Repeated administration of the food additive E171 to mice results in accumulation in intestine and liver and promotes an inflammatory status

Abstract

Titanium dioxide (TiO₂) is widely used in pharmaceuticals preparations, cosmetics, and as a food additive (E171). It contains microparticles and a fraction of nanoparticles (NPs) which can be absorbed systemically by humans after ingestion. Increasing concern has been aroused about the impact of oral exposure to TiO₂ NPs from dietary and non-dietary sources on human health. In spite of several toxicological studies conducted in recent years, a solid risk assessment of oral exposure to E171 has not been satisfactorily achieved. We investigated whether repeated oral administration of E171 to mice at a dose level (5 mg/kg body weight for 3 days/week for 3 weeks) comparable to estimated human dietary exposure, results in TiO₂ deposition in the digestive system and internal organs, and in molecular and cellular alterations associated with an inflammatory response. To reproduce the first phase of digestion, a new administration approach involving the dripping of the E171 suspension into the mouth of mice was applied. Significant accumulation of titanium was observed in the liver and intestine of E171-fed mice; in the latter a threefold increase in the number of TiO₂ particles was also measured. Titanium accumulation in liver was associated with necroinflammatory foci containing tissue monocytes/macrophages. Three days after the last dose, increased superoxide production and inflammation were observed in the stomach and intestine. Overall, the present study indicates that the risk for human health associated with dietary exposure to E171 needs to be carefully considered.

Keywords:

• Titanium dioxide
• E171
• nanoparticles
• gastrointestinal tract
• inflammation

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Acknowledgements

We thank An Jacobs of the Flemish Institute for Technological Research, Belgium, for her technical help in the ELISA and MSD assays.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

NLT was supported by a Swiss National Science Foundation Fellowship [P2GEP3_171976]. This study was partially supported by grants from the Ministero della Salute [RF-2011-02346754 to GS], the Associazione Italiana Ricerca sul Cancro [IG-18468 to GS], QualityNano Project (http://www.qualitynano.eu/) which is financed by European Community Research Infrastructure Action under the FP7 ‘Capacities’ Program [Grant Agreement No. 262163 to IN] and the EU FP7 FutureNanoNeeds project [Grant Agreement No. 604602 to PB and LD].