ABSTRACT
Metals can have a variety of physiological effects, and it is often possible to demonstrate the toxicity of any given metal in any given organ, provided that the dose is both high and prolonged (but not so high and prolonged that the primary target organ receives a fatal dose). Essential elements may be toxic at a dose that overwhelms homeostatic controls on absorption and excretion, and the mechanism of toxicity is commonly related to an essential physiological role of the metal (e.g., control of osmolarity for sodium consumption in excess of water intake, neurotransmission for potassium consumption in excess of water intake, redox reactions for iron intake in excess of
protein binding capacity). Physiological actions of nonessential elements include substituting for essential elements in enzymatic reactions, energy metabolism, neurotransmission, structural components (bone), reacting covalently or noncovalently with enzymes, membranes, DNA, and stimulating the production of active oxygen species [257]. The variety of physiological effects makes it difficult to determine which action is responsible for toxicity in the most sensitive target organ. In some cases, organs are most sensitive for a biochemical reason (e.g., thallium interferes with energy metabolism, and target organs are those with the highest energy requirement); in other cases, the most sensitive organ is simply the organ in which the accumulation is greatest (e.g., cadmium and uranium accumulate in the kidneys, which are the target organs). Metals can interact with each other either to enhance toxicity (e.g., by affecting the same target organ) or to reduce toxicity (e.g., by stimulating defense mechanisms); this must be particularly kept in mind for the interpretation of animal experiments (e.g., levels of calcium, iron, and zinc should be controlled in investigations of cadmium toxicity) and epidemiological studies (e.g., fluoride reduces the incidence of dental caries; therefore, a population with the lowest fluoride exposure is likely to have the highest exposure to mercury and other metals used in dental restorations). The number of combinations
subpopulation is identified (e.g., individuals with insufficient intake of specific nutrients) or when a specific mechanism is revealed. Few treatments for metal toxicity are based on interfering with the mechanism of action; rather, measures are designed to reduce gastrointestinal absorption (from acute poisoning) by removing or binding the metal or are designed to speed elimination from the body (e.g., chelation therapy) [203]. Prevention of excessive exposure is generally the best way to reduce the potential for metal toxicity.
