Toxicological and hygienic assessment of titanium dioxide nanoparticles as a component of E171 food additive (review of the literature and metahanalysis)

Abstract

The review focuses on exposure values, biological availability, toxic effects, and risks caused by nanoparticles of TiO2 under their oral introduction into a body as a food coloring agent or E171 food additive, or as a significant component in its structure. According to toxicological assessment performed by JECFA in 1969, TiO2 is considered to be insignificantly hazardous. However, at present experts employed by several foreign and international organizations that deal with food safety believe that the assessment should be reviewed as there are new scientific data on adverse effects produced by nano-sized TiO2 on a human body. Overall intake of TiO2 by people with food products, cosmetics (tooth pastes) and medications can vary from 0.5 to 5 mg a day; children aged 3-9 and teenagers aged 10-17 are the most exposed population groups. Despite insignificant intestinal absorption of TiO2 nano- and micro-sized particles, a lot of scientific works revealed their overall toxic effects produced on a body under oral and intragastric introduction. Detected effects produced by TiO2 include organotoxic (mostly hepatotoxic) ones, genotoxicity, immune toxicity, reproductive toxicity, and neurotoxicity. Still, there haven't been any data on carcinogenic effects produced by TiO2 when it is introduced into the gastrointestinal tract. Presumably, some effects produced by TiO2 nanoparticles are mediated by their local impacts on the lymphoid tissue associated with an intestinal mucosa as well as on the structure and activity of intestinal microbiocenosis, and nanoparticles are not necessarily absorbed in the intestines in the process. We performed meta-analysis of 64 articles (published over 2007-2019) which complied with criteria related to scientific authenticity and completeness; the meta-analysis revealed that a probable NOAEL for nano-sized TiO2 amounted to less than 10 mg/kg of body weight a day, and a daily reference safe dose of the substance is estimated as being equal to 0.1 mg/kg of body weight. Given all the above-mentioned, a risk caused by TiO2 intake as E171 food additive depends on nanoparticles fracture in its composition and it can be unacceptably high if this fracture exceeds 10 % of the overall TiO2 mass. Therefore, it is necessary to control and regulate TiO2 nanoparticles contents in the structure of E171 food additive that is applied in food industry.