers (CNT/F). To date, no studies in the US have directly examined the relationship between occupational exposure and potential human health effects. OBJECTIVES: Our goal was to measure CNT/F exposures among US workers with representative job types, from non-exposed to highly exposed, for an epidemiologic study relating exposure to early biologic effects. METHODS: 108 participants were enrolled from 12 facilities across the US. Personal, full-shift exposures were assessed based on the mass of elemental carbon (EC) at the respirable and inhalable aerosol particle size fractions, along with quantitatively characterizing CNT/F and estimating particle size via transmission electron microscopy (TEM). Additionally, sputum and dermal samples were collected and analyzed to determine internal exposures and exposures to the hands/wrists. RESULTS: The mean exposure to EC was 1.00 µg/m3 at the respirable size fraction and 6.22 µg/m3 at the inhalable fraction. Analysis by TEM found a mean exposure of 0.1275 CNT/F structures/cm3, generally to agglomerated materials between 2 and 10 µm. Internal exposures to CNT/F via sputum analysis were confirmed in 18% of participants while ∼70% had positive dermal exposures. CONCLUSIONS: We demonstrated the occurrence of a broad range of exposures to CNT/F within 12 facilities across the US. Analysis of collected sputum indicated internal exposures are currently occurring within the workplace. This is an important first step in determining if exposures in the workforce have any acute or lasting health effects.

Characterizing workforces exposed to current and emerging non-carbonaceous nanomaterials in the U.S.

OBJECTIVE: Toxicology studies suggest that exposure to certain types of engineered nanomaterials (ENMs) may cause adverse health effects, but little is known about the workforce in the United States that produces or uses these materials. In addition, occupational exposure control strategies in this industry are not well characterized. This study identified U.S. ENM manufacturers and users (other than carbon nanotubes and nanofibers, which have been characterized elsewhere), determined workforce size, characterized types and quantities of materials used, occupational exposure control strategies, and the feasibility of occupational ENM exposure studies. METHODS: Eligible companies were identified and information was collected through phone surveys on nanomaterials produced or used, workforce size, location, work practices, and exposure control strategies. The companies were classified into groups for additional examinations. RESULTS: Forty-nine companies producing or using ENMs in the U.S. were identified. These companies employed at least 1,500 workers. Most companies produced or used some form of nanoscale metal. More than half of the eligible companies were suppliers for the coatings, composite materials, or general industries. Each company provided information about worker exposure reduction strategies through engineering controls, administrative controls, or personal protective equipment. Production-scale companies reported greater use of specific exposure control strategies for ENMs than laboratory-scale companies. CONCLUSIONS: Workplaces producing or using ENMs report using engineering and administrative controls as well as personal protective equipment to control worker exposure. Industrywide exposure assessment studies appear feasible due to workforce size. However, more effort must be taken to target industries using specific ENMs based on known toxicological effects and health risks.

In Vivo Toxicity Assessment of Occupational Components of the Carbon Nanotube Life Cycle To Provide Context to Potential Health Effects.

Pulmonary toxicity studies on carbon nanotubes focus primarily on as-produced materials and rarely are guided by a life cycle perspective or integration with exposure assessment. Understanding toxicity beyond the as-produced, or pure native material, is critical, due to modifications needed to overcome barriers to commercialization of applications. In the first series of studies, the toxicity of as-produced carbon nanotubes and their polymer-coated counterparts was evaluated in reference to exposure assessment, material characterization, and stability of the polymer coating in biological fluids. The second series of studies examined the toxicity of aerosols generated from sanding polymer-coated carbon-nanotube-embedded or neat composites. Postproduction modification by polymer coating did not enhance pulmonary injury, inflammation, and pathology or in vitro genotoxicity of as-produced carbon nanotubes, and for a particular coating, toxicity was significantly attenuated. The aerosols generated from sanding composites embedded with polymer-coated carbon nanotubes contained no evidence of free nanotubes. The percent weight incorporation of polymer-coated carbon nanotubes, 0.15% or 3% by mass, and composite matrix utilized altered the particle size distribution and, in certain circumstances, influenced acute in vivo toxicity. Our study provides perspective that, while the number of workers and consumers increases along the life cycle, toxicity and/or potential for exposure to the as-produced material may greatly diminish.

Bridging the gap between exposure assessment and inhalation toxicology: Some insights from the carbon nanotube experience.

The early incorporation of exposure assessment can be invaluable to help design, prioritize, and interpret toxicological studies or outcomes. The sum total of the exposure assessment findings combined with preliminary toxicology results allows for exposure-informed toxicological study design and the findings can then be integrated, together with available epidemiologic data, to provide health effect relevance. With regard to engineered nanomaterial inhalation toxicology in particular, a single type of material (e.g. carbon nanotube, graphene) can have a vast array of physicochemical characteristics resulting in the potential for varying toxicities. To compound the matter, the methodologies necessary to establish a material adequate for in vivo exposure testing raises questions on the applicability of the outcomes. From insights gained from evaluating carbon nanotubes, we recommend the following integrated approach involving exposure-informed hazard assessment and hazard-informed exposure assessment especially for materials as diverse as engineered nanomaterials: 1) market-informed identification of potential hazards and potentially exposed populations, 2) initial toxicity screening to drive prioritized assessments of exposure, 3) development of exposure assessment-informed chronic and sub-chronic in vivo studies, and 4) conduct of exposure- and hazard-informed epidemiological studies.

Refinement of the Nanoparticle Emission Assessment Technique into the Nanomaterial Exposure Assessment Technique (NEAT 2.0).

Engineered nanomaterial emission and exposure characterization studies have been completed at more than 60 different facilities by the National Institute for Occupational Safety and Health (NIOSH). These experiences have provided NIOSH the opportunity to refine an earlier published technique, the Nanoparticle Emission Assessment Technique (NEAT 1.0), into a more comprehensive technique for assessing worker and workplace exposures to engineered nanomaterials. This change is reflected in the new name Nanomaterial Exposure Assessment Technique (NEAT 2.0) which distinguishes it from NEAT 1.0. NEAT 2.0 places a stronger emphasis on time-integrated, filter-based sampling (i.e., elemental mass analysis and particle morphology) in the worker's breathing zone (full shift and task specific) and area samples to develop job exposure matrices. NEAT 2.0 includes a comprehensive assessment of emissions at processes and job tasks, using direct-reading instruments (i.e., particle counters) in data-logging mode to better understand peak emission periods. Evaluation of worker practices, ventilation efficacy, and other engineering exposure control systems and risk management strategies serve to allow for a comprehensive exposure assessment.

Creation of a retrospective job-exposure matrix using surrogate measures of exposure for a cohort of US career firefighters from San Francisco, Chicago and Philadelphia.

OBJECTIVES: To construct a cohort-specific job-exposure matrix (JEM) using surrogate metrics of exposure for a cancer study on career firefighters from the Chicago, Philadelphia and San Francisco Fire Departments. METHODS: Departmental work history records, along with data on historical annual fire-runs and hours, were collected from 1950 to 2009 and coded into separate databases. These data were used to create a JEM based on standardised job titles and fire apparatus assignments using several surrogate exposure metrics to estimate firefighters' exposure to the combustion byproducts of fire. The metrics included duration of exposure (cumulative time with a standardised exposed job title and assignment), fire-runs (cumulative events of potential fire exposure) and time at fire (cumulative hours of potential fire exposure). RESULTS: The JEM consisted of 2298 unique job titles alongside 16,174 fire apparatus assignments from the three departments, which were collapsed into 15 standardised job titles and 15 standardised job assignments. Correlations were found between fire-runs and time at fires (Pearson coefficient=0.92), duration of exposure and time at fires (Pearson coefficient=0.85), and duration of exposure and fire-runs (Pearson coefficient=0.82). Total misclassification rates were found to be between 16-30% when using duration of employment as an exposure surrogate, which has been traditionally used in most epidemiological studies, compared with using the duration of exposure surrogate metric. CONCLUSIONS: The constructed JEM successfully differentiated firefighters based on gradient levels of potential exposure to the combustion byproducts of fire using multiple surrogate exposure metrics.

Carbon Nanotube and Nanofiber Exposure Assessments: An Analysis of 14 Site Visits.

Recent evidence has suggested the potential for wide-ranging health effects that could result from exposure to carbon nanotubes (CNT) and carbon nanofibers (CNF). In response, the National Institute for Occupational Safety and Health (NIOSH) set a recommended exposure limit (REL) for CNT and CNF: 1 µg m(-3) as an 8-h time weighted average (TWA) of elemental carbon (EC) for the respirable size fraction. The purpose of this study was to conduct an industrywide exposure assessment among US CNT and CNF manufacturers and users. Fourteen total sites were visited to assess exposures to CNT (13 sites) and CNF (1 site). Personal breathing zone (PBZ) and area samples were collected for both the inhalable and respirable mass concentration of EC, using NIOSH Method 5040. Inhalable PBZ samples were collected at nine sites while at the remaining five sites both respirable and inhalable PBZ samples were collected side-by-side. Transmission electron microscopy (TEM) PBZ and area samples were also collected at the inhalable size fraction and analyzed to quantify and size CNT and CNF agglomerate and fibrous exposures. Respirable EC PBZ concentrations ranged from 0.02 to 2.94 µg m(-3) with a geometric mean (GM) of 0.34 µg m(-3) and an 8-h TWA of 0.16 µg m(-3). PBZ samples at the inhalable size fraction for EC ranged from 0.01 to 79.57 µg m(-3) with a GM of 1.21 µg m(-3). PBZ samples analyzed by TEM showed concentrations ranging from 0.0001 to 1.613 CNT or CNF-structures per cm(3) with a GM of 0.008 and an 8-h TWA concentration of 0.003. The most common CNT structure sizes were found to be larger agglomerates in the 2-5 µm range as well as agglomerates >5 µm. A statistically significant correlation was observed between the inhalable samples for the mass of EC and structure counts by TEM (Spearman ρ = 0.39, P < 0.0001). Overall, EC PBZ and area TWA samples were below the NIOSH REL (96% were <1 µg m(-3) at the respirable size fraction), while 30% of the inhalable PBZ EC samples were found to be >1 µg m(-3). Until more information is known about health effects associated with larger agglomerates, it seems prudent to assess worker exposure to airborne CNT and CNF materials by monitoring EC at both the respirable and inhalable size fractions. Concurrent TEM samples should be collected to confirm the presence of CNT and CNF.