Registration, Evaluation, Authorisation, Categorisation and Tools to Evaluate Nanomaterials – Opportunities and Weaknesses (REACT NOW)

Abstract

Nanotechnology and nanomaterials (NMs) have become an integrated part of our lives in the past decade, whether we realise it or not, and we have entered a phase where the early hype about the benefits of this mind-blowing technology is over. Concerns have been raised throughout this period about the adverse impacts of NMs, and although these have previously been very loud, they are now slowly quieting down. This is not because we have resolved the challenges related to assessing and managing the risks of NMs but rather because we seem to have caught a sense of “nanorisk-immunity” where we gradually have become more and more indifferent to hearing about the potential risks of NMs. Instead of implementing a regulatory framework tailored to NMs, the European Commission has initiated multiple reviews of state-of-the-scientific literature in regard to environmental, health and safety, and seems to be discussing the same risk assessment and regulatory challenges over and over. If history in regard to emerging risks and hazards can be used as a guide, we can now expect 15-20 years of univocal environmental, health and safety research that will not provide definitive answers but only dropwise glimpse into the true nature of the risks of NMs. This thesis summarises the state of research and regulatory affairs within the field of nanomaterial regulation and risk assessment. Specifically, the focus is on areas of research with which I have been involved since 2009 in regard to: 1) mapping current uses of NMs in Europe, 2) understanding the limitations of existing legislation and, finally, 3) addressing the restraints of risk assessment and alternatives to risk assessment when it comes to NMs. In order to obtain an overview of consumer products in Europe that are claimed to contain NMs or are claimed to be based on nanotechnology, we established an online inventory, The Nanodatabase (www.nanodb.dk), back in 2012 and started systematically to collect information about the proclaimed nanoproducts name, producers “nanoclaim”, country of origin, used NMs, location of the NM in the product, most likely exposure route among other. The Nanodatabase originally contained a little more than 1,200 products and now has information about more than 3,000 products. Through our research, we found that most of the products fall into the category of “Health and Fitness” and “Home and Garden”. The most used NMs are silver and titanium dioxide, but it is not possible to identify the NMs used for almost 60% of the products in the database. The safety evaluation tool, NanoRiskCat, was developed and integrated into The Nanodatabase with the purpose of communicating what is known about the hazard and exposure potential of consumer products containing NMs. In its simplest form, the final NanoRiskCat evaluation of a specific nanomaterial in a given application can be communicated in the form of a short title describing the use of the NM and a colour code whereby the first three coloured bullets (•••׀••) refer to the potential exposure of professional end-users, consumers and the environment – in that sequence – and the last two coloured bullets refer to the hazard potential for humans and the environment. The colours assigned to the exposure and hazard potential are green (•), yellow (•), red (•) and grey (•), corresponding to high, medium, low and unknown, respectively. A data analysis of the products in The Nanodatabase shows that for most product categories, the dominant route of exposure is dermal, and that the NanoRiskCat exposure potential as well as human and environmental hazard potential of most products is either “high (•)” or “unknown (•)”. In order to address the potential risks of NMs and take the unique properties of NMs into account, a number of EU regulations and directives have been amended in recent years such as, for instance, the biocidal product regulation. However, the research presented in this thesis identifies three major weaknesses to the current regulation, namely how to define “nanomaterials”, threshold values and information requirements not tailored to the nanoscale and how to overcome the obstacles of chemical risk assessment applied to NMs. The outcome of this research has led me to conclude that the fact that NMs are covered by the scope of existing legislation is not enough to ensure the protection of human health and the environment. We therefore need a new regulatory framework tailored for NMs and their applications. A proposal of such a framework termed “Registration, Evaluation, Authorisation, Categorisation and Tools to Evaluate Nanomaterials – Opportunities and Weaknesses (REACT NOW)” is proposed and presented herein. The thesis consists of nine chapters. An introduction is provided in chapter 1. In chapter 2, what is known about the current uses of NMs is presented in detail, and it is established that there is a general lack of data and access to data on, for example, production volumes and uses of NMs which hampers qualitative and quantitative occupational, consumer and environmental exposure assessment of NMs – and this in turn impedes the completion of any kind of risk assessment. The latter has repetitively led to questions being raised by politicians, NGOs, academics and members of the public about whether current regulatory frameworks are up to the job, as many of them rely heavily on, for instance, the completion of meaningful risk assessments. Chapter 3 is devoted to an analysis of the revisions that have been made to existing regulatory frameworks, such as REACH, BPR and food legislation, whereas Chapter 4 is allocated to an evaluation of proposed revisions made by a number of EU member states and REACH competent authorities such as German UBA, BfR and BAuA and the Swedish KEMI, as well as the NGOs CIEL, ClientEarth and BUND. It is concluded that the revisions that have been implemented for existing EU legislation and the proposed revisions by UBA, BfR and BAuA, KEMI and CIEL, ClientEarth and BUND collectively provide a lot of opportunities. However, a number of weaknesses have also been identified and these are elaborated on and discussed in Chapter 5, as they continue to dog the effective regulation of NMs and still need to be addressed. In recognition of the challenges that traditional chemical risk assessments entail, and outstanding scientific research questions that still need to be resolved, no less than 50 alternative decision-support tools, or supplements to traditional risk assessments, have been explored and proposed in recent years. These are analysed in Chapter 6, in order to identify tools that could potentially be used to support a new regulatory framework tailored specifically for NMs and their applications throughout the life cycle. This evaluation is based on a series of recent scientific publications which provide substantial reviews of these alternative tools applied in regard to risk governance, worker protection, consumer exposure, environmental assessment, waste, etc. This led to the realisation that we need a tool that is both regulatory-relevant and can be applied despite the lack of data and lack of access to information. Safety evaluation plays a key role in REACT NOW and the safety evaluation tool NanoRiskCat developed by Hansen et al. (2014, 2017c) is presented in detail in chapter 7. A strength of NanoRiskCat is that it has been applied to more than 2,000 products claimed to include NMs or to be based on nanotechnology. The outcome of this is presented in this thesis. Finally, in Chapter 8, REACT NOW is introduced and key components of the framework are outlined. As part of REACT NOW, I recommend that manufacturers and importers of NMs should be required to register their NM(s) prior to commercialisation and independent of production and import volumes. For NM(s) already being sold, manufacturers and importers should be required to register and fulfil the REACT NOW requirements within a certain time period e.g. six months of the adoption of the framework. NMs are defined according to SCENIHR’s definition and not the one recommended by the EC. Primary particle size distribution, shape (including aspect ratio), specific surface area and surface treatment are considered “identifiers” and not the “characterisers” as suggested by UBA, BfR and BAuA (2013). In practice, this means that any variation in size, shape, surface area and surface-treated NM that is commercialised in the EU has to be identified, named, registered and safety-evaluated separately, before it is placed into a separate registration dossier. The European Chemicals Agency is identified as the European authority that should be responsible for the management and carrying out the technical and administrative aspects of REACT NOW, however the burden of proof of safety should be placed on industry to ensure that data are generated in good time. In order to ensure the protection of health and the environment, I recommend that the registrant should be required to explain a relevant product’s functional use, provide justification for its use and carry out an effectiveness evaluation prior to the commercialisation of any nanomaterial. Following the requirements of REACT NOW, all uses of NMs have to be evaluated according to NanoRiskCat. The health and environmental hazard information required as part of the information requirements focuses on enabling the application of NanoRiskCat. In regard to human health it includes High Aspect Ratio Nanoparticles (HARN), bulk CLP classification, acutely toxicity, genotoxicity and mutagenicity, carcinogenicity and respiratory toxicity. For the environment, it includes bulk CLP classification, aquatic toxicity, freshwater tests for degradation, bioaccumulation and a scientific review in regard to dispersive or long-range transport, ecosystem effects and novelty. It is important to note that NanoRiskCat uses a tiered approach and that the registrant only has to submit enough information to enable the categorisation of the health and environmental hazard potential of the specific NM into high (•), medium (•), low (•) or unknown (•). Depending on the outcome of the NanoRiskCat evaluation, manufacturers and importers of NMs and producers of NM products might have to seek authorisation, which can only be given for specific uses of NMs and nanoproducts that are deemed necessary, efficient and have a functional use. For NMs that have undergone a NanoRiskCat evaluation and have 1) a red professional end-user and/or a consumer exposure profile combined with a red human health hazard profile and/or 2) a red environmental exposure profile combined with a red environmental hazard profile, the registrant is required to complete an “Alternatives Assessment” and the agency responsible for REACT NOW is required to seek opinion on safe use from the European scientific committee of relevance. In such cases, authorisation should be granted, but only if the specific use under consideration is deemed safe and necessary. Uses of NMs deemed not to be safe by the scientific committees e.g. dispersive uses of HARN, indoor consumer uses of spray products with NMs associated with respiratory toxicity, should not be granted authorisation and should not be given permission to be marketed in Europe. For all other combinations of exposure and hazard profiles, i.e. NanoRiskCat categories 2-4, the agency responsible for REACT NOW can ask for an opinion from the scientific committees of relevance on a case-by-case basis. As a general rule, authorisation should only be given for specific professional end-user and consumer applications of NMs and nanoproducts, if they have a green human health hazard profile combined with a green professional end-user exposure profile and a consumer exposure profile, respectively. The same goes for uses that are expected to lead to environmental exposure that should only be granted authorisation if the NM in question has a green environmental hazard profile. Should the agency or the scientific committees have questions about the safety of a given NM and its specific use, the agency can make a request for additional information, to be generated within 3 years, within which time conditional authorisation can be granted. For combinations of yellow exposure and hazard profiles, conditional authorisation is possible for a time-limited period during which time the agency should request the generation of additional information by the registrant. In order to assist industry and especially Small and Medium-sized Enterprises in the process of implementing REACT NOW, technical and non-technical assistance is needed and should be provided by the European Commission Joint Research Centre and the European Chemicals Agency. REACT NOW is the first attempt to present a comprehensive and transparent decision-making framework tailored to regulate the use of NMs, but as no framework is without either potential or limitations, the opportunities and weaknesses related to the implementation of REACT NOW are pinpointed. Strengths include that NanoRiskCat can be used despite lack of data and information, whereas the lack of clear-cut definitions of “necessity” and “effectiveness” could be considered a weakness along with the arguably crude exposure assessment in NanoRiskCat. In the appendix, the 28 peer reviewed journal papers on which this thesis is based are included. It is worth pointing out that most of the topics briefly discussed and presented in Chapters 2-8 are detailed in the journal papers and that this thesis is written to present REACT NOW and to give the reader an overview of the original achievements of the work.