## 8 The Distinction between Essential and Non-Essential Metal Ions  
In the past, analytical instrumentation faced limitations in sensitivity, and scientific reports focused mainly on total metal ion concentrations in biological tissues. Major ad vances in instrumentation and methodologies, such as the use of fluorescent chelating agents, have documented an uneven distribution of metal ions and established fluctuations of metal ion concentrations in cellular space and time [67]. Modern analytical instrumentation, in particular inductively coupled plasma-mass spectrometry (ICP-MS), is sensitive enough to detect the presence of almost all the natural elements in a human body [68]. This achievement highlights yet another significant area, namely the role of \"non-essential elements\". An essential element is clearly linked to functions. However, the term \"non-essential element\" is not synonymous with \"non-functional element\". We are not even certain whether the list of essential metals for humans (or life) is complete as uncertainty lingers about the functions of some metals present at very low abundance. For example, chromium is classified as an essential metal in many countries, although its molecular mode of action remains unknown [69]. Chromium biology illustrates opposing functions of different oxidation states of metal ions. Chromium(III) is considered essential while chromium(VI) in the form of chromate is a carcinogen. Moreover, our knowledge of the functions of metalloids--chemical elements classified by having chemical properties between those of metals and non-metals--is incomplete. Essential roles of some elements have been found only in the last decade, e.g., bromine for humans or lanthanides for some bacteria [70]. Variations in the complement of essential elements used in bacteria compared to humans are also gaining recognition as being important as the human body lives in symbiosis with trillions of cells from microorganisms--in our gut, within our airways and upon our skin. To feed the commensal microbiota properly, elements that are not essential to us are needed by microorganisms. Most recently, 24 bacterial species in our gut microbiome were found to require tungsten, an element that is not essential to humans and normally occurs at extremely low concentrations [71]. These bacteria are involved in detoxifying aldehydes produced in the gut from our diet. Hence, there is a constant chemical and biochemical tug-of-war between the host and its microorganisms in terms of controlling metal availability and ensuring that each obtains its proper share or does not obtain its share as in the case of parasitic microorganisms, which also need essential metal ions for survival. Furthermore, some non-essential elements (strontium, rubidium, nickel) are present at higher amounts than some essential elements in humans. The consequences are largely unknown. Non-essential elements are certainly not passive bystanders; some are mutagens and suspected carcinogens, others compete with essential metals for binding sites. Moreover, if there is no homeostatic control for them--as is often the case, because many have only been introduced to our environment since the industrial revolution and hence have not exerted selection pressure during our evolution: What are their safe upper limits? We know even less about them, largely because we have considered them as non-functional. For many of them we do not know the consequence of their natural presence or their presence upon exposure, except for some toxic ones, and even in these cases our knowledge is limited, e.g., the accumulation of cadmium in the human body with age and its effect on ageing healthily [72].