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

Our plain-English summary of The carcinogenic potential of nanomaterials, their release from products and options for regulating them, by H. Becker, F. Herzberg, A. Schulte, et al (International Journal of Hygiene and Environmental Health, 2011).

The study

• Authors: H. Becker, F. Herzberg, A. Schulte, M. Kolossa-Gehring
• Journal: International Journal of Hygiene and Environmental Health
• Published: 2011;214(3):231-8
• Type of article: Review
• Cited by: 53 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

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 TiO(2) 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-TiO(2)) 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.

Copyright © 2010 Elsevier GmbH. All rights reserved.

In plain English

This article was a review. It summarised a joint opinion by two German federal agencies on whether nanomaterials may cause cancer. The authors examined published studies on titanium dioxide, carbon nanotubes (CNTs) and amorphous silicon dioxide. For nano-sized titanium dioxide, rat studies by others found more lung tumours. In one instillation study, up to 70% of rats given 60 mg developed tumours, versus 30% given fine titanium dioxide. Worker studies gave no particle-size data, so no conclusion about the nano form was possible. The authors described CNTs as structurally similar to asbestos. In one study, CNTs injected into the abdomen of p53-deficient mice caused mesotheliomas of the peritoneum. In another, lab-synthesized multi-wall CNTs injected into rats' abdominal cavities produced no evidence of tumours. No long-term inhalation studies or human studies of CNTs existed. The authors stated that, by current knowledge, amorphous silicon dioxide lacked carcinogenic potential after inhalation or oral uptake. They judged a 6% tumour rate after instillation to be of questionable relevance. The authors concluded that decisions currently depend on case-by-case assessment and that nano and bulk forms need separate classification.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Review (summary of a joint opinion by two German federal agencies on the published literature)
• Who was studied: Published human, animal and other studies on three nanomaterials: titanium dioxide, carbon nanotubes and amorphous silicon dioxide
• Exposure: Nanoscale titanium dioxide, carbon nanotubes (single-wall and multi-wall) and amorphous silicon dioxide, compared with larger ('fine') particles. The authors described CNTs as structurally similar to asbestos.
• Main results:
  • Reviewed rat inhalation studies (Heinrich et al., 1995) showed a higher incidence of lung tumours at high concentrations of nano-titanium dioxide.
  • In the reviewed '19 dusts study' (Pott and Roller, 2005), rats given repeated instillations totalling 60 mg of titanium dioxide had a tumour incidence of up to 70%, compared with 30% in rats given fine titanium dioxide particles.
  • The reviewed studies of titanium dioxide workers gave no particle-size data, so the authors found it impossible to draw conclusions about cancer risk from nano-titanium dioxide.
  • In a reviewed study (Takagi et al., 2008), a single high dose of CNTs injected into the abdominal cavity of transgenic p53-deficient mice induced mesotheliomas in the peritoneum.
  • In a reviewed mouse study (Poland et al., 2008), long multi-wall CNTs injected into the abdominal cavity caused granulomas, and the positive asbestos control produced similar effects. Ground or tangled CNTs did not produce asbestos-like effects.
  • In another reviewed study (Muller et al., 2009), lab-synthesized multi-wall CNTs (2 mg or 20 mg) injected into the abdominal cavity of rats produced no evidence of tumour development.
  • A reviewed mouse study (Ryman-Rasmussen et al., 2009) reported that inhaled CNTs reached the subpleura. The authors stated that long-term inhalation studies are needed.
  • According to the authors, current knowledge indicates that amorphous silicon dioxide does not have carcinogenic potential after inhalation or oral uptake.
  • In the '19 dusts study', rats given a total of 15 mg of amorphous silicon dioxide by repeated instillation had a tumour incidence of 6%. The authors called the relevance of this finding questionable because no other supporting data were available.
  • The authors stated that, until validated tests exist, authorities depend on case-by-case decisions to estimate the carcinogenic potential of nanomaterials.
  • On release from products, the authors judged that consumer sprays containing nanoparticles must be viewed as critical with regard to possible exposure.
• The authors' conclusion: The authors concluded that bulk and nano forms of a substance should be classified separately, even when they otherwise have the same substance identity.
• Limitations the authors state:
  • The reviewed studies differed in test design, which limited how far their findings could be compared.
  • Instillation experiments were considered less suitable for deriving threshold values and for quantitative risk assessment.
  • No conclusive long-term inhalation studies of CNTs were available.

Topics

Medical terms in this study, explained in our Lexicon: Carcinogenic, Dose Metric, Retention TIme.

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