We analyzed the example of multi-walled carbon nanotubes
Broadly, it is possible to say that there are no chemicals that do not have toxicity. In fact, there are no chemicals that do not have harmful effects on biological systems. It will always be necessary to evaluate the type of effect produced, the needed dose to produce this effect, the characteristics and properties of the substance, and some information about the exposure.
This is a summary of some principles that determine toxicity analysis. These analyzes are composed of a set of standardized tests that are regularly performed, for example, in the context of registration of new substances and medicines.
With the emergence and advancement of nanotechnology, questions regarding the safety and risks of these new materials have been raised. Thus, investigations about the adverse effects of nanoforms on human health and for other organisms have been executed for more than 15 years.
Would nanoforms, formerly called nanoparticles, have specific adverse effects? Would size, its nanometric scale, cause unknown effects, drawing a new paradigm within toxicology? Would this behavior be more similar to the toxicology of fibers and particles or molecular chemical substances?
These were key questions that conducted several pieces of research in the area.
And today, what is known? How do nanoforms interact with biological systems?
In a very direct and short answer: it depends. This relationship will depend on the characteristics and properties of the two elements of this equation. The size, the surface area, the polarity, the presence of impurities, for example, are important properties related to nanoforms. The size determines the interaction and it is more important than another property. On the other hand, the type of cell, the composition of the membrane, and the medium are also important factors that will determine the form of interaction. In some cases, the nanoforms cluster in the medium and are not available to organisms. Otherwise, due to the polarity of the two elements, they are repelled, or the other way around. Finally, the complexity of this environment and the elements determines this relationship, such as for any other substance.
The effects of this interaction on the cell, tissue, or organism can be measured in different ways, and it is from these results that it is possible to determine whether a substance or material has a toxic effect or not. The toxic effect refers to the relationship between the severity and the intensity of the damage/effect caused, and the classification depends on comparisons (for example, with defined limits or control samples).
Regarding the evaluation of the toxicity of nanoforms, with the advances in research, it was noted that the great challenge is to understand the relationships between the physical and chemical properties of nanoparticles with their toxicity. So far, there is great uncertainty, and it is not possible to assure that, for example, samples of carbon nanotubes of the same diameter, length, and surface area, have the same effect during a genotoxicity evaluation. The difficulty in grouping/relating these properties with their effects makes it difficult to harmonize data and limits advances in regulations in the area.
The toxicity of carbon nanotubes – a case study
A complete evaluation of toxicity of multi-walled carbon nanotubes (MWCNT) was recently published by the European Chemicals Agency (ECHA). The report was prepared by the German agency Baua and aims to answer whether a specific substance that had the registration requested, in this case, the carbon nanotubes, presents a risk to human health or the environment. Here, we put the main facts covered in this detailed document, as an example of the current situation of nanoforms toxicology. Let’s remember that carbon nanotubes are one of the first nanomaterials to have their production scaled, with a considerable increase in production volumes at the beginning of the 21st century.
Based on the supplied data, the production volume of this nanomaterial varies between 100 and 1000 tons per year, and it’s used industrially as additives in various materials, such as rubbers, plastics, cement, glass, and metals. The use in research and development activities has also been reported.
The report is based on dossiers submitted by companies producing carbon nanotubes for registration with ECHA. In addition to detailed information for each toxicity analysis, data on the physical and chemical characterizations of the nanomaterial are described. In this case, the multi-walled carbon nanotubes had an outside diameter below 30nm (D90 <= 30nm) and a length less than 5µm.
Evaluations of toxicity and ecotoxicity of carbon nanotubes (MWCTN)
According to the report, the main concerns about the toxicity of MWCNT are:
– the wide use of this nanomaterial, including by the consumer;
– discrepancies in the risk self-classification between the different registrants of the substance;
– the differences in physicochemical properties that affect toxicity. For example, the number of different registered nanoforms and the choice of representative test materials;
– the suspicion of toxicity for specific target organs after repeated exposure to STOT-RE;
– suspected carcinogenicity;
– effects on environmental organisms;
– suspected environmental exposure;
– suspicion of persistence;
– cumulative exposure.
In order to clarify these points, several endpoints related to human health risk assessments, such as toxicokinetics, carcinogenicity, and the environment were evaluated. The report is divided into these topics.
Notably, the main conclusion reported refers to the insufficiency of data and the impossibility of crossing and grouping the presented results and considering them representative of the analyzed multi-walled carbon nanotubes. It was not possible to answer all the questions initially raised. Still, the lack of (standard) information, methodological deficiencies, as well as insufficient clarification of potential dangers observed in the lack of data presented for some endpoints were recurrent.
Despite the lack or inconsistency of the data delivered by the MWCTN producers, the literature often supported the evaluators’ decision not to exclude the potential risk – in the case of respiratory sensitization and mutagenicity, for example. The potential risk of exposure of nanotubes to the soil, although not considered in the dossiers, cannot be excluded either. According to the evaluators, the possibility that exposure to nanotubes can cause carcinogenic effects and damage to human reproduction cannot be disregarded.
Exposure to workers, consumers, and the environment was also evaluated. Available information on worker exposure in dossiers indicates that potential exposure is very low for some of the nanoforms, but is generally insufficient to conclude about the resulting exposure in the workplace for all the nanoforms. Regarding consumers and environmental exposure, it was also not possible to conclude about the risks, since insufficient information was presented.
What we know about the toxicity of carbon nanotubes
Through the analysis of data from commercial nanotubes, delivered in a context of market registration, the report prepared by Baua, in the Nanos point of view, allows to identify, in practice, the challenges and the current status of the area of nanotoxicology, and health and safety in nano.
The advances are remarkable, some answers to the initial questions were given, in the case of carbon nanotubes , we know the dangers of their inhalation, for example. Skin sensitization has also been reported as an identified effect. These are essential facts to outline precautionary actions to this type of exposure, even more in the work environment. We know that the nanoforms do not present a greater risk than another chemical substance because it presents itself in a nanometric dimension. But we still don’t know how the physicochemical properties relate to the effects, we don’t know how to measure various effects, and we still haven’t been able to group and extrapolate conclusions about tests with similar properties nanoforms.
In this environment of uncertainty, the precautionary principle should guide safety actions. The case-by-case analysis and the look of nanotoxicology specialists in the field will be essential for the next steps and to ensure the minimization of the risks of nanotechnology.
Bibliographic references
1 BAuA: Substance Evaluation Conclusion. 2020. Available at <https://echa.europa.eu/documents/10162/801e9ee1-1347-0072-44a5-b044510e79b5>
