Since ancient times exposure to metallic agents has been associated with adverse health effects. Many metals (iron, copper, cobalt, zinc, manganese, molybdenum) are co-factors for biological reactions; so, both deficiencies and excessive exposures to these essential metals may cause disease. However, some metals or metalloids (lead, cadmium, mercury, arsenic, uranium) are non-essential and, hence, even low degrees of exposure to these elements may lead to disease. The toxicological effects of metallic agents depend on the chemical nature (« speciation ») of the metal, the exposure dose (concentration x duration), the exposure conditions (route and rate of exposure, co-exposures) and host factors (age, genetics, immunology). An important aspect in metal toxicology is the toxicokinetic behaviour of metals, especially the rapidity of their elimination from the body and, a contrario, the degree to which certain metals may accumulate in some tissues (brain, kidney, bone). Finally, although we have a relatively solid knowledge of the clinical effects of high or moderate exposures to toxic metals, many gaps still remain in our knowledge and understanding of the possibly subtle consequences of low environmental exposures to metallic agents. This uncertainty about the risks of very low exposures to potentially toxic agents sometimes leads to anxiety and also unfounded therapies for non-existing risks.
In industrially developed countries, exposures to the most toxic metals (such as lead, cadmium, mercury, arsenic) are generally well controlled and overt poisoning by these agents has become rare. However, in developing countries, high environmental or dietary contamination by metals may affect entire populations, especially children. The existence of such contamination, let alone the health impact of environmental pollution, is often completely ignored.
Substantial exposure to toxic metals and, hence, metal poisoning may occur in the workplace, especially in poorly regulated workplaces. It should be realized that, on the one hand, occupational exposure to metals is not confined to metal mining or metallurgy and that, on the other hand, disease in metal-exposed workers may be due to non-metallic agents. Sources of exposure outside the workplace must also be envisaged, such as the use of folk medicines or cosmetics, contamination of the home environment, and even criminal intent. To discover such rather infrequent causes of disease it is most important first to think about the possibility of a toxic etiology and then to question the patient thoroughly about his or her habits, including consumption of products purchased via the internet, past and current work and hobbies, travel to heavily polluted areas, and other unusual or peculiar circumstances.
A suspected toxic exposure must be documented by appropriate laboratory tests. In general, measuring the concentration of metals in a spot sample of urine (nowadays generally performed by ICP-MS thus allowing the quantification of multiple metals in a single sample) is sufficient to demonstrate or exclude a high ongoing exposure to metallic agents. A blood analysis may also be requested, but this is not necessarily more sensitive for the purpose of identifying a toxic etiology. When laboratory tests reveal a high exposure to a particular metal, it is important to verify in the scientific literature whether the symptoms and signs of the patients can be explained by this metal.
There are, of course, situations in which assessing current or recent exposure will not necessarily reveal a toxic etiology. This is the case for conditions with a long latency between exposure and disease manifestations, such as cancer, autoimmune disease or neurodegenerative disorders. In such instances, proving a causal relation, if any, between the disease and occupational or environmental exposure is much more difficult and one has to rely on historical data and existing epidemiological evidence. Sometimes, it is possible to document an abundant presence of metallic agents in tissue biopsies and this may provide suggestive arguments for an environmental etiology of the disease.
Other instances without a clear relation between exposure level and disease manifestations are found for diseases caused by immunological sensitization, such as allergic contact dermatitis and some forms of bronchial asthma or interstitial lung disease, which may be caused by a number of metals, most notably platinum, nickel, chromium, cobalt or beryllium. In such immune-mediated diseases, measuring concentrations of the suspected metal in urine or blood will generally not contribute to discover the etiologic factor or to establish a causal relation, because the disease manifestations occur with normal or even low exposure levels of the offending agent. However, demonstration of specific sensitization to metallic agents may be obtained by in vivo tests (e.g. skin prick tests to document allergy to complex platinum salts or patch testing to document allergy to nickel, chromium or cobalt) or ex vivo tests (e.g. lymphocyte proliferation test for chronic beryllium disease).
Finally, some patients with functional somatic syndromes – mainly multiple chemical sensitivity, but also chronic fatigue syndrome or fibromyalgia – believe that their condition is due to « metal allergy » or « chronic low level heavy metal poisoning », with mercury-containing dental fillings often being incriminated. These beliefs often rest on alarming messages found on internet sites and they are sometimes reinforced by experts specialized in environmental toxicology (so-called clinical ecologists), who may undertake unwarranted and inefficient treatments, such as chelation therapy. The complaints of these patients must be taken seriously and exogenous causes, including toxic exposures, must be considered among other possible etiologies. However, if no excess metal concentrations can be documented, if no sensitization can be demonstrated to a specific agent, and certainly if no plausible sources of metal exposure can be identified, then the patient should be vigorously reassured that his / her condition is not due to metal poisoning. This is not always easy.