Occupational and toxicological relevance of the solubility of dusts

Status:

ongoing

Aims:

The vast majority of fatal health impairments caused by occupational exposures result from the inhalation of particles. Which particle properties predict adverse health effects upon inhalation is not yet fully understood. Biological solubility defined as solubility within the lung and/or within cells may be a key determinant of particle toxicity in humans and could enable rapid hazard assessment of novel, previously untested particles.

This concept must be clearly distinguished from water solubility, which has traditionally been used to define biopersistence (e.g., in TRGS * 527). In line with this, the DF4nanoGrouping * approach of the European Union proposes grouping nanomaterials according to their specific modes of action. However, validated methods for assessing biological solubility are currently lacking.

The proposed project aims to establish a foundation for assessing both the biological solubility of particles and their toxicological effects. Within a cell-based system, particles with varying degrees of biological solubility and known or suspected toxic effects will be synthesized, thoroughly characterized, and tested. The study will include dusts considered to be "insoluble" such as zinc oxide, barium sulfate, and alpha-aluminum oxide (corundum) for which some degree of biological solubility has been described or is suspected. The predictive value of biological solubility for toxic effects will be assessed using standard cell-based assays already established at the IPA (Institute for Prevention and Occupational Medicine). In addition, biomarkers will be identified that could later be used in human exposure studies for effect monitoring.

* Technische Regeln für Gefahrstoffe (TRGS)
** decision-making framework for the grouping and testing of nanomaterials

Activities/Methods:

Extensive investigations of the solubility of so-called "insoluble" particles under simulated in vivo conditions – and the correlation of these results with occupational exposure limits and occupational health requirements are at the core of this project.

Soluble and insoluble dusts (particles) will be produced, subjected to detailed physicochemical characterization, and their effects subsequently compared using a functional in vitro assay (PICMA*) that has already proven successful in previous studies. This test models particle-induced migration of inflammatory cells (macrophages and granulocytes) into the lung. In addition, changes in gene expression of these immune cells will be examined. On the protein level, the generation of biomarkers related to chemotaxis and inflammation will be quantified from cell culture supernatants using ELISA**. Finally, based on the collected data, a toxicological evaluation of the particles will be conducted.

* Particle-Induced Cell Migration Assay
** Enzyme-linked Immunosorbent Assay

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