The chronic exposure of human populations to toxic metals remains a global public health concern. Although chronic Cd exposure is linked to kidney damage, osteoporosis and cancer, the underlying biomolecular mechanisms remain incompletely understood. Since other diseases could also be causally linked to chronic Cd exposure, a systems toxicology-based approach is needed to gain new insight into the underlying exposure-disease relationship. This approach requires one to integrate the cascade of dynamic bioinorganic chemistry events that unfold in the bloodstream after Cd enters with toxicological events that unfold in target organs over time. To this end, we have conducted a systematic literature search to identify all molecular targets of Cd in plasma and in red blood cells (RBCs). Based on this information it is impossible to describe the metabolism of Cd and the toxicological relevance of it binding to molecular targets in/on RBCs is elusive. Perhaps most importantly, the role that peptides, amino acids and inorganic ions, including HCO₃⁻, Cl⁻ and HSeO₃⁻ play in terms of mediating the translocation of Cd to target organs and its detoxification is poorly understood. Causally linking human exposure to this metal with diseases requires a much better integration of the bioinorganic chemistry of Cd that unfolds in the bloodstream with target organs. This from a public health point of view important goal will require collaborations between scientists from different disciplines to untangle the complex mechanisms which causally link Cd exposure to disease.

人类长期接触有毒金属仍然是一个全球公共卫生问题。尽管慢性镉暴露与肾损伤、骨质疏松症和癌症有关，但其潜在的生物分子机制仍未完全了解。由于其他疾病也可能与慢性 Cd 暴露有因果关系，因此需要一种基于系统毒理学的方法来获得对潜在暴露与疾病关系的新见解。这种方法需要将镉进入后在血流中展开的一连串动态生物无机化学事件与在靶器官中随时间展开的毒理学事件相结合。为此，我们进行了系统的文献检索，以确定血浆和红细胞 (RBC) 中 Cd 的所有分子靶标。基于这些信息，不可能描述 Cd 的代谢，并且它与 RBC 中/上的分子靶标结合的毒理学相关性是难以捉摸的。也许最重要的是，肽、氨基酸和无机离子（包括 HCO）的作用₃ ^-、Cl ^-和HSeO ₃ ^-在介导Cd 向靶器官的易位及其解毒方面的作用知之甚少。要将人类接触这种金属与疾病联系起来，需要更好地整合在血液中展开的 Cd 的生物无机化学与靶器官。从公共卫生的角度来看，这一重要目标将需要来自不同学科的科学家之间的合作，以解开将镉暴露与疾病因果联系起来的复杂机制。