Endogenous formation of Fe-bearing particles and their differentiation from exogenous exposure

Accurately distinguishing between the endogenous formation and exogenous exposure of Fe-bearing particles (e.g., magnetic Fe particles) within biological organisms is the prerequisite for scientifically evaluating their health risks. However, this remains a challenging task due to lacking the comprehensive understanding of the endogenous formation process of Fe-bearing particles. Here, we report the formation dynamics of Fe-bearing particles under conditions closely resembling actual physiological conditions, and compare the morphological and structural differences between endogenous and exogenous Fe-bearing particles. We find that Fe-bearing particles can indeed form under physiological conditions at 37 °C. In this process, phosphate plays a crucial role in the oxidation and mineralization of iron ions. Moreover, endogenously formed Fe-bearing particles typically have a diameter of less than 8 nm, and iron is the only metal element present. Therefore, we propose that Fe-bearing particles found in the body with a diameter larger than 8 nm are mainly derived from exogenous exposure. For Fe-bearing particles smaller than 8 nm, it is necessary to combine associated elements and crystal structure characteristics to distinguish between endogenous and exogenous sources. This study provides direct evidence from endogenous metabolism for tracing Fe-bearing particles, especially magnetic iron particles, within the human body.