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Interview with Dr. Peter Gehr of University of Bern

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ICON: What is the most important thing that readers should take away from this work?

Peter Gehr: There is increasing concern about MWCNT eventually causing mesothelioma (cancer of the epithelial lining of all thoracic and abdominal organs and the walls, caused mainly by exposure to asbestos). In general, one can say that there is evidence for health problems to develop when exposed to long asbestos-like fibres of MWCNT. Long MWCNT result in asbestos-like pathogenic behaviour including inflammation and formation of granulomas in mice, as the Nature Nanotechnology paper very convincingly shows. The J. Tox Sci. paper goes even further; reporting that exposure to MWCNT is inducing mesothelioma.

Important questions are dose and time, i.e. how much do we need to be exposed to in order to experience adverse effects in lung tissue and cells which may lead to serious health problems eventually ultimately to mesothelioma; and how long does it take for these long fibres to travel from the internal lung surface to the periphery, the mesothelium (visceral pleura)? From mesothelioma one knows that it may take decades from exposure to asbestos to the onset of symptoms (latency), and the risk remains lifelong. So far, it was mainly asbestos fibres which have caused mesothelioma. The article of Takagi et al. clearly reports that MWCNT induce mesothelioma (along with crocidolite, blue asbestos, when administered intraperitoneally to p53 heterozygous knockout mice (frequently used for carcinogenesis studies)). There are publications which say that MWCNT are even more toxic than chrysotile asbestos fibres (e.g. Murr et al., Int. J. Environ. Res. Public Health, 2005).

Other important questions are the chemical and catalytic properties of nanomaterials. How does this influence the effect of e.g. MWCNT (Limbach et al., Environ. Sci. Technol., 2007). The test system used may be another problem. Wörle-Knirsch et al. ( Nano. Lett., 2006) strongly recommend verifying cytotoxicity data with more than one independent test system.

ICON: Overall, what did you think of the conclusions drawn by these studies? Did these findings surprise you or were they expected given current knowledge in the filed?

PG: The findings were not totally unexpected to me, knowing what asbestos fibres can cause, and learning about the similarity of MWCNT to asbestos fibres. Therefore MWCNT have to be handled with care, this is particularly the case in places where they are produced, where people could be exposed to airborne (free) MWCNT (protection of workers whenever they are dealing with airborne MWCNT; as it was the case, and unfortunately still is, with asbestos fibres). Another problem is indoor vs. outdoor exposure. Indoor number concentrations for MWCNT may be many times the outdoor concentration. Virtually all gas combustion processes are effective sources to various degrees (Murr et al., In. J. Environ. Res. Public Health, 2005).

However, if the MWCNT are bound, like e.g. in a bike frame or else, I consider them not to be a health problem.

As soon as it was known that the long MWCNT occur in a structural form which is similar to long amosite (brown asbestos, an amphibole form of asbestos) fibres, one had to take into consideration that long MWCNT could be a health problem (generally spoken; again, not considering dose and time etc., see above).

ICON: Were the techniques used in the experiments standard or was there something unique or special about them?

PG: The techniques were not unusual, but they were, particularly in the work of Poland et al., very vigilantly applied. This does not mean that the work of Takagi et al. was not carefully done. Similarly, the conclusions are cautiously but therefore not less clearly drawn by the authors. Both papers conclude with the comment that the results suggest that it would be prudent to implement strategies which include a careful investigation of MWCNT’s biological and carcinogenic properties, in particular also their biopersistence, before introducing products into the market. This prudent analysis of the situation shall particularly be applied at the workplace where MWCNT may be released into the air.

ICON: There has been speculation about nanoparticle fibres (in this case long MWCNT) being like asbestos fibres. Do you think that these studies make the case conclusively? If so why?

PG: They make it stronger as the pathogenic responses found (inflammation, granuloma) are similar to those found for exposures to asbestos. The study of Takagi et al. has even clearly found mesothelioma. The extrapolation of both studies from mice to men needs to be verified.

Dose and time experiments, experiments on the particle’s properties, and the analysis of the test system are all needed. More than one test system, independent from each other, should be taken into consideration, before conclusions are drawn.

Minimal analytical characterization of the different types of MWCNT will be needed for the important hazard assessment of the potential critical MWCNT. The material used in the different experiments needs to be standardized in order to allow for comparisons. Very importantly, biopersistence experiments are needed.

The experimental protocols have also to be standardized, again, in order to allow for comparisons between the findings of different experiments.

In light of these two papers, it is truly not possible to consider MWCNT harmless.

There has very recently been held a workshop on the effect of nanoparticles, including CNT on the environment from which a report has been released (in German). It summarizes that nano is not a problem for the environment at the moment, a conclusion drawn on the basis of results from very interesting acute experiments. It was mentioned that data from chronic exposures are not available yet ( http://www.empa.ch/plugin/template/empa/3/71665/---/l=1). Two publications underline the conclusions at this workshop (Nowack and Müller, Environ. Sci. Technol., 2008Behra and Krug, Nature Nanotechnol., 2008). But, unfortunately, it was not mentioned that there is strong evidence from published work that adverse effects by CNT (similar to those caused by asbestos) have to be considered, particularly in the long run. Safety of manufactured nanoparticles for human health and for the environment should have highest priority. It has to be added though that a lot of research work is still needed in this field.

ICON: Would these findings about nanotubes apply to other nanoparticles as well?

PG: Generally not, as has been clearly shown by both papers.

ICON: What would account for only long multi-wall carbon nanotubes causing the effect? Why would short multi-wall fibres not have the same effect?

PG: The Donaldson paper shows very clearly that it is only the asbestos-like structure (long, fibrous) which causes the asbestos-like effects. A number of other properties have to be taken into consideration as well, though, like the chemical and catalytic properties. It is well described in the Donaldson paper that, due to the aspect ratio, the biopersistence (not dissolving or breaking up) the cells dealing with the intruders may become frustrated and chronically activated, which leads to the described adverse effects, like activation of inflammatory cells, genotoxicity, fibrosis and last but not least to cancer.

ICON: How should people interpret these findings within the larger context of nanotechnology environment, health and safety research?

PG: People should know that MWCNT may be a problem if there is exposure toairborne particles. Mainly exposed, however, are most probably people at workplaces where MWCNT are manufactured and assembled. Therefore, particular attention has to be paid to workplace situations, i.e. workers have to be protected.

Apparently one has to consider indoor exposure where gas combustion processes are occurring.

We do not know, however, the dose needed to cause adverse health effects, nor do we know how long it would take to cause adverse health effects. Also, we do not know whether the results from the experiments described in the two papers (and in other publications) can be directly extrapolated to man. Hence, besides the fact that asbestos-like pathology exists there is a lot of uncertainty for the public. And, as in other such situations, if there is uncertainty about a risk, we usually behave ourselves with caution. It is quite sure that, if bound, the MWCNT are not a problem.

ICON: Comment on the likely impact of the work on other researchers, industrialists, policymakers, workers, the legal community or the public as appropriate.

PG: For researchers: more research is needed, and tests are recommended to be performed with at least 2 independent test systems (see above). Risk and hazard assessment studies are recommended. Furthermore, experimental materials and protocols need to be standardized.

For industrialists: It would be prudent to implement strategies to keep good control of exposure to MWCNT both in the workplace and in the future market. Risk and hazard assessment studies are recommended, and scientific publications should be carefully kept track of. The safety of engineered CNT for human health should have highest priority. Industrialists may consider self-declaration of materials containing CNT.

Policymakers: In Switzerland, very recently an Action Plan on nanoparticulate material has been implemented by the government (as in other countries before). I would suggest following this to policymakers where no Action Plan exists yet. Policymakers should carefully keep track with the scientific publications.

Workers: Workers at workplaces where MWCNT are manufactured should insist on safety regulations, i.e. they should make sure that they are never exposed to airborne MWCNT.

Legal community: The more we know, and there are progressively more scientific papers published, the more should the legal community deal with the problem, and depending on the risk and hazards found by scientists, consider strict regulations. Scientific publications should carefully be kept track of.

Public: The public shouldn’t panic. There is clearly no reason to do so. But the public should be informed or inform itself about the possibility of risk and hazards. The public could ask for declaration of materials etc. manufactured from MWCNT in order to have the possibility to choose non-MWCNT materials.

ICON: What are the seminal papers in the field?

PG: In addition to the publications mentioned above, there are many more recent publications of the years 2007 and 2008, which can easily be retrieved from PubMed. They are already too numerous to be listed here. The number grows progressively.

ICON: Is there anything else you’d like to add? Any obvious questions we are not asking about work?

PG: Particularly for the public: The public should clearly know that bound MWCNT are not thought to be a problem. If a problem has to be taken into consideration, it is mainly at workplaces where MWCNT are manufactured and may get into the air. Moreover, MWCNT may be occurring indoor where gas combustion processes are the sources. This problem can be solved by opening the windows.

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Professor Peter Gehr received his PhD in Biology at the University of Bern, held a postdoctoral fellowship at the same University, and has held posts as visiting assistant professor at the Harvard School of Public Health, visiting lecturer at the University of Nairobi in Kenya, head of the Division of Histology at the Institute of Anatomy of the University of Bern, professor and chair of the Institute of Anatomy at the University of Bern (current).

For twenty years he has actively investigated particle-lung interaction, particle-tissue and particle-cell interaction, particle trafficking in and nanotoxicology of cells, cell and molecular biological studies, quantitative (stereological) structural studies with confocal laser scanning microscopy, conventional electron microscopy, energy filtering transmission electron microscopy, electron tomography (to be started).

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This work is supported in part by the Nanoscale Science and Engineering Initiative of the National Science Foundation
under NSF Award Number EEC-0118007.

Rice University