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.

Occupational safety and health, green chemistry, and sustainability: a review of areas of convergence.

With increasing numbers and quantities of chemicals in commerce and use, scientific attention continues to focus on the environmental and public health consequences of chemical production processes and exposures. Concerns about environmental stewardship have been gaining broader traction through emphases on sustainability and "green chemistry" principles. Occupational safety and health has not been fully promoted as a component of environmental sustainability. However, there is a natural convergence of green chemistry/sustainability and occupational safety and health efforts. Addressing both together can have a synergistic effect. Failure to promote this convergence could lead to increasing worker hazards and lack of support for sustainability efforts. The National Institute for Occupational Safety and Health has made a concerted effort involving multiple stakeholders to anticipate and identify potential hazards associated with sustainable practices and green jobs for workers. Examples of potential hazards are presented in case studies with suggested solutions such as implementing the hierarchy of controls and prevention through design principles in green chemistry and green building practices. Practical considerations and strategies for green chemistry, and environmental stewardship could benefit from the incorporation of occupational safety and health concepts which in turn protect affected workers.

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.

A strategy for assessing workplace exposures to nanomaterials.

This article describes a highly tailorable exposure assessment strategy for nanomaterials that enables effective and efficient exposure management (i.e., a strategy that can identify jobs or tasks that have clearly unacceptable exposures), while simultaneously requiring only a modest level of resources to conduct. The strategy is based on strategy general framework from AIHA® that is adapted for nanomaterials and seeks to ensure that the risks to workers handling nanomaterials are being managed properly. The strategy relies on a general framework as the basic foundation while building and elaborating on elements essential to an effective and efficient strategy to arrive at decisions based on collecting and interpreting available information. This article provides useful guidance on conducting workplace characterization; understanding exposure potential to nanomaterials; accounting methods for background aerosols; constructing SEGs; and selecting appropriate instrumentation for monitoring, providing appropriate choice of exposure limits, and describing criteria by which exposure management decisions should be made. The article is intended to be a practical guide for industrial hygienists for managing engineered nanomaterial risks in their workplaces.

Challenges in assessing nanomaterial toxicology: a personal perspective.

Nanotechnology exploits the fact that nanoparticles exhibit unique physicochemical properties, which are distinct from fine-sized particles of the same composition. It follows that nanoparticles may also express distinct bioactivity and unique interactions with biological systems. Therefore, it is essential to assess the potential health risks of exposure to nanoparticles to allow development and implementation of prevention measures. Risk assessment requires data concerning hazard and exposure. Several challenges face the field of nanotoxicology in obtaining the necessary data for assessment of the bioactivity of nanoparticles. They include: (1) the vast number of nanoparticle types to be evaluated, (2) the need to use nanoparticle doses and structure sizes in cellular and animal test systems which are relevant to anticipated workplace exposures, and (3) artifactual in vitro results due to absorption of nutrients or assay indicator compounds from the culture media. This 'opinion' reviews the progress made in the field of nanotoxicology in recent years to overcome these challenges.

Issues in the development of epidemiologic studies of workers exposed to engineered nanoparticles.

OBJECTIVE: Capitalizing on phenomena at the nanoscale may present great benefits to society. Nevertheless, until the hazards and risks of engineered nanoparticles are determined, the technological products and advances of nanotechnology may be impeded by the societal concerns. Although animal data provide the necessary first step in hazard and risk assessment, ultimately epidemiological studies will be required, especially studies of workers exposed to engineered nanoparticles. It may be too soon to conduct informative epidemiological studies but it is now appropriate to identify issues that will be pertinent and prepare strategies to address them. METHODS: The published scientific literature on incidental and engineered nanoparticles and air pollution were reviewed to identify issues in the conduct of epidemiological studies of workers exposed to engineered nanoparticles. RESULTS: Twelve important issues were identified-the most critical pertaining to particle heterogeneity, temporal factors, exposure characterization, disease endpoints, and identification of the study population. CONCLUSION: Consideration of these issues provides the foundation for initiating epidemiologic research on workers exposed to engineered nanoparticles.

National Prevention through Design (PtD) Initiative.

INTRODUCTION: The most effective means of preventing and controlling occupational injuries, illness, and fatalities is to "design out" hazards and hazardous exposures from the workplace. There is a long history of designing for safety for the general public and to a lesser degree for workers. METHOD: We now have the experience and insight from thoughtful, previous efforts to call for a comprehensive national strategy to implement a Prevention through Design (PtD) Initiative. RESULTS: This paper describes that initiative in terms of four overarching areas where action can be directed: practice, policy, research, and education. To obtain stakeholder input for issues in these four areas and to focus implementation efforts, eight sector divisions of the economy will be addressed. A seven year strategy is envisioned.

Options for occupational health surveillance of workers potentially exposed to engineered nanoparticles: state of the science.

OBJECTIVE: Health authorities, employers, and worker representatives are increasingly faced with making decisions about occupational health surveillance of workers potentially exposed to engineered nanoparticles. This article was developed to identify options that can be considered. METHODS: The published scientific literature on health effects from engineered and incidental nanoparticles and the principles of occupational health surveillance were reviewed to describe possible options and the evidence base for them. RESULTS: Various options for occupational health surveillance were identified. The options ranged from no action targeted to nanotechnology workers to an approach that includes documentation of the presence of engineered nanoparticles, identification of potentially exposed workers, and general and targeted medical testing. CONCLUSIONS: Although the first priority should be to implement appropriate primary preventive measures, additional efforts to monitor employee health may be warranted. Continued research is needed, and the collection of such information for exposure registries may be useful for future epidemiologic studies.