The use of food additives is subject to a specific European regulatory framework: authorisations are issued by the European Commission on the basis of scientific assessments carried out by EFSA, Europe's reference authority with regard to food additive assessment.
When re-assessing E171 in 2016, EFSA's expert panel had not identified any concerns regarding genotoxicity and carcinogenicity after oral administration. Based on exposure data and the no observed adverse effect level (NOAEL), they had concluded that the additive E171 did not raise health concerns for consumers. However, they did identify gaps in the data and the panel had recommended conducting reproductive toxicity studies in order to establish an acceptable daily intake for E171.
In 2021, in the context of an updated risk assessment based on new data, EFSA now believes that titanium dioxide can no longer be considered safe when used as a food additive, mainly because genotoxic effects cannot be ruled out.
This update primarily drew on data from the scientific literature, a call for data issued by the European Commission and data generated by an industrial consortium. As the additive E171 contains nanometric particles, the re-assessment was conducted according to the guidance EFSA established in 2018 on risk assessment of the application of nanoscience and nanotechnologies in the food and feed chain.
Regarding general toxicity, EFSA's experts found that E171 is poorly absorbed but can accumulate in different organs over time. Although the reproductive and developmental toxicity data did not show any effects with E171 at the highest dose tested, other data may indicate adverse effects of the food additive in terms of immunotoxicity and inflammation, and potential neurotoxicity for nanoparticulate forms of titanium dioxide. There are no studies currently available enabling a proper assessment of the carcinogenicity of titanium dioxide nanoparticles induced by the oral route.
Regarding the data on genotoxicity, studies have shown that TiO2 particles have the potential to induce DNA breaks and chromosomal damage. Concerns about the genotoxicity of titanium dioxide particles in the food additive E171 could not therefore be ruled out. The EFSA re-assessment did not find any clear correlation between genotoxicity and certain physico-chemical properties of titanium dioxide such as size, shape or crystalline form.
ANSES points out that in 2017 and then in 2019, it twice questioned the lack of data for robustly characterising the hazard and then assessing the risk of the additive E171.
In 2017, ANSES had produced a specific opinion on the NANOGUT study by INRA, which showed a possible link between chronic oral exposure of rats to the additive E171 and the appearance of precancerous colorectal lesions. In its conclusions, the Agency had stressed that although the results did not call into question the re-assessment of the food additive carried out by EFSA in 2016, they did however demonstrate effects that had not previously been identified; specifically, potential promoting effects for carcinogenesis. As a result, the Agency highlighted the need to conduct studies to better characterise the potential health effects associated with ingestion of the food additive E171.
In an opinion published in 2019, the Agency again examined the potential oral toxicity of E171 by reviewing 25 more recent studies. None of these studies confirmed or ruled out a potential carcinogenesis-promoting effect for this additive. Although some of them highlighted new signals such as the modification of cellular biological mechanisms in mice, developmental defects in invertebrates, or in vitro genotoxic effects of several forms of nanoparticulate TiO2 – including E171 – via oxidative stress, these data were not sufficient to reach a conclusion about a toxic effect. In its conclusions, ANSES reiterated its recommendations to better characterise the possible E171 hazard, through the rapid acquisition of additional data that could help reach a decision on the various observed signals.
ANSES's 2019 conclusions were among the elements taken into account by the French government when deciding to suspend the marketing in France of foodstuffs containing the additive E171. The first one-year suspension from 1 January 2020 was extended to 1 January 2022, mainly in anticipation of the studies to come.
EFSA's assessment will be taken into account by ANSES for its future work on nanoscale forms of food additives in general.
In 2021, ANSES will continue its work on developing a risk assessment methodology tailored to engineered nanomaterials. It will test the applicability of this methodology on substances previously identified as engineered nanomaterials, including titanium dioxide. The main aim will be to test the robustness of the methodology, update the toxicological and exposure data and, in light of the quality of these data, consider a possible risk assessment. The results of all or part of these studies will be published in 2021.
The methodology developed by ANSES is part of the same effort to improve assessment and protect consumers from the risks associated with substances added to food.