Titanium dioxide (TiO2) has safely been used as a pigment in thousands of food and drug products all over the world for more than fifty years. Known in Europe and many other parts of the world as E171, TiO2 is commonly used in solid oral dosage forms and topical drug products as well as in various liquid drug products where some opacity is desired.
In a September 2016 opinion, the European Food Safety Authority (EFSA) reviewed the available safety information for E171 and communicated no concerns about its continued use as a food additive. However, EFSA did call for additional data to complete their review and fill in some gaps related to modern toxicology and analytical standards that didn’t exist when E171 was initially approved. EFSA stated that the data was needed to facilitate the development of an acceptable daily intake (ADI). The Titanium Dioxide Manufacturers Association (TDMA) committed to EFSA to provide the data requested by August 2019.
In 2017, the French Agency for Food Environmental and Occupational Health and Safety (ANSES) published an opinion on a new paper from the French National Institute for Agricultural Research (the Bettini study). The agency concluded that the findings did not allow ANSES to question the EFSA opinion on the safety of E171 as a food additive. However, since the authors of the Bettini study alleged that E171 may have potential adverse health effects, the French government asked the European Commission to request EFSA to further assess the Bettini study and three other studies that had been published after EFSA’s 2016 opinion. EFSA finalized its assessment in June 2018, concluding that the four studies do not merit EFSA changing its existing opinion that E171 is safe.
While the Bettini study has significant design flaws that render its conclusions questionable, based on requests from France, EFSA updated its call for data to include additional studies investigating the concerns raised in Bettini. TDMA committed to perform these additional studies but indicated that the final results could not be provided to EFSA until July 2020. EFSA agreed to this new deadline.
Despite this agreement, France is suspending the marketing of foods containing E171 beginning January 1, 2020 for one year. The justification for the suspension is that the studies required to set the ADI won’t be completed by the August 2019 deadline, though it was the French government’s request for more data that created the delay.
In May 2019, at the annual meeting of the EU Standing Committee on Plants, Animals, Food and Feed (SCoPAFF), France presented its case for an EU-wide suspension of E171 in foods. While the committee made no final decisions during the meeting, most member states appeared to prefer a harmonized approach throughout Europe and for France to postpone suspending E171 until after EFSA’s final opinion in 2020. The EU member states now have to decide if they will formally object to France’s proposed suspension and potentially prevent its implementation. While EFSA’s opinion is that E171 is safe and no actions need to be taken until after the new studies are completed and assessed in 2020, the outcome remains uncertain, and E171 is a politically sensitive topic in France. Some French consumer groups are calling for the planned suspension to extend beyond foods to pharmaceuticals and cosmetics. This would cause significant problems for the availability of drug products in France, since there is no good alternative with similar properties to E171, and reformulating drug products containing E171 could take significant time. Such reformulations would also likely reduce product shelf lives and result in different colors for all existing products, which would cause patient confusion. The significant cost implications may also cause some companies to no longer supply their drug products to France, which could create long-term drug shortages.
One can only hope that science will prevail and that a “perceived” safety problem isn’t allowed to create chaos while providing no additional benefit to patient safety.
David R. Schoneker is vice chair of science and regulatory policy at IPEC-Americas.