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Nanosafety Aspects of Scale-Up

This article is part of a 5 article series ‘Scale up to Success’ published by the INSPIRED project.  The series tracks the essential aspects of scale up for nanomaterials in printed electronics, and articles will be published every 2 weeks until the end of 2018. You can read articles published to date through the INSPIRED website.

Nanosafety Aspects of Scale-Up

Many people are led to think that the safety of nanomaterials is unclear. However, significant work has been done in recent years to ensure that the use of nanomaterials is safe. This includes adopting the same standard safety protocols as conventional chemicals, such as creating material safety data sheets (MSDS) and following appropriate safety guidelines. Additionally, there are many regulations in place, such as Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) that address nanomaterials, as well as sector-specific regulations in many other fields, such as food, biocides and cosmetics. The difference between nanomaterials and conventional chemicals, is that nanomaterials often require some additional regulatory requirements due to their small size and the specific properties derived due to their size. 

There are many guidelines available that can be followed to ensure safety is considered during scale-up. It may be more complex for nanomaterials, but this is also because nanomaterials are constantly evolving – as it is one of the most rapidly advancing areas of science. With any new advances, especially those which provide significant changes, regulations need to keep up with the current landscape. Luckily, regulators now know more about how nanomaterials should, and do, behave, so this task has become easier in recent years due to the large investment in developing new knowledge. The NanoSafety Cluster is one such example, with over 40 safety projects, often global in scale, funded by the European Commission over the last two Framework Programmes.

 Projects such as INSPIREDare currently bringing together diverse partners in different sectors of the nanotechnology industry to help study the safety of nanomaterials through different scale-up processes.

Industry, by law, has strict regulations and standards. Therefore, it is in the best position to further study the safety of nanomaterials when companies perform new processes (such as a new scale-up method). The academic landscape is different. The academic world will not often immediately study the safety, toxicity or potential health concerns when creating a new material, although it is rapidly improving.  This may bring challenges where potential applications are cited, only for them to fail because they are non-compliant with the appropriate regulations.  Industry has the key role to help facilitate the safety of nanomaterials, especially during the scale-up process and this research is often performed in close cooperation with academia. The emergence of validated risk assessment tools for nanomaterial development also enable earlier stage researchers to assess potential safety issues at the earliest stages of development.

Thomas Swan Case Study

Thomas Swan (UK) is one of the manufacturing partners in the INSPIRED project and was looking to scale up the production of graphene nanoplatelets (GNPs) before formulating them into functional inks. 

Throughout the project, Thomas Swan followed a strict series of protocols. As there are no standardised methods available for nanosafety, Thomas Swan worked alongside Tecnalia and BioNanoNet and followed Safe by Design (SbD) methodology concepts. Thomas Swan, alongside the project partners, undertook a very safe process which used water as the solvent of choice, and used qualitative/semi-quantitative risk assessments across all stages of the scale-up and focused on hazard/risk avoidance.

During the project, no new nanosafety hazards were identified, but this is due in part to a risk characterisation step preventing worker exposure by using closed systems with air recirculation and following NIOSH 5040 for elemental carbon—with the graphene possessing a concentration of elemental carbon below the benchmark risk limit. It was also identified that inhalation exposure to free nanoparticles in suspension was unlikely during the scale up. Both Thomas Swan and associated partners have stated that there were no difficulties with regulatory and compliance requirements but are considering REACH registration and relevant global regulations as the production progresses further.

The project was not free of existing nanosafety challenges. One of the challenges for Thomas Swan was in the production of a closed system that protected the workers, rather than using a fume hood, which had been employed in the early stages of the project to keep a contained atmosphere at the bench scale. This was overcome through collaboration and consultation with expert partners andby using process design experience to build an appropriate system. Two identified nanosafety issues were identified during the INSPIRED project at Thomas Swan.  These were i) the possibility of inhaling dried graphene nanoplatelets if a spillage occurred (and not cleaned up) and  ii) the possibility of dermal exposure during the handling of dispersions and cleaning—although the latter was minimised through PPE and strict safety protocols.

 

Safety in the scale-up

Safety of the nanomaterial in the end-user market and its potential impact on health and the environment must be addressed before placing a product on the market. During scale-up, both the safety of the local environment and the personnel working on the scale-up need to be considered.  Current mitigation processes for conventional chemicals are also applicable for nanomaterials, such as exhaust ventilation, containment, clean rooms, as well as extensive use of personal protective equipment (PPE).

There are many already known hazards of nanomaterials, with the risk that these may increase as the production volume is scaled-up, and they should be considered if there are plans to use a nanomaterial in a commercial capacity. 

Nanomaterials have a much larger specific area than their bulk counterparts and this, in general, makes them more reactive. Whilst creating a large mass of highly active surface area needs to be factored in from a safety point of view, once the materials are contained within a sealed reaction chamber, they are unlikely to pose any risk unless there is a leak, or if the equipment is compromised.

Nanoparticles also may have a high translocation potential, which is the ability to reach regions of a biological system inaccessible to larger particles. When creating a large mass of highly translocatable particles, the extent of how these particles agglomerate and de-agglomerate needs to be considered from a health perspective, especially when these particles can access the body through inhalation.

Another hazard to consider is the environmental impact of nanoparticles suspending out of solution. There are concerns that some nanoparticle systems are unstable and may cause damage to the environment, especially if they are not biodegradable. However, this is not a concern limited to just nanomaterials, as many chemicals are bio-persistent.

There are always concerns with using larger volumes of chemicals/materials, regardless of the process. Although nanomaterials are young (from a commercial production perspective), there are many long-term studies surrounding the exposure to particles such as PM2.5.  In general, being exposed to individual nanoparticles is unlikely, due to their tendency to agglomerate/aggregate.  Any chemical scale-up process requires a significant amount of care, and a precautionary approach should always be taken, especially if it is a new process. Therefore, stringent protocols should be adopted to minimise occupational exposure to nanomaterials as well as for chemicals in general.

Manufacturers involved with scaling-up nanomaterial production need to always ensure the safe handling of nanomaterials and e.g. fill out appropriate Control of Substances Hazardous to Health (COSHH) forms where required. Care should also be taken to minimize the exposure of nanomaterials to personnel, through appropriate protective clothing, to prevent both inhalation and dermal exposure.  Monitoring of nanomaterials in the scale-up environment is important, with an emphasis of the potential for them to be released into the atmosphere and where they may encounter other process environments, e.g. high pressures or temperatures that could affect the properties of the nanomaterial and cause them to react in unexpected ways.

In summary, manufacturers have a duty of care to their employees, their customers and the environment to ensure that the nanomaterial being scaled-up is safe for use and will not adversely affect the local environment. Nanosafety should also be communicated by a manufacturer to address any concerns that consumers may have around using nanomaterials because, as well as actual hazards, there are also many perceived hazards. This should take the form of accurate risk assessments throughout the different manufacturing processes, and if necessary, any tests that prove that the nanomaterials are safe for use (in both production and end-use).

Nanogap Case Study

Nanogap (ES) is another nanomaterial manufacturer in the INSPIRED project which focuses on scaling up production of silver nanowires and their subsequent formulation into functional inks. Nanogap also worked alongside the project partners Tecnalia and BioNanoNet on issues regarding nanosafety.

From an occupational hazard point of view there were no issues regarding nanoparticle exposure, as all manufacturing steps were performed in a liquid phase, with the only potential nanosafety issues again coming from dermal exposure after spillages or nanomaterial handling. NIOSH methods 7300 and 7301 were employed to determine that the release of silver nanowires to the workplace was well below (less than one tenth) the recommended exposure limits.

Nanogap did not undertake any special changes towards nanosafety. However, it refined processes to reduce the amount of potentially hazardous waste being produced, and reused more of the silver from the waste—which reduced the overall costs involved with the scale-up. Aside from financial benefits, the ability to reduce the waste made nanosafety a more manageable problem; because as the production was scaled up, the exposure time of potentially hazardous nanomaterials coming into contact with both personnel and the surrounding environment was reduced.  This,  in turn, has led to an overall reduction in the occupational exposure risk during the scale up of Nanogap’s silver nanowires.

There were also no issues with regulatory and compliance requirements, as the volumes were not at a capacity that required the implementation of a REACH dossier