Titanium Dioxide in food, cosmetics and your gut AKA ‘E171 gut gate’.

So this morning I logged onto Facebook and almost immediately fell down a science-ing worm hole (I have no idea how that should be spelled).  It was catalysed by on line discussions about the safety of Titanium Dioxide as used in cosmetics (and foods) as a colourant. It turns out that this interest was sparked by a scientific report published by the University of Sydney last week and discussed on popular TV show ‘The Project’ which I didn’t see. I have since read the article, the scientific report abstract (which is all there is so far, and, (nerd alert) I spoke to the lead author, Professor Wojtek Chrzanowski PhD. So let’s see what all the fuss is about shall we…

Titanium Dioxide.

So, it turns out that while this was the molecule of study, the E171 food additive that has grabbed the headlines. It is the size of this molecule that is more interesting than its chemistry. That said, we should investigate its chemistry.

Titanium Dioxide is an inorganic chemical (it contains no carbon) that exists in nature. It forms in nature  in blocks or lattice structures where several Ti’s and O’s get together and don’t let go. These are the primary particles.  Titanium Dioxide can also be manufactured to make purer, more even grades with more marketable features and so it is important to note that the way you manufacture Titanium Dioxide will determine how big (or small) these primary particles will be.   Different manufacturing methods create materials that are better suited to certain jobs – sunscreen particles are different to food particles for example.

In addition to the particle size, there are also the 8 ways that titanium dioxide likes to get its self together – think of there being 8 different ways you can combine the same few lego bricks.  The most common of these are Anatase and Rutile.

Titanium Dioxide as a chemical is pretty un-reactive in the body and most bodies will poop it out. However, with any particle you get a particle size distribution which means that you buy a bag of titanium dioxide with an average particle size of 200 nm it will have some particles that are bigger and some that are larger. Their distribution will usually look like a camel hump on a graph.  Better quality products generally have a steeper hump as the particle distribution is smaller.

Any particles that are 100nm or smaller are in the nanoparticle range and in this study the average primary particle size was definitely less than 100nm.  There is another part to the cosmetic definition of ‘nano particle’ which talks about ‘intentionally made’ so as to differentiate manufactured nanoparticles from  naturally occurring ones but I’m not sure that will be relevant in this case.

The Study.

The study here found that nano titanium dioxide was affecting the gut microbiota.

I found that immediately interesting and used my Deep Dyvve subscription to look for other papers in this area. I found a few including this one that confirmed an affect on the intestinal brush border.

PAUSE.

I’ll just stop here and show you a bit of a mind-map of how I start interacting with new information that comes across my desk.  This very brief diagram shows you that I consider the original paper, play around with it in my mind, evaluating it against my prior knowledge to see how well it addresses or confirms what I know about Titanium Dioxide and/ or nanoparticles – at this stage I also have to check and note any bias I have. I then look to the wider context and for more papers, develop my own questions and finally call the author!

 

My Big Question.

So one thing that confused me after reading this paper and comparing it to other papers was whether it was the titanium dioxide chemistry or the particle size that was causing changes. I put that question to Professor Chrzanowski and he set me straight.  I won’t quote him verbatim as it wasn’t that kind of chat but this is the crux of it in laymen terms.

Answer: It’s the size. The Titanium Dioxide is likely not an issue per se.

Before we go into that I was reminded that titanium (and zinc) particles are usually in agglomerates when they are purchased.  This basically means that the product contains loosely bonded clumps of particles that are lots bigger than their specified primary particle size.  The first step of the scientific process is to de-agglomerate them and then to identify the particle size distribution. Apparently this is typical of what would happen in our digestion anyway and is how our gut will eventually see the particles. The situation in sunscreens is somewhat different which again reminds me that what we put in the body isn’t dealt with in the same way as what we put on the body.

The nanoparticles enter the body naked but don’t stay naked for long. The body dresses them up with a protein coating as part of the digestion process.  I got the feeling that the body dresses up all of its food that way if it gets a chance so this is just standard procedure.

Once this protein wrapped nano particle gets into the gut, the gut tries to eat it but it finds it can’t because it doesn’t like eating titanium dioxide.   The down side in this case is that in attempting to eat the wrapper, the gut unleashes a nanoparticle and that’s when the trouble starts with the nanoparticle then causing some disruption to the micro biome and brush border.

The exact dynamics of this process is actually quite hard to study as Professor Chrzanowiski mentioned that this is a good example of where there is almost no correlation between animal studies and humans.  I did notice that many of the other studies I read through used in-vitro methodology – cell culture and models.  There is quite a bit more work to do to correctly map cause-and-effect from this understanding in terms of how much, for how long and how damaging this type of upset to the gut turns out to be.

The last step is excretion and titanium dioxide has been found to pass through the body happily via either toilet route depending on its size, dose and solubility I presume.

We know from lots of work in the pharmaceutical area that titanium dioxide in large form does pass out via the poo and this work helps to pinpoint particle size as the real issue to focus on.

So why mention Titanium Dioxide when it’s Nano that is at fault?

Basically in this study, the titanium was just the nano particle that demonstrated the concept, it wasn’t the problem, it was just the gimp…

The reason that Titanium Dioxide is grabbing the headlines is:

Titanium Dioxide is a potentially unnecessary source of unhelpful nanoparticles in our diet.  

Titanium Dioxide is used to make food whiter or more opaque. It may be mixed with other colourants to produce pastel colours or used on its own.  It has a similar function in cosmetics plus it can be used as a sunscreen. It does appear in lipstick formulations which, I feel, is important to note and why I, as a cosmetic chemist, am particularly interested.

More Details about this study.

I don’t know, at this point, whether any damage seen or suspected from the nanoparticle ‘hit’ is permanent or recoverable, how long damage might last or even how the dose used in this study compares to what we would be exposed to in ‘real life’.

In ‘real-life’ applications food grade titanium dioxide has been found to have somewhere in the region of 15-35% particles in the nano range. In the USA Titanium Dioxide is permitted as a whitening agent at levels up to 1% in food. France is looking to implement a ban in using this as a food colourant from 2020.  France has banned things before that other countries have not. Whether this is good governance or something else is up for debate.

The answers to these, my supplementary questions, will come out when the full data is published, when more work is done and when further funding for more detailed investigations become possible.  As Professor Chrzanowski said to me, this is fundamental research and as such it acts as a scaffold upon which more applied research can be built but we are not done yet, we haven’t finished with the fundamentals yet. We don’t yet understand everything.

So what does this mean for cosmetics?

I must say that this research has resonated with me as being a) interesting b) representing a new level of understanding. c) potentially game-changing when it comes to how we think about and handle man-made nano materials.

I wish to iterate that this is NOT about titanium dioxide as a chemical molecule and that banning or being ‘free from’ that will NOT guarantee you a formula that is ‘free from’ nanoparticles, especially if you just swap this with any old alternative that may also be particulate and contain some nanoparticles.

We don’t eat our cosmetics but there are times when we incidentally ingest them, especially lipsticks and sometimes sunscreen. Maybe we should be looking into ways to make our cosmetic nanoparticles easier to pass through the body (and, while we are at it, easy to digest by the right microbes once they get into the environment).

What I was heartened by is the fact that the team behind this research do seem excited about the potentials that understanding this brings.  We now have more insight on one thing that causes gut damage (ingested nanoparticles that reach this part of the gut), now we can start forming ideas about how we might engineer a solution. Whether we need,  want or can afford to or not is another matter.

In terms of what to do as a cosmetic manufacturer/ formulator, I feel I want to  keep my eyes peeled and doing some more reading into the fate of nanoparticles  in our water treatment plants and in the soil/ on soil microbes. I would be focusing not only on our own health and safety but also of the product life-cycle as a whole.

I  feel it is important to reflect on what this, and other studies have found and work  to limit the potential for cosmetic nanoparticles to be ingested so claims like ‘food grade’ on cosmetic products are probably a bit reckless and maybe use directions could be tightened.

So my take on this is that we should keep our eyes on the science, our minds open wide and keep those nanoparticles on the outside!

See you another day

Amanda x