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 respiratory distress syndrome with respiratory failure and death. Survivors of severe pulmonary toxicity 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.30
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.15,16,40,58,88 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.
The current US Occupational Safety and Health Administration permissible exposure limit for mercury vapor is 0.1 mg/m3 of air as a ceiling limit.66
As with other inhaled toxins, children may be more sensitive to the pulmonary toxicity of mercury vapor because of their ratio of minute ventilation to body size.58 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.103 Gradual volatilization of elemental mercury results in chronic toxicity from improper handling, such as vacuuming spilled mercury.83
The clinical importance of volatilized metallic mercury from dental amalgams for both the dentist and patient is controversial. 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 exceedingly rare cases will immunologic hypersensitivity to mercury amalgam (manifested as cutaneous signs and symptoms and confirmed by patch testing) necessitate removal of the amalgam.27,28, and 29,49,87
Unusual cases of chronic toxicity have resulted from intentional subcutaneous or IV injection of elemental mercury (Fig. 5–6 and Fig. 98–1).39,60 Aside from management of 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. (Used with permission of 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.94 The life-threatening manifestations of severe acute mercuric salt ingestion are hemorrhagic gastroenteritis, massive fluid loss resulting in shock, and kidney failure.81
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.94 In this series, fatality was associated with the early development of oliguria (within 3 days) likely due in large part to lack of routinely available hemodialysis. 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 both from direct toxicity to renal tubules and from renal hypoperfusion caused by shock. Consequently, aggressive fluid therapy to maintain perfusion is useful.82
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.52,55 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.84 Patent39 and Ayurvedic80 medicines are also associated with unintentional inorganic mercury poisoning.43 These xenobiotics are not subject to US Food and Drug Administration (FDA) regulation, available without prescription, of variable composition, and are often inadequately labeled (Chap. 45).
Subacute or chronic mercury poisoning occurs after inhalation, aspiration, or injection of elemental mercury; ingestion or application of 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.98 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 (Chap. 24) 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.98 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.3,95
Thimerosal is an example of an aryl mercury compound that results in chronic inorganic mercury toxicity. It is a compound that was widely used as a preservative in the pharmaceutical industry (Chap. 55). Although initial kinetics have suggested 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).70,76
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.4 In particular, controversy exists whether thimerosal causes autism. Although sensitization after use in vaccinations has been reported in atopic children,69 clinical mercury toxicity has not been reported in appropriately immunized children. Moreover, many studies suggest that the incidence of autism is unrelated to the use of thimerosal-containing vaccines.7,53,68,89 Similarly, no causal association with early thimerosal exposure and adverse neuropsychological outcomes was shown in children tested at 7 to 10 years of age.93 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. In 2010, US courts rejected a causal relationship between thimerosal and autism.26
Thimerosal continues to be used in medically underserved nations as a preservative in mutidose vials in areas with inadequate refrigeration.31 Nevertheless, since 2001, routinely administered childhood vaccines in the United States no longer contain thimerosal.4,37
Organic Mercury Compounds
By 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.100 In addition, abnormalities on electrocardiography (ECG; ST segment changes) and renal tubular dysfunction are associated with this poisoning.35
The lipophilic property and slower elimination of methylmercury may contribute to its profound neurologic effects. 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.46 In one series of lactating women, mercury concentrations in milk were approximately 30% of the concentrations found in blood.67 Seven year-old children from the Faroe Islands, who have a diet traditionally high in mercury-containing sea mammals, breast-fed as infants exhibited a diminished benefit (but not deficit) on neuropsychological testing when compared with their counterparts fed formula.38
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.62,78,79 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.5 Of the 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.
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.72,96 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 17 years of age in the Seychelles Islands.22,23
However, in the studies done in the Faroe Islands and New Zealand, a subtle but significant effect on neuropsychological development was seen.20,32,90 In the Faroe Islands, this effect persisted when children were retested at 14 years of age.25 One reason for the discrepancy that occurs between the two populations may be the different patterns of seafood consumption and concentrations of methylmercury in the seafood consumed by each. The Faroese consume low-level mercury containing fish one to three times a week with episodic feasts of highly contaminated pilot whale, whereas the Seychellois consume a more steady diet of low-level contaminated fish on average 12 times per week. The pilot whales consumed in the Faroe Islands were also contaminated with neurotoxic polychlorinated biphenyls, although these compounds were measured and controlled for as a potential confounding variable. 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. By contrast, the mean methylmercury content of Seychellois fish was 0.3 μg/g.61 The threshold concentration for neuropsychological effects may lie between these concentrations.
No increase in cardiovascular disease risk was seen with mercury exposure in a large cohort of US adults.59
The FDA recommends that at-risk populations (ie, pregnant women and women who may become pregnant, nursing mothers, and young children) avoid large predator fish (eg, shark, swordfish, tilefish, and king mackerel) that contain concentrations of methylmercury approaching 1 ppm (1 μg/g). The 2004 FDA/EPA consumer advisory emphasizes the health benefits of eating fish and allow for up to 12 ounces per week of fish and shellfish lower in mercury such as shrimp, canned light tuna, salmon, pollock and catfish and up to 6 ounces of albacore tuna per week. Given the beneficial effects of seafood, efforts should be aimed at decreasing anthropogenic release of mercury rather than elimination of dietary exposure.73
Although methylmercury has greater importance worldwide, the extreme toxicity of another organic mercurial, 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.63 Over a period of several days, she developed progressive difficulty with speech, vision, and gait. Despite chelation and exchange transfusion, she died of mercury neurotoxicity within several months of the exposure.