The toxicological effects of particles relevant for occupational medicine: Influence of particle size, particle shape, and particle surface

Status:

completed 06/2021

Aims:

Health risks caused by particles and fibers constitute still an important challenge for health protection at the workplace. Although particles are responsible for the majority of deaths resulting from occupational diseases, particles with a variety of parameters have been recently developed and commercially introduced into the market for many new applications, especially in the field of nanotechnology, for example for surface coating or medical and cosmetic applications, without any toxicological investigations on possible health hazards. A targeted synthesis of inorganic oxide particles, using various synthesis strategies, will enable us to characterize chemically identical particles with different size, surface and shape, in terms of their physicochemical, biological and toxicological effects. The project is focused primarily on particle parameters which lead to an attraction (chemotaxis) of inflammatory cells. These can be specific effects that already occur below toxic particle concentrations (in the subtoxic range).

Activities/Methods:

• Synthesisation of the following particle systems, of particular importance in occupational medicine, in different size and shape: titanium dioxide, silicon dioxide (as crystalline quartz and as amorphous silica) and zinc oxide.
• Detailed characterisation in terms of their colloidal stability and purity.
• In vitro incubating of relevant cells from the pulmonary tract (lung macrophages) with these particles.
• Analytical study of generated inflammation factors and parallel recording in regard to the accumulation of inflammatory cells using an in vitro lung cell model (PICMA).
• Testing of the obtained data concerning correlation between particle parameters and particle dose and the strength of the immune reactions of macrophages (chemotaxis, release of biomarkers of inflammation).

Results:

With the exception of quartz particles, various oxide particle systems (silica, ZnO, TiO2 particles) with defined particle shape, size and crystallinity have been successfully synthesized using preparative methods. After subsequent examination of colloidal stability and purity, the particles were compared for potential toxicity. The in vitro analysis of cell reactions on particles (of all particle types) of alveolar macrophages (in particular the influence of particle size and shape) did not reveal any indications of inflammatory reactions that could serve as early markers of the subtoxic range. For the project, there were only indications of a possible apoptosis-inducing effect, due to ZnO particles, and a possible apoptosis-inhibiting effect, due to TiO2 particles. Overall, only minor risks and minor significant differences in the sub-toxic range could be determined for synthesized particles (silica, TiO2, ZnO) with simultaneous modifications of various particle parameters within the particle systems. As expected, ZnO particles were more toxic than, practically insoluble, silica and TiO2 particles, due to the release of free Zn²⁺ ions into biological media.

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