Pharmaceutical/food grade titanium dioxide particles are absorbed into the bloodstream of human volunteers

Abstract

BackgroundExposure to persistent engineered nano and micro particles via the oral route is well established. Animal studies have demonstrated that, once ingested, a small proportion of such particles translocate from the gastrointestinal tract to other tissues. Exposure to titanium dioxide is widespread via the oral route, but only one study has provided indirect evidence (total titanium analyses) of absorption into the blood stream in humans. We sought to replicate these observations and to provide additional evidence for particulate uptake.FindingsHuman volunteers with normal intestinal permeability were orally administered 100 mg pharmaceutical/food grade titanium dioxide. Blood samples were collected from 0.5 to 10 h post ingestion and analysed for the presence of reflectant bodies (particles) by dark field microscopy, and for total titanium by inductively coupled plasma mass spectrometry (ICP-MS). Blood film analyses implied early absorption of particles (2 h) with a peak maximum at 6 h following ingestion. The presence of these reflectant particles in blood roughly mirrored the levels of total titanium by ICP-MS, providing good evidence for the latter being a measure of whole particle (titanium dioxide) absorption.ConclusionsThis study shows that a fraction of pharmaceutical/food grade titanium dioxide is absorbed systemically by humans following ingestion. It confirms that at least two routes of particle uptake may exist in the human gut- one proximal and one distal. Further work should quantify human exposure and uptake of such persistent particles.

Imaging flow cytometry assays for quantifying pigment grade titanium dioxide particle internalization and interactions with immune cells in whole blood

“…Interestingly, the imaging flow technique detected low levels of “reflectance‐positive” cells in all of the donor's baseline samples (i.e., no added TiO 2 ). This is likely to be genuine background TiO 2 as implied by prior ICP‐MS analyses of baseline human blood samples 7. Food, toothpaste, nutraceuticals, and pharmaceutical products account for the average UK adult ingesting around 3 mg TiO 2 per day 6, some of which reaches the blood stream 7, 8.…”

“…This is likely to be genuine background TiO 2 as implied by prior ICP‐MS analyses of baseline human blood samples 7. Food, toothpaste, nutraceuticals, and pharmaceutical products account for the average UK adult ingesting around 3 mg TiO 2 per day 6, some of which reaches the blood stream 7, 8. Hence, due to widespread daily human exposure to TiO 2 it is likely that baseline blood samples will always have a degree of ‘natural background’ signal, so it is difficult to ascertain with certainty where the limit of detection exists for imaging flow cytometry.…”

“…The research of our group with TiO 2 has focused on the oral route in terms of quantifying human exposure, gastrointestinal uptake and, more recently, describing absorption into the circulation 2, 3, 4, 5, 6, 7. In common with other groups we have used inductively coupled plasma (ICP)‐based techniques to quantify titanium as well as reflectance microscopy, including darkfield microscopy, to detect TiO 2 particles at the cellular level 7, 8. Recently, we showed that darkfield microscopy of blood films allows easy semiquantitative assessment of TiO 2 in the human circulation if validated against ICP measures of Ti in the same samples 7.…”

“…In common with other groups we have used inductively coupled plasma (ICP)‐based techniques to quantify titanium as well as reflectance microscopy, including darkfield microscopy, to detect TiO 2 particles at the cellular level 7, 8. Recently, we showed that darkfield microscopy of blood films allows easy semiquantitative assessment of TiO 2 in the human circulation if validated against ICP measures of Ti in the same samples 7. Nonetheless, a number of important questions remain unanswered in terms of the absorption of TiO 2 particles into the circulation of humans, notably; Are the TiO 2 particles associated with cells?…”

Rationales for the Food and Agricultural Applications of Nanotechnology and Exposure Science Required for Its Regulation

“…For example, scientists have determined that polystyrene beads of up to 240 nanometers in diameter can pierce the human placental barrier, with possible harmful consequences for fetal development (WICK ET AL, 2014). Furthermore, one of the very few human volunteer studies about the effects of ingesting Nano-titanium dioxide has documented how those bio-accumulating ENMs pass from the human gut into the bloodstream (Pele et al, 2015). Nanoscale titanium dioxide has been detected in a wide range of foods commercialized in Australia, including candy (Reed et al, 2015).…”