The beneficial applications, both diagnostic and therapeutic, of ENM are also highlighted. This book fills an important need in terms of bridging the gap between experimental findings and human exposure to ENM, and the clinical and pathological consequences of such exposure in the human population. Enter your mobile number or email address below and we'll send you a link to download the free Kindle App. Then you can start reading Kindle books on your smartphone, tablet, or computer - no Kindle device required.
To get the free app, enter your mobile phone number. There are clear images throughout which have been used in particular effect to simplify and summarise models being discussed…Overall this is a useful book which will be of particular interest to students or researchers new to the field of nanotoxicology. Adverse Effects of Engineered Nanomaterials: Exposure, Toxicology, and Impact on Human Health is a critical and authoritative resource that provides an orientation for toxicologists, pharmacologists, and clinicians, as well as regulators and policymakers, and others directly involved in nanosafety.
This book, written by leading international experts in nanotoxicology and nanomedicine, gives a comprehensive view of the health impact of engineered nanomaterials ENM , focusing on their potential adverse effects in exposed workers, consumers and patients. By reviewing and translating current research, this essential reference bridges the gap between experimental findings on toxicological effects of ENM and occupational and environmental exposure to ENM, and the clinico-pathological consequences of such exposure in the human population. Contains information on occupational exposure assessment and biomonitoring of exposure and adverse health effects of ENM Provides a critical discussion of commonly used in vitro and in vivo toxicity tests and of computational approaches to nanosafety Offers a systematic evaluation of the human organs and organ systems which may be affected by exposure to ENM Highlights current and future biomedical applications of nanoparticles in relation to nanosafety Provides global, clinical, occupational, and regulatory perspectives given the backgrounds of the well-renowned contributing authors and their expertise in health and safety issues related to ENM Related Titles:.
Interpretation and Relevance in Drug Safety Evaluation, 4 th edition, , Risks, Regulation and Management, , Would you like to tell us about a lower price? Multi-authored book written by leading US and European experts on nanotoxicology and nanomedicine Discusses the health implications and a clinical translation of experimental data in this area Takes a schematic, non-exhaustive approach to summarize the most important research data in this field Includes a glossary, with a brief explanation of the term and with a reference to where the term or phrase has been used will be included within the book.
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Kindle Cloud Reader Read instantly in your browser. However, a new study incorporated a physiologically-based lung model and data of particle sizes of airborne titania ENM during manufacturing to estimate anatase and rutile titania ENM burdens and adverse effects in lung cells. The authors concluded that workers exposed to relatively high airborne to nm anatase titania are unlikely to have substantial risk for lung inflammatory responses, but are at risk for cytotoxicity [ ]. Risk characterization and assessment and gap analysis case studies were conducted with fullerenes, CNTs, silver as a example of a metal, and titania as an example of a metal oxide ENM [ ].
Numerous additional data gaps were identified for each. There are no existing regulations or standards for ENMs within the three jurisdictions that have the largest nanotechnology funding, the U. The respiratory protection standard requires employers provide workers with NIOSH-certified respirators or other PPE when engineering controls are not adequate to protect health.
Suggested implementation includes many of the primary prevention measures discussed in this review and an occupational health surveillance program of exposure and medical monitoring.
The goal in managing the potential risks from ENMs is to minimize exposure. In the absence of specific information on ENMs, the extensive scientific literature on airborne, respirable aerosols and fibers has been used to develop interim guidance for working safely with ENMs [ ] [ http: Occupational health surveillance, which includes hazard and medical surveillance, is the process whereby information from any of these activities is collected and used to support or modify what is done at a higher step in the hierachy, as shown by the upward pointing arrow [ ].
Those steps in the hierachy that have been investigated for ENMs are further discussed below. Elements of occupational health protection. The continuum of prevention and the heirarchy of exposure control left arrow and occupational health surveillance right arrow. Adapted from [ ] and [ ]. ENM exposure can be reduced through the use of engineering controls, such as process changes, material containment, and enclosures operating at negative pressure compared to the worker's breathing zone; worker isolation; separated rooms; the use of robots; and local exhaust ventilation LEV.
Given the lack of occupational exposure standards to provide guidance, the most prudent approach is to minimize exposure. A survey found that engineering controls in Switzerland were more commonly used in the production of powder than liquid ENMs.
It is anticipated that as this industry matures and knowledge is gained, control will more commonly include superior methods in the hierarchy of exposure control [ ]. Some companies a minority were using inappropriate occupational environmental clean-up methods, such as sweeping and compressed air [ ]. These results suggest more widespread adoption of nano-specific environmental health and safety programs and the use of PPE in the absence of superior controls are appropriate.
However, one should also consider that these methods can release ENMs into the environment, potentially creating environmental pollution and loss of costly material. ENM handling is often conducted in fume hoods. Field sampling conducted to determine fume hood, work zone, and background concentrations of PM 2. Monitoring aerosolized particles during chemical vapor deposition CVD SWCNT synthesis and aerosol-assisted CVD MWCNT synthesis in a fume hood showed significant release at the source, but not outside of the hood, suggesting fume hood use did not create fugitive airborne emissions and was necessary to protect workers [ ].
These authors also determined the release of dry powder alumina 27 to 56 nm primary particle size, nm agglomerates and 60 nm silver ENM into the researcher's breathing zone and laboratory environment when poured or transferred in 3 fume hoods; 1 a conventional hood that has a constant air flow with velocity inversely related to sash height, 2 a by-pass hood which attempts to maintain a constant velocity by use of a by-pass grill above the hood which becomes uncovered, allowing more air flow through it rather than the hood face as the sash is lowered, and 3 a constant velocity variable air volume hood that uses a motor to vary fan speed as the sash is moved.
The results showed significant release of ENMs into the researcher's breathing zone and laboratory environment and identified the variables affecting release. The constant velocity hood performed better than the by-pass hood, which in turn performed better than the conventional hood [ ]. The newly developed air-curtain hood is evidently not commercially available. The results showed much lower levels with the air curtain hood [ ].
Sash height, which affected hood face velocity, affected ENM release. Worker motion and body size affected ENM release from a traditional, but not the air-curtain, hood. The authors found that ENM handling in traditional fume hoods with a face velocity of 0. In the Center for High Rate Manufacturing recommended locating equipment at least 6 inches 15 cm behind the sash, minimizing hood clutter, and avoiding rapid or violent motions while working in the hood [ ].
In a study conducted in an industrial setting, use of an exhaust hood during procedures that are more likely to release ENMs their production, handling, measurement, and reactor cleanout resulted in no significant increase of ENMs in the workplace [ ]. These studies show that significant reduction of worker exposure to ENMs can be achieved using available fume hoods and consideration of worker activities within these hoods. It has an all stainless steel interior for ease of cleaning, perforated rear baffle to reduce turbulence, and a replaceable HEPA filter.
It is available with a built-in ionizer to attract particles to the interior surface of the hood, and an external exhaust for volatiles.
Adverse Effects of Engineered Nanomaterials: Exposure, Toxicology, and Impact on Human Health Edited by Bengt Fadeel, Antonio Pietroiusti & Anna A. Adverse Effects of Engineered Nanomaterials: Exposure, Toxicology, and Impact on Human Health, Second Edition, provides a systematic.
Air-displacement ventilation in an industrial setting was accomplished by introduction of supply air that entered at low velocity at the floor level and was cooler than room air. As the air rose it became warmer and was exhausted close to the ceiling. This provided efficient clearing of ENMs from the breathing zone [ ]. A well-designed exhaust ventilation system with a HEPA filter should effectively capture airborne nanoparticles. A "down flow" booth, "elephant trunk", or fume hood may not provide sufficient protection because they may cause turbulence, spinning the ENM out of the airflow [ ].
The effectiveness of engineering controls in ENM production and research facilities has been demonstrated in a few cases. Prior to use of engineering-control measures, total airborne mass concentrations of MWCNTs, measured by area sampling, were 0. After enclosing and ventilating the blending equipment and re-locating another piece of equipment that produced considerable vibration, the concentration decreased to below the limit of detection [ ].
In another study, the effectiveness of LEV was assessed during clean-out of slag and waste, which used brushes and scrapers, of reactors that produced 15 to 50 nm diameter ENMs. A portable LEV unit was used that had been shown to reduce welding fume exposure [ ]. The poor performance of the custom fume hood may have been due to the lack of a front sash and rear baffles, and to low face velocity 0.
Respirable particles were an order of magnitude lower when the work was conducted in a BSC than on a work table [ ]. These results illustrate the importance of good exhaust hood design as well as the worker protection provided by a BSC. When engineering controls are not feasible for reducing exposure, administrative controls should be implemented.
These are policies and procedures aimed at limiting worker exposure to a hazard [ ]. These could include a nanoscale material hygiene plan; preparation, training in, and monitoring use of standard operating procedures; reduction of exposure time; modification of work practices; and good workplace and housekeeping practices. For example, one laboratory was thoroughly cleaned after high air concentrations of nanoscale materials were measured in a facility engaged in the commercial compounding of nanocomposites [ ]. A large decrease of airborne 30 to nm particles resulted. Subsequent routine maintenance kept the particles below those originally observed, leading the authors to conclude that this administrative control was beneficial in reducing potential exposure.
It is discussed below. The last line of defense in the hierarchy of exposure control is the use of PPE, such as respirators, protective clothing, and gloves. The filter's resistance to oil is designated as N, R, and P; N not resistant to oil , R resistant to oil , and P oil proof. Some industrial oils can remove electrostatic charges from filter media, reducing filter efficiency. Airborne nanoparticles behave much like gas particles. Charged particles are trapped by electrostatic attraction, which involves an electrically charged particle and an electrically charged electret fiber.
Electret filters are constructed from charged fibers. This appears to be a significant mechanism for respirator trapping of ENMs [ ]. Neutral particles that pass through a charged fiber can be polarized by the electric field, thereby inducing charge to the particle. In dry conditions, ENM penetration decreases with time. With continued use, however, ENM penetration through an electrostatic filter increases; this was suggested to be due to the humidity of exhalation [ ]. Soaking fiber filters in isopropanol removes electrostatic charge.
The mechanisms of ENM association with fiber materials. Each panel shows particles carried by airstreams, indicated by the bands with right pointing arrows. Some particles are retained by the fiber. Those that are not continue on the airstream past the fiber. The upper panel shows a large particle that is unable to follow the airstream around the fiber and collides with the fiber due to inertial impaction. The particle trapped by interception comes close enough to the fiber within the particle radius that it is captured by the fiber.
Electrostatic attraction is discussed in the text VI, C, 1. Small particles collide with each other, gas molecules, and other suspended matter in the air stream, resulting in Brownian motion and a random zigzagging path of movement, which may cause the particle to hit the fiber, as shown in the diffusion panel. Most of the studies were conducted with different sizes of NaCl, but a few used silver, graphite or titania.
The results show that dust masks purchased at hardware or home improvement stores would not be expected to protect the wearer. Increasing flow rate increased penetration. This highest flow rate was intended to model an instantaneous peak inspiratory flow during moderate to strenuous work. A similar result of ENM penetration positively correlating with air flow rate is shown in Panel F, where 5. Particle penetration through dust masks and facepiece respirators.
Circle Results from 6 3M Engineered nanoparticles and particulate respirators [ http: N95 respirators at two flow rates. Panel G shows greater penetration of titania than graphite through FFP3 respirators under the same experimental conditions. These results suggest further work is warranted to understand the influence of the physico-chemical properties of ENMs, particularly size, charge, and shape, on their penetration through filtering facepiece respirators.
An issue that significantly impacts filtering facepiece respirator effectiveness is its seal around the face. Shaffer quoted in [ ]. This underscores the importance of a proper fit for face mask respirators. There is a particle size that maximally penetrates each filter material; the most penetrating particle size MPPS.
This is approximately the same size of spherical ENMs that appear to contribute to their greatest differences in biological systems from solution and bulk forms of the same materials, as discussed in II, A, 2. This feature raises concern because the size of ENMs that may have the greatest effects in people are those that are best able to penetrate filtering facepiece respirators.
Until results are obtained from clinical-laboratory or work-place studies, traditional respirator selection guidelines should be used. Recommendations for selection, use, care and maintenance. No guidelines are available on the selection of clothing or other apparel e. This is due in part to the minimal data available on the efficacy of existing protective clothing, including gloves. Pore structure of the various fabrics greatly influenced penetration [ ]. Although nonwoven fabrics were much more effective to protect workers from ENM exposure than woven fabrics, they are much less comfortable to wear, suggesting improvements in fabric design or selection are needed to address this disincentive to use more effective PPE.
The selection of laboratory coat materials can greatly influence the potential penetration of ENMs, which may end up on or penetrating street clothing, resulting in worker absorption or their even greater dispersion into the environment. An unpublished study reported in the interaction of alumina and organoclay ENMs with powder-free natural rubber latex, powder-free synthetic latex nitrile, and cotton gloves [ ].
Although these surface imperfections were not complete holes, they may serve as pathways for the penetration of nanoparticles under unfavorable conditions, such as stretching and tearing. The surface pores may be important if they collect nanoparticles and the user does not remove the gloves when going to another location, thereby transporting the ENMs. Not surprisingly, there were wider gaps between the fibers in cotton gloves.
The authors pointed out that ENMs may be treated with special coatings to enhance their dispersion characteristics, which may alter their permeability through glove materials. This study, however, did not determine the penetration of ENMs through gloves. Double gloving has been suggested [ ], which should reduce material penetration when there is glove perforation as well as dermal contamination when removing a contaminated outer glove.
However, double gloving has not been shown to significantly decrease material penetration [ ]. Occupational health surveillance is the ongoing systematic collection, analysis, and dissemination of exposure and health data on groups of workers for the purpose of early detection and injury.
It includes hazard surveillence, the periodic identification of potentially hazardous practices or exposures in the workplace, assessing the extent to which they can be linked to workers, the effectiveness of controls, and the reliability of exposure measures. A goal is to help define effective elements of the risk management program for exposed workers. Occupational health surveillance also includes medical surveillance, which examines health status to determine whether an employee is able to perform essential job functions [ ].
This is different than medical screening or monitoring, a form of medical surveillance designed to detect early signs of work-related illness by administering tests to apparently healthy persons to detect those with early stages of disease or those at risk of disease. The third level in the continuum of prevention and heirarchy of exposure control, tertiary prevention, includes diagnosis, therapy, and rehabilitation.
Owing to the lack of documented episodes of ENM exposure in humans that have resulted in adverse outcome, there is little experience with treatments of ENM exposure. One example that illustrates clever application of the knowledge of ENM properties was the use of UV light to visualize and treat the accidental dermal exposure of a human to quantum dots suspended in solution [ ]. Based on the current knowledge of ENM exposure risks, some good workplace practices have been suggested.
They are shown in Appendix 1. The investigators established a measure of risk for each potential hazard and suggested improvement actions. These were then addressed with administrative controls, environmental monitoring, PPE and good workplace practices. The following are some published guidelines, not regulations, for safe handling and use of ENMs. Guidelines for safe research practices" as their Safety Net guidelines [ http: Guide to safe handling and disposal of manufactured nanomaterials" in , as their publication PD The American Society for Testing and Materials prepared.
This is a guide for use when no specific information on ENMs or toxicity is available. OSHA prepared "Occupational exposure to hazardous chemicals in laboratories", as their publication This guidance is designed for lab scale i. The Center for High-Rate Nanomanufacturing and NIOSH are preparing a guide to safe practices for working with nanomaterials that is anticipated to be released in early Some websites that have considerable information on nanoscale materials are Nano Safe at [ http: An extensive variety of ENMs has been created.
ENMs have already been utilized in many products and much more extensive use is anticipated in the future. There are reports of toxicity following in vitro and in vivo exposure to many ENMs, albeit often after very high doses, and generally lacking dose-response assessment. There is a small amount of exposure assessment information, and a paucity of information required for a risk characterization.
Until more research and workplace monitoring information becomes available to refine the current knowledge of ENM risks, good workplace practices and guidelines based on ultrafine materials are guiding the occupational safety and health practices in working with ENMs. Appropriate clothing and PPE generally includes closed-toed shoes, long pants without cuffs, long-sleeved shirt, laboratory coat, nitrile gloves, eye protection and perhaps a respirator, e.
Do not dry sweep or use compressed air. Both authors contributed to the revision of the review, responding to the reviewers' comments. Both authors read and approved the final manuscript. The authors thank Matt H. Hazzard and Robin L. Boyes, EPA, for their helpful comments on a prior version of this review, and an anonymous journal reviewer whose extensive comments surely improved this manuscript. This manuscript has been reviewed by the National Health and Environmental Effects Research Laboratory and approved for publication.
Approval does not signify that the contents reflect the views of the Agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use. National Center for Biotechnology Information , U. J Occup Med Toxicol. Published online Mar Author information Article notes Copyright and License information Disclaimer.
Received Oct 8; Accepted Mar This article has been cited by other articles in PMC. Abstract Nanotechnology presents the possibility of revolutionizing many aspects of our lives. The objectives of this review Although there has been considerable work to advance nanotechnology and its applications, understanding the occupational, health and safety aspects of engineered nanomaterials ENMs is still in its formative stage.
Engineered nanomaterials Nano is a prefix derived from the Greek word for dwarf.
Open in a separate window. Some uses of ENMs and the projected market and workforce There is considerable interest in developing ENMs because their properties differ in fundamental and valuable ways from those of individual atoms, molecules, and bulk matter. Uncertainties regarding the adverse effects of ENMs There have been concerns about the safety and public acceptance of this burgeoning technology, particularly in the past 5 years, due to the lack of much information about potential adverse effects [ 32 ].
Hazard identification In the occupational context, hazard identification can be re-stated as "What effects do ENMs have on workers' health? The physico-chemical properties of ENMs that impact their uptake Hazard identification has revealed that the physico-chemical properties of ENMs can greatly influence their uptake. The role of surface coating in ENM uptake and effects ENMs are rapidly coated in biological milieu, primarily by proteins [ 62 , 64 - 66 ].
ENM uptake from the initial sites of exposure To understand ENM-induced effects and their mechanisms of action, cells in culture and other in vitro systems have been utilized. Lungs There has been much interest in the health effects of airborne particles, specifically PM 10 thoracic fraction , PM 2.
Dermal exposure Skin is composed of 3 primary layers, the outermost epidermis which contains the stratum corneum, stratum granulosum and stratum spinosum , dermis, and hypodermis. Oral exposure Little is known about the bioavailability of ENMs from the buccal cavity or the sub-lingual site, or possible adverse effects from oral ingestion. Ocular and mucous membrane exposure Ocular exposure might occur from ENMs that are airborne, intentionally placed near the eye e.
The effects of ENM exposure on target organs and those distal to the site of uptake Public concerns about ENMs and health may arise with reports of some effect s in a laboratory study or their presence in human tissue or another organism. ENM exposure effects in the lung Studies of ENM inhalation and intratracheal instillation as well as with lung-derived cells in culture have increased concern about potential adverse health effects of ENMs.
ENM exposure effects seen in the skin Potential toxicity from dermal exposure was demonstrated with silver ENMs, that decreased human epidermal keratinocyte viability [ ]. Summary of the effects of ENM exposure on target organs and those distal to the site of uptake Common findings of many studies are induction of inflammatory processes and oxidative stress. The clearance of ENMs, their translocation to distal sites, and persistence As with the above studies that inform about uptake, the clearance and translocation of ENMs from the initial site of exposure to distal sites is best understood from whole-animal studies.
The physico-chemical properties of ENMs that impact their hazard - The role of surface coating in ENM effects Many surface coatings have been investigated in order to develop ENMs as carriers for drug delivery. The effects of ENMs at distal sites Reported systemic effects of pulmonary-originating CNTs include acute mitochondrial DNA damage, atherosclerosis, distressed aortic mitochondrial homeostasis, accelerated atherogenesis, increased serum inflammatory proteins, blood coagulation, hepatotoxicity, eosinophil activation suggesting an allergic response , release of IL-6 the main inducer of the acute phase inflammatory response , and an increase of plasminogen activator inhibitor-1 a pro-coagulant acute phase protein [ ].
Risk Characterization The giant insurance firm Lloyd's of London conducted a risk assessment and concluded "Our exposure to nanotechnology must therefore be considered and examined very carefully" [ http: Risk Management There are no existing regulations or standards for ENMs within the three jurisdictions that have the largest nanotechnology funding, the U.
Engineering controls ENM exposure can be reduced through the use of engineering controls, such as process changes, material containment, and enclosures operating at negative pressure compared to the worker's breathing zone; worker isolation; separated rooms; the use of robots; and local exhaust ventilation LEV. Local exhaust ventilation LEV Air-displacement ventilation in an industrial setting was accomplished by introduction of supply air that entered at low velocity at the floor level and was cooler than room air.
Administrative controls When engineering controls are not feasible for reducing exposure, administrative controls should be implemented. Personal protective equipment The last line of defense in the hierarchy of exposure control is the use of PPE, such as respirators, protective clothing, and gloves. Protective clothing No guidelines are available on the selection of clothing or other apparel e. Gloves An unpublished study reported in the interaction of alumina and organoclay ENMs with powder-free natural rubber latex, powder-free synthetic latex nitrile, and cotton gloves [ ].
Diagnosis, therapy, and rehabilitation The third level in the continuum of prevention and heirarchy of exposure control, tertiary prevention, includes diagnosis, therapy, and rehabilitation. Good work practices Based on the current knowledge of ENM exposure risks, some good workplace practices have been suggested. Some published guidelines for safe handling and use of ENMs The following are some published guidelines, not regulations, for safe handling and use of ENMs. Conclusions An extensive variety of ENMs has been created. Some good workplace practices - Post signs indicating potential hazards, PPE requirements, and administrative controls at entrances to areas where ENMs are handled.
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Hazard, exposure, risk assessment 1. In Vitro and In Vivo 4. Regulation and Legislation 8. Adverse effects on human health 9. Respiratory System, Part One: Respiratory System, Part Two: Allergy and Asthma