The carcinogenic potential of nanomaterials, their release from products and options for regulating them

doi:10.1016/j.ijheh.2010.11.004

International Journal of Hygiene and Environmental Health

Volume 214, Issue 3, June 2011, Pages 231-238

https://doi.org/10.1016/j.ijheh.2010.11.004 Get rights and content

Abstract

A summary of a critical review by a working group of the German Federal Environment Agency and the German Federal Institute for Risk Assessment on the carcinogenic potential of nanomaterials is presented. After a critical review of the available data, we conclude that the potential carcinogenic risk of nanomaterials can currently be assessed only on a case-by-case basis. There is certain evidence that different forms of CNTs (carbon nanotubes) and nanoscale TiO₂ particles may induce tumours in sensitive animal models. It is assumed that the mode of action of the inhalation toxicity of asbestos-like fibres and of inhalable fractions of biopersistent fine dusts of low toxicity (nano-TiO₂) is linked to chronic inflammatory processes. Existing epidemiological studies on carcinogenicity for these manufactured nanomaterials are not sufficiently conclusive.

Generally speaking, the database is not adequate for an assessment of the carcinogenic potential of nanomaterials. Whereas a number of studies provide evidence of a nano-specific potential to induce tumours, other studies did not. This is possibly due to insufficient characterisation of the test material, difference in the experimental design, the use of different animal models and species and/or differences in dosimetry (both with regard to the appropriate dose metric and the estimated effective dose quantities).

An assessment of the carcinogenic potential and its relevance for humans are currently fraught with uncertainty. Furthermore, the nano-specificity of the carcinogenic effects observed cannot be conclusively evaluated. Specific carcinogenic effects of nanomaterials may be both quantitative and qualitative. In quantitative terms, the carcinogenic effects of nanoparticles are thought to be simply more pronounced compared to the corresponding bulk material (due, for example, to the considerably larger surface area and higher number of particles relative to the mass concentration). On the other hand, certain nano-properties such as small size, shape and reactivity, retention time and distribution in the body after overcoming biological barriers, as well as subcellular and molecular interactions may play a role in determining the toxicity in qualitative terms, i.e. the carcinogenic potential of the nanomaterial and the non-nanoscale comparison substance may be fundamentally different.

All of these factors leave no doubt about the fact that there is a great need for research in this area and that new standardised test methods need to be developed or existing ones adapted at the very least to achieve valid answers regarding the carcinogenic potential of nanomaterials. Global production of nanomaterials is set to increase in the years to come, and new materials with new properties will be developed, so that greater human exposure to them must be anticipated.

No reliable conclusions can currently be drawn about exposure to nanoparticles and their release from products. Firstly, there are substantial deficits in information about the processing of nanomaterials in products and preparations. Secondly, there are only a small number of studies on nanoparticle release, and reliable techniques for measuring and monitoring nanomaterials in different environmental media are still being developed which is both complex and costly.

Despite the uncertainties, the findings to date on the carcinogenic potential of nanomaterials must be taken seriously, and precautionary measures to minimise exposure should go hand in hand with the development of a comprehensive and conclusive toxicological methodology and testing procedure for nanostructured materials that includes all possible exposure routes.

With regard to possible legal classification of nanomaterials and the transferability of classifications of their non-nanomaterial counterparts, we believe it is necessary to have separate procedures for nano and non-nano forms. Furthermore, criteria for evaluating nano-specific carcinogenic properties should be constantly updated and adapted to the state of knowledge. There is a need here for amendments to be made to EU legislation, as currently nanoforms do not represent a separate category of substance in their own right.

Section snippets

General considerations

Some scientists assume that, as a result of their specific properties, nanomaterials may be carcinogenic irrespective of their chemical composition (Roller, 2009). This hypothesis is based on mechanistic considerations and on a number of findings from animal experiments using high to very high doses. However, experimental evidence of the carcinogenicity of nanomaterials per se is currently inadequate, although there are clear indications that some nanomaterials have carcinogenic potential or

Q2. What is the current level of knowledge on the release from products of nanoparticles and their agglomerates? Apart from the workplace risk, are there other exposure scenarios for humans that must be regarded as particularly critical?

It is not yet possible to make any general statements on the release of nanoparticles from different products and their use. Initial studies on the release of nanoparticles from products are currently being conducted. For example, Vorbau et al. (2009) have investigated the emissions that occur when processing coatings containing nanomaterials.

Currently, very little information on the release of nanoparticles is available. The next key steps involve developing the appropriate metrology for

Q3. Can existing classifications of non-nanoscale materials (e.g. the IARC 2B classification for titanium dioxide) be transferred to nanomaterials? Must additional criteria be considered or existing criteria be modified? What criteria are essential to appropriately classify nanomaterials?

Principally, the existing criteria for classifying a substance as carcinogenic according to the CLP Regulation (EC) No. 1272/2008 have to be applied. Since, in terms of chemical legislation, nanoforms have to date not been defined as a separate category of substance but fall under the regulations for the fine particles of the substance in question, any classification of a substance as carcinogenic in Annex VI to the CLP Regulation (EC) No. 1272/2008 would also apply to the nanoform. Here the

Acknowledgements

The authors would like to thank Wolfgang Kreyling, Thomas Kuhlbusch, Carsten Kneuer and Bernd Schäfer for valuable comments and critical review of the manuscript.

References (55)

H. Ernst et al.
Pulmonary inflammation in rats after intratracheal instillation of quartz, amorphous SiO2, carbon black, and coal dust and the influence of poly-2-vinylpyridine-N-oxide (PVNO)
Exp. Toxicol. Pathol.
(2002)
K.P. Lee et al.
Pulmonary response to impaired lung clearance in rats following excessive TiO₂ dust deposition
Environ. Res.
(1986)
K.P. Lee et al.
Translocation of particle-laden alveolar macrophages and intra-alveolar granuloma formation in rats exposed to Ludox colloidal amorphous silica by inhalation
Toxicology
(1993)
K.P. Lee et al.
Pulmonary response of rats exposed to titanium dioxide (TiO₂) by inhalation for two years
Toxicol. Appl. Pharmacol.
(1985)
K.P. Lee et al.
Transmigration of titanium dioxide (TiO₂) particles in rats after inhalation exposure
Exp. Mol. Pathol.
(1985)
J. Lewinson et al.
Characterization and toxicological behavior of synthetic amorphous hydrophobic silica
Regal. Toxicol. Pharmacol.
(1994)
A. Morgan et al.
The effect of quartz, administered by intratracheal instillation, on the rat lung. I. The cellular response
Environ. Res.
(1980)
P.E. Morrow
Possible mechanisms to explain dust overloading of the lungs
Fundam. Appl. Toxicol.
(1988)
H. Muhle et al.
Lung response to test toner upon 2-year inhalation exposure in rats
Exp. Pathol.
(1989)
G. Oberdörster
Lung particle overload: implications for occupational exposures to particles
Regul. Toxicol. Pharmacol.
(1995)

C. Pelucchi et al.

Occupational silica exposure and lung cancer risk: a review of epidemiological studies

Ann. Oncol.

(2006)

K.M. Reiser et al.

Silicosis and fibrogenesis: fact and artifact

Toxicology

(1979)

P.G.J. Reuzel et al.

Subchronic inhalation toxicity of amorphous silicas and quartz dust in rats

Food Chem. Toxicol.

(1991)

M. Vorbau et al.

Method for the characterization of the abrasion induced nanoparticle release into air from surface coatings

J. Aero Sci.

(2009)

D.B. Warheit et al.

Pulmonary toxicity study in rats with three forms of ultrafine-TiO₂ particles: differential responses related to surface properties

Toxicology

(2007)

R.A. Baan

Carcinogenic hazards from inhaled carbon black, titanium dioxide, and talc not containing asbestos or asbestiform fibers: recent evaluations by an IARC Monographs Working Group

Inhal. Toxicol.

(2007)

R.B. Baggs et al.

Regression of pulmonary lesions produced by inhaled titanium dioxide in rats

Vet. Pathol.

(1997)

E. Bermudez et al.

Long-term pulmonary responses of three laboratory rodent species to subchronic inhalation of pigmentary titanium dioxide particles

Toxicol. Sci.

(2002)

E. Bermudez et al.

Pulmonary responses of mice, rats, and hamsters to subchronic inhalation of ultrafine titanium dioxide particles

Toxicol. Sci.

(2004)

P. Boffetta et al.

Exposure to titanium dioxide and risk of lung cancer in a population-based study from Montreal

Scand J. Work Environ. Health

(2001)

P. Boffetta et al.

Mortality among workers employed in the titanium dioxide production industry in Europe

Cancer Causes Control

(2004)

P.J.A. Borm et al.

Inhaled particles and lung cancer. Part B: Paradigms and risk assessment

Int. J. Cancer

(2004)

P.J.A. Borm et al.

Chronic inflammation and tumour formation in rats after intratracheal instillation of high doses of coal dusts, titanium dioxides, and quartz

Inhal Toxicol.

(2000)

D.H. Bowden et al.

The role of cell injury and the continuing inflammatory response in the generation of silicotic pulmonary fibrosis

J. Pathol.

(1984)

J.L. Chen et al.

Epidemiologic study of workers exposed to titanium dioxide

J. Occup. Med.

(1988)

K.E. Driscoll et al.

Antioxidant defense mechanisms and the toxicity of fibrous and nonfibrous particles

Inhal. toxicol.

(2002)

J. Ferin et al.

Pulmonary retention of ultrafine and fine particles in rats

Am. J. Respir. Cell Mol. Biol.

(1992)

Cited by (98)

Silver-based conductive coatings as lightning strike protection for composite aircraft
2023, Results in Materials
Lightning strike protection of composite structures is an increasingly studied subject in the aerospace industry due to the need for finding novel protection solutions for low conductive composites. This work presents two silver-based lightning protective conductive coatings for potential replacement of expanded copper foil (ECF) as lightning strike protection (LSP). The first solution consists of an electroless method to produce silver-coated carbon fibres (SCCF). The SCCF are integrated as a sacrificial ply on a carbon fibre reinforced polymer (CFRP) panel with four different areal densities, using an epoxy-based primer or a PEDOT:PSS conductive ink as binder. The second solution is a silver-based commercial product consisting of a two-part epoxy with silver flakes, which acts as a sprayable thin coating beneath the paint layer.
The protected CFRP panels were covered with aerospace-grade paint for realistic finishing and were subjected to high impulse current strikes. All four conductive coatings containing SCCF exhibited around 45%–50% retention of flexural strength, although largely inferior to painted expanded copper foil's resistance to emulated lightning strikes. The silver-based commercial product showed 83% retention of flexural strength and 97% retention of effective bending modulus, with a comparable performance to the painted expanded copper foil. The resulting retention of flexural strength, the absence of severe damage to the structure, its versatility for complex geometries and the easy manufacturability of the silver-based commercial coating makes this approach a good candidate for the replacement of ECF as a solution for LSP.
Water-energy nexus: Cutting edge water desalination technologies and hybridized renewable-assisted systems; challenges and future roadmaps
2023, Sustainable Energy Technologies and Assessments
The sustainability in water-energy nexus is critical for human civilization as they are inextricably interwoven. Recently, because of ever-increasing development in the industrial and agricultural sectors, advanced living standards, and significant population growth, a grave shortage in the water-energy nexus is inevitable. Although water desalination is energy-intensive technology, it is the most promising solution to water scarcity. The combination of renewable energy sources (RES) into water desalination systems due to the considerable mitigation of detrimental effects of carbon, as the major culprit in air pollution, has become greatly appealing. However, some inherent challenges associated with them must be effectively overcome, as they overshadow the widespread conduction of RES-assisted desalination systems. In this paper, the conventional desalination systems were studied briefly. Moreover, innovative and promising water desalination technologies, such as graphene-based membranes, temperature swing solvent extraction (TSSE), low temperature thermal desalination (LTTD) and solar still which can potentially change the demarcation of conventional desalination, are discussed. Major challenges and perspectives in the water-energy-environment nexus with emphasis on carbon capture are proposed to delineate sustainability pathways in the field of water desalination. Finally, different challenges and future roadmaps are clearly presented to bridge the technical gaps in the sustainable water-energy nexus. It concludes that despite various notable advancements in both integrated systems and state-of-the-art desalination technologies, there are still enormous capacities to substantially advance their long-term efficiency, overcome their energy-intensive nature, and minimize environmental footprints.
Environmental Systems Science: Theory and Practical Applications
2021, Environmental Systems Science: Theory and Practical Applications
Green nanotechnology: Isolation of bioactive molecules and modified approach of biosynthesis
2021, Biogenic Nanoparticles for Cancer Theranostics
Green nanotechnology can be described as the use of biological techniques as a cost-effective, environmentally benign, and simple route for generation, manipulation, and use of materials at the scale of 1 to 100 nm. Green nanotechnology refers to the ability of nature to minimize the potential environmental and human health risks and costs for nanomaterials preparations. Among different biological sources, plants have attracted significant attention for preparation of nanomaterials. The phytochemicals such as alkaloids, terpenes, saponins, phenols, alcohols, and proteins play the role of reducing and capping agents. The isolated phytochemicals help to increase the reproducibility of size and shape-controlled nanomaterials. These nanomaterials are bioactive and have a wide range of biomedical and pharmaceutical applications. In this study, we provided an updated comprehensive overview of the role of isolated bioactive molecules for green synthesis of nanomaterials as well as bioactivity and biocompatibility of green-synthesized nanomaterials.
Recent advances in analytical, bioanalytical and miscellaneous applications of green nanomaterial
2020, TrAC - Trends in Analytical Chemistry
Green nanomaterials synthesized from green or sustainable methods of synthesis are biocompatible, biodegradable, non-toxic, economical, easily tunable, and ecofriendly in nature. Due to these properties, they have various applications ranging from the analytical and bioanalytical application to biomedical, pharmaceutical, bio labeling, bioimaging, and food packaging. Nanocellulose is the most abundant green nanomaterial present in nature. For the analytical application, it can be used as a sorbent material in different analytical techniques. Green carbon-based nanomaterials are synthesized from natural extracts, and their analytical application includes the utilization of C-dots as catalytic material and the use of green carbon dots as sensors. The bioanalytical application includes the detection of different types of chemicals and biological compounds. Biocomposites are derived from materials of biological or renewable origin and comprise of the reinforced and polymeric matrix. Their different applications include pH detectors, detectors for pathogenic microorganisms, freshness indicators, and detectors for pesticides and adulterants present in samples.
One-year chronic toxicity evaluation of single dose intravenously administered silica nanoparticles in mice and their Ex vivo human hemocompatibility
2020, Journal of Controlled Release
Chronic toxicity evaluations of nanotechnology-based drugs are essential to support initiation of clinical trials. Ideally such evaluations should address the dosing strategy in human applications and provide sufficient information for long-term usage. Herein, we investigated one-year toxicity of non-surface modified silica nanoparticles (SNPs) with variations in size and porosity (Stöber SNPs 46 ± 4.9 and 432.0 ± 18.7 nm and mesoporous SNPs 466.0 ± 86.0 nm) upon single dose intravenous administration to female and male BALB/c mice (10 animal/sex/group) along with their human blood compatibility. Our evidence of clinical observation and blood parameters showed no significant changes in body weight, cell blood count, nor plasma biomarker indices. No significant changes were noted in post necropsy examination of internal organs and organ-to-body weight ratio. However, microscopic examination revealed significant amount of liver inflammation and aggregates of histocytes with neutrophils within the spleen suggesting an ongoing or resolving injury. The fast accumulation of these plain SNPs in the liver and spleen upon IV administration and the duration needed for their clearance caused these injuries. There were also subtle changes which were attributed to prior infarctions or resolved intravascular thrombosis and included calcifications in pulmonary vessels, focal cardiac fibrosis with calcifications, and focal renal injury. Most of the pathologic lesions were observed when large, non-porous SNPs were administered. Statistically significant chronic toxicity was not observed for the small non-porous particles and for the mesoporous particles. This one-year post-exposure evaluation indicate that female and male BALB/c mice need up to one year to recover from acute tissue toxic effects of silica nanoparticles upon single dose intravenous administration at their 10-day maximum tolerated dose. Further, ex vivo testing with human blood and plasma revealed no hemolysis or complement activation following incubation with these silica nanoparticles. These results can inform the potential utility of silica nanoparticles in biomedical applications such as controlled drug delivery where intravenous injection of the particles is intended.

View all citing articles on Scopus

¹: These authors contributed equally to this work.

View full text

The carcinogenic potential of nanomaterials, their release from products and options for regulating them

Abstract

Section snippets

General considerations

Q2. What is the current level of knowledge on the release from products of nanoparticles and their agglomerates? Apart from the workplace risk, are there other exposure scenarios for humans that must be regarded as particularly critical?

Q3. Can existing classifications of non-nanoscale materials (e.g. the IARC 2B classification for titanium dioxide) be transferred to nanomaterials? Must additional criteria be considered or existing criteria be modified? What criteria are essential to appropriately classify nanomaterials?

Acknowledgements

Exp. Toxicol. Pathol.

Environ. Res.

Toxicology

Toxicol. Appl. Pharmacol.

Exp. Mol. Pathol.

Regal. Toxicol. Pharmacol.

Environ. Res.

Fundam. Appl. Toxicol.

Exp. Pathol.

Regul. Toxicol. Pharmacol.

Ann. Oncol.

Toxicology

Food Chem. Toxicol.

J. Aero Sci.

Toxicology

Carcinogenic hazards from inhaled carbon black, titanium dioxide, and talc not containing asbestos or asbestiform fibers: recent evaluations by an IARC Monographs Working Group

Inhal. Toxicol.

Regression of pulmonary lesions produced by inhaled titanium dioxide in rats

Vet. Pathol.

Long-term pulmonary responses of three laboratory rodent species to subchronic inhalation of pigmentary titanium dioxide particles

Toxicol. Sci.

Pulmonary responses of mice, rats, and hamsters to subchronic inhalation of ultrafine titanium dioxide particles

Toxicol. Sci.

Exposure to titanium dioxide and risk of lung cancer in a population-based study from Montreal

Scand J. Work Environ. Health

Mortality among workers employed in the titanium dioxide production industry in Europe

Cancer Causes Control

Inhaled particles and lung cancer. Part B: Paradigms and risk assessment

Int. J. Cancer

Chronic inflammation and tumour formation in rats after intratracheal instillation of high doses of coal dusts, titanium dioxides, and quartz

Inhal Toxicol.

The role of cell injury and the continuing inflammatory response in the generation of silicotic pulmonary fibrosis

J. Pathol.

Epidemiologic study of workers exposed to titanium dioxide

J. Occup. Med.

Antioxidant defense mechanisms and the toxicity of fibrous and nonfibrous particles

Inhal. toxicol.

Pulmonary retention of ultrafine and fine particles in rats

Am. J. Respir. Cell Mol. Biol.