Food‐grade titanium dioxide (E171) by solid or liquid matrix administration induces inflammation, germ cells sloughing in seminiferous tubules and blood‐testis barrier disruption in mice

Food‐grade titanium dioxide labeled as E171 has been approved for human consumption by the Food and Drug Administration (USA) and by the European Union for five decades. However, titanium dioxide has been classified as a possible carcinogen for humans by the International Agency of Research in Cancer raising concerns of its oral intake and the translocation to bloodstream, which could disturb barriers such as the blood‐testis barrier. There is evidence that titanium dioxide by intragastric/intraperitoneal/intravenous administration induced alterations on testosterone levels, testicular function and architecture, but studies of the E171 effects on the testicle structure and blood‐testis barrier are limited. E171 is contained not only in foods in liquid matrix but also in solid ones, which can exert different biological effects. We aimed to compare the effects of E171 consumption in a solid matrix (0.1%, 0.5% and 1% in pellets) and liquid suspension (5 mg/kg body weight) on testis structure, inflammation infiltrate and blood‐testis barrier disruption of male BALB/c mice. Results showed that none of the administration routes had influence on body weight but an increase in germ cell sloughing and the infiltrate of inflammatory cells in seminiferous tubules, together with disruption of the blood‐testis barrier were similar in testis of both groups even if the dose received in mice in liquid matrix was 136 or 260 times lower than the dose reached by oral intake in solid E171 pellets in 0.5% E171 and 1% E171, respectively. This study highlights the attention on matrix food containing E171 and possible adverse effects on testis when E171 is consumed in a liquid matrix. Food‐grade titanium dioxide (E171) is a widely used additive in solid and liquid food products. After oral exposure, E171 reaches blood stream and other organs such as the testicles, in which toxic effects are under research. Additionally, it is unknown if the administration of E171 by solid or liquid matrix induces differences in the biological responses. We compared the effects of E171 administration by solid or liquid matrix on testis structure, inflammatory markers and blood‐testis barrier integrity in mice. Results showed an increase in germ cells sloughing, inflammation and disruption of blood‐testis barrier after E171 administration by solid or liquid matrix; however the liquid matrix exhibited higher toxicity in those parameters than solid matrix. This study points out the relevance of E171