PRINCIPLES OF TOXICOLOGY - Biology East Borneo

14.4 TOXICITY OF METALS 331reflex in response to orally ingested toxicants, including metals. Metals may also be excreted in thesweat and saliva or incorporated into growing hair and fingernails. The body’s attempt to excrete excessmercury and lead in the saliva often results in visible “lead lines” along the gums. However, urine andfeces remain the primary route of excretion for most ingested metals.Usually, excretion consists of a combination of these pathways, which may differ according to theroute of exposure and the speciation of the metal. Inhaled elemental mercury vapor, for instance, isexcreted in the urine, feces, and breath, while ingested elemental mercury is primarily excreted in thefeces. Methyl mercury is excreted very slowly, primarily in the feces after transformation to inorganicforms of mercury.14.4 TOXICITY OF METALSAcute ExposureThe numerous toxic effects of metals may be broadly divided into two main modes of action. The firstis related to the fact that many metals have a strong affinity for common protein moieties, such as thesulfhydryl (–SH) group. By forming covalent bonds with these groups, metals may inhibit the activityof important enzymes or disrupt the integrity of cell membranes. The other way in which metals mayexert toxicity is by competing with and displacing essential cations. For instance, lead can displace theessential element zinc in certain zinc-requiring enzymes, thus inhibiting their function.Acute toxicity is caused by a relatively large dose of a metal over a short period of time. The durationof time from initial exposure to the onset of clinical symptoms is usually short, typically on the orderof hours or days. Because of their generally disruptive effects on cell membranes, metals can producevarious localized effects at their initial point of contact. Common symptoms of acute metal poisoningby the oral route include nausea, vomiting, and damage to the intestinal mucosa and gastrointestinaltract. Acute inhalation exposure to metals often results in nose and throat irritation, coughing orwheezing, and damage to the lungs and the respiratory lining. Acute dermal exposure can result inlocalized rash and skin irritation or discoloration.Certain metals tend to target specific organs or systems. Acute exposure to high lead levels mayresult in severe neurological symptoms, including convulsions or coma, as well as disruption of thehematopoietic system, specifically heme production. The toxic effects of acute mercury poisoning canvary depending on the form present in the body. Exposure to large amounts of elemental mercuryvapors or methyl mercury is more likely to cause central nervous system effects than is exposure toinorganic mercury because of differences in transport to the brain. Methyl mercury, because of itslipophilic nature, can easily cross the blood-brain barrier while inorganic mercury cannot. Elementalmercury vapors can cross membranes with relative ease.Chronic ExposureLong-term exposure to low levels of some metals may result in gradual development of symptoms andoften, but not always, less severe symptomology than observed in acute events. Carcinogenicity, asdiscussed in the next section, may be the result of chronic exposure to a few metals. Also, some metalscan be stored for long periods within biological tissues. Lead may displace calcium in developing bone,resulting in long-term storage and slow release of this metal, which may cause toxic symptoms thatpersist long after the exposure has ceased.Damage to and impaired function of the kidneys and liver are typical effects of chronic exposureto many metals, probably due to the role of these two organs in concentrating, detoxifying, andexcreting toxic metals. Mucosal degeneration and inhibition of hepatic and renal enzymes are commonresults of chronic metal overexposure. Chronic lead, chromium, mercury, and cadmium poisoning arecommonly associated with kidney damage, while the role of the liver in copper storage and excretionmakes this organ vulnerable to damage from chronic copper exposure.