Titanium Dioxide, in the eye of the storm ?

It’s fair to say that’s a kind of rhetorical question.

Since 2022 the European Food Safety Authority (EFSA) has banned E171, a food additive being the chemical species Titanium Dioxide (TiO2).  

Titanium Dioxide has quite some advantages in its use in the food industry, e.g. as a whitening agent,  a stabilizer, a thickening agent, etcetera ….  

Reasons for the EU-ban on E171 are the (alleged) safety concerns due to the potential for genotoxicity, accumulation in the body and associated health risks. These concerns have triggered concerns for the use of this chemical species in medicinal products (within the EU for sure), more specifically whether it should  be banned as well in these applications.

And let’s not forget, though it’s less discussed in scientific articles, TiO2 is a frequently used and highly effective polymer additive, hence present when in pharmaceutical packaging and applications, equally in materials for medical devices.

Based on their evaluation of multiple datasets and studies , EFSA decided a few years ago -in 2022- to ban additive E171 (TiO2) in food leading to an urgent search for alternatives for the well established and understood additive TiO2. This is not an easy search and a huge challenge!

Next to the complexity of the numerous changes this ban induced, there’s no global alignment as we can observe too often in many domains.

For example markets and authorities like Canada, the US, Japan, the United Kingdom, Australia,…. did not ban TiO2 as a food additive after their own evaluation of the available data. They deemed and concluded there’s insufficient proof of health risks to actually ban TiO2.

A recent Product Quality Research Institute (PQRI) workshop on TiO2 concluded, after a review and discussion on the available data, there’s no scientific reason to ban Titanium Dioxide in food.

This obviously adds complexity to the use of Titanium Dioxide.

One could fairly state that a collateral damage of this EU/Food evaluation and ban versus no-ban and non-alignment, involves the use of Titanium Dioxide in medicinal products / pharmaceutical excipients. Here the use can be summarized as follows (non-limitative): an opacifying agent, a coating agent, a stabilizer, etcetera …

And, yes, again an evaluation, a discussion, a non-alignment on the question if this additive should be replaced or banned or ..... Will the EU still proceed with a ban in 2025?

One should not be easy-going on this question and its “conclusion” as the impact is huge. It involves Change Control in a Pharma context,  next to the search for good alternatives for the established additive, alternatives which should also be safe for people’s health.

It’s bring back memories on the (recent) replacement of DEHP (Bis(2-ethylhexyl)phthalate) or BPA (Bisphenol A) in polymers for certain applications after a ban.

And let’s not forget that Titanium Dioxide (TiO2) is also a frequently used polymer additive as it provides the white color to e.g. bottles or devices. It’s there already for decades, its behavior and toxicological assessment is well understood, pharmaceutical packaging and applications have been used and tested in Extractables and Leachables studies, it’s part of submission files for medical devices, … Change Control is there!

Moreover, Pharmacopeial monographs like e.g. the Ph.Eur. 3.1 series on materials, describe mandatory tests on extractable Ti in some polymers (a.o. polyolefines).

Clearly a tremendous change control would be the result of a mandatory change (after a ban e.g.) and of course Safety comes first, but with a hard preference this should only be the case after a thorough research, debate and aligned conclusion.

It’s quite certain the debate on the use of Titanium Dioxide as an additive in food and pharmaceutical excipients (also in polymers for pharma?) will continue.

Stay informed, stay ahead of the game if you can !

References

C. Dand, A. Bajaj and S. Wairkar, EFSA prohibits titanium dioxide in food – should pharmaceuticals be next ?, Toxicology, 2025, 513, 154089

D. Schoneker, D. Kirkland, D. Cragin, D. Lockley, S.M. Cohen, L. Blevins, M. Tobyn, K. Hughes, B. Baert, J. Melnick, A. Abend, B. Hancock, PQRI Position Paper Is there a Case for Banning Titanium Dioxide (E171) in Pharmaceuticals?, 2024, PQRI Website