Solubility of Indium-Tin Oxide in simulated lung and gastric fluids: Pathways for human assimilation NERC grant NE/L001896/1

From being a metal with very limited natural distribution,indium (In) has recently become disseminated throughout the human society. Little is know of how In compounds behave in the natural environment, but recent medical studies link exposure to In compounds to elevated risk of respiratory disorders. Animal tests suggest that exposure may lead to more widespread damage in the body, notably testicular cancer. In this paper, we investigate the solubility of the most widely used In compound, indium-tin oxide (ITO) in simulated lung and gastric fluids in order to better understand the potential pathways for metals to be introduced into the bloodstream. Our results show significant potential for release of In and tin (Sn) in the deep parts of the lungs (artificial lysosomal fluid) and digestive fluids, while the solubility in the upper parts of the lungs (the respiratory tract or tracheobronchial tree, simulated by Gamble's solution) is very low. Our study confirms that ITO is likely to remain as solid particles in the upper parts of the lungs, but that particles are likely to at dissolve in the deep lungs. Considering the prolonged residence time of inhaled particles in the deep lung and the high solubility of ITO in artificial lysosomal fluids, the environment of the deep lungs is likely to provide the major route for assimilation of In and Sn from inhaled ITO nano- and microparticles. Digestion is likely to also lead to assimilation through dissolution in the stomach and interaction with digestive enzymes in the pancreatic juice. However, this route is less likely to lead to substantial assimilation because of the much shorter residence times of particles in the digestive system.

从原本在自然界中分布极为有限的金属元素，铟（In）近年来已广泛分布于人类社会。关于铟化合物在自然环境中的行为所知甚少，但近期医学研究表明，接触铟化合物与呼吸系统疾病风险增加有关。动物实验表明，接触铟化合物可能导致体内更广泛的损害，尤其是睾丸癌。在本研究中，我们探讨了最广泛使用的铟化合物——氧化铟锡（ITO）在模拟肺和胃液中溶解度的研究，以期更好地理解金属进入血液循环的潜在途径。我们的研究结果显示，在肺深部（模拟人工溶酶体液）和消化液中，铟（In）和锡（Sn）有显著的释放潜力，而在肺的上部（呼吸道或气管-支气管树，由 Gamble 溶液模拟）的溶解度非常低。本研究证实，ITO 在肺的上部可能以固体颗粒的形式存在，但在肺深部，颗粒可能溶解。鉴于吸入颗粒在肺深部的长期停留时间和 ITO 在人工溶酶体液中的高溶解度，肺深部环境可能为吸入的 ITO 纳米和微颗粒中铟和锡的吸收提供主要途径。消化过程也可能通过在胃液中溶解并与胰腺液中的消化酶相互作用，导致铟和锡的吸收。然而，由于颗粒在消化系统中的停留时间相对较短，这一途径不太可能导致显著的吸收。