Mercury (Hg) is a naturally occurring metal that is mined chiefly as HgS in cinnabar ore. It is converted to three primary forms, each with a distinct toxicology: elemental (metallic) mercury (Hg⁰), inorganic mercury salts (eg, mercuric chloride [HgCl₂]), and organic (alkyl and aryl) mercury (eg, methylmercury). Approximately one-half to one-third of commercial mercury use is in the manufacture of chlorine and caustic soda, one-half to one-third in electric equipment, and the remainder in various applications, such as dental amalgam, fluorescent lamps, switches, thermostats, and artisanal gold production. Newer technology is replacing the use of mercury in chloralkali plants. In the United States, mercury use in batteries and paints has been discontinued. Previous use in pharmaceuticals and biocides has declined sharply, although mercuric chloride is still used as a stool fixative, and some organomercury compounds (such as mercurochrome, phenylmercuric acetate, and thimerosal) are still used as topical antiseptics or preservatives. Some folk medicines contain inorganic mercury compounds, and some Latin American and Caribbean communities have used elemental mercury in religious or cultural rituals. Hazardous exposure has resulted from dermal use of imported skin lightening creams formulated with mercury. Aquatic organisms can convert inorganic mercury into methylmercury, with resulting bioaccumulation in large carnivorous fish such as swordfish. Mercury is released to the environment from the burning of coal. Artisanal and small-scale gold mining now represent the largest source of mercury emissions worldwide. Effective 2020, the UN Minamata Convention on Mercury bans the manufacture, import or export of numerous mercury-added products, including most lamps and bulbs, batteries, pesticides, biocides and antiseptics, and measurement devices (eg, thermometers and barometers).

Mercury reacts with sulfhydryl (SH) groups, resulting in enzyme inhibition and pathologic alteration of cellular membranes. Inorganic mercury and methylmercury inhibit the activity of selenoproteins, increasing intracellular oxidative stress.

1. Elemental mercury vapor is a pulmonary irritant.
2. Inorganic mercuric salts are corrosive to the skin, eyes, and GI tract and are nephrotoxic.
3. Inorganic and organic mercury compounds may cause contact dermatitis.
4. All forms of mercury, especially organic forms, are toxic to the CNS.

The pattern and severity of toxicity are highly dependent on the form of mercury and the route of exposure, mostly because of different pharmacokinetic profiles. Chronic exposure to any form may result in toxicity (see Table II-35 for a summary of absorption and toxicity).

1. Elemental (metallic) mercury is a volatile liquid at room temperature.
   1. Hg⁰ vapor is absorbed rapidly by the lungs and distributed to the CNS. Airborne exposure to 10 mg/m³ is considered immediately dangerous to life or health (IDLH), and chemical pneumonitis may occur at levels in excess of 1 mg/m³. In occupational settings, overt signs and symptoms of elemental mercury intoxication generally have required months to years of sustained daily exposure to airborne mercury levels of 0.05-0.2 mg/m³. The recommended workplace limit (ACGIH TLV-TWA) is 0.025 mg/m³ as an 8-hour time-weighted average; however, some studies suggest that subclinical effects on the CNS and kidneys may occur below this level. The US Agency for Toxic Substances and Disease Registry (ATSDR) recommends evacuation from residences at 0.01 mg/m³ and avoidance of long-term occupancy if levels exceed 0.001 mg/m³.
   2. Liquid metallic mercury is poorly absorbed from the GI tract, and acute ingestion has been associated with poisoning only in the presence of abnormal gut motility that markedly delays normal fecal elimination or after peritoneal contamination.
2. Inorganic mercuric salts. The acute lethal oral dose of mercuric chloride is approximately 1-4 g. Severe toxicity and death have been reported after use of peritoneal lavage solutions containing mercuric chloride in concentrations of 0.2-0.8%. Weeks to years of dermal application of skin lightening creams and other topical preparations containing 0.1% to >10% inorganic mercury (often as mercurous chloride or mercuric ammonium chloride) has resulted in neurotoxicity or nephrotoxicity.
3. Organic mercury
   1. Mercury-containing antiseptics such as mercurochrome have limited skin penetration; however, in rare cases, such as topical application to an infected omphalocele, intoxication has resulted. Oral absorption is significant and may also pose a hazard.
   2. Methylmercury is well absorbed after inhalation, ingestion, and probably dermal exposure. Ingestion of 10-60 mg/kg may be lethal, and chronic daily ingestion of 10 mcg/kg may be associated with overt adverse neurologic and reproductive effects. The US Environmental Protection Agency reference dose (RfD), the daily lifetime dose believed to be without potential hazard, is 0.1 mcg/kg/d. The RfD was derived from studies of subclinical neuropsychological deficits arising from in utero exposure in humans. To minimize neurodevelopmental risk while optimizing nutrition, the US EPA and FDA in 2014 issued revised draft guidance advising pregnant women, women who may become pregnant, nursing mothers, and young children to avoid consumption of fish with high levels of mercury (eg, swordfish) and to limit consumption of albacore tuna to 6 oz a week, but to otherwise consume 8-12 oz of fish per week.
   3. Dimethylmercury, a highly toxic synthetic liquid used in analytic chemistry, is well absorbed through the skin, and cutaneous exposure to only a few drops has resulted in a delayed but fatal encephalopathy.
4. Toxicokinetics. Elemental mercury and inorganic mercury follow a biphasic elimination rate (initially rapid, then slow), and both urinary and fecal excretion occur. The urinary elimination half-life is approximately 40 days. Methylmercury undergoes biliary excretion and enterohepatic recirculation, with 90% eventually excreted in the feces. The half-life of methylmercury in blood is variable but averages 50 days.

1. Acute inhalation of high concentrations of metallic mercury vapor may cause severe chemical pneumonitis and noncardiogenic pulmonary edema. Acute gingivostomatitis may also occur.
2. Chronic intoxication from inhalation of mercury vapor produces a classic triad of tremor, neuropsychiatric disturbances, and gingivostomatitis.
   1. Early stages feature a fine intention tremor of the fingers, but involvement of the face and progression to choreiform movements of the limbs may occur.
   2. Neuropsychiatric manifestations include fatigue, insomnia, anorexia, and memory loss. There may be an insidious change in mood to shyness, withdrawal, and depression, combined with explosive irritability and frequent blushing (“erethism”).
   3. Subclinical changes in peripheral nerve function and renal function have been reported, but frank neuropathy and nephropathy are rare.
   4. Acrodynia, a rare idiosyncratic reaction to chronic mercury exposure, occurs mainly in children and has the following features: pain in the extremities, often accompanied by pinkish discoloration and desquamation (“pink disease”); hypertension; profuse sweating; anorexia, insomnia, irritability, and/or apathy; and a miliary rash.
3. Acute ingestion of inorganic mercuric salts, particularly mercuric chloride, causes an abrupt onset of hemorrhagic gastroenteritis and abdominal pain. Intestinal necrosis, shock, and death may ensue. Acute oliguric renal failure from acute tubular necrosis may occur within days. Chronic exposure may result in CNS toxicity.
4. Organic mercury compounds, particularly short-chain alkyl compounds such as methylmercury, primarily affect the CNS, causing paresthesias, ataxia, dysarthria, hearing impairment, and progressive constriction of the visual fields. Symptoms first become apparent after a latent interval of several weeks or months.
   1. Ethylmercury undergoes less CNS penetration than does methylmercury and has faster total-body clearance. In addition to neurotoxicity, symptoms of acute poisoning may include gastroenteritis and nephrotoxicity. Thimerosal (ethylmercury thiosalicylate), a preservative that undergoes metabolism to ethylmercury, was removed from most childhood vaccines in the United States on a precautionary basis. No causal link between thimerosal-containing vaccines and neurodevelopmental disorders has been established.
   2. Phenylmercury compounds, which undergo deacylation in vivo, produce a pattern of toxicity intermediate between those of alkyl mercury and inorganic mercury.
   3. Methylmercury is a potent reproductive toxin, and perinatal exposure has caused a spectrum of adverse effects ranging from subclinical neuropsychiatric effects to intellectual disability and a cerebral palsy-type syndrome in offspring

Depends on integration of characteristic findings with a history of known or potential exposure and the presence of elevated mercury blood levels or urinary excretion.

1. Specific levels. Mercury can be measured in blood and urine; the preferred matrix depends on the chemical form and duration of exposure (see below). Urine mercury may be reported as the mass of the metal per volume of urine (ie, micrograms per liter) or as the mass of the metal per gram of creatinine (ie, micrograms per gram of creatinine). Adjustment for creatinine, which reduces the impact of variation in urine flow rate, can be of value in comparing serial measurements obtained in the same individual (eg, workplace biomonitoring) or in evaluating dose-response trends in small population studies. However, specimens in which the creatinine concentration is very low (eg, <0.5 g/L) or very high (>3 g/L) may be unreliable and should be interpreted cautiously. The urine creatinine concentration of adults is on average close to 1 g/L, and therefore urine mercury values expressed as micrograms per gram of creatinine will often be similar to values expressed as micrograms per liter. In infants, creatinine-corrected values may appear anomalously elevated owing to infants' relatively low rate of creatinine excretion. Note: a spot urine sample may be sufficient for clinical diagnosis, as the concentration of mercury in first void morning samples correlate well with 24-hour urine collections.
   1. Metallic and inorganic mercury. Whole-blood and urine mercury levels are useful in confirming exposure. Shortly after acute exposures, whole-blood mercury values may rise faster than urine mercury levels. Decline in blood mercury then follows a biphasic pattern, with respective half-times of approximately 4 and 45 days. Urine mercury levels, reflecting the mercury content of the kidneys, are in general a better biomarker of chronic exposure. In most people without occupational exposure, whole-blood mercury is less than 5 mcg/L and urine mercury is less than 3 mcg/L. The median urine mercury concentration for the US general population in the 2009-2010 National Health and Nutrition Examination Survey (NHANES) was less than 0.130 mcg/L (the limit of detection). Based on the ACGIH biological exposure index for workers exposed to elemental or inorganic mercury, it has been recommended that pre-shift urine mercury level remain less than 20 mcg/g of creatinine. Studies have noted a small, reversible increase in urinary N-acetyl-glucosaminidase, a biomarker of perturbation in renal tubular function, in workers with urinary mercury levels of 25-35 mcg/L. Overt neurologic effects have occurred in persons with chronic urine mercury levels greater than 100-200 mcg/L, although lower levels have been reported in some pediatric cases of acrodynia. In patients with acute inorganic mercury poisoning resulting in gastroenteritis and acute tubular necrosis, blood mercury levels are often greater than 500 mcg/L. Two randomized trials of dental amalgam in children detected no overall adverse effect of low-level elemental mercury exposure (urine mercury <5 mcg/L) on neurocognitive development, although further analysis of one trial suggested effects may be influenced by genetic polymorphisms.
   2. Organic mercury. Whole blood mercury is the preferred matrix for diagnosis. Although most commercial laboratories will only report total blood mercury, analysis for methylmercury is available from specialized reference laboratories. Whole-blood mercury levels greater than 200 mcg/L have been associated with symptoms. In a 2001 analysis, the US EPA considered umbilical cord blood mercury levels of 46-79 mcg/L to represent lower-boundary estimates of levels associated with a significant increase in adverse neurodevelopmental effects in children. The geometric mean total blood mercury concentration in the US population assessed in the 2015-2016 NHANES was 0.678 mcg/L; the median was 0.600 mcg/L. According to a WHO review, the median blood mercury concentration among inhabitants of costal Pacific nations, who consume relatively higher quantities of seafood, was estimated to be 2.5 mcg/L. Because methylmercury undergoes bioconcentration across the placenta, umbilical cord blood mercury levels are on average 1.7 times higher than maternal whole-blood mercury levels.Hair levels have been used to document remote or chronic exposure to methylmercury. In US females age 16-49 years (NHANES 1999-2000), the geometric mean hair mercury concentration was 0.20 mcg/g and the 95th percentile was 1.73 mcg/g. A 2015 survey of 408 women aged 18-49 residing in a coastal Florida county found a geometric mean hair mercury concentration of 0.371 mcg/g.
2. Other useful laboratory studies include electrolytes, glucose, BUN, creatinine, liver aminotransferases, urinalysis, chest radiography, and arterial blood gases (if pneumonitis is suspected). Urinary markers of early nephrotoxicity (microalbuminuria, retinol-binding protein, beta₂-microglobulin, alpha-1-microglobulin, and N-acetylglucosaminidase) may aid in the detection of early adverse effects. Formal visual field examination may be useful for organic mercury exposure. Note: Empiric protocols that measure urine mercury concentration after administration of a single dose of a chelating agent such as unithiol (DMPS) have been described, but their diagnostic or prognostic utility has not been established and their use is discouraged. After administration of a dose of unithiol, urine mercury concentration may transiently increase on the order of 10-fold regardless of whether basal (prechallenge) levels are low or high.

1. Emergency and supportive measures
   1. Inhalation. Observe closely for several hours for the development of acute pneumonitis and pulmonary edema and give supplemental oxygen if indicated.
   2. Mercuric salt ingestion. Anticipate severe gastroenteritis and treat shock aggressively with IV fluid replacement. Vigorous hydration may also help maintain urine output. Acute renal failure is usually reversible, but hemodialysis may be required for 1-2 weeks.
   3. Organic mercury ingestion. Provide symptomatic supportive care.
2. Specific drugs and antidotes
   1. Metallic (elemental) mercury. In acute or chronic poisoning, oral succimer (DMSA) or oral unithiol (DMPS) may enhance urinary mercury excretion (although its effect on clinical outcome has not been fully studied). Although penicillamine is an alternative oral treatment, it may be associated with more side effects and less efficient mercury excretion.
   2. Inorganic mercury salts. Treatment with IV unithiol (DMPS) or IM BAL, if begun within minutes to a few hours after ingestion, may reduce or avert severe renal injury. Because prompt intervention is necessary, do not delay treatment while waiting for specific laboratory confirmation. Oral succimer (DMSA) is also effective, but its absorption may be limited by gastroenteritis and shock, and it is more appropriately used as a follow-up to DMPS or BAL treatment.
   3. Organic mercury. In methylmercury intoxication, limited data suggest that oral succimer (DMSA) and oral N-acetylcysteine (NAC) may be effective in decreasing mercury levels in tissues, including the brain.
   4. Because BAL may redistribute mercury to the brain from other tissue sites, it should not be used in poisoning by metallic or organic mercury because the brain is a key target organ.
3. Decontamination
   1. Inhalation
      1. Immediately remove the victim from exposure and give supplemental oxygen if needed.
      2. Even minute indoor spills (eg, 1 mL) of metallic mercury can result in hazardous chronic airborne levels. Cover the spill with powdered sulfur and carefully clean up and discard all residue and contaminated carpeting, porous furniture, and permeable floor covering. Do not use a home vacuum cleaner, as this may disperse the liquid mercury, increasing its airborne concentration. Professional guidance and cleanup with self-contained vacuum systems is recommended for spills of more mercury than the amount present in a thermometer or compact fluorescent light. Instruments that provide instantaneous (real-time) measurement of mercury vapor concentration are available for monitoring contamination and cleanup. Guidance on the management of mercury spills and contaminated buildings and residences is available from ATSDR (http://www.atsdr.cdc.gov/emergency_response/action_levels_for_elemental_mercury_spills_2012.pdf). Spills of more than 2 tablespoons of elemental mercury should be reported to the US government's National Response Center, available 24 hours a day, 7 days a week at 1-800-424-8802 (telephone).
   2. Ingestion of metallic mercury. In healthy persons, metallic mercury passes through the intestinal tract with minimal absorption, and there is no need for gut decontamination after minor ingestions. With large ingestions or in patients with abnormally diminished bowel motility or intestinal perforation, there is a risk for chronic intoxication. Whole-bowel irrigation or even surgical removal may be necessary, depending on radiographic evidence of mercury retention or elevated blood or urine mercury levels.
   3. Ingestion of inorganic mercuric salts
      1. Prehospital. Administer activated charcoal if available. Do not induce vomiting because of the risk for serious corrosive injury.
      2. Hospital. Consider gastric lavage. Administer activated charcoal, which has a very high adsorbent capacity for mercuric chloride.
      3. Arrange for endoscopic examination if corrosive injury is suspected.
   4. Ingestion of organic mercury. After acute ingestion, perform gastric lavage and administer activated charcoal. Immediately stop breastfeeding but continue to express and discard milk, as some data suggest this may accelerate reduction of blood mercury levels.
4. Enhanced elimination
   1. There is no role for dialysis, hemoperfusion, or repeat-dose charcoal in removing metallic or inorganic mercury. However, dialysis may be required for supportive treatment of renal failure, and it may slightly enhance removal of the mercury-chelator complex in patients with renal failure (hemodialysis clearance of the mercury-BAL complex is about 5 mL/min). A somewhat higher rate of mercury clearance (10 mL/min) was described when high-flux continuous venovenous hemodiafiltration was combined with unithiol in the treatment of mercuric sulfate-induced acute renal failure.
   2. In patients with chronic methylmercury intoxication, repeated oral administration of an experimental polythiol resin was effective in enhancing mercury elimination by interrupting enterohepatic recirculation.