Critical review of public health regulations of titanium dioxide, a human food additive

Abstract

From 1916 to 2011, an estimated total of 165 050 000 metric tons of titanium dioxide (TiO2) pigment were produced worldwide. Current safety regulations on the usage of the TiO2 pigment as an inactive ingredient additive in human food are based on legislation from 1969 and are arguably outdated. This article compiles new research results to provide fresh data for potential risk reassessment. However, even after 45 years, few scientific research reports have provided truly reliable data. For example, administration of very high doses of TiO2 is not relevant to daily human uptake. Nevertheless, because dose makes the poison, the literature provides a valuable source for understanding potential TiO2 toxicity after oral ingestion. Numerous scientific articles have observed that TiO2 can pass and be absorbed by the mammalian gastrointestinal tract; can bioconcentrate, bioaccumulate, and biomagnify in the tissues of mammals and other vertebrates; has a very limited elimination rate; and can cause histopathological and physiological changes in various organs of animals. Such action is contrary to the 1969 decision to approve the use of TiO2 as an inactive ingredient in human food without an established acceptable daily intake, stating that neither significant absorption nor tissue storage following ingestion of TiO2 was possible. Thus, relevant governmental agencies should reassess the safety of TiO2 as an additive in human food and consider establishing an acceptable maximum daily intake as a precautionary measure. Integr Environ Assess Manag 2015;11:10–20. © 2014 The Author. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of SETAC.

Review: the potential impact of surface crystalline states of titanium for biomedical applications

“…Consistently with in vitro studies, experiments in mice also showed that titanium induces increased expression of pro-inflammatory cytokines (TNFα, IL-1β and IL-6), chemokines (CCL2 and CCL3), NLPR3, ROS and RNS (Huang et al, 2015, Jovanovic, 2015, Sang et al, 2012, Warme et al, 2004, Yazdi et al, 2010.…”

Is nano safe in foods? Establishing the factors impacting the gastrointestinal fate and toxicity of organic and inorganic food-grade nanoparticles

“…55 Typically, the TiO 2 ingredients utilized in the food industry as lightening agents are optimized to have particle sizes of 100-300 nanometers to increase their light scattering properties. 56 Nevertheless, these ingredients contain a range of different particle sizes and there may be a significant proportion of particles with diameters <100 nm, which can therefore be considered to be nanoparticles. 57 For example, the mean diameter of the particles in food grade TiO 2 (E171) powders obtained from several manufacturers was reported to be about 110 nm, with >36% of the particles being below 100 nm.…”

“…56 Acute and subchronic studies of the oral toxicity of TiO 2 nanoparticles have been carried out in rodents. A single oral dose of TiO 2 nanoparticles (25, 80, or 155 nm at 5000 mg/kg body weight) resulted in their accumulation in the liver, spleen, kidney, and lung tissues of mice, and also led to hepatic injury, nephrotoxicity and myocardial damage.…”

Nanoscience and nanotechnologies for biobased materials, packaging and food applications: New opportunities and concerns

“…The amount of TiO2 that gets absorbed by the body is actually extremely low (Cho, Kang et al 2013;Jovanović 2015). This was first proved by detecting up to 43.2±4.6 µg/L of TiO2 in the blood of volunteers after oral ingestion of 22.9 mg of TiO2 incorporated in gelatin capsules (Böckmann, Lahl et al 2000).…”