Mercury toxicity

INTRODUCTION — Mercury exists in elemental, inorganic, and organic forms, all of which may be toxic [1-4]. The toxic manifestation depends on the form of exposure. This topic reviews sources of mercury exposure, the clinical manifestations, and the treatment and prevention of mercury toxicity.

Potential toxicity from ingestion of fish during pregnancy is discussed elsewhere. (See "Fish consumption and marine omega-3 fatty acid supplementation in pregnancy" and "Nutrition in pregnancy: Assessment and counseling", section on 'Guidelines for safe seafood consumption'.)

The use of thimerosal in vaccines is discussed elsewhere. (See "Autism spectrum disorder and chronic disease: No evidence for vaccines or thimerosal as a contributing factor".)

ELEMENTAL MERCURY TOXICITY — Elemental mercury is a silver-colored liquid ("quicksilver") that is volatile at room temperature and causes pulmonary and neurologic toxicity, as well as nephrotoxicity in severe or prolonged exposures [5]. Elemental mercury forms a vapor at room temperature, and the major route of absorption is through the lungs [6]. Elemental mercury is poorly absorbed via the gastrointestinal tract or skin [6]. Although a small fraction of the mercury vapor taken into the lung is eliminated via exhalation, most absorbed mercury is eliminated in the feces [7,8].

The central nervous system is the major site of deposition for mercury derived from inhalation exposure of vapor.

Sources of exposure — Potential occupational sources of exposure to elemental mercury include:

●Manufacturing processes – Mercury is still used in the manufacture of some instruments, including sphygmomanometers, manometers, thermometers, and barometers, although non-mercury based forms of these devices are more common [9,10]. Mercury is also contained in compact fluorescent light bulbs. Mercury toxicity may result from inhalation of mercury vapor during the manufacturing or recycling of such bulbs [11-13].

●Artisanal gold mining – Liquid elemental mercury can be used to concentrate gold from crushed ore or sediments. While mercury was historically used throughout the world to extract gold from ore [14,15], more efficient processes are now used in large-scale industrial mining. In over 70 developing nations, mercury toxicity remains a concern among artisanal and often illegal small-scale mining practices, which involve over 10 million workers [16], and a growing practice of recreational home gold extraction in the United States has led to case reports of toxicity [17]. More recently, a patient developed acute mercury toxicity from using elemental mercury to recover gold and silver from computer components [18].

●Dentistry – Amalgam tooth fillings are widely used in dentistry around the world. Amalgam, or dental silver, is an alloy of 50 percent metallic mercury and 50 percent metal powder (which is usually composed of silver, tin, copper, and zinc in certain proportions) [3]. A small amount of elemental mercury is released from amalgam fillings. The magnitude of release is proportional to the number of fillings and the total amalgam surface area. Individuals who habitually grind their teeth release more mercury from their dental fillings than those who do not [19].

Amalgam fillings are not believed to cause mercury toxicity. An expert committee from the World Health Organization believes that the average exposure from dental amalgam is approximately 10 mcg/day, well below toxic levels [6]. The exposure to mercury vapor from dental amalgams is usually far less than mercury exposure from foods such as predatory fish. (See 'Sources of exposure' below.)

According to the US Department of Health and Human Services Agency for Toxic Substances and Disease Registry, exposure to mercury from dental amalgams is less than 1 percent of the daily vapor dose that is considered to be safe in the occupational setting [20]. Although some small studies have suggested that chronic occupational exposure to these low levels by dental workers may cause subtle neuropsychiatric effects [21,22], studies have not correlated any symptoms or clinically significant health effects with absorption from dental amalgams [7,23-28].

There is little or no evidence to support the removal of existing fillings [7].

Other sources include chloralkali industries, gold gilders, metal refineries, skin-lightening cosmetics, deposition from coal-fueled power plants, and cement production [29-32].

Decreasing exposure — Exposure to mercury has significantly lessened during recent years because of increased attention to minimizing exposure. Previously, gold and silver miners and chloralkali industrial workers commonly encountered air concentrations of mercury in excess of the Occupational Health and Safety Administration (OSHA) permissible exposure limit (PEL) of 100 mcg/m³ during an eight-hour work day, with air concentrations reported as high at 500 mcg/m³ in connection with some mining operations [33]. Clinically significant health effects including neuropsychological abnormalities, pulmonary toxicity, and kidney dysfunction were common at such exposures [34,35]. The occupational threshold limit value (TLV) has been lowered to 50 mcg/m³ or less in most countries. The Federal OSHA in the United States has set a mercury PEL of 100 mcg/m³ (eight-hour time-weighted average [TWA]), but some state OSHA programs regulate a stricter limit at 50 mcg/m³ (eight-hour TWA) [36]. Despite these regulations, small-scale artisanal miners around the world remain at risk of mercury toxicity due to lack of regulations in often illegal mining operations [16].

Measurements of mercury in blood and urine are useful in quantifying the degree of exposure [4]. (See 'Diagnosis' below.)

There is a linear relationship between air and urine concentrations of mercury in most situations. The urine concentration (in mcg/L) corresponds to air concentration (in mcg/m³) multiplied by 1 to 2 [37].

Exposure to mercury vapor has also declined in dentistry, where ambient mercury concentrations between 1960 and 1970 were frequently approximately 25 mcg/m³; present values are below 5 mcg/m³ due to improved ventilation and handling of amalgam. Dental amalgam is still used in dentistry, although use is declining due to unfounded concerns from the public regarding mercury toxicity. Health problems associated with exposure due to mercury in dental amalgams have only been reported in dental workers with persistent high concentration exposures due to poor workplace ventilation, resulting in fatigue, generalized weakness, and anorexia [38].

Clinical manifestations — The predominant clinical manifestations of toxicity from exposure to elemental mercury vapor depend on the acuity and severity of exposure.

Acute — A severe and potentially fatal interstitial pneumonitis may result when mercury vapor is inhaled at concentrations greater than 1000 mcg/m³. Individuals at risk for toxicity due to inhaled mercury include those who work in settings involved in either manufacture or recycling of products containing mercury such as fluorescent bulbs, thermometers, manometers, barometers, valves, batteries, and switches [39]. A worker with a concerning occupational history presenting with the symptoms described below should be evaluated for acute mercury toxicity [6,18,40-44]:

●Cough, dyspnea, and chest pain

●Stomatitis, inflammation of the gums, and excessive salivation

●Severe nausea, vomiting, and diarrhea, which can lead to shock

●Conjunctivitis and dermatitis

A variety of the above signs and symptoms may also occur after acute exposure to lower air concentrations of mercury in the range of 100 to 1000 mcg/m³.

Chronic — Chronic exposure to lower concentrations of elemental mercury vapors results in predominantly nervous system effects. Mild neuropsychiatric symptoms such as tremor and insomnia may occur due to chronic exposure to mercury vapors at concentrations as low as 25 mcg/m³ [6]. While symptoms typically remain mild below the OSHA PEL of 100 mcg/m³, higher concentrations may lead to severe symptoms, such as intention tremors of the fingers and hands that make handwriting difficult. A hallmark of mercury poisoning is erethism or erethismus mercurialis, historically known as Mad Hatter syndrome, features of which include a change in personality, anxiety, irritability, excitability, fearfulness, pathologic shyness, insomnia, memory loss, depression, fatigue, weakness, and drowsiness [4,6,34,35,41]. Other symptoms may include diaphoresis, a desquamating rash, and hair loss.

Even more subtle central nervous system effects may also occur. The early effects of mercury exposure have been studied in occupational health studies [7]. Several studies have shown a dose-response relationship between subjective symptoms and/or impaired performance on psychologic tests [34,35,45].

As with higher exposures, the chronically exposed patient may also describe tender and inflamed gums, excessive salivation, and swollen salivary glands.

In severe cases, permanent central nervous system impairment may result [4,6,41,46]. Fetal toxicity from methylmercury from maternal seafood ingestion has resulted in irreversible brain damage but is discussed elsewhere. (See "Occupational and environmental risks to reproduction in females: Specific exposures and impact", section on 'Reproductive health impact'.)

Cases of nephrotic syndrome (usually with organic mercury salts) related to chronic occupational exposure to elemental mercury have been reported. Two cases of membranous nephropathy were reported from a fluorescent-tube recycling industry in Germany [47]. Heavy occupational exposure to mercury was evident from markedly elevated urinary excretion of mercury (118 and 158 mcg Hg/L, respectively). Two years after withdrawal from exposure to mercury, urinary excretion of mercury and protein was almost normal in one patient. The second patient was treated but lost to follow-up. Membranous nephropathy has also been reported among two members of the same family due to inadvertent residential exposure to mercury [48]. Membranous nephropathy from mercury toxicity was seen in a 14-year-old male with previous reflux nephropathy [48]. The boy lived in a small trailer home where fluid metallic mercury had been spilled on counter tops, under the floor tiles, and on the carpet. The boy's blood mercury level was 41 mcg Hg/L and 24-hour urine mercury level 43 mcg Hg/24 hours.

A Chinese poisoning treatment center reported data on nearly 300 patients with chronic mercury poisoning, mainly due to occupational exposure and inappropriate use of mercury-containing cosmetics [49]. The most common manifestations were neurologic (50 percent), though a substantial proportion of patients (14 percent) had nephrotic-range proteinuria, most commonly secondary to membranous nephropathy.

Occupation exposure to elemental mercury has been associated with renal tubular abnormalities. (See 'Tubular dysfunction' below.)

A worker with an occupational history concerning for risk of chronic mercury toxicity who presents with neuropsychiatric symptoms, rash, diaphoresis, salivation, or gingivitis should be evaluated for chronic mercury toxicity [39].

Acrodynia — Acrodynia ("pink disease") is a specific syndrome that has been reported in small children after exposure to elemental mercury, inorganic salts, and organic phenylmercury compounds, which have been used historically in both indoor and outdoor paints [50]. Acrodynia is characterized by a body rash, extremity edema, and irritation of palms and soles, followed by skin desquamation, irritability, photophobia, fever, insomnia, and profuse sweating [4,51,52].

Acrodynia was common among infants in the United Kingdom and the United States until the late 1940s, when it was realized that the condition was primarily caused by exposure to calomel (mercurous chloride, an inorganic mercury salt) in teething powders and in anthelminthic preparations [53]. Thought to be a hypersensitivity reaction to mercury influenced by a highly variable individual susceptibility, acrodynia affected almost exclusively infants and small children. The syndrome develops in only a small proportion of those who are exposed (<1 percent) [51].

While cases of acrodynia have been historically due to chronic topical exposure to teething or antihelminthic agents, more recent reports have been secondary to respiratory exposure over weeks to months to spilled elemental mercury (ie, from broken sphygmomanometers or vials of "quicksilver") [54,55].

Tubular dysfunction — Occupational exposure to both elemental mercury vapor and inorganic mercury has been associated with subtle abnormalities in kidney tubular function. One study found a slightly higher prevalence of elevated urinary excretion of albumin, transferrin, retinol-binding protein, and the tubular enzyme, beta-galactosidase, in chloralkali workers with a urinary excretion of mercury exceeding 50 mcg/g creatinine [56].

These changes presumably reflected tubular injury, leading to the excretion of smaller proteins that are normally filtered and then largely reabsorbed. The tubular lesions are probably dose related (with large doses [grams] causing acute tubular necrosis) [6].

Analysis of the tubular enzyme N-acetyl-beta-D-glucosaminidase (NAG) may provide early evidence of nephrotoxicity from mercury [57-60]. In a thorough cross-sectional examination of chloralkali workers exposed to mercury at air concentrations of approximately 25 mcg/m³, a significant correlation and dose-response relationship were observed between the urinary excretion of mercury and NAG [59]. No significant differences were observed between exposed and control patients with respect to other kidney parameters, including urinary excretion of albumin, orosomucoid, beta2-microglobulin, or copper, or in the serum creatinine concentration.

The more subtle, tubular effects from mercury may be reversible. As an example, nephrotoxicity was not observed after extensive examination among workers who were exposed to relatively low levels of mercury an average of six years prior [61].

Diagnosis — The diagnosis of elemental mercury toxicity should be suspected among individuals who present with consistent clinical manifestations and who have a history of exposure risk via occupation such as artisanal mining [16] or smelting [18], work with fluorescent bulbs or other mercury-containing products [39], or have days to weeks of exposure to elemental mercury via a broken mercury-containing device or other mercury spill [54,55].

The diagnosis is confirmed by measuring mercury in blood and/or 24-hour urine. The preferred test depends on whether the patient is suspected of having acute or chronic mercury exposure. Whole-blood mercury should be measured in the unstable patient who has suspected acute toxicity. However, 24-hour urine mercury measurement is the preferred test to assess toxicity in patients who have suspected stable and chronic exposure to elemental mercury. While whole-blood mercury concentrations can accurately reflect a very large, acute mercury exposure, this test becomes less reliable as redistribution to tissues takes place, making 24-hour urine testing more reliable in stable, chronic, or low-grade mercury exposures.

Treatment — All patients with toxicity from elemental mercury should be immediately removed from the source of mercury exposure. Supportive care should be provided and a whole-blood mercury level and 24-hour urine sent for measurement of mercury concentration to determine if chelation is needed [5]. For patients with suspected chronic mercury exposure, 24-hour urine mercury is used to determine if chelation is indicated. For unstable patients with acute, severe toxicity, rapid assessment for mercury toxicity can be performed using blood mercury testing as rapid testing will facilitate early chelation. Other measures depend on the form and severity of exposure (algorithm 1).

General measures and supportive care — Patients with acute elemental mercury vapor exposure by inhalation who present with respiratory symptoms should receive supportive care including supplemental oxygen, bronchodilators, and imaging to evaluate for pneumonitis or pulmonary edema. (See "Aspiration pneumonia in adults", section on 'Treatment'.)

Patients with acute elemental mercury vapor exposure who have gastrointestinal symptoms should receive fluid resuscitation and monitoring for electrolyte abnormalities or kidney injury from fluid and electrolyte losses.

Patients with symptoms who have 24-hour urine testing with concentration of 100 mcg/L or greater should receive chelation treatment. As noted above, in an unstable patient with suspected acute toxicity, a whole-blood level may be used to determine whether chelation is required. (See 'Chelator treatment' below.)

Patients with oral elemental mercury exposure generally do not require specific treatment, since gastrointestinal absorption of elemental mercury is negligible. (See 'Sources of exposure' above.)

Chelator treatment — Treatment with a chelating agent is indicated in selected patients. We treat patients with known or suspected elemental mercury exposure who have a 24-hour urine concentration (or, in the patient with suspected acute toxicity, a whole-blood mercury concentration) of 100 mcg/L or greater and who have symptoms that are attributed to mercury exposure. Clinical signs and symptoms from acute poisoning of mercury are unlikely if blood and urine concentrations are <100 mcg/L, although subclinical toxicity may occur below this level.

Chelators increase the urinary excretion of mercury [34]. Several studies and case reports of patients with symptomatic mercury toxicity accompanied by elevated urine mercury concentrations have shown clinical improvement after chelation therapy [62-64]. Chelation is recommended by the World Health Organization for patients with severe mercury toxicity [37].

The agents available to treat mercury poisoning are thiol-based chelating agents including dimercaprol (British anti-Lewisite [BAL]), penicillamine, unithiol (2,3 dimercaptopropane-1-sulfonate [DMPS]), and succimer (dimercaptosuccinic acid [DMSA]) [4,34,65]. The preferred agents are DMSA (if in the United States) or DMPS (if outside the United States). All of the studies of efficacy of chelating agents have used DMPS [62-64]. DMPS is not available in the United States; DMSA is believed to be equivalent to DMPS.

●If DMSA is used, a preferred regimen is 10 mg/kg orally three times daily for five days, then twice daily for 14 days. If patients are unable to tolerate oral intake, dimercaprol (BAL) may be used. Dimercaprol (BAL) is administered by deep intramuscular (IM) injection, 5 mg/kg/dose every four hours for 48 hours, then 2.5 mg/kg/dose every six hours for 48 hours, then 2.5 mg/kg/dose every 12 hours for seven days [5]. Patients initially treated with BAL who subsequently tolerate oral intake may be transitioned to DMSA treatment as tolerated [5].

●If DMPS is used, a preferred regimen is 250 mg IM or intravenous (IV) every four hours on day 1, 250 mg IM or IV every six hours on day 2, and 250 mg IM or IV every six to eight hours for days 3 to 5.

Penicillamine is rarely used because of significant gastrointestinal side effects, as well as a risk of thrombocytopenia and leukopenia [5]. However, penicillamine may be given at doses of 500 mg orally every six hours for five days, often in combination with pyridoxine (vitamin B6) in doses of 10 to 25 mg/day.

The efficacy of chelation therapy should be monitored by repeated clinical assessment and by measurement of mercury in 24-hour urine to ensure urine concentrations are approaching background levels of 20 mcg/L or lower [5,50].

Treatment may be required for a greater duration of time in severe cases of mercury poisoning.

Prognosis — Most of the pulmonary and kidney manifestations of mercury toxicity resolve after exposure has ceased. Likewise, some recovery occurs in most cases of elemental mercury neurotoxicity, but the extent of such recoveries varied considerably by individual and endpoint [66].

INORGANIC MERCURY SALTS TOXICITY — Inorganic mercury is present in various oxidation states as mercuric salts, which, if ingested, can cause severe gastroenteritis, shock, and kidney failure [67-70]. Exposure to inorganic mercury (ie, mercury salts) occurs via ingestion or from absorption across skin or mucosa [53]. Gastrointestinal absorption of both Hg⁺¹ and Hg⁺² is approximately 10 to 15 percent. The kidney is the major site of deposition for mercury derived from inorganic mercury compounds [5,71].

Sources of exposure — Exposure to inorganic mercury may occur in chloralkali industries, industries that use electroplating, or via exposure to laboratory reagents. Exposure may also occur via ingestion of mercury-containing oral or topical medications [72-76].

Historically, inorganic mercury was used for the treatment of syphilis, psoriasis, and as a potent diuretic for congestive heart failure [77-79]. Mercury-containing compounds are still used in vaccines, antiseptics, Chinese traditional medicines, and skin-lightening creams or hair dyes [1-3,80], although these compounds have markedly different safety profiles.

Clinical manifestations — The manifestations of toxicity from inorganic mercury vary depending on acuity and severity of exposure.

Acute — The acute ingestion of mercury salts may cause severe abdominal pain, accompanied by hemorrhagic gastroenteritis and associated severe volume depletion within several hours of ingestion. Ultimately, death may occur from cardiovascular collapse and shock. Patients who survive the acute insult may develop acute kidney injury related to acute tubular necrosis [50].

Chronic — Chronic exposure to lower concentrations of inorganic mercury salts causes irritability, colitis, gingivitis, stomatitis, excessive salivation, and nephrotic syndrome with varying pathologic features. Much of our knowledge of the effects of chronic exposure is from case reports of patients who were treated with mercury-containing oral or topical medications, including mercury-containing diuretics [68-70,81-85] and other medications [72,83,86-91].

Glomerular lesions causing nephrotic syndrome have been associated with mercury exposure [80,87,89-91]. In most reports, the nephrotic syndrome remitted after withdrawal of mercury compounds or treatment with a chelating agent [73,74,83,87].

Most cases of inorganic mercury-related nephrotic syndrome are due to membranous nephropathy [72,75,80,81,83]. However, minimal change disease also has been reported [75,76,88,92]. In a review of 25 individuals with mercury-associated nephrotic-range proteinuria, kidney biopsy showed membranous glomerulonephritis in 15 and minimal change disease in 4 [75]. In a case series from China, none of 13 patients with membranous nephropathy in the setting of long-term mercury exposure had evidence of phospholipase A2 receptor (PLA2R)-associated disease [92].

In addition to nephrotic syndrome, exposure to inorganic mercury salts has been associated with renal tubular abnormalities. (See 'Tubular dysfunction' above.)

Acrodynia — Acrodynia ("pink disease") is a specific syndrome that has been reported in small children after exposure to elemental mercury, inorganic salts, and organic phenylmercury compounds. (See 'Acrodynia' above.)

Tubular dysfunction — As with exposure to elemental mercury vapor, exposure to inorganic mercury has been associated with subtle abnormalities in kidney tubular function. (See 'Tubular dysfunction' above.)

Diagnosis — The diagnosis of mercury toxicity from inorganic mercury exposure should be suspected in patients who have consistent clinical features and have a history of exposure to mercury. A careful review of medications and over-the-counter products, including cosmetics or remedies purchased outside of the United States, may reveal a source of mercury exposure.

The diagnosis is confirmed by measuring mercury in blood and/or 24-hour urine. The preferred test depends on whether the patient is suspected of having acute or chronic mercury exposure. Whole-blood mercury should be measured in the unstable patient who has suspected acute toxicity. However, 24-hour urine mercury measurement is the preferred test to assess toxicity in patients who have suspected stable and chronic exposure to mercury. While whole-blood mercury concentrations can reflect very large acute mercury exposure, this test becomes less reliable as redistribution to tissues takes place, making 24-hour urine testing more reliable in stable, chronic, or low-grade mercury exposures.

Treatment — All patients with toxicity from exposure to inorganic mercury should have all potential sources of mercury exposure removed. Supportive care should be provided and a 24-hour urine sent for measurement of mercury concentration [5]. Other measures depend on the form and severity of exposure (algorithm 1).

General measures and supportive care — Patients with inorganic mercury ingestion require aggressive fluid resuscitation, given the high risk of severe gastrointestinal symptoms leading to shock and acute kidney injury. All patients should be followed closely for electrolyte abnormalities or kidney injury from fluid and electrolyte losses.

Patients who have symptoms consistent with mercury poisoning and have either whole blood (for patients with suspected acute toxicity) or 24-hour urine testing (for patients with suspected chronic toxicity) with a concentration of 100 mcg/L or greater should receive chelation treatment. (See 'Chelation treatment' below.)

Chelation treatment — We chelate patients with known or suspected inorganic mercury salt ingestion exposure who have 24-hour urine or whole-blood concentration of 100 mcg/L or greater and who have symptoms that are attributed to mercury exposure. Clinical signs and symptoms from acute poisoning of mercury are unlikely if blood and urine concentrations are <100 mcg/L, although subclinical toxicity may occur below this level. The preferred agent and dose are the same as for elemental mercury toxicity. (See 'Chelator treatment' above.)

The efficacy of chelation therapy should be monitored by repeated clinical assessment and by measurement of mercury in 24-hour urine to ensure urine concentrations are approaching background levels of 20 mcg/L or lower [5,50].

Treatment may be required for a greater duration of time in severe cases of mercury poisoning.

Kidney toxicity — No specific treatment is recommended for chronic kidney toxicity from mercury in the otherwise asymptomatic patient. The most important action is to eliminate or minimize exposure to mercury as nephrotic syndrome due to mercury is usually reversible, although it may take several months [90,91].

Patients who have kidney toxicity resulting from an acute exposure to mercury may have an indication for chelation treatment. (See 'Chelator treatment' above.)

While hemodialysis may become necessary in cases of severe kidney failure due to mercury toxicity, the efficacy of hemodialysis for removal of the mercury moiety itself is limited by its large volume of distribution and significant protein binding [67].

ORGANIC MERCURY TOXICITY — The ingestion of organic mercury as part of organomercuric compounds causes severe neurologic toxicity [6,7,93,94]. Alkyl mercurials such as methylmercury are efficiently absorbed from the gastrointestinal tract. Organic mercury compounds are lipophilic. The lipophilicity facilitates distribution to the central nervous system and passage across the placenta [95]. The kidney, liver, hair, and central nervous system are major sites of deposition [96].

Organic mercury compounds are defined by their bound hydrocarbon moieties. Among these compounds, dimethylmercury is particularly toxic [97,98]. In one case report, accidental dermal exposure to approximately 1.3 g of dimethylmercury (contained in approximately 0.44 mL) resulted in severe delayed neurotoxicity and death despite aggressive treatment [97].

Chronic consumption of organic mercury compounds has caused severe epidemics of poisoning in Japan and Iraq [4,6,99-101].

Sources of exposure — Exposure to organic mercury is mostly via consumption of mercury-contaminated fish. Concerns of a potential health risk resulting from exposure to thimerosal, which is a preservative used in some vaccines that releases ethylmercury, have been raised by the lay public. However, there is no evidence to suggest that exposure to thimerosal causes pediatric neurodevelopmental disorders [102-104]. While controversy surrounding mercury exposure led to the reduction in its use in American vaccinations, thimerosal is still used as a pharmaceutical preservative in other nations [105]. This issue is further discussed in separate topic reviews. (See "Allergic reactions to vaccines", section on 'Thimerosal, aluminum, and phenoxyethanol' and "Autism spectrum disorder and chronic disease: No evidence for vaccines or thimerosal as a contributing factor".)

Potential occupational exposures to organic mercury also include wood preservation and outdoor painting.

The concentration of mercury is very low in most food (<0.02 mg/kg). However, certain types of marine fish (such as shark, swordfish, and tuna) and certain fish taken from polluted fresh waters (such as pike, walleye, and bass) may contain high concentrations of mercury, almost completely in the form of methylmercury. According to the US Food and Drug Administration Monitoring Program 1990 to 2010, concentrations of methylmercury in these fish may be 1 mg/kg (1 ppm) or even higher. A concentration of more than 0.5 mg/kg (0.5 ppm) is considered very high. Epidemics of severe neurologic disease were caused by the consumption of food contaminated with methylmercury in Minamata, Japan, in the 1940s and in Iraq in 1971 [99-101,106].

According to the Natural Resources Defense Council, fish with 0.3 to 0.49 mg/kg (0.3 to 0.49 ppm) may be safely consumed three times per month. Fish with >0.5 mg/kg should be avoided. The Environmental Protection Agency recommends a maximum daily exposure to mercury of 0.1 mcg/kg of body weight, which will typically result in a blood mercury concentration of less than 6 mcg/L.

Monitoring of mercury in blood or urine may be used to identify and quantify exposure to methylmercury [37]. Heavy consumers of fish and, in particular, those who eat species such as swordfish or shark may have blood mercury levels more than 20 mcg/L (normal value <5 mcg/L). While adult patients with excessive organic mercury consumption may present with subtle neurocognitive effects such as mild deficits in fine motor, verbal memory, and attention, effects in children exposed as fetuses may be more severe [107].

Recommended dietary allowances for children and fetuses (via the mother) are lower [108]. (See "Nutrition in pregnancy: Assessment and counseling", section on 'Guidelines for safe seafood consumption'.)

Clinical manifestations — Significant organic mercury exposure causes acute gastrointestinal and respiratory symptoms, followed by neurologic symptoms that include paresthesias (notably around the mouth), malaise, constriction of the visual field, deafness, and ataxia [94]. The fetus is particularly vulnerable.

Acrodynia — Acrodynia ("pink disease") is a specific syndrome that has been reported in small children after exposure to elemental mercury, inorganic salts, and organic phenylmercury compounds. (See 'Acrodynia' above.)

Diagnosis — The diagnosis of organic mercury toxicity should be suspected among individuals who present with consistent clinical manifestations and who have a history of ingestion of potentially contaminated fish or the rare case of occupational exposure. (See 'Clinical manifestations' above.)

In contrast to testing for elemental or inorganic mercury toxicity, the preferred test for determining toxicity from organic mercury is a whole-blood mercury level. Organic mercury is eliminated via the fecal route, rendering urine mercury testing less useful in organic mercury poisoning.

Mercury should not be measured in hair. Because mercury accumulates in the hair, hair analysis was previously used to measure mercury burden in chronic exposure. However, hair avidly binds to noningested environmental mercury, and metal incorporation into hair reflects only past exposure. As such, the reliability of this method for informing clinical management is questionable and is not recommended by toxicologists.

Treatment — All patients with potential organic mercury toxicity should cease all exposure to organic mercury. A 24-hour urine should be sent for measurement of mercury concentration [5].There is no effective treatment for patients with toxic exposure to organic mercury. Neurologic damage due to organic mercury exposure may be profound, permanent, and is generally resistant to treatment with chelating agents. Prevention of exposure to organic mercury is the most important aspect of management [5,50].

We do not use chelating agents for patients with toxic exposure to organic mercury, although the use of chelating agents is controversial among such patients. Central nervous system toxicity due to exposure to organic mercury is usually resistant to treatment with chelation. Furthermore, chelation with dimercaprol (British anti-Lewisite [BAL]) should not be used in organic mercury exposure, because it increases the mobilization of mercury to the brain. Treatment with oral dimercaptosuccinic acid (DMSA) is unlikely to reverse neurologic damage [5,50].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Chronic kidney disease in adults" and "Society guideline links: Lead and other heavy metal poisoning".)

SUMMARY AND RECOMMENDATIONS

●Different forms of mercury – Mercury exists in elemental, inorganic, and organic forms, all of which may be toxic. The toxic manifestation depends on the form of exposure. (See 'Introduction' above.)

●Elemental mercury toxicity – Acute inhalation of high levels of elemental mercury vapor predominantly causes interstitial pneumonitis. Chronic exposure to lower concentrations of elemental mercury vapors results in predominantly nervous system effects that may be severe and irreversible. The diagnosis of elemental mercury toxicity is confirmed by measuring mercury in blood and/or 24-hour urine. Whole-blood mercury should be measured in the unstable patient who has suspected acute elemental mercury toxicity. Twenty-four-hour urine mercury measurement is the preferred test to assess toxicity in patients who have suspected stable and chronic exposure to elemental mercury. (See 'Elemental mercury toxicity' above.)

●Inorganic mercury toxicity – The acute ingestion of inorganic mercury in the form of mercury salts may cause severe abdominal pain accompanied by a hemorrhagic gastroenteritis and severe volume depletion within several hours of ingestion. Ultimately, death may occur from cardiovascular collapse and shock. Chronic exposure to lower concentrations of inorganic mercury salts may cause neurologic symptoms and a nephrotic syndrome, typically of minimal change or membranous type. The diagnosis of inorganic mercury toxicity is confirmed by measuring mercury in blood and/or 24-hour urine. Whole-blood mercury should be measured in the unstable patient who has suspected acute inorganic mercury toxicity. Twenty-four-hour urine mercury measurement is the preferred test to assess toxicity in patients who have suspected stable and chronic exposure to inorganic mercury. (See 'Inorganic mercury salts toxicity' above.)

●Organic mercury toxicity – Organic mercury exposure causes acute gastrointestinal and respiratory symptoms, followed by neurologic symptoms. The toxicity of prenatal organic mercury to the fetus can be profound and causes irreversible neurologic damage. The preferred test for determining toxicity from organic mercury is a whole-blood mercury level. (See 'Organic mercury toxicity' above.)

●Management of elemental and inorganic mercury toxicity – The management of mercury toxicity begins with removing the patient from the source of exposure. Other measures depend on the form and severity of exposure (algorithm 1).

•Supportive care – All patients should receive initial supportive care measures.

-Patients with acute elemental mercury vapor exposure who present with respiratory symptoms should receive supportive care including supplemental oxygen, bronchodilators, and imaging to evaluate for pneumonitis or pulmonary edema. (See 'General measures and supportive care' above.)

-Patients with acute inorganic mercury ingestion require aggressive fluid resuscitation, given the high risk of severe gastrointestinal symptoms leading to shock and kidney failure. All patients should be monitored for electrolyte abnormalities or kidney injury from fluid and electrolyte losses. (See 'General measures and supportive care' above.)

•Chelation therapy – Among symptomatic patients with elemental or inorganic mercury exposure who have urine or whole-blood mercury concentrations of 100 mcg/L or greater, we recommend chelation treatment (Grade 1B). The preferred agents are dimercaptosuccinic acid (DMSA; if in the United States) or 2,3 dimercaptopropane-1-sulfonate (DMPS; if outside the United States).(See 'Chelator treatment' above.)

-If DMSA is used, a preferred regimen is 10 mg/kg orally three times daily for five days, then twice daily for 14 days.

If patients are unable to tolerate oral intake, dimercaprol (British anti-Lewisite [BAL]) is administered by deep intramuscular (IM) injection, 5 mg/kg/dose every four hours for 48 hours, then 2.5 mg/kg/dose every six hours for 48 hours, then 2.5 mg/kg/dose every 12 hours for seven days. Patients initially treated with BAL who subsequently are able to tolerate oral intake may be transitioned to DMSA treatment.

-If DMPS is used, a preferred regimen is 250 mg IM or intravenous (IV) every four hours on day 1, 250 mg IM or IV every six hours on day 2, and 250 mg IM or IV every six to eight hours for days 3 to 5.

●Management of organic mercury toxicity – There is no effective treatment for toxic exposure to organic mercury. All patients with potential organic mercury toxicity should cease all exposure to mercury. Symptoms are generally resistant to treatment with chelators (algorithm 1). Dimercaprol (BAL) should NOT be used, because it increases the mobilization of mercury to the brain. Treatment with oral DMSA is unlikely to reverse neurologic damage. (See 'Treatment' above.)