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.

Nano-metal oxides: Exposure and engineering control assessment.

In January 2007, the National Institute for Occupational Safety and Health (NIOSH) conducted a field study to evaluate process specific emissions during the production of ENMs. This study was performed using the nanoparticle emission assessment technique (NEAT). During this study, it was determined that ENMs were released during production and cleaning of the process reactor. Airborne concentrations of silver, nickel, and iron were found both in the employee's personal breathing zone and area samples during reactor cleaning. At the completion of this initial survey, it was suggested that a flanged attachment be added to the local exhaust ventilation system. NIOSH re-evaluated the facility in December 2011 to assess worker exposures following an increase in production rates. This study included a fully comprehensive emissions, exposure, and engineering control evaluation of the entire process. This study made use of the nanoparticle exposure assessment technique (NEAT 2.0). Data obtained from filter-based samples and direct reading instruments indicate that reactor cleanout increased the overall particle concentration in the immediate area. However, it does not appear that these concentrations affect areas outside of the production floor. As the distance between the reactor and the sample location increased, the observed particle number concentration decreased, creating a concentration gradient with respect to the reactor. The results of this study confirm that the flanged attachment on the local exhaust ventilation system served to decrease exposure potential. Given the available toxicological data of the metals evaluated, caution is warranted. One should always keep in mind that occupational exposure levels were not developed specifically for nanoscale particles. With data suggesting that certain nanoparticles may be more toxic than the larger counterparts of the same material; employers should attempt to control emissions of these particles at the source, to limit the potential for exposure.

NIOSH field studies team assessment: Worker exposure to aerosolized metal oxide nanoparticles in a semiconductor fabrication facility.

The ubiquitous use of engineered nanomaterials-particulate materials measuring approximately 1-100 nanometers (nm) on their smallest axis, intentionally engineered to express novel properties-in semiconductor fabrication poses unique issues for protecting worker health and safety. Use of new substances or substances in a new form may present hazards that have yet to be characterized for their acute or chronic health effects. Uncharacterized or emerging occupational health hazards may exist when there is insufficient validated hazard data available to make a decision on potential hazard and risk to exposed workers under condition of use. To advance the knowledge of potential worker exposure to engineered nanomaterials, the National Institute for Occupational Safety and Health Nanotechnology Field Studies Team conducted an on-site field evaluation in collaboration with on-site researchers at a semiconductor research and development facility on April 18-21, 2011. The Nanomaterial Exposure Assessment Technique (2.0) was used to perform a complete exposure assessment. A combination of filter-based sampling and direct-reading instruments was used to identify, characterize, and quantify the potential for worker inhalation exposure to airborne alumina and amorphous silica nanoparticles associated with th e chemical mechanical planarization wafer polishing process. Engineering controls and work practices were evaluated to characterize tasks that might contribute to potential exposures and to assess existing engineering controls. Metal oxide structures were identified in all sampling areas, as individual nanoparticles and agglomerates ranging in size from 60 nm to >1,000 nm, with varying structure morphology, from long and narrow to compact. Filter-based samples indicated very little aerosolized material in task areas or worker breathing zone. Direct-reading instrument data indicated increased particle counts relative to background in the wastewater treatment area; however, particle counts were very low overall, indicating a well-controlled working environment. Recommendations for employees handling or potentially exposed to engineered nanomaterials include hazard communication, standard operating procedures, conservative ventilation systems, and prevention through design in locations where engineered nanomaterials are used or stored, and routine air sampling for occupational exposure assessment and analysis.

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.

Characterizing adoption of precautionary risk management guidance for nanomaterials, an emerging occupational hazard.

Exposure to engineered nanomaterials (substances with at least one dimension of 1-100 nm) has been of increased interest, with the recent growth in production and use of nanomaterials worldwide. Various organizations have recommended methods to minimize exposure to engineered nanomaterials. The purpose of this study was to evaluate available data to examine the extent to which studied U.S. companies (which represent a small fraction of all companies using certain forms of engineered nanomaterials) follow the guidelines for reducing occupational exposures to engineered nanomaterials that have been issued by the National Institute for Occupational Safety and Health (NIOSH) and other organizations. Survey data, field reports, and field notes for all NIOSH nanomaterial exposure assessments conducted between 2006 and 2011 were collected and reviewed to: (1) determine the level of adoption of precautionary guidance on engineering controls and personal protective equipment (PPE), and (2) evaluate the reliability of companies' self-reported use of engineering controls and PPE. Use of PPE was observed among 89% [95% confidence interval (CI): 76%-96%] of 46 visited companies, and use of containment-based engineering controls for at least some processes was observed among 83% (95% CI: 76%-96%). In on-site evaluations, more than 90% of the 16 engineered carbonaceous nanomaterial companies that responded to an industrywide survey were observed to be using engineering controls and PPE as reported or more stringently than reported. Since PPE use was slightly more prevalent than engineering controls, better communication may be necessary to reinforce the importance of the hierarchy of controls. These findings may also be useful in conducting exposure assessment and epidemiologic research among U.S. workers handling nanomaterials.

In Vivo Evaluation of the Pulmonary Toxicity of Cellulose Nanocrystals: A Renewable and Sustainable Nanomaterial of the Future.

The use of cellulose as building blocks for the development of novel functional materials is rapidly growing. Cellulose nanocrystals (CNC), with advantageous chemical and mechanical properties, have gained prominence in a number of applications, such as in nanofillers in polymer composites, building materials, cosmetics, food, and the drug industry. Therefore, it becomes critical to evaluate the potential health effects associated with CNC exposures. The objective of this study was to compare pulmonary outcomes caused by exposure of C57BL/6 mice to two different processed forms of CNC derived from wood, i.e., CNCS (10 wt %; gel/suspension) and CNCP (powder), and compare to asbestos induced responses. Pharyngeal aspiration with CNCS and CNCP was found to facilitate innate inflammatory response assessed by an increase in leukocytes and eosinophils recovered by bronchoalveolar lavage (BAL). Biomarkers of tissue damage were elevated to a higher extent in mice exposed to CNCP. Compared to CNCP, CNCS caused a significant increase in the accumulation of oxidatively modified proteins. The up-regulation of inflammatory cytokines was higher in the lungs after CNCS treatments. Most importantly, CNCP materials were significantly longer than CNCS. Taken together, our data suggests that particle morphology and nanosize dimensions of CNCs, regardless of the same source, may be critical factors affecting the type of innate immune inflammatory responses. Because various processes have been developed for producing highly sophisticated nanocellulose materials, detailed assessment of specific health outcomes with respect to their physical-structural-chemical properties is highly warranted.

Risk assessment and risk management of nanomaterials in the workplace: translating research to practice.

In the last decade since the rise in occupational safety and health (OSH) research focusing on nanomaterials, some progress has been made in generating the health effects and exposure data needed to perform risk assessment and develop risk management guidance. Yet, substantial research gaps remain, as do challenges in the translation of these research findings to OSH guidance and workplace practice. Risk assessment is a process that integrates the hazard, exposure, and dose-response data to characterize risk in a population (e.g. workers), in order to provide health information needed for risk management decision-making. Thus, the research priorities for risk assessment are those studies that will reduce the uncertainty in the key factors that influence the estimates. Current knowledge of OSH in nanotechnology includes the following: (i) nanomaterials can be measured using standard measurement methods (respirable mass or number concentration), (ii) workplace exposures to nanomaterials can be reduced using engineering controls and personal protective equipment, and (iii) current toxicity testing and risk assessment methods are applicable to nanomaterials. Yet, to ensure protection of workers' health, research is still needed to develop (i) sensitive and quantitative measures of workers' exposure to nanomaterials, (ii) validation methods for exposure controls, and (iii) standardized criteria to categorize hazard data, including better prediction of chronic effects. This article provides a state-of-the-art overview on translating current hazard research data and risk assessment methods for nanomaterials to the development and implementation of effective risk management guidance.

Focused actions to protect carbon nanotube workers.

There is still uncertainty about the potential health hazards of carbon nanotubes (CNTs) particularly involving carcinogenicity. However, the evidence is growing that some types of CNTs and nanofibers may have carcinogenic properties. The critical question is that while the carcinogenic potential of CNTs is being further investigated, what steps should be taken to protect workers who face exposure to CNTs, current and future, if CNTs are ultimately found to be carcinogenic? This paper addresses five areas to help focus action to protect workers: (i) review of the current evidence on the carcinogenic potential of CNTs; (ii) role of physical and chemical properties related to cancer development; (iii) CNT doses associated with genotoxicity in vitro and in vivo; (iv) workplace exposures to CNT; and (v) specific risk management actions needed to protect workers.