Toxicokinetics of titanium dioxide nanoparticles using in vitro and in vivo models (ongoing)

Last updated:
24 February 2010
This project will generate baseline data on the toxicokinetics of titanium dioxide nanoparticles as a basis for future studies. The in vitro work will assess the potential of titanium dioxide nanoparticles to cross the gut epithelial barrier. The in vivo study will be used to generate absorption, distribution, metabolism and excretion data, which will be validated for future safety assessments.
Study duration: February 2010 to December 2012
Project code: FS231025 (T01062)
Contractor: The Food and Environment Research Agency (FERA)

Background

There is increasing interest in the use of nanomaterials (small particles that measure up to 100 nanometres in diameter) in relation to food and animal feed. The chemical properties of such materials can be different from those at the larger scale; this is because nanomaterials have a relatively larger surface area which can make them more chemically reactive.

In its draft scientific opinion on nanoscience and nanotechnologies in relation to food and feed safety, The European Food Safety Authority (EFSA) drew attention to the gaps that exist in understanding the risks posed by nanomaterials and highlighted the need for more research aimed at understanding how to assess and manage the risks they pose. In 2008, during discussions of the EFSA draft scientific opinion, The Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment (COT) expressed disappointment and concern regarding the paucity of basic toxicological data on nanomaterials. The COT stressed that there was an urgent need to obtain toxicological data on a representative selection of nanomaterials.

Research Approach

A Caco-2 and M-cells co-culture in vitro model will be used to assess the ability of titanium dioxide nanoparticles to cross the gut epithelial barrier. The translocation of the nanomaterial will be determined by means of mass spectrometry (HDC-ICP) in combination with limited electron microscopy and Dynamic Light Scattering (a technique used to determine the size and distribution profile of small particles in suspension).

The in vivo study will collect ADME data for 3 particle sizes of nano-titanium dioxide and one micron sized particle using a rat model. The study will involve oral gavage of titanium dioxide nano- and micro-particles to adult male rats. Samples of blood, urine and faeces will be collected at appropriate time intervals after dosing. Tissue samples will be collected and quantified using mass spectrometry (ICP-MS). This will be coupled with limited microscopy investigations into the particulate nature of titanium dioxide to ascertain whether the titanium dioxide remains as free nanoparticles or agglomerates in biological samples.

Analysis of the data on concentration of titanium in blood will be used to determine pharmacokinetic constants relating to absorption and distribution for each size of particle. Data from analysis of urine and faeces will be used to estimate changes in excretion of titanium that may be associated with different sizes of particle. Finally, data for titanium in different tissues will be used to identify any changes in tissue distribution that may be related to particle size.

Results

Additional Info

Dissemination

Published Papers