Toxicokinetics and toxicodynamics of iron poisoning

Iron is a unique poison because it is not a xenobiotic. It is an essential element and highly reactive. Because of the critical dependence upon iron and its potential to damage tissues, elaborate mechanisms have evolved for its efficient absorption, transport, cellular uptake, storage and conservation. These are incompletely understood with even less being known after the ingestion of an overdose. Thus little is known of iron's toxicokinetics. Less is known regarding its absorption. A saturable active receptor mediated mechanism has been described, however, a passive mechanism is speculated to exist. After overdose, the amount absorbed is unknown but is likely in the order of 10%. Transferrin capacity is saturated after the absorption of a toxic dose resulting in much of the circulating iron being hydrated ferric ion. The liver clears most of the circulating iron and the plasma half-life after overdose is similar to the 4-6 h observed after therapeutic dosing. There is no mechanism for iron excretion. The toxicodynamics are a consequence of the chief mechanism for iron-induced tissue damage, free radical production with resultant lipid peroxidation. Therefore target organs and tissues are those exposed to high concentrations of iron and have a high metabolic activity. These are the gastrointestinal epithelium, cardiovascular system and the liver. Five distinct clinical phases are recognized: Gastrointestinal Toxicity, Relative Stability, Circulatory Shock and Acidosis, Hepatotoxicity and Gastrointestinal Scarring. Rational treatment of iron poisoning requires a thorough understanding of its toxicokinetics and toxicodynamics.