No inflammatory effects after acute inhalation of barium sulfate particles in human volunteers

Abstract

Background: Most threshold limit values are based on animal experiments. Often, the question remains whether these data reflect the situation in humans. As part of a series of investigations in our exposure lab, this study investigates whether the results on the inflammatory effects of particles that have been demonstrated in animal models can be confirmed in acute inhalation studies in humans. Such studies have not been conducted so far for barium sulfate particles (BaSO₄), a substance with very low solubility and without known substance-specific toxicity. Previous inhalation studies with zinc oxide (ZnO), which has a substance-specific toxicity, have shown local and systemic inflammatory respones. The design of these human ZnO inhalation studies was adopted for BaSO₄ to compare the effects of particles with known inflammatory activity and supposedly inert particles. For further comparison, in vitro investigations on inflammatory processes were carried out.

Methods: Sixteen healthy volunteers were exposed to filtered air and BaSO₄ particles (4.0 mg/m³) for two hours including one hour of ergometric cycling at moderate workload. Effect parameters were clinical signs, body temperature, and inflammatory markers in blood and induced sputum. In addition, particle-induced in vitro-chemotaxis of BaSO₄ was investigated with regard to mode of action and differences between in vivo and in vitro effects.

Results: No local or systemic clinical signs were observed after acute BaSO₄ inhalation and, in contrast to our previous human exposure studies with ZnO, no elevated values of biomarkers of inflammation were measured after the challenge. The in vitro chemotaxis induced by BaSO₄ particles was minimal and 15-fold lower compared to ZnO.

Conclusion: The results of this study indicate that BaSO₄ as a representative of granular biopersistent particles without specific toxicity does not induce inflammatory effects in humans after acute inhalation. Moreover, the in vitro data fit in with these in vivo results. Despite the careful and complex investigations, limitations must be admitted because the number of local effect parameters were limited and chronic toxicity could not be studied.

Keywords: Barium sulfate; Granular biopersitent particles; Human inhalation study; Induced sputum; Inflammatory markers; Particle-induced chemotaxis; Zinc oxide.