02 Aug 2017 Nanomaterials in Food Contact.
When I wrote my Nanocoatings book Nanocoatings: Principles and Practice with Dr Nigel Holmes we had to write a chapter on nanosafety. This was back in 2013 and our private opinion was that a lot of the debate was unhelpfully shrill and that much of the nanotox data was of very poor quality. We could not give our non-expert opinion on the nanotox data as we lacked the qualifications. Fortunately, the Open Access paper by Prof Harald F. Krug, “Nanosafety Research—Are We on the Right Track?”, Angew. Chem. Int. Ed. 2014, 53, 12304 – 12319 said in public what we had thought in private. Although since then I have had to teach some classes on nanosafety, my focus was safety within the lab and production, plus my views on the science of knowing if a nanoproduct would be safe for the consumer. I had no reason to check on how the task of bringing a product to market had changed, though I knew that things had moved on since I last dug into the detailed regulations.
So when I saw that my publisher DEStech Publications had produced a new book The Use of Nanomaterials in Food Contact Materials edited by Dr Rob Veraart I was very keen to read it. Not only did I read it, but I wrote a detailed review AND updated two of my apps with some important work on nanoparticle diffusion. Although the book is about food contact and therefore sets a high standard for safety, most of the content applies to other uses of nanomaterials. Here is the review, just slightly modified for the purposes of this blog.
The Use of Nanomaterials in Food Contact Materials: Design, Application, Safety.
Edited by Rob Veraart, DEStech Publications, Lancaster, PA, USA, 2017, 394pp. ISBN: 978-1-60595-136-2.
The decision to use something nano in a product has far-reaching consequences. Introducing nanoparticles raises lots of difficult technical questions, many of which involve keeping the nano from becoming micro. But however well-prepared you are for the technical challenges, you also need to know and understand the regulatory ones. Indeed, the planning and budgeting for not violating regulatory and legal standards should be part of any project from day 1, and it is here where the book under review stands out.
This book offers valuable and not readily accessible information on global rules governing the application of nano in food-contact materials, plus technical data on how the rules are determined. Even if your product is not food-related, most of the content of the book can be applied to nanomaterials in a wide range of consumer goods. If you know how to achieve food contact standards, meeting the standards required of your specific industry is not likely to be any harder.
As a scientist, you might think your specific nanomaterial poses no significant threat compared to a non-nano equivalent. You might simply be using a particle size smaller than that used in similar common and safe products. But like it or not, regulatory authorities in many countries have identified nano as a potential hazard requiring specific attention because of unknown unknowns. It is up to you to prove your nano-containing product is safe, and not for them to prove it is not safe. In addition, relevant national regulations are confused, confusing, and arguably out of proportion to the objective risks.
How should you address this situation? The first step is to have everyone on your team read this book, which is amazingly accessible and never hides behind legalistic or bureaucratic language. Technical specialists will find plenty of insightful science connected to legal requirements. At the same time, regulatory experts have here a clear and reasoned exposition of rules and requirements from large and small nations in all trade zones. Because there are so many technical and regulatory documents to consider, the book is worth it just for the links it provides to (mostly online) resources.
Once the scope of regulations is realized, the real work must begin, which is to provide authorities with proof that your nanomaterial in your product will not cause harm. If the material is commonly used and if your technical team decide the bulk of it can be comfortably over 100nm in each dimension, then you might decide that some technical compromises compared to, say, 80nm particles, are outweighed by the fact that things over 100nm are accepted around the world as non-nano. How close to the edge can you go and not fall into a statutory definition of “nano”? That’s for you to decide after a close reading of the discussions in the book about multiple definitions. For example, is your particle more than 50% number average over 100nm for Europe and more than 90% weight average for the US and Canada? For those on the team who don’t understand the distinction between number and weight average, the book has a clear explanation.
To prove your nano product is safe you have to prove a negative- - that it poses no risks. How do you do that? Here the book has case studies where suppliers do what they do with any other material (e.g., for REACH regulations): patiently show due diligence in analyzing possible risks. Regulatory authorities can be convinced that particles locked into a matrix are not going to pose a risk, provided you do the relevant studies and calculations to show particles will not escape under plausible circumstances. For example, TiN nanoparticles within polymers are accepted because manufacturers have demonstrated how well they are locked in AND that the levels of Ti are far lower than those found in cornflakes AND that the level of Ti-containing nanoparticles is far below naturally-occurring levels. In other cases, some alarming increases in measured concentrations of the key element in a nanoparticle could be shown to be due to dissolved material, not nanoparticles. And since dissolved material is no longer nano and given that its conventional safety profile is known, the fact that a nanomaterial dissolves is a major factor in demonstrating an absence of extra risk.
How do we know the authorities can be convinced by rational arguments, and what would they accept as rational? Here the book offers specific help. The JRC has issued guidelines and the book not only provides links to those guidelines but takes us through the chain of logic required. I typed “JRC” deliberately. The nanosafety field is littered with acronyms, which the book is forced to use. I often forgot what was what, but there is a wonderful look-up table with over 300 acronyms, and it never let me down. “JRC” refers to the initials of the EU’s Joint Research Centre, an entity expending considerable resources to help define the levels of risks of nanomaterials. If you want to demonstrate low migration, you have to have a plausible material to migrate into. For foods, this will one of the commonly accepted simulants. Knowing the simulant, how do you prepare your sample and how do you identify how much nanoparticle has migrated? The regulators realize these are difficult questions; the book has plenty of plausible answers written by technical people who clearly know what they are talking about and who do not mask the practical problems.
You cannot test everything, so you also have to model migration. The chapter on modelling is superb. Having set the scene with models of smaller molecules diffusing through common polymers, the same equations can be used with defensible values of diffusion coefficients for nanoparticles of a given size. Anyone familiar with the field will know that these diffusion coefficients are super-small (the book estimates D=10-45 for a 10nm particle in PET). So, the calculations will generally yield the obvious answer that very little migrates out. The conclusion may be obvious, but if you do the work using rational models (and citing the models in the book would be my choice of “rational”), then you have shown necessary due diligence. I have implemented some of the diffusion coefficient equations from the book in the Diffusion Coefficients app within the Diffusion Science section of my Practical Solubility website. You can estimate the super-low diffusion coefficients then model them in my Fickian Diffusion app. If you can then point out that, for example, your particles are chemically locked into the matrix and that the low diffusion rate is an upper limit, so much the better.
Having proven only a small number of particles can escape, how do you then prove that that small number is safe? For non-nano contaminants, if you can show that migration levels are <0.05mg/kg of food, then the tox data you have to provide is limited. For nanomaterials, even low levels are considered to be potentially risky, so full tox testing (including on rats) is required. You have to show “no migration” to avoid all this. What is “no migration”? My reading of the advice is that this means “no particles detected using sensible techniques,” but here again the burden of proof remains with you. The details of the requirements will vary for non-food applications, but the principles are the same.
I read the book with the mindset of “if I had to bring a nano-containing product to market, how helpful would it be to have this book?” Writing this review forced me to go back and forth through the book checking whether it really covered X or provided any useful information on Y. In this context, the book does an outstanding job against a mission impossible. There are no easy answers because the regulatory authorities are struggling to come to terms with the challenges of nano. Whatever happens, you have to prepare a safety dossier, even if the same material in non-nano form is already acceptably safe. The more evidence you have that the substance itself is not harmful (so the data from the non-nano form is useful) and that it is locked safely away, the easier it is to demonstrate an absence of harm in the nano form.
Books with multiple authors can often be repetitive and lack purpose. The editor has done a good job of constructing a coherent narrative, with each chapter contributing something unique to the overall picture and with rather little duplication.
My conclusion repeats what I stated earlier. Do not proceed with a nano product development until everyone on the team has had a chance to read this excellent book. It provides regulations and the technical reasons for them, along with analytical guidance and modeling information, thus enabling all users of nano to carry out their own experiments and independently examine the risks of adding nanoparticles to products.
One final note. Because it focuses on the safety of finished products, the book does not cover the many safety issues in creating and handling nanoparticles during processing. In my (biased) view, the best guide on how to work with unknown unknowns in the lab and in production is the final chapter of another DEStech book, Nanocoatings: Principles and Practice, by Abbott and Holmes.