Solubility of indium-tin oxide in simulated lung and gastric fluids: Pathways for human intake

From being a metal with very limited natural distribution, indium (In) has recently become disseminated throughout the human society. Little is known 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 the liver, kidneys and spleen. 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 tract, while the solubility in the upper parts of the lungs (the respiratory tract or tracheobronchial tree) 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 slowly dissolve in the deep lungs. Considering the prolonged residence time of inhaled particles in the deep lung, this environment is likely to provide the major route for uptake of In and Sn from inhaled ITO nano- and microparticles. Although dissolution through digestion may also lead to some uptake, the much shorter residence time is likely to lead to much lower risk of uptake. - Highlights: • The deep lung environment is likely to be the principal route of metal transfer from indium-tin oxide into the bloodstream. • Indium-tin oxide is also soluble in stomach acid, but the short residence time limits metal transfer into the bloodstream. • Trypsin (and possibly other digestive enzymes) may enhance the solubility of indium-tin oxide in the digestive tract • Indium-tin oxide is inert in the upper respiratory tract, although minor fractional dissolution of tin may occur.