Threshold in the toxicology of metals: Challenges and pitfalls of the concept

Metals qualitatively dominate the chemical elements found on Earth, but life has found a use for only a minority of them. Most metals are mobilized as cations, and thereby interact and are processed by living species. Animals are exposed to environmental metals at chronic low concentrations through food, air particles, and other ways, under conditions that are too rarely reproduced in laboratory settings. Actual metal detoxification systems in animals are not many and of limited efficiency which casts doubt on the existence of any safe concentration — a threshold for nonessential metals. Hence the mechanisms of action of toxic metals at very low doses still have to be adequately addressed to provide means for knowledge-based risk assessment that is increasingly requested by diverse communities.