Host: The Japanese Society of Toxicology
Name : The 50th Annual Meeting of the Japanese Society of Toxicology
Date : June 19, 2023 - June 21, 2023
Male F344 rats were given a single intratracheal dose of tungsten carbide-cobalt, ferric oxide, titanium dioxide, zinc oxide, aluminum, alumina, crystalline silica or sintered indium tin oxide (ITO), and analyzed at 4 weeks, 13 weeks and 26 weeks after administration. Aluminum, alumina, silica and ITO increased neutrophil counts and lactate dehydrogenase (LDH) activity in the bronchoalveolar lavage fluid at all recovery periods. These changes were transient and minor in the ferric oxide, titanium dioxide and zinc oxide groups only after 4 weeks of treatment, and were not significant in the tungsten carbide-cobalt group. A similar trend was confirmed for plasma surfactant protein-D levels. Histopathological examination revealed that ITO and zinc oxide caused alveolar proteinosis via potent macrophage injury, and suppurative inflammation after 4 weeks of treatment, respectively, but the former was progressive and the latter recovered after 13 weeks of treatment. Ferric oxide, titanium dioxide, aluminum, alumina and silica showed interstitial predominant lesions, including accumulation of dust-phagocytosed macrophages in the alveolar interstitium, while tungsten carbide-cobalt was characterized by interstitial lesions with scar shrinkage, all of which tended to progress over time. Plasma metabolomics suggested an increase in fatty acid amides such as stearamide and oleamide, and these altered components may be biomarkers for lung disease due to hazardous dusts.
