Symptoms of acute elemental mercury inhalation occur within hours of exposure and consist of cough, chills, fever, and shortness of breath. GI complaints include nausea, vomiting, and diarrhea accompanied by a metallic taste, dysphagia, salivation, weakness, headaches, and visual disturbances. Chest radiography during the acute phase may reveal interstitial pneumonitis and both patchy atelectasis and emphysema. Symptoms may resolve or progress to acute lung injury, respiratory failure, and death. Survivors of severe pulmonary manifestations may develop interstitial fibrosis and residual restrictive pulmonary disease. The acute respiratory symptoms may occur concomitantly with or lead to the development of subacute inorganic mercury poisoning manifested by tremor, renal dysfunction, and gingivostomatitis.13,44,75 Thrombocytopenia may also occur during the acute phase.31
Although acute exposure to elemental mercury vapor occurs most commonly in the occupational setting, poisonings caused by mishandling of the metal in the home are well reported.16,40,59,89 In fact, attempts at home metallurgy using metallic mercury have resulted in fatalities with ambient air concentrations of mercury as high as 0.9 mg/m3 (National Institute for Occupational Safety and Health recommended exposure level 8-hour time-weighted average 0.05 mg/m3 for mercury vapor).15 The lethal dose of inhaled elemental mercury has not been determined. As with other inhaled toxins, younger individuals may be more sensitive to the pulmonary toxicity of mercury vapor.59 Although pulmonary toxicity from elemental mercury usually results from inhalation of vapor, massive endobronchial hemorrhage followed by death has occurred secondary to direct aspiration of metallic mercury into the tracheobronchial tree.109
Gradual volatilization of elemental mercury results in chronic toxicity from improper handling, such as vacuuming spilled mercury.84
The clinical importance of volatilized metallic mercury from dental amalgams for both the dentist and patient has been a point of contention. The preponderance of evidence refutes the idea that dental amalgam causes mercury poisoning. Several comprehensive reviews of the subject conclude that (1) occupational exposure to mercury from dental amalgam is acceptably low, provided that recommended preventive measures such as adequate ventilation are adhered to; (2) the quantity of mercury vaporized from dental amalgam by mechanical forces, such as chewing, is clinically insignificant; and (3) only in very rare cases will immunologic hypersensitivity to mercury amalgam (manifested as cutaneous signs and symptoms and confirmed by patch testing) necessitate removal of the amalgam.27,29,30,50,88
Unusual cases of chronic toxicity have resulted from intentional subcutaneous or IV injection of elemental mercury (see Figs. 5-6 and 96–1).39,61 Aside from management of local and systemic mercury toxicity, local wound care and excision of deposits of mercury are additional therapeutic challenges presented by these cases. Serial or repeat radiographs are useful in guiding the removal of the radiopaque deposits.
Anteroposterior (A) and lateral (B) views of the elbow after an unsuccessful suicidal gesture involving an attempted intravenous injection of mercury in the antecubital fossa. Note the extensive subcutaneous mercury deposition, which was partially removed by surgical intervention. (Images contributed by Diane Sauter, MD.)
Acute ingestion of mercuric salts produces a characteristic spectrum from severe irritant to caustic gastroenteritis. Immediately after the ingestion, a grayish discoloration of mucous membranes and metallic taste may accompany local oropharyngeal pain, nausea, vomiting, and diarrhea followed by abdominal pain, hematemesis, and hematochezia. The lethal dose of mercuric chloride is estimated to be 30 to 50 mg/kg.96 The hallmarks of severe acute mercuric salt ingestion are hemorrhagic gastroenteritis, massive fluid loss resulting in shock, and acute tubular necrosis.82
Oropharyngeal injury, nausea, hematemesis, hematochezia, and abdominal pain were the most prominent symptoms in a series of 54 patients who presented after ingesting up to 4 g of mercuric chloride.96 In this series, a fatal outcome was associated with the early development of oliguria (within 3 days). The development of anuria appeared to be related to the dose of mercuric chloride ingested. The histopathologic finding of proximal tubular necrosis after mercuric salt poisoning results from both direct toxicity to renal tubules by mercuric ions and renal hypoperfusion caused by shock. Consequently, aggressive fluid therapy is useful.83
Acute ingestion of mercuric salts is usually intentional, but unintentional ingestion occurs sporadically in both children and adults.41 Although ingestion of button batteries containing mercuric oxide is associated with a greater incidence of fragmentation than with other batteries, clinically significant systemic mercury toxicity by this route has not been reported.53,56
Mercuric chloride–containing stool preservatives are another potential source of unintentional inorganic mercury poisoning. Ingestion of 10 to 20 mL of a polyvinyl alcohol preservative that contained 4.5% mercuric chloride resulted in bloody gastroenteritis and proteinuria.85 Patent39 and Ayurvedic80,81 medicines are also associated with unintentional inorganic mercury poisoning.43 Not subject to Food and Drug Administration (FDA) regulation and available without prescription, these xenobiotics are often inadequately labeled and of variable composition (see Chap. 43).
Subacute or chronic mercury poisoning occurs after inhalation, aspiration, or injection of elemental mercury; ingestion or application of inorganic mercury salts; or ingestion of aryl or long-chain alkyl mercury compounds. Slow in vivo oxidation of elemental mercury and dissociation of the carbon–mercury bond of aryl or long-chain alkyl mercury compounds result in the production of the inorganic mercurous and mercuric ions.
The predominant manifestations of subacute or chronic mercury toxicity include GI symptoms, neurologic abnormalities, and renal dysfunction. GI symptoms consist of a metallic taste and burning sensation in the mouth, loose teeth and gingivostomatitis, hypersalivation (ptyalism), and nausea.102 The neurologic manifestations of chronic inorganic mercurialism include tremor, as well as the syndromes of neurasthenia and erethism. Neurasthenia is a symptom complex that includes fatigue, depression, headaches, hypersensitivity to stimuli, psychosomatic complaints, weakness, and loss of concentrating ability. Erethism, derived from the Greek word red, describes the easy blushing and extreme shyness of affected individuals. Other symptoms of erethism include anxiety, emotional lability, irritability, insomnia, anorexia, weight loss, and delirium. Mercury produces a characteristic central intention tremor (see Chap. 18) that is abolished during sleep. In the most severe forms of mercury-associated tremor, choreoathetosis and spasmodic ballismus may be present. Other neurologic manifestations of inorganic mercurialism include a mixed sensorimotor neuropathy, ataxia, concentric constriction of visual fields ("tunnel vision"), and anosmia.
Chronic poisoning with mercuric ions is associated with renal dysfunction, which ranges from asymptomatic, reversible proteinuria to nephrotic syndrome with edema and hypoproteinemia. An idiosyncratic hypersensitivity to mercury ions is thought to be responsible for acrodynia, or "pink disease," which is an erythematous, edematous, and hyperkeratotic induration of the palms, soles, and face, and a pink papular rash that was first described in a subset of children exposed to mercurous chloride powders.102 The rash is described as morbilliform, urticarial, vesicular, and hemorrhagic. This symptom complex also includes excessive sweating, tachycardia, irritability, anorexia, photophobia, insomnia, tremors, paresthesias, decreased deep-tendon reflexes, and weakness. The acral rash may progress to desquamation and ulceration. The prognosis is favorable after withdrawal from mercury exposure. Childhood acrodynia has become uncommon since the abandonment of mercurial teething powders and diaper rinses. Occasional case reports are still noted, however, with fluorescent light bulbs and phenylmercuric acetate–containing paint implicated.2,97
Thimerosal is an example of an aryl or long-chain alkyl mercury compound that results in chronic inorganic mercury toxicity. It is a compound that was widely used as a preservative in the pharmaceutical industry (see Chap. 55). Although initial kinetics suggest a stable ethyl–mercury bond, the later elimination phase more closely resembles that of the inorganic mercury compounds. Thimerosal is approximately 50% mercury by weight. Generally considered safe, toxicity and death can nevertheless occur after both intentional overdose and excessive therapeutic application of Merthiolate (0.1% thimerosal or 600 μg/mL mercury).71,76
Concern that the cumulative dose of thimerosal in childhood immunizations may exceed federally recommended maximum mercury doses (EPA, 0.1 μg/kg/d; Agency for Toxic Substances and Disease Registry, 0.3 μg/kg/d; FDA, 0.4 μg/kg/d) led to a call by the American Academy of Pediatrics to reduce or eliminate thimerosal from vaccines.3 In particular, controversy exists whether thimerosal causes autism. Although sensitization after use in vaccinations has been reported in atopic children,70 clinical mercury toxicity has not been reported in appropriately immunized children. Moreover, a number of studies suggest that the incidence of autism is unrelated to the use of thimerosal-containing vaccines.6,54,69,90 Similarly, no causal association with early thimerosal exposure and adverse neuropsychological outcomes was shown in children tested at 7 to 10 years of age.95 At the present time, there is clearly more evidence for risk to child health from the diseases targeted for prevention by the vaccines than from thimerosal. Nevertheless, since 2001, routinely administered childhood vaccines in the United States, with the exception of injectable influenza vaccine, contain only trace amounts of thimerosal.38
Organic Mercury Compounds
In contrast to the inorganic mercurials, methylmercury produces an almost purely neurologic disease that is usually permanent except in the mildest of cases. Although the predominant syndrome associated with methylmercury is that of a delayed neurotoxicity, acute GI symptoms, tremor, respiratory distress, and dermatitis may occur.22,104 In addition, electrocardiographic (ECG) abnormalities (ST segment changes) and renal tubular dysfunction are associated with this poisoning.28,36
The lipophilic property and slower elimination of methylmercury may contribute to its profound neurologic effects.28 Characteristically, clinical manifestations occur after the initial poisoning by a latent period of weeks to months. Consequently, the lethal dose of methylmercury is difficult to determine. As noted previously, infants exposed prenatally to methylmercury were the most severely affected individuals in Minamata. Often born to mothers with little or no manifestation of methylmercury toxicity themselves, exposed infants exhibited decreased birth weight and muscle tone, profound developmental delay, seizure disorders, deafness, blindness, and severe spasticity. The development of neurologic symptoms in infants exclusively breastfed by women exposed to methylmercury after delivery and the detection of mercury in the milk of lactating women implies a risk for mercury poisoning via breast milk.47 In one series of lactating women, mercury concentrations in milk were approximately 30% of the concentrations found in blood.68 The rapid decline of blood mercury concentrations in both suckling rats and breastfeeding human infants is attributed to rapid growth of body volume combined with limited transport of mercury by milk.63,78,79
Several weeks after methylmercury-contaminated grain was ingested in Iraq, patients began to appear with paresthesias involving the lips, nose, and distal extremities. Symptomatic patients also noted headaches, fatigue, and tremor. More serious cases progressed to ataxia, dysarthria, visual field constriction, and blindness. Other neurologic deficits included hyperreflexia, hearing disturbances, movement disorders, salivation, and dementia. The most severely affected patients lay in a mute, rigid posture punctuated only by spontaneous crying, primitive reflexive movements, or feeding efforts.77
Although the outlook for methylmercury neurotoxicity is generally considered dismal, observations over the subsequent 2 years in 49 Iraqi children poisoned during the 1971 outbreak revealed complete resolution or partial improvement in all but the most severely affected.4 Of 40 symptomatic children, 33 mildly to severely affected children showed partial to complete resolution of symptoms, but the seven children classified as "very severely poisoned" remained physically and mentally incapacitated.
The extreme toxicity of dimethylmercury was tragically demonstrated by the delayed fatal neurotoxicity that developed in a chemist who inadvertently spilled dimethylmercury on a break in the gloves on her hands. Over a period of several days, she developed progressive difficulty with speech, vision, and gait. Despite chelation and exchange transfusion, she died within several months of the exposure.64
An important route of organic mercury exposure is through seafood consumption. The safe level of methylmercury in seafood remains controversial. The FDA action concentration of 1 ppm for methylmercury in fish was set to limit consumption of methylmercury to less than one-tenth of levels found in cases of symptomatic poisoning. The EPA established a reference dose for methylmercury of 0.1 μg/kg/d.73,98 Although elevated blood concentrations (19–53 μg/L) of mercury were found in one group of self-reported high consumers of seafood, increased incidence of cognitive and GI complaints were not.42 Even so, concentrations at which fetuses experience adverse effects are unknown. Longitudinal studies of fish-eating populations are conflicting. No effect of a high prenatal fish diet was found on developmental markers in children followed to 11 years of age in the Seychelles Islands.24 In the Faroe Island and New Zealand studies, however, a subtle but significant effect on neuropsychological development was seen.21,33,91 In the Faroe Islands, this effect persisted when children were retested at 14 years of age.26 One reason for the discrepancy that occurs between the two populations may be the different concentrations of methylmercury in the seafood consumed by each. The mean concentration of methylmercury in the whale meat consumed in the Faroe Islands was 1.6 μg/g, and the mean concentration of mercury found in New Zealand shark was 2.2 μg/g. In contrast, the mean methylmercury content of Seychellois fish was 0.3 μg/g.62 The threshold concentration for neuropsychological effects may lie between these concentrations. The FDA recommends that at-risk populations (ie, pregnant women and women who may become pregnant, nursing mothers, and young children) avoid the large predator fish (eg, shark, swordfish, tilefish, and king mackerel) that contain concentrations of methylmercury approaching 1 ppm (1 μg/g).99 The FDA has ruled that consumption advice is not indicated for the top 10 seafood species, which make up 80% of all seafood consumed: canned (nonalbacore) tuna, shrimp, pollock, salmon, cod, catfish, clams, flatfish, crabs, and scallops. These species contain concentrations of mercury less than 0.2 ppm and are rarely consumed in quantities in excess of the recommended weekly limit of 2.2 pounds. The recommendations are not as clear for albacore tuna, which may have concentrations of mercury as high as 0.34 ppm. The FDA-recommended limit of albacore tuna consumption by at-risk populations is less than 6 oz per week, but some consumer advocacy groups believe that the limit should be lower.20 Others continue to believe that the benefits of modest fish ingestion, excepting a few select species, also outweigh the risks.60