Tag Archives: European Food Safety Agency

Findings on oral exposure to nanoscale titanium dioxide

It’s been a while since I’ve run a piece on health concerns and nanoparticles. The nanoparticles in question are titanium dioxide and the concerns centre on oral exposure to them according to a Jan. 24, 2017 news item on Nanowerk,

Researchers from INRA [French National Institute for Agricultural Research] and their partners have studied the effects of oral exposure to titanium dioxide, an additive (E171) commonly used in foodstuffs, especially confectionary. They have shown for the first time that E171 crosses the intestinal barrier in animals and reaches other parts of the body.

Immune system disorders linked to the absorption of the nanoscale fraction of E171 particles were observed. The researchers also showed that chronic oral exposure to the additive spontaneously induced preneoplastic lesions in the colon, a non-malignant stage of carcinogenesis, in 40% of exposed animals.

Moreover, E171 was found to accelerate the development of lesions previously induced for experimental purposes. While the findings show that the additive plays a role in initiating and promoting the early stages of colorectal carcinogenesis, they cannot be extrapolated to humans or more advanced stages of the disease. [emphasis mine]

A Jan. 20, 2017 IINRA press release, which originated the news item,  provides more detail about European use of titanium dioxide as a food additive and about the research,

Present in many products including cosmetics, sunscreens, paint and building materials, titanium dioxide (or TiO2), known as E171 in Europe, is also widely used as an additive in the food industry to whiten or give opacity to products. It is commonly found in sweets, chocolate products, biscuits, chewing gum and food supplements, as well as in toothpaste and pharmaceutical products. Composed of micro- and nanoparticles, E171 is nevertheless not labelled a “nanomaterial”, since it does not contain more than 50% of nanoparticles (in general it contains from 10-40%). The International Agency for Research on Cancer (IARC) evaluated the risk of exposure to titanium dioxide by inhalation (occupational exposure), resulting in a Group 2B classification, reserved for potential carcinogens for humans.

Today, oral exposure to E171 is a concern, especially in children who tend to eat a lot of sweets. INRA researchers studied the product as a whole (that is, its mixed composition of micro- and nanoparticules), and have also evaluated the effect of the nanoscale particle fraction alone, by comparing it to a model nanoparticle.

Titanium dioxide crosses the intestinal barrier and passes into the bloodstream

The researchers exposed rats orally to a dose of 10mg of E171 per kilogram of body weight per day, similar to the exposure humans experience through food consumption (data from European Food Safety Agency, September 20162). They showed for the first time in vivo that titanium dioxide is absorbed by the intestine and passes into the bloodstream. Indeed, the researchers found titanium dioxide particles in the animals’ livers.

Titanium dioxide alters intestinal and systemic immune response

Titanium dioxide nanoparticles were present in the lining of the small intestine and in the colon, and entered the nuclei of the immune cells of Peyer’s patches, which induce immune response in the intestine. The researchers showed an imbalance in immune response, ranging from a defect in the production of cytokines in Peyer’s patches to the development of micro-inflammation in colon mucosa. In the spleen, representative of systemic immunity, exposure to E171 increases the capacity of immune cells to produce pro-inflammatory cytokines when they are activated in vitro.

Chronic oral exposure to titanium dioxide plays a role in initiating and promoting early stages of colorectal carcinogenesis

The researchers exposed rats to regular oral doses of titanium dioxide through drinking water for 100 days. In a group of rats previously treated with an experimental carcinogen, exposure to TiO2 led to an increase in the size of preneoplastic lesions. In a group of healthy rats exposed to E171, four out of eleven spontaneously developed preneoplastic lesions in the intestinal epithelium. Non-exposed animals presented no anomalies at the end of the 100-day study. These results indicate that E171 both initiates and promotes the early stages of colorectal carcinogenesis in animals.

These studies show for the first time that the additive E171 is a source of titanium dioxide nanoparticles in the intestine and the entire body, with consequences for both immune function and the development of preneoplastic lesions in the colon. These first findings justify a carcinogenesis study carried out under OECD [Organization for Economic Cooperation and Development] guidelines to continue observations at a later stage of cancer. They provide new data for evaluating the risks of the E171 additive in humans.

These studies were carried out within the framework of the Nanogut project, financed by the French Agency for Food, Environmental and Occupational Health & Safety (ANSES) within the French national programme for research related to the environment, health and the workplace (PNR EST) and coordinated by INRA. Sarah Bettini’s university thesis contract was financed by the French laboratory of excellence LabEx SERENADE.

Here’s a link to and a citation for the paper,

Food-grade TiO2 impairs intestinal and systemic immune homeostasis, initiates preneoplastic lesions and promotes aberrant crypt development in the rat colon by Sarah Bettini, Elisa Boutet-Robinet, Christel Cartier, Christine Coméra, Eric Gaultier, Jacques Dupuy, Nathalie Naud, Sylviane Taché, Patrick Grysan, Solenn Reguer, Nathalie Thieriet, Matthieu Réfrégiers, Dominique Thiaudière, Jean-Pierre Cravedi, Marie Carrière, Jean-Nicolas Audinot, Fabrice H. Pierre, Laurence Guzylack-Piriou, & Eric Houdeau. Scientific Reports 7, Article number: 40373 (2017) doi:10.1038/srep40373 Published online: 20 January 2017

This paper is open access.

The research is concerning but they don’t want to draw any conclusions yet, which explains the recommendation for further research.

Dunkin’ Donuts and nano titanium dioxide

It’s been a busy few days for titanium dioxide, nano and otherwise, as the news about its removal from powdered sugar in Dunkin’ Donuts products ripples through the nano blogosphere. A March 6, 2015 news item on Azonano kicks off the discussion with an announcement,

Dunkin’ Brands, the parent company of the Dunkin’ Donuts chain, has agreed to remove titanium dioxide, a whitening agent that is commonly a source of nanomaterials, from all powdered sugar used to make the company’s donuts. As a result of this progress, the advocacy group As You Sow has withdrawn a shareholder proposal asking Dunkin’ to assess and reduce the risks of using nanomaterials in its food products.

Here’s a brief recent history of Dunkin’ Donuts and nano titanium dioxide from my Aug. 21, 2014 posting titled, FOE, nano, and food: part two of three (the problem with research),

Returning to the ‘debate’, a July 11, 2014 article by Sarah Shemkus for a sponsored section in the UK’s Guardian newspaper highlights an initiative taken by an environmental organization, As You Sow, concerning titanium dioxide in Dunkin’ Donuts’ products (Note: A link has been removed),

The activists at environmental nonprofit As You Sow want you to take another look at your breakfast doughnut. The organization recently filed a shareholder resolution asking Dunkin’ Brands, the parent company of Dunkin’ Donuts, to identify products that may contain nanomaterials and to prepare a report assessing the risks of using these substances in foods.

Their resolution received a fair amount of support: at the company’s annual general meeting in May, 18.7% of shareholders, representing $547m in investment, voted for it. Danielle Fugere, As You Sow’s president, claims that it was the first such resolution to ever receive a vote. Though it did not pass, she says that she is encouraged by the support it received.

“That’s a substantial number of votes in favor, especially for a first-time resolution,” she says.

The measure was driven by recent testing sponsored by As You Sow, which found nanoparticles of titanium dioxide in the powdered sugar that coats some of the donut chain’s products. [emphasis mine] An additive widely used to boost whiteness in products from toothpaste to plastic, microscopic titanium dioxide has not been conclusively proven unsafe for human consumption. Then again, As You Sow contends, there also isn’t proof that it is harmless.

“Until a company can demonstrate the use of nanomaterials is safe, we’re asking companies either to not use them or to provide labels,” says Fugere. “It would make more sense to understand these materials before putting them in our food.”

As I understand it, Dunkin’ Donuts will be removing all titanium dioxide, nano-sized or other, from powdered sugar used in its products. It seems As You Sow’s promise to withdraw its July 2104 shareholder resolution is the main reason for Dunkin’ Donuts’ decision. While I was and am critical of Dunkin’ Donuts’ handling of the situation with As You Sow, I am somewhat distressed that the company seems to have acquiesced on the basis of research which is, at best, inconclusive.

Dr. Andrew Maynard, director of the University of Michigan Risk Science Centre, has written a substantive analysis of the current situation regarding nano titanium dioxide in a March 12, 2015 post on his 2020 Science blog (Note: Links have been removed),

Titanium dioxide (which isn’t the same thing as the metal titanium) is an inert, insoluble material that’s used as a whitener in everything from paper and paint to plastics. It’s the active ingredient in many mineral-based sunscreens. And as a pigment, is also used to make food products look more appealing.

Part of the appeal to food producers is that titanium dioxide is a pretty dull chemical. It doesn’t dissolve in water. It isn’t particularly reactive. It isn’t easily absorbed into the body from food. And it doesn’t seem to cause adverse health problems. It just seems to do what manufacturers want it to do – make food look better. It’s what makes the powdered sugar coating on donuts appear so dense and snow white. Titanium dioxide gives it a boost.

And you’ve probably been consuming it for years without knowing. In the US, the Food and Drug Administration allows food products to contain up to 1% food-grade titanium dioxide without the need to include it on the ingredient label. Help yourself to a slice of bread, a bar of chocolate, a spoonful of mayonnaise or a donut, and chances are you’ll be eating a small amount of the substance.

Andrew goes on to describe the concerns that groups such as You As Sow have (Note: Links have been removed),

For some years now, researchers have recognized that some powders become more toxic the smaller the individual particles are, and titanium dioxide is no exception. Pigment grade titanium dioxide – the stuff typically used in consumer products and food – contains particles around 200 nanometers in diameter, or around one five hundredth the width of a human hair. Inhale large quantities of these titanium dioxide particles (I’m thinking “can’t see your hand in front of your face” quantities), and your lungs would begin to feel it.

If the particles are smaller though, it takes much less material to cause the same effect.

But you’d still need to inhale very large quantities of the material for it to be harmful. And while eating a powdered donut can certainly be messy, it’s highly unlikely that you’re going to end up stuck in a cloud of titanium dioxide-tinted powdered sugar coating!

… Depending on what they are made of and what shape they are, research has shown that some nanoparticles are capable of getting to parts of the body that are inaccessible to larger particles. And some particles are more chemically reactive because of their small size. Some may cause unexpected harm simply because they are small enough to throw a nano-wrench into the nano-workings of your cells.

This body of research is why organizations like As You Sow have been advocating caution in using nanoparticles in products without appropriate testing – especially in food. But the science about nanoparticles isn’t as straightforward as it seems.

As Andrew notes,

First of all, particles of the same size but made of different materials can behave in radically different ways. Assuming one type of nanoparticle is potentially harmful because of what another type does is the equivalent of avoiding apples because you’re allergic to oysters.

He describes some of the research on nano titanium dioxide (Note: Links have been removed),

… In 2004 the European Food Safety Agency carried out a comprehensive safety review of the material. After considering the available evidence on the same materials that are currently being used in products like Dunkin’ Donuts, the review panel concluded that there no evidence for safety concerns.

Most research on titanium dioxide nanoparticles has been carried out on ones that are inhaled, not ones we eat. Yet nanoparticles in the gut are a very different proposition to those that are breathed in.

Studies into the impacts of ingested nanoparticles are still in their infancy, and more research is definitely needed. Early indications are that the gastrointestinal tract is pretty good at handling small quantities of these fine particles. This stands to reason given the naturally occurring nanoparticles we inadvertently eat every day, from charred foods and soil residue on veggies and salad, to more esoteric products such as clay-baked potatoes. There’s even evidence that nanoparticles occur naturally inside the gastrointestinal tract.

He also probes the issue’s, nanoparticles, be they titanium dioxide or otherwise, and toxicity, complexity (Note: Links have been removed),

There’s a small possibility that we haven’t been looking in the right places when it comes to possible health issues. Maybe – just maybe – there could be long term health problems from this seemingly ubiquitous diet of small, insoluble particles that we just haven’t spotted yet. It’s the sort of question that scientists love to ask, because it opens up new avenues of research. It doesn’t mean that there is an issue, just that there is sufficient wiggle room in what we don’t know to ask interesting questions.

… While there is no evidence of a causal association between titanium dioxide in food and ill health, some studies – but not all by any means – suggest that large quantities of titanium dioxide nanoparticles can cause harm if they get to specific parts of the body.

For instance, there are a growing number of published studies that indicate nanometer sized titanium dioxide particles may cause DNA damage at high concentrations if it can get into cells. But while these studies demonstrate the potential for harm to occur, they lack information on how much material is needed, and under what conditions, for significant harm. And they tend to be associated with much larger quantities of material than anyone is likely to be ingesting on a regular basis.

They are also counterbalanced by studies that show no effects, indicating that there is still considerable uncertainty over the toxicity or otherwise of the material. It’s as if we’ve just discovered that paper can cause cuts, but we’re not sure yet whether this is a minor inconvenience or potentially life threatening. In the case of nanoscale titanium dioxide, it’s the classic case of “more research is needed.”

I strongly suggest reading Andrew’s post in its entirety either here on the University of Michigan website or here on The Conversation website.

Dexter Johnson in a March 11, 2015 post on his Nanoclast blog also weighs in on the discussion. He provides a very neat summary of the issues along with these observations (Note Links have been removed),

With decades of TiO2 being in our food supply and no reports of toxic reactions, it would seem that the threshold for proof is extremely high, especially when you combine the term “nano” with “asbestos”.

As You Sow makes sure to point out that asbestos is a nanoparticle. While the average diameter of an asbestos fiber is around 20 to 90 nm, their lengths varied between 200 nm and 200 micrometers.

The toxic aspect of asbestos was not its diameter, but its length. …

In addition to his summary Dexter highlights As You Sows attempt to link titanium dioxide nanoparticles to asbestos. I suggest reading his post for an informed description of what made asbestos so toxic (here) and why the linkage seems specious at this time.

For anyone interested in how As You Sow managed to introduce asbestos toxicity issues into a discussion about nano titanium dioxide and food products, there’s this from As You Sow’s FAQs (frequently asked questions) about nanomaterials in food page,

Why are nanomaterials in food important to investors?

When technology is used before ensuring that it is safe for humans and the environment, and before regulatory standards exist, companies can be exposed to significant financial, legal, and reputational risk. The limited studies that exist on nanomaterials, including nanoscale titanium dioxide*, have indicated that ingestion of these particles may pose health hazards.

The inaction of regulators does not protect companies, especially when the regulators themselves warn of the dangers of nanoparticles’ largely unknown risks. Draft guidance issued by the U.S. Food and Drug Administration raises questions about the safety of nanoparticles and demonstrates the general lack of knowledge about the technology and its effects. (1)

Asbestos litigation is a good example of the risks that can arise from using an emerging technology before it is proven safe. Use of asbestos (a nanomaterial) has created the longest, most expensive mass tort in national history with total U.S. costs now standing at over $250 billion. (2) If companies been asked to investigate and minimize or avoid risks prior to adopting asbestos technology, a sad and expensive chapter in worker harm could have been avoided.

* Titanium dioxide is a common pigment and FDA-approved food additive. It is used as a whitener, a dispersant, and a thickener.

While I don’t particularly appreciate fear-mongering as a tactic, the strategy of targeting investors and their concerns, seems to have helped As You Sow win its way.