InhalT-90: 90 days inhalation testing with CeO2 in the rat and subsequent analysis of gene expression profiles for the early detection of toxic / carcinogenic effects
In the past ten years, toxicological characterisation and evaluation have been attaching enormous weight and interest to the technically versatile synthetic nanoparticles used in chemistry, medicine, environmental engineering, and energy technology. This development is mainly due to the fact that on account of their “viral” size, nanoparticles, in comparison to their microscale equivalents, have very large reaction surfaces and a high translocation capability when they actually act as isolated particles instead of as agglomerates. As there was an ongoing discussion of a possible tumorigenic potential of nanoparticles after inhalation, an exemplary carcinogenicity study in the rat model was suggested within the framework of the EU-project NanoREG. To exclude lung overloads, an explicitly low dose regimen ranging from 0.1 – 3 mg/m3 was chosen. This regulatory chronic study has been financed by BASF SE, and is currently performed using cerium dioxide nanoparticles (CeO2) in powder form.
Parallel to the BASF long-term project, the BMBF-funded project InhalT-90 is carried out under identical exposure conditions using a rat model and CeO2 nanoparticles as well. New innovative approaches are applied to identify early indicators of toxic and/or carcinogenic effects through gene expression analyses that allow drawing conclusions as to a change in gene expression profiles. The InhalT-90 project focuses essentially on finding answers to the question as to whether such changes can be triggered by nanoparticles or nanopowders for certain concentration ranges. A toxic effect could be identified already at a very early stage. In addition, the identification of certain recurring effects referred to as biomarkers could be transferred to other nanoparticles such that fast screenings of the toxicity of nanoparticles could be developed.
Findings of cancer cells often come at the end of a long chain of developments starting early in life through some damage to the genes or tedious long-time inflammatory reactions. The approach chosen in this project hence intends to contribute to the mechanistic clarification of a potential genotoxicity of nanoparticles.
The cerium dioxide nanoparticles selected for the purpose of the InhalT-90 project are, for example, used as additives in diesel fuels to boost combustion. The distribution of these nanoparticles in the lung and in the body is investigated by means of element analysis and particularly sensitive spectroscopic methods such as ion beam microscopy (IBM) and confocal Raman microspectroscopy (CRM).
Grant Number: BMBF - FKZ 03X0149
Duration: 01.08.2014 - 31.07.2017 (extended to 31.12.2017)