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A systematic literature review on the emerging hazard of nanoparticles causing occupational respiratory nanotoxicology: case study

Introduction

Nanotoxicology has become a high-interest field as a result of the increased and rapid development of the nanotechnology industry. According to Pronk et al. (2006, p. 2), respiratory injury is only one of the potential risks posed by nanoparticles due to the high levels of these particles in the workplace. As a result, those working in nanotechnology industries have an increased risk of suffering from lung injury due to inhaled nanoparticles in the workplace environment. This essay will seek to identify the process of respiratory nanotoxicology, management of nanotoxicity, and preventive measures. This will be done through analysis of a selected case study – Occupational Exposure Assessment in Carbon Nanotube and Nanofiber Primary and Secondary Manufacturers, by Dahm et al. (2012, p. 542-556).

Case study summary

The study was conducted in the US and was focused on carbon nanotubes (CNT) and carbon nanofibers (CNF), which are one of the nanoparticles potential of respiratory nanotoxicity. The significance of the study was to assess exposure information from six selected sites which where identified as CNT/CNF primary of secondary manufacturers. Based on toxicological evidence, the risk of occupational nanotoxicology is very high in CNT/CNF sites and result to a wide range of health effects. The National Institute for Occupational Safety and Health (NIOSH), which is the body governing and regulation occupation safety, has issued the recommended exposure limit (REL). However, few studies have reported concentration of CNT/CNF at a personal breathing zone (PBZ) in an occupational setting.

The study was done through personal and area filter basis of data sampling. Samples collected were for inhalable mass concentration, and the respiratory mass concentration of elemental carbon and CNT structure count analysis (Dahm et al. 2012, p. 542). Sampling was done through transmission electron microscopy to assess exposure. In the sampling exercise, full-shift PBZ samples were collected when possible with the area samples being collected through a task-based approach.

The study results showed that the majority of the samples collected indicated a lower than the REL of 7 µg/m3. Among the three surveyed manufacturers considered secondary, two were found to have concentration of CNT/CNF that where above the REL. For all of the regarded-primary manufacturers, none was found to CNT/CNF concentration above the REL. presence of CNT/CNF particles in all sites was evidenced though visual and microscopy based analysis with highest count of these particles being found in the samples collected from secondary manufacturing sites. A statistical correlation analysis between fiber-based samples for the mass concentration of EC and CNT structure counts showed a general trend between the two with a P-value of 0.001 and a corresponding Pearson correlation coefficient of 0.44.

Based on these results, the study concluded that the concentration of CNT/CNF was above the REL for two of the secondary manufacturing sites for PBZ. These two facilities use the materials for commercial purposes and the samples were collected during dry power handling processes for example mixing and weighing of large quantities of the CNTs and CNFs.

Definition of terms

Primary – those manufacturers who are involved with the production of the elements

Secondary manufacturers – those facilities which are second, third…n users of the elements (downstream users)

Clearance – the removal of particles or substances out of an organism, usually via urine or stool

Chelator – a chemical agent that binds reversibly to a metal ion, forming a metallic complex.

Granuloma – tissue resulting from aggregation of inflammation-fighting cells unable to destroy foreign substances

Macrophage – a phagocytic tissue cell of the reticuloendothelial system that is derived from the blood monocyte.

Oxidative stress – an imbalance in favor of pro-oxidant versus antioxidant chemicals.

Analysis of the case study

Carbon nanotubes and carbon nanofibers are widely used in industries as well as in numerous high performance intermediates in the present date (Methner et al. 2010, p. 164). Some of the uses include coatings and components of aerospace, automobiles, electronics, in construction, displays, batteries, and in various health care applications. Based on the increased prevalence of CNTs and CNFs, they are the most common nanoelements that might be responsible of any cases of nanotoxicology. Therefore, the study of the two nanoelements is sure to offer more and relevant insights in the field of nanotoxicology, hence the study by Dahm et al is considered to be highly relevant.

The sampling method used was guided by the PBZ and it was the right method based on the significance of the study. However, as stated by Han et al. (2008, p. 742), the collection of samples in the facility should be evenly distributed and guided by the room and worker location. For example, if the samples are to be collected during product handling processes like mixing, it should be done at the same time in all the facilities for data uniformity. In addition, the sampling proximity of the sampling region should be almost similar in all the facilities. The time of collecting the sample after the start of handling process is also vital to allow for uniform distribution of the elements in the sampling area. Methner et al. (2010, p. 165) recommends sampling to be done at the location of the worker manning the process and sampling be done at given intervals for the entire REL.

Even though the objective of the study is to assess the concentration of CNTs/CNFs in PBZ, the study would have been more relevant if data collection was also done on the person working in the sampling area. Some of the measurements would have been analysis of in vitro as well as in vivo lung biopsy and the period of time the person has been working in the plant. Study of persons who have worked in the same position previously would be effective. According to Rip & Shelley- Egan (2009), nanoparticles have the tendency of accumulating in body parts and the effects are manifested after a while. Therefore, study of former employee would help to determine the long term effects of exposure to nanoparticles.

For each of the facilities included in the study, there were between 5 and 20 employees. However, these were not full-shift because the facilities were still handling nanotechnology experiments at experimental levels (Dahm et al, 2012, p 554). The study identifies this as a limitation. Due to lack of human nanotoxicity result, the study relies on rodent toxicological results from literature reviews (p, 543).

The study is published in peer reviewed life science and social journal, Journal of occupational hygiene. The guidelines of the study were done as per NIOSH requirements which included the collection of sample, the determination and collection of the control, and the analysis of the samples collected. Based on these aspects, it is concluded that the study is an authentic case study.

Definition

Nanomaterials are likely to enter the environment from manufacturing facilities. These materials are produced through the production of large amount of materials and reach the environment through manufacturing effluents or through spillage of mishandling during packaging or shipping (Rial-González, 2005). Apart from the manufacturing facilities, nanoparticles are currently being used in consumer products for example, cosmetic products. Through this avenue, these products are released into the environment when these cosmetics are washed off (Oberdorster et al. 2005, p. 825). Through such avenues, the release and accumulation of nanoparticles in the environment is on continuous basis.

In addition to the avenues considered to be contamination, nanoparticles are also being introduced into the environment through strategies considered to be remediation. One of them is the injection of nano-iron. The safety of these nanoparticles has not been determined which poses a threat especially for the large wildlife (Balbus 2007, p. 1654). The injection of NPs into soil is one of the remediation strategies being use by scientists. However, the arising concern is that the migration of these particles might not be fast enough as to enable remediation.

In the manufacturer of NPs, release of these particles into the environment poses a threat for the employee. One of the immediate risks is inhalation of the particles causing. The inhalation of NPs causes a number of conditions which manifest through various signs.

Epidemiology of inhaled NPs

Toxic nanoparticles can enter the body though involuntary or incidental episodes. In the workplace, this happens mainly through ignorance of protective measures for occupation safety (European Agency for Safety and Health at Work, 2007). The major avenues through which NPs enter the body include inhalation, cutaneous absorption, and ingestion. Inhalation accounts for the majority of entry at 72% (Dahm et al, 2012, p. 543). Entry of toxic NPs through the respiratory system affects the entire system. However, the effects of the deposition of NPs in the tract can be divided into three parts; nasopharyngeal, tracheabrachial, and alveolar.

According to Kreyling et al. (2009), the effect of inhaled NPs is not universal across all humans. The effect is dependent on the individual body response mechanisms. Specific body defense mechanism are able to protect the body from harmful materials at the point of entry however, these mechanism are renders incapable by inhaled toxic NPs. The deposition of inhaled NPs through the respiratory route will depend on the size of the particle. For 1 nm particles, 90% are deposited on the nasopharyngeal, 10% on the tracheabronchial and almost nothing in the alveolar region; 20 nm particles means more particles are deposited in the alveolar region (Han et al 2008, p. 745).

The resulting condition is dependent on the amount of particles deposited a region. Some of the conditions resulting from NPs deposition in the lungs include inflammation, development of granulomatous and persistent fibrosis (Kreyling, 2009).

Etiology of inhaled NPs

Inhaled NPs are removed though from the respiratory system through lung clearance and transportation system. Clearance in the lungs happens through macrophages phagocytosis (Balbus 2007, p. 1657). For particles measuring 10 nm and below can reach the lower parts of the wind pipe. The effect of these particles is dependent on the chemical status of the material. For the majority of naturally occurring nontoxic NPs, they are cleared from the respiratory system and no effects. However, for the toxic NPs, even though they might be cleared from the respiratory system, for the time they remain there, because clearance takes it, they cause health conditions (Kreyling et al. 2009).

One of the most common health conditions caused by inhaled NPs is inflammation. When toxic NPs are deposited on the respiratory wall or in the alveoli, the body responds by detecting the particles as foreign bodies and causing the body defense system to act. Through the release of immune mechanisms, the epithelia cells next to the particles swell up to accommodate increased blood hence inflammation.

For toxic particles of 20 nm size, they are deposited in the alveoli. Alveoli macrophages are able to phagocyte particles that are equal to their size, therefore, due to this inefficiency, particles are able to evade the cleanup process and enter the alveolar epithelium into the interstitial space (Methner et al. 2010, p. 167). These particles pose the threat of nervous system related conditions.

Pathogenesis of inhaled NPs

The mode of develops of the lung conditions due to inhaled NPs is largely dependent on the type of NPs, their chemical component, and duration of exposure (Pronk et al, 2006, p. 7). Due to the clearance mechanism and the protective mucosal lining, the majority of NPs are trapped and removed from the system. Moreover, because these particles are non living organisms, pathogenesis of their action is limited to body response to the chemical properties of the particle and exposure period.

For NPs that enter the interstitial space, they can enter body cells. The mechanism of entry is similar to that of nanorganism (viruses) (Oberdorster et al. 2005, p. 827). In the cell, the particle is able to interact with subcelluar structure depending on the particles size, chemical properties, and shape. The activities that NPs have been shown to interfere with include cellular uptake processes, cell localization, and the ability to catalyze products. According to Dahm et al. (2012, p. 552), the mechanisms through which NPs enter the cell is through adhesive interaction or passive uptake. This uptake is believed to be initiated by electrostatic charges, static interactions, Ven Der Waals forces, and interfacial tension.

Clinical symptoms

Symptoms due to nanoparticles inhalation will largely depend on the type of NPs. Nevertheless and according to Rip & Shelley-Egan (2009), there are some universal symptoms which include terminal cough (for the period of exposure to the NPs), chest pain, and heavy breath in advanced cases.

For the case of CNTs and CNFs, experiments on mice depicted varying indication depending on amount inhaled and the duration of exposure. The investigation involved introduction of CNT to mice trachea under anesthesia. After seven days, five of the mice which had high levels of nanotubes introduced to them died. After examination of the dead mice, the indication revealed included epithelial granulomas, tumor nodules of bloated white blood cells on the lining of the lungs, and cases of inflammation of the lungs. The surviving mice where investigated on the 90th day after being put to death. The indication found showed inflammation around the bronchi and extensive necrosis (Methner et al. 2010, p. 167).

For those mice unto which lower levels of CNTs was introduced, 0.5 mg of nickel-yttrium containing nanotubes, investigations on the 90th day revealed indication which included lethargy, decrease in body weight, and inactivity. Upon opening up of the mice, the lungs showed aggregates of macrophages forming dark patches on the lungs. The level of lesions was directly proportional with the level of nanotubes introduced (Methner et al. 2010, p. 168).

Diagnosis

Diagnosis of CNTs and CNFs in humans is considerably tricky. For clear and concise diagnosis, it requires examination of lung tissue (Parent-Thirion et al. 2007). However, in cases of human inhalation of CNTs/CNTs, diagnosis is limited to observation of the respiratory system. In both short term and long term exposure, analysis of respiratory mucosal lining is the first diagnosis (Han et al. 2008, p. 747). In short term exposure to inhalable NPs, the inhaled particles are deposited on the respiratory system lining, depending on the particle size. Even though these deposited particles are cleared through the respiratory system clearance mechanism, it takes time. Therefore, analysis of the lining will show residues in NPs are present.

For long term depositions, which is indicated by weight loss and heavy breathing, X-ray imaging of the lung is a diagnostic strategy. This method shows the presence of particle depositions which appear as dark section on the X-ray image (Rip & Shelley- Egan, 2009). Nanoparticles of sized 20 nm will reach the alveolar region of the respiratory system. In the lungs, these particles form aggregations due to attack by lung macrophages. Because the macrophages are unable to synthesis and break the particles, the result to aggregation; the X-ray image shows these as lesion on the lungs.

Other diagnostic measures for inhaled NPs are a check of breathing rate and movement of the torso (Rial-González et al. 2005). In cases of increased NPs inhalation, the result is increase of breathing rate to compensate for oxygen intake and distribution into the lungs. The alveolar with NPs depositions are rendered ineffective in gaseous exchange reading to increased breathing rate. Torso movement on the other hand shows the energy used for breathing; intensive torso movement indicates more energy hence an indication of problematic breathing.

Prognosis

Nanotoxicology prognosis is highly dependent on the exposure time. In moist cases, and especially in primary facilities manufacturing CNTs/CNFs and other nanoparticles, the conditions are controlled by the NIOSH. These include the REL and the PBZ. For companies that strictly adhere to these conditions, the level of NPs inhaled through occupational exposure is very low (Kreyling et al, 2009, p. 56). In such cases, prognosis of nanotoxicology is short term and the slight amounts of NPs deposited in the respiratory systems are cleared.

On the other hand, small nanoparticles particle of 20 nm and below are capable of going through the respiratory system to settle at the alveolar region. With increased exposure, the concentration of particles deposited increases as a result of inability to clear these particles. Some NPs for example, CNTs and CNF do exhibit asbestos like effects. In such cases, the final result is death.

Management of nanotoxicology

So far, there is no successful treatment for nanotoxicology, especially NPs deposited in the lungs. With the absence of nanotoxicology treatment measure, the available medical treatments for the management of the condition include anti-inflammatory drugs, antioxidants, and metal chelators (Rip & Shelley- Egan 2009). Antioxidant instillation into mice already instilled with NPs showed 60% reduction of inflammation. In advanced cases of NPs penetration into the interstitial space, antioxidants are used to protect against arteriosclerosis, hypertension, and cardiomyopathies, and coronary heart disease. Metal chelators help to diminish the adverse health effects of transition of metals for metallic NPs.

In addition to the management of NPs in the interstitial space, antioxidants and metal chelators are used for the management and treatment of neuronal uptake of NPs.

Prevention

Protection of workers is the best ways towards prevention of occupational inhalation of NPs. In the US, the NIOSH has issued guidelines of workplace safety measures as well as the right gear for workers in NPs risky facilities. Production and use of NP has a number of risks attached to it; toxic products, chemical incompatibility, explosions, high temperatures, fire, and electrical risks, among others.

It is the responsibility of the facility’s administration to ensure adherence to the stipulated occupational safety measures as the legal responsibility is attached to them (European Agency for Safety and Health at Work, 2007). To prevent occupational in halation of NPs, their employer is required to adhere to the stipulated employee protection gear. These include protective clothing, gas mask, gloves, and helmet.

In addition to protective gear, workers should under go undergo thorough safety related training before they join the facility. According to Han et al (2008, p. 748), the majority of safety breaches in Nanotechnology are due to unawareness of the risks posed by the technology. Even though information available is still scanty on the risks of nanoparticles, training of employee on the right procedures when handling nanoparticles is core towards the prevention of nanotoxicology.

Adherence to professionally protocols when handling nanoparticle elements: in the US, the NIOSH has set the occupational protocols o guide handling of NPs. It is important that employees as well as anyone handling nanoparticle products observes these protocols to the latter. In the Dahm et al (2012, p. 553), the level of CNTs is higher than the recommended rate in secondary facilities probably due to non-adherence to set occupational guidelines.

 

References

Balbus J. (2007). Hazard Assessment for Nanoparticles: Report from an Interdisciplinary Workshop, Environmental Health Perspectives, 115: 1654-1659.

Dahm, M.A., Evans, D.E., Schubauer-Berigan, M.K., Birch, M.E. & Fernback, J.E. (2012). Occupational Exposure Assessment in Carbon Nanotube and Nanofiber Primary and Secondary Manufacturers, Annals of Occupational Hygiene, 56 (5):542-556.

European Agency for Safety and Health at Work, (2007). Expert forecast on emerging biological risks related to occupational safety and health, Office for Official Publications of the European Communities, Luxembourg.

Han, .J.H., Lee, E.J., Lee, J.H., So, K.P., Lee, Y.H., Bae, G.N., Lee, S.B., Ji, J.H., Cho, M.H., Yu, I.J. (2008): Monitoring multiwalled carbon nanotube exposure in carbon nanotube research facility. Inhalation Toxicology, 20:741-749.

Kreyling, W.G., Semmler-Behnke, M., Seitz, J. (2009). Size Dependence of the Translocation of Inhaled Iridium and Carbon Nanoparticle Aggregates from the Lung of Rats to the Blood and Secondary Target Organs. Inhalation Toxicology 21, 1: 55-60

Methner, M.M., Hodson, L., & Dames, A. (2010) Nanoparticle emission assessment technique (NEAT) for the identification and measurement of potential inhalation exposure to engineered nanomaterials—part B: results from 12 field studies. Journal of Occupational Environ Hygiene; 7: 163–76

Oberdorster, G.; Oberdorster, E.; Oberdorster, J. (2005). Nanotoxicology: An emerging discipline evolving from studies of ultrafine particles. Environmental Health Perspectives, 113 (7), 823-839.

Parent-Thirion, A., Fernandez Macias, E., Hurley, J. & Vermeylen, G. (2007). Fourth European Working Conditions Survey, European Foundation for the Improvement of Living and Working Conditions, Luxembourg,

Pronk, A., Tielemans, E., Skarping, G., Bobeldiuk, I., Van Hemmen, J., Heederik, D., Preller, L. (2006). Inhalation exposure to isocyanates of car body repair shop workers and industrial spray painters, Annals of Occupational Hygiene, Vol. 50, pp. 1-14.

Rial-Gonzalez, E., Copsey, S., Paoli, P. & Schneider, E. (2005). Priorities for occupational safety and health research in the EU-25, European Agency for Safety and Health at Work, Office for Official Publications of the European Communities, Luxembourg,

Rip, A, and C. Shelley- Egan (2009), Positions and responsibilities in the “real” world of nanotechnology, unpublished manuscript.


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