TiO2 or Ti OH NO!? Is food grade titanium dioxide safe as a food additive?

Author: Kimberley Jerwood , Toxicologist at bibra (peer-reviewed by James Hopkins and Peter Watts, Toxicology Directors at bibra)

A bit of background to start with:

Titanium dioxide (TiO2) exists in nature in different crystalline forms: anatase and rutile being the two most common. The food grade material, used as a colouring, E171 in Euro-speak, is composed of both nano- and micro-sized particles. It has also been widely used in cosmetics and medicines.

Let us set the scene:

In 2021, the EFSA Panel on Food Additives and Flavourings (FAF) caused a stir, when it concluded that E171 is no longer considered safe as a food additive. The main area of uncertainty involved genotoxicity (although uncertainties with immunotoxicity, inflammation and neurotoxicity were also flagged). The now huge database on genotoxicity has shown to the Panel’s satisfaction that TiO2 nanoparticles exhibit the potential to interact with DNA, produce DNA strand breaks, and induce chromosome aberrations. As no clear correlation had been observed between the physico-chemical properties (including the size) of the particles and the outcome of either in vitro or in vivo genotoxicity assays, “a concern for genotoxicity of TiO2 particles that may be present in E171 could therefore not be ruled out”.

Since August 2022, following the publication of Commission Regulation (EU) 2022/63, amending Annexes II and III to Regulation (EC) No. 1333, the use of E171 as a food additive is no longer permitted in the EU. It is currently still authorised in the UK in both anatase and rutile forms. Which raises the question: should the UK population view its continuing exposure to E171 as a possible Brexit bonus?

But what’s that? Is it a bird? Is it a plane? No, it’s the COT and COM!

The UK’s two Committees on Toxicity and Mutagenicity (the COT and COM, respectively) in October this year joined the E171 debate, giving their views on the key studies analysed in the EFSA Panel (2021) opinion and any other relevant studies published subsequently. The COM concluded that there is “little evidence” that titanium dioxide nanoparticles are genotoxic in vitro or that there is “a health concern related to in vivo genotoxicity induction by TiO2”. The Committee did note though that “a definitive assessment of the safety of food grade E171 is difficult when there are no high-quality OECD-compliant studies that adequately incorporate the study design considerations and characterisation of the nanoparticulate fraction present in E171”. They apparently felt able to conclude that “any genotoxicity risk” from E171 would be “low”. The COT, confident that none of the issues raised by the EFSA Panel undermined the toxicological acceptability of E171, derived a new safety benchmark for food grade TiO2, an oral Health-Based Guidance Value (HBGV). This was based on a high-quality Extended-One-Generation Reproductive Toxicity study in rats that found no clear evidence of toxicity at the maximum tested dose of 1000 mg/kg bw/day, and this No-Observed-Adverse-Effect Level (NOAEL) was selected as the foundation of the HBGV. An overall Uncertainty Factor of 100, comprising factors of 10 for interspecies variability and 10 for individual variability, described as conservative by the Committee, was applied to the NOAEL generating the HBGV of 10 mg/kg bw/day. Overall, the Committee concluded that dietary exposure to E171 is unlikely to pose a health risk to the UK population.

Who is out of step here, the EFSA Panel or the CoT?

In 2022 reviews of TiO2 actually triggered by the EFSA Panel’s shock opinion, Health Canada, although accepting that there were some uncertainties in the toxicity profile that would benefit from further research, did not identify any compelling health concerns over the use of TiO2 as a food additive (Health Canada, 2022), whereas Antipodean Experts concluded that “there is no evidence to suggest that dietary exposures to food-grade TiO2 are of concern for human health” (FSANZ, 2022). The Joint FAO/WHO Expert Committee on Food Additives at a 2024 meeting was essentially on the same page, admitting, for example, that whilst there were uncertainties in the genotoxicity data, they were not of a nature to undermine JECFA’s long-standing opinion, first expressed in 1969, of the toxicological acceptability of TiO2 of a food grade purity (JECFA, 2024).

Oh dear, TiO2 joins bisphenol A as an EFSA toxicological outlier. The great and the good of toxicology willing to serve on Expert Groups used to be a far more harmonious community. This current contrast in opinions has significant implications for important consumer product ranges and does the reputation of traditional applied toxicology no good at all.

Relevant links:

EFSA (2021). Scientific opinion on the safety assessment of titanium dioxide (E171) as a food additive. EFSA Panel on Food Additives and Flavourings (FAF). EFSA Journal 2021;19 (5):6586. https://efsa.onlinelibrary.wiley.com/doi/epdf/10.2903/j.efsa.2021.6585

Committee on the Toxicity of Chemicals in Food, Consumer Products and the Environment (COT) (2024). https://cot.food.gov.uk/sites/default/files/2024-10/Final%20statement%20on%20TiO2%20Acc%20V%20SO.pdf

Committee on the Mutagenicity of Chemicals in Food, Consumer Products and the Environment (COM) (2024). https://www.gov.uk/government/publications/statement-on-the-com-assessment-of-in-vitro-and-in-vivo-genotoxicity-of-titanium-dioxide/statement-on-the-com-assessment-of-in-vitro-and-in-vivo-genotoxicity-of-titanium-dioxide

FSANZ (2022). Food Standards Australia and New Zealand. Titanium Dioxide as a Food Additive. https://www.foodstandards.gov.au/sites/default/files/consumer/foodtech/Documents/FSANZ_TiO2_Assessment_report.pdf

Health Canada (2022). State of the Science of Titanium Dioxide (TiO2) as a Food Additive. https://publications.gc.ca/collections/collection_2022/sc-hc/H164-341-2022-eng.pdf

JECFA (2024). Evaluation of certain food additives: ninety-seventh report of the Joint FAO/WHO Expert Committee on Food Additives. WHO technical report series 1051. https://iris.who.int/bitstream/handle/10665/376462/9789240090026-eng.pdf?sequence=1