HSE و بهداشت حرفه ای

Executive Summary

Nanotechnology, the manipulation of matter at a nanometer scale to produce new materials, structures, and devices having new properties, may revolutionize life in the future. It has the potential to impact medicine through improved disease diagnosis and treatment technologies and to impact manufacturing by creating smaller, lighter, stronger, and more efficient products. Nanotechnology could potentially decrease the impact of pollution by improving methods for water purification or energy conservation. Although engineered nanomaterials present seemingly limitless possibilities, they bring with them new challenges for identifying and controlling potential safety and health risks to workers. Of particular concern is the growing body of evidence that occupational exposure to some engineered nanomaterials can cause adverse health effects.

As with any new technology or new material, the earliest exposures will likely occur for those workers conducting discovery research in laboratories or developing production processes in pilot plants. The research community is at the front line of creating new nanomaterials, testing their usefulness in a variety of applications and determining their toxicological and environmental impacts. Researchers handling engineered nanomaterials in laboratories should perform that work in a manner that protects their safety and health. This guidance document provides the best information currently available on engineering controls and safe work practices to be followed when working with engineered nanomaterials in research laboratories.

Risk Management

Risk management is an integral part of occupational health and safety. Potential exposures to nanomaterials can be controlled in research laboratories through a flexible and adaptive risk management program. An effective program provides the framework to anticipate the emergence of this technology into laboratory settings, recognize the potential hazards, evaluate the exposure to the nanomaterial, develop controls to prevent or minimize exposure, and confirm the effectiveness of those controls.

Hazard Identification

Experimental animal studies indicate that potentially adverse health effects may result from exposure to nanomaterials. Experimental studies in rodents and cell cultures have shown that the toxicity of ultrafine particles or nanoparticles is greater than the toxicity of the same mass of larger particles of similar chemical composition.

Research demonstrates that inhalation is a significant route of exposure for nanomaterials. Evidence from animal studies indicates that inhaled nanoparticles may deposit deep in lung tissue, possibly interfering with lung function. It is also theorized that

nanoparticles may enter the bloodstream through the lungs and transfer to other organs. Dermal exposure and subsequent penetration of nanomaterials may cause local or systemic effects. Ingestion is a third potential route of exposure. Little is known about the possible adverse effects of ingestion of nanomaterials, although some evidence suggests that nanosized particles can be transferred across the intestinal wall.

Exposure Assessment

Exposure assessment is a key element of an effective risk management program. The exposure assessment should identify tasks that contribute to nanomaterial exposure and the workers conducting those tasks. An inventory of tasks should be developed that includes information on the duration and frequency of tasks that may result in exposure, along with the quantity of the material being handled, dustiness of the nanomaterial, and its physical form. A thorough understanding of the exposure potential will guide exposure assessment measurements, which will help determine the type of controls required for exposure mitigation.

Exposure Control

Exposure control is the use of a set of tools or strategies for decreasing or eliminating worker exposure to a particular agent. Exposure control consists of a standardized hierarchy to include (in priority order): elimination, substitution, isolation, engineering controls, administrative controls, or if no other option is available, personal protective equipment (PPE).

Substitution or elimination is not often feasible for workers performing research with nanomaterials; however, it may be possible to change some aspects of the physical form of the nanomaterial or the process in a way that reduces nanomaterial release.

Isolation includes the physical separation and containment of a process or piece of equipment, either by placing it in an area separate from the worker or by putting it within an enclosure that contains any nanomaterials that might be released.

Engineering controls include any physical change to the process that reduces emissions or exposure to the material being contained or controlled. Ventilation is a form of engineering control that can be used to reduce occupational exposures to airborne particulates. General exhaust ventilation (GEV), also known as dilution ventilation, permits the release of the contaminant into the workplace air and then dilutes the concentration to an acceptable level. GEV alone is not an appropriate control for engineered nanomaterials or any other uncharacterized new chemical entity. Local exhaust ventilation (LEV), such as the standard laboratory chemical hood (formerly known as a laboratory fume hood), captures emissions at the source and thereby removes contaminants from

the immediate occupational environment. Using selected forms of LEV properly is appropriate for control of engineered nanomaterials.

Administrative controls can limit workers’ exposures through techniques such as using job-rotation schedules that reduce the time an individual is exposed to a substance. Administrative controls may consist of standard operating procedures, general or specialized housekeeping procedures, spill prevention and control, and proper labeling and storage of nanomaterials. Employee training on the appropriate use and handling of nanomaterials is also an important administrative function.

PPE creates a barrier between the worker and nanomaterials in order to reduce exposures. PPE may include laboratory coats, impervious clothing, closed-toe shoes, long pants, safety glasses, face shields, impervious gloves, and respirators.

Other Considerations

Control verification or confirmation is essential to ensure that the implemented tools or strategies are performing as specified. Control verification can be performed with traditional industrial hygiene sampling methods, including area sampling, personal sampling, and real-time measurements. Control verification may also be achieved by monitoring the performance parameters of the control device to ensure that design and performance criteria are met.

Other important considerations for effective risk management of nanomaterial exposure include fire and explosion control. Some studies indicate that nanomaterials may be more prone to explosion and combustion than an equivalent mass concentration of larger particles.

Occupational health surveillance is used to identify possible injuries and illnesses and is recommended as a key element in an effective risk management program. Basic medical screening is prudent and should be conducted under the oversight of a qualified health-care professional.

1 Introduction

According to The International Organization for Standardization Technical Commit­tee 229 (Nanotechnologies) (ISO/TS 27687:2008), a nano-object is a material with one, two, or three external dimensions in the 1- to 100-nm size range. Nano-objects are fre­quently incorporated into a larger matrix known as a nanomaterial. Nanoparticles are a specific type of nano-object, with all three external dimensions at the nanoscale. An additional term, ultrafine particles, is used to describe nanometer-diameter particles that have not been intentionally produced but are the incidental products of processes [NIOSH 2009a]. For purposes of this document, the term nanomaterial is used to de­scribe engineered nano-objects, including engineered nanoparticles.

Nanomaterials are increasingly being used in optoelectronic, electronic, magnetic, med­ical imaging, drug delivery, cosmetic, catalytic, and other applications. Although nano­materials present seemingly limitless possibilities, they bring with them new challenges to understanding, predicting, and managing potential safety and health risks to work­ers. Exposures to nanomaterials can involve a wide range of nanomaterial sizes, shapes, functionalities, concentrations, chemical compositions, and exposure frequencies or durations. Researchers working with engineered nanomaterials have the potential to be exposed through a variety of sources and processes, including leaks from equipment used in the synthesis of nanomaterials, manipulating dry nanopowders, sonicating liq­uid suspensions, or mechanically disrupting materials containing or coated with nano­materials [Aitken et al. 2004; Johnson et al. 2010]. A growing body of evidence indicates that exposure to some of these engineered nanomaterials can cause adverse health ef­fects. Based on this preliminary toxicological data, prudent practice dictates controlling occupational exposure to nanomaterials.

2 Scope

As with any new technology, the earliest exposures will likely occur among those work­ers conducting research in laboratories and pilot plants. Researchers handling engi­neered nanomaterials in laboratories and pilot scale operations should perform that work in a manner that is protective of their safety and health. Although incidental nanoparticles (also known as ultrafine particles) exist in nature, the focus of this docu­ment is to provide guidance on the safe handling of purposely designed, engineered nanomaterials in research laboratories. The information may also be applicable in some pilot-scale facilities.

Research laboratories include any facility performing basic or applied research involv­ing nanomaterials. Nanomaterial research laboratories may be housed at universities, government agencies, and private companies. Research laboratories may produce their own nanomaterials, work with nanomaterials produced by others, or some combination 2

of both. Laboratory-scale production typically consists of relatively small amounts of nanomaterial, ranging from a few milligrams for highly sophisticated materials such as quantum dots to a few kilograms for less-sophisticated materials such as metal oxides. Laboratories conducting applied research may also produce materials on a pilot scale, which typically increases material volumes by a factor of 10 or more. Pilot-scale equip­ment is generally similar to industrial-scale processes, but it produces much smaller quantities of nanomaterial.

3 Risk Management

Exposures to engineered nanomaterials can be controlled in the research laboratory by a comprehensive risk management program that includes task hazard/risk analysis, en­gineering controls, administrative controls, and use of PPE. Implementing an effective program should address the following elements of hazard surveillance.

Hazard Identification: Is there reason to believe that the nanomaterial of interest could be harmful?

Exposure Assessment: Is there potential for exposure to the nanomaterial or other chemical or physical hazards?

Exposure Control: What procedures are in place or should be developed to minimize or eliminate worker exposure(s)?

The answers to these questions will help to formulate a program that includes the following:

                        A written health and safety policy covering all types of chemical and physical hazards in the workplace, in accordance with the U.S. regulatory requirement 29 CFR 1910.1450, the Occupational Safety and Health Administration’s (OSHA’s) laboratory standard, including development of a Chemical Hygiene Plan.

                        A clear delineation of roles and responsibilities for everyone involved in labora­tory or pilot plant research.

                        Effective procedures for documentation, communication, and employee training.

                        Incorporation of input from safety professionals, industrial hygienists, and oc­cupational health professionals, as appropriate.

Figure 1 illustrates components of an overall health and safety program that includes nanomaterial risk management [Schulte et al. 2008a]. Additional guidance on prudent practices in the laboratory [NRC 2011] can be obtained from the National Academy of Sciences (NAS).3

4 Hazard Identification

The unique properties of materials at the nanoscale have raised concerns regarding health effects that might result from occupational exposures. The toxicity of a nanoma­terial will be a function of its substance-specific toxicity, as influenced by physicochemi­cal characteristics (including those unique to the nanoscale form of the substance) and contaminants [Trout and Schulte 2010].

Results of studies in which animals and humans were exposed to ultrafine or other respi­rable particles provide a basis of concern for possible adverse health effects due to engi­neered nanomaterial exposures. Experimental studies in rodents and cell cultures have shown that the toxicity of ultrafine or nanoparticles is greater than that of the same mass of larger particles of similar chemical composition [Oberdörster et al. 1992; Oberdörster et al. 1994; Lison et al. 1997; Tran et al. 1999; Tran et al. 2000; Brown et al. 2001; Barlow et al. 2005; Duffin et al. 2007]. In addition to particle size and surface area, other particle characteristics may influence toxicity, including surface functional groups or coatings, solubility, shape, and the ability to generate reactive oxygen species [Duffin et al. 2002; Maynard and Kuempel 2005; Oberdörster et al. 2005; Donaldson et al. 2006].

Several articles have investigated the toxicity of carbon nanotubes (CNTs) in experi­mental animal studies [Lam et al. 2004; Shvedova et al. 2005; Donaldson et al. 2006;

Figure 1. Components of an overall health and safety program. Modified from Schulte et al. [2008].4

Lam et al. 2006; Kisin et al. 2007; Li et al. 2007; Kane and Hurt 2008; Miyawaki et al. 2008; Poland et al. 2008; Shvedova et al. 2008; Erdely et al. 2009; Ma-Hock et al. 2009; Shvedova et al. 2009; Pauluhn 2010]. The results from these studies indicate potential respiratory health risks from exposure to CNTs, including granulomatous pneumonia and fibrosis. Evidence also indicates that when multi-walled carbon nanotubes (MW­CNTs) are administered intraperitoneally to mice, the MWCNTs have asbestos-like pathogenicity [Poland et al. 2008; Takagi et al. 2008]. Although a causal link has not been established, there is concern about possible cancer hazards in addition to potential for fibrosis/nonmalignant respiratory disease.

Additional studies have investigated the DNA damage caused by nanosized metals and metal oxides [Karlsson et al. 2009; Singh et al. 2009]. Although it cannot be concluded that metal oxide nanoparticles are always more toxic than their micrometer counterparts, nanosized copper oxide (CuO) was found to be much more toxic than micrometer-sized CuO [Karlsson et al. 2009].

Inhalation is considered the primary route of potential exposure in the nanomateri­al workplace. Evidence indicates discrete nanoparticles are deposited in the lungs to a greater extent than larger respirable particles [ICRP 1994]. Some nanoparticles are thought to enter the bloodstream from the lungs and then transfer to other organs [Tak­enaka et al. 2001; Nemmar et al. 2002; Oberdörster et al. 2002; Geiser et al. 2005]. It is further postulated that some nanomaterials may move from the nose to the brain though the blood-brain barrier [Oberdörster et al. 2004; Elder et al. 2006].

Dermal exposure to nanomaterials is also a potential exposure pathway. Possible harm­ful effects may occur locally, or the substances may be absorbed through the skin and cause systemic effects. Studies indicate particles smaller than 1 μm in diameter may penetrate intact skin [Tinkle et al. 2003; Ryman-Rasmussen et al. 2006]. Dermal ir­ritation has been seen following topical application of single-walled carbon nanotubes (SWCNTs) to nude mice [Shvedova et al. 2003; Murray et al. 2007], although it is not known whether skin penetration could occur and result in adverse health effects. Ad­ditional data are needed to extrapolate these findings for identifying any occupational health risks and for investigating the dermal toxicity of other nanomaterials.

Ingestion of nanomaterials might occur due to unintentional hand-to-mouth contact, thereby allowing possible transfer to other body organs via the gastrointestinal tract. The mucociliary escalator system, where particles that are deposited in the lung are transferred by coughing to the pharynx and subsequently swallowed, is an additional path to ingestion. Little is known about possible adverse effects from ingestion of nano­materials; however, some evidence indicates smaller particles can be transferred across the intestinal wall more readily than larger particles [Behrens et al. 2002].5

5 Exposure Assessment

An exposure assessment should identify tasks that may expose workers to nanomateri­als and also identify the researchers conducting those tasks. Such an assessment would review the process and material flow plans for the facility and the status of specific proj­ects. It would include staff interviews and a walk-through of the facility (laboratory) to ensure that all activities and potential exposure pathways are identified. The inventory of tasks and workers should include information on the potential magnitude, duration, and frequency of exposure during different job tasks, or at specific processes, and the amounts of materials being used. Current work practices and existing engineering con­trols should be evaluated.

The work tasks should be inventoried and prioritized according to the potential for occupational exposure. Examples of tasks and product activities include the following:

                        Material receipt, unpacking, and delivery.

                        Laboratory operations (synthesis, analytical, and quality assurance activities).

                        Cleaning and maintenance.

                        Storage, packaging, and shipping.

                        Reasonably foreseeable emergencies.

                        Waste management.

Determinants of potential exposure to nanomaterials may include dustiness, type of process, quantity of material handled, and duration and frequency of employee expo­sure. These elements are summarized below and should be taken into account when implementing exposure control measures.

Dustiness

The dustiness of the nanomaterial can influence potential exposures and the selection of the appropriate engineering control. Dustiness describes the tendency of particles to become and/or stay airborne and refers not only to the physical form of the nanomate­rial but also to the electrostatic repulsive forces inherent in the particle. For example, the “dustiness” of the nanomaterial is influenced by its particle bulk density and mor­phology (shape, diameter, and length), as well as the incorporation of the nanomaterial into slurries or liquid suspensions. Nanomaterials in dry powder form tend to pose the greatest risk for inhalation exposure, while nanomaterials suspended in a liquid typically present less risk via inhalation. Exceptions have been identified during some laboratory processes such as sonication, which resulted in an increase in airborne nano­materials [Johnson et al. 2010]. Electrostatic forces influence the stability of particle dispersion in air. These electrostatic forces therefore affect dustiness and should be con­trolled where possible. Nanomaterials with little or no repulsive forces will tend to be 6

more likely to form aggregates and therefore be less dusty. Nanomaterials incorporated into a solid matrix present the least risk for inhalation exposure because of their limited mobility as long as they are maintained within the matrix.

Process

Some material handling, synthesis, and manufacturing processes can increase the risk of employee exposure. Open, manual handling of bulk nanomaterials, as well as high-energy processes such as milling, sonication, grinding, and high-speed blending, could cause the release of nanomaterials [Gohler et al. 2010; Johnson et al. 2010]. Consid­eration should also be given to the possibility of intentional or inadvertent chemical changes during a work task that may alter the toxicity of a nanomaterial.

Quantity, Duration, and Frequency of Task

The quantity of the nanomaterial that is synthesized, received, or handled in the labora­tory will significantly influence exposure potential. Research laboratories may handle quantities ranging from milligrams to several grams or even kilograms of a nanomate­rial. As quantities increase, consideration of additional control measures may be re­quired. Exposure potential may be influenced by the duration and frequency of the task(s). Small quantities used on an infrequent basis may not require the same level of control measure that large quantities used daily would require.

Engineering controls should be the primary means of controlling exposures, except in situations (e.g., emergencies) where such controls may not be feasible. In those circum­stances, other control measures may be required (e.g., respirator use).

5.1 Safety Through the Life Cycle of a Nanomaterial

To ensure the health and safety of those working with nanomaterials, the exposure sources during the nanomaterial product life cycle should be evaluated. Exposure sources include nanomaterial synthesis reactors, nanoparticle collection and handling, product fabrication with nanomaterials, product use, and product disposal [Sahu and Biswas 2010]. Table 1 contains some selected activities with potential exposure sources and recommended engineering controls. The ultimate disposal of the nanomaterial and contaminated refuse should follow all applicable federal, state, and local regulations.

Consideration should be given to installing high-efficiency particulate air (HEPA) fil­ters on laboratory chemical hoods or other individual exhaust duct systems. The deci­sion to use HEPA filtration should be based on evaluation of the contaminant charac­teristics, maintenance and protection of the fan motor and other exhaust parts, energy 7

Table 1. Employee activities and recommended minimum controls.