MetalSafety – Development of evaluation concepts for fibrous and granular metal compounds – bioavailability, toxicological efficacy profiles and comparative in vitro, ex vivo and in vivo studies
Metals and their compounds are ubiquitously present in our daily life, for example as components of stainless steel, catalysts, and pigments. Furthermore, metal compounds are being used in numerous innovative processes such as inks for 3D printing or as semiconductors in electronic engineering and medical devices. Apart from granular compounds of different particle sizes, the use of metal-based fibrous materials, so-called nanowires, in various products is increasing. However, many metals and their compounds reveal inflammatory and/or even carcinogenic potentials. Hereby, the toxicity often depends on the respective metal species; decisive factors are oxidation state and solubility and – in case of metal particles – their size (nano-/micro-scaled) as well as structure (granular or fibrous).
The aim of the scientific project MetalSafety is to design comparatively easy-to-use in vitro models for the toxicological evaluation and grouping of different metal-based compounds, which differ in their solubility and bioavailability. One main focus within this project lies on metal-based nanowires, since their toxicological potentials are hardly known. The toxicological profiles of these fibrous structures will be compared to the respective nano-scaled granular as well as water-soluble compounds.
For this purpose, an air-liquid interface (ALI) exposure system will be established to apply fibrous as well as granular structures on in vitro cellular models and to directly measure the deposited mass of the respective compound. The toxicological “finger prints” will be assessed using gene expression profiles, complemented by solubility, uptake and genotoxicity studies.
Afterwards, the results will be compared to complex ex vivo as well as in vivo studies and evaluated with regard to their predictability of the toxicological potential, the mode of action and the dose-response relationship. Species differences between human and rat with respect to toxicodynamic interactions will be obtained on the level of cell culture and precision cut lung slices (PCLS). The respective results will finally compared with data from in vivo studies in rats.
Altogether, the identification of relevant modes of actions by different metals and their compounds is an important prerequisite for a scientific-based derivation of workplace and environmental exposure limit values, including new, innovative metal fibres and granular metal compounds.
Grant Number: BMBF - 03XP0211
Duration: 01.03.2019 - 28.02.2022 (extended to 31.05.2023)