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Toxicity, Mercury

Author: Barry M Diner, MD, MPH, FACEP, Assistant Clinical Professor, Department of Emergency Medicine, Emory University School of Medicine; Attending Physician, St Luke's Episcopal Hospital, Houston, Texas
Coauthor(s): Barry E Brenner, MD, PhD, FACEP, Professor of Emergency Medicine, Professor of Internal Medicine, Program Director, Emergency Medicine, University Hospitals, Case Medical Center
Contributor Information and Disclosures

Updated: Sep 18, 2009

Introduction

Background

Throughout the centuries, several incidents of mercury toxicity have been reported. Mercury has been found in Egyptian tombs, indicating it was used as early as 1500 BC. In the late 18th century, antisyphilitic agents contained mercury. It was during the 1800s that the phrase "mad as a hatter" was coined because of the chronic mercury exposure that the felters faced because mercury was used in hat making.

In the 1940s and 1950s, mercury became known as the product that caused acrodynia, also known as pink disease. Manifestations of acrodynia include pain and erythema of the palms and soles, irritability, insomnia, anorexia, diaphoresis, photophobia, and rash.

Some of the more recent occurrences include exposures in Minamata Bay in Japan (1960); mercury contaminated fish in Canada; methylmercury-treated grain in Iraq (1960, 1970); and, in the United States (1996), a beauty cream product from Mexico called "Crèma de Belleza-Manning."

For centuries, mercury was an essential part of many different medicines, such as diuretics, antibacterial agents, antiseptics, and laxatives. More recently, these drugs have been substituted and drug-induced signs of mercury toxicity are rare. Mercury toxicity in environmental pollution is a major concern because of increased usage of fossil fuels and agricultural products, both of which contain mercury.

Mercury poisoning is usually misdiagnosed because of the insidious onset, nonspecific signs and symptoms, and lack of knowledge within the medical profession.

Mercury is found in many industries, such as battery, thermometer, and barometer manufacturing. Mercury can be found in fungicides used in the agricultural industry. Before 1990, paints contained mercury as an antimildew agent. In medicine, mercury is used in dental amalgams and various antiseptic agents.

On July 7, 1999, a joint statement by the American Academy of Pediatrics (AAP) and the US Public Health Service (USPHS) was issued alerting clinicians and the public of thimerosal, a mercury-containing preservative used in some vaccines. Subsequent investigation has not proven any definite link between this small amount of mercury and any known disease.

Most recently, 2 areas have caused public concern regarding mercury toxicity: (1) the potential risk associated with eating fish, especially when dealing with pregnancy and (2) the use of dental amalgams, or fillings, by dentists. In May 2001, one of Canada's largest newspapers, the National Post, featured an exposé on the pros and cons of eating fish titled, "One fish, two fish, good fish, bad fish" in its "Health and Medicine" section.

Pathophysiology

Mercury is the only metal that is liquid at room temperature. Its elemental symbol is Hg, which is derived from the Greek word hydrargyrias, meaning "water silver." Mercury is found in organic and inorganic forms. The inorganic form can be further divided into elemental mercury and mercuric salts. Organic mercury can be found in long and short alkyl and aryl compounds.

Mercury in any form is toxic. The difference lies in how it is absorbed, the clinical signs and symptoms, and the response to treatment modalities. Mercury poisoning can result from vapor inhalation, ingestion, injection, or absorption through the skin.

Neurologic, gastrointestinal, and renal systems are the most commonly affected organ systems in mercury exposure.

• Organic mercury - Most devastating to the CNS
  • Short-chained (methylmercury) - Affects the CNS
  • Long-chained - Subacute/chronic effects similar to that of inorganic mercury exposure
• Elemental mercury - Primary neurologic toxicity
• Inorganic mercury salts
  • Acute - Severe corrosive gastroenteritis, acute tubular necrosis
  • Subacute or chronic - GI, neurologic, and renal dysfunction

Elemental mercury (Hg) is found in liquid form, which easily vaporizes at room temperature and is well absorbed (80%) through inhalation. Its lipid-soluble property allows for easy passage through the alveoli into the bloodstream and red blood cells (RBCs). Once inhaled, elemental mercury is mostly converted to an inorganic divalent or mercuric form by catalase in the erythrocytes. This inorganic form has similar properties to inorganic mercury (eg, poor lipid solubility, limited permeability to the blood-brain barrier, and excretion in feces). Small amounts of nonoxidized elemental mercury continue to persist and account for central nervous system toxicity.

Elemental mercury as a vapor has the ability to penetrate the CNS, where it is ionized and trapped, attributing to its significant toxic effects. Elemental mercury is not well absorbed by the GI tract and, therefore, when ingested (eg, thermometers), is only mildly toxic.

Inorganic mercury, found mostly in the mercuric salt form (eg, batteries), is highly toxic and corrosive. It gains access to the body orally or dermally and is absorbed at a rate of 10% of that ingested. It has a nonuniform mode of distribution secondary to poor lipid solubility and accumulates mostly in the kidney, causing significant renal damage. Although poor lipid solubility characteristics limit CNS penetration, slow elimination and chronic exposure allow for significant CNS accumulation of mercuric ions and subsequent toxicity. Long-term dermal exposure to inorganic mercury may also lead to toxicity.

Excretion of inorganic mercury, as with organic mercury, is mostly through feces. Renal excretion of mercury is considered insufficient and attributes to its chronic exposure and accumulation within the brain, causing CNS effects.

Organic mercury can be found in 3 forms, aryl and short- and long-chain alkyl compounds. Organic mercurials are absorbed more completely from the GI tract than inorganic salts are; this is because of intrinsic properties, such as lipid solubility and mild corrosiveness (although much less corrosive than inorganic mercury). Once absorbed, the aryl and long-chain alkyl compounds are converted to their inorganic forms and possess similar toxic properties to inorganic mercury. The short-chain alkyl mercurials are readily absorbed in the GI tract (90-95%) and remain stable in their initial forms. Alkyl organic mercury has high lipid solubility and is distributed uniformly throughout the body, accumulating in the brain, kidney, liver, hair, and skin. Organic mercurials also cross the blood-brain barrier and placenta and penetrate erythrocytes, attributing to neurological symptoms, teratogenic effects, and high blood to plasma ratio, respectively.

Methylmercury has a high affinity for sulfhydryl groups, which attributes to its effect on enzyme dysfunction. One enzyme that is inhibited is choline acetyl transferase, which is involved in the final step of acetylcholine production. This inhibition may lead to acetylcholine deficiency, contributing to the signs and symptoms of motor dysfunction.

Excretion of alkyl mercury occurs mostly in the form of feces (90%), secondary to significant enterohepatic circulation. The biological half-life of methylmercury is approximately 65 days. Organic mercury is found most commonly in antiseptics, fungicides, and industrial run-off.

Frequency

United States

The 2008 Annual Report of the American Association of Poison Control Centers' National Poison Data System documented about 2400 single exposures to mercury or compounds containing mercury.¹ Of these, 305 were in children younger than 6 years and 983 were in persons older than 19 years. Overall, 45 individuals were reported to have moderate effects, 3 had major effects, and none died as a result of mercury exposure.

Mortality/Morbidity

Long-term neurologic effects are a major concern with chronic mercury exposure. Three widely publicized topics of concern to the general population are dental fillings, or amalgams, and fish consumption, especially in children and pregnant women, and vaccines

After an exhaustive investigation and review of the evidence, including the form of mercury in question, the route of exposure, and the dose, the Public Health Service concluded that dental amalgams do not pose a serious health risk.²

The primary source of environmental exposure to mercury in the general population is through the consumption of contaminated fish.³ Fish consumption has clear health benefits, and the risk posed by mercury exposure is currently speculative. The fetal brain is more susceptible to mercury-induced damage than that of an adult. As a result of this data, the Environmental Protection Agency (EPA) reduced the allowable intake of methylmercury from 0.5 mcg to 0.1 mcg of mercury per kilogram per day, which is lower than the amount allowable according to other regulatory agencies.⁴ The EPA guideline is derived from reports of subtle and small neuropsychologic changes in children in the Faeroe Islands study, whose exposure was mainly from whale consumption.⁵ A similar study in the Seychelles found no adverse effects from fish consumption alone.⁶

The Food and Drug Administration (FDA) has recommended that pregnant women, breastfeeding mothers, and young children avoid eating fish with a high mercury content (>1 ppm), such as shark, swordfish, tilefish, and king mackerel. This also includes fresh and frozen tuna (mercury content between 0.5 ppm and 1.5 ppm) but not canned tuna, which consists of smaller, shorter-lived species with lower mercury levels. From a nonprofessional perspective, this translates into a weekly consumption of one can (198 g or 7 oz) of tuna for an adult.⁷ Rather than ban the sale of these species, Health Canada recommends that they be consumed no more than once per week or once per month by children and by women of childbearing age.⁸ Mercury levels in freshwater fish vary, but, in general, bass, pike, muskellunge, and walleye have high levels of mercury and should be eaten in moderation. Provincial guidelines for sport fish often mirror federal seafood recommendations.⁹

Thimerosal is a mercury-containing preservative used in some vaccines and other products since the 1930s. No harmful effects have been reported from thimerosal at doses used in vaccines, except for minor reactions like redness and swelling at the injection site. However, in July 1999, the Public Health Service (PHS) agencies, the American Academy of Pediatrics (AAP), and vaccine manufacturers agreed that thimerosal should be reduced or eliminated in vaccines as a precautionary measure. Today, with the exception of some influenza vaccines, none of the vaccines used in the United States to protect preschool children against 12 infectious diseases contain thimerosal as a preservative.¹⁰

In 2004, Immunization Safety Review Committee of the IOM shifted from the position of neutrality to the conclusion that "the evidence favors rejection of a causal relationship between thimerosal-containing vaccines and autism."¹¹  Since 2004, two cohort studies from the United Kingdom examined the relationship between thimerosal contained within vaccines and autism, and their conclusions were in agreement with the IOM that there is no casual relationship between the two.

Race

No scientific evidence has demonstrated any difference in the outcome of mercury exposure that is attributable to race.

Sex

No scientific evidence has demonstrated any difference in the outcome of mercury exposure that is attributable to sex.

Clinical

History

The diagnostic approach for patients with suspected mercury toxicity begins with a thorough history that includes occupations, hobbies, and levels of seafood intake. All toxic presentations, whether acute, chronic, or subacute, are difficult diagnoses because multiple organ systems are affected (eg, CNS, kidney, mucous membranes) and can mimic a variety of other diseases. If no such history exists, clinical suspicion can be confirmed by laboratory analysis.

The clinical presentation of mercury toxicity can manifest in a variety of ways, depending on the nature of the exposure, the intensity of the exposure, and the chemical form. Acute toxicity usually is related to the inhalation of elemental mercury or ingestion of inorganic mercury. Exposure to organic mercury leads to chronic toxicity and, occasionally, acute toxicity.
 

• Acute exposure caused by inhaled elemental mercury can lead to pulmonary symptoms. Initial signs and symptoms, such as fever, chills, shortness of breath, metallic taste, and pleuritic chest pain, may be confused with metal fume fever. Other possible symptoms could include stomatitis, lethargy, confusion, and vomiting. In addition, elemental mercury can also be injected causing a life-threatening pulmonary embolism.
• Recovery is usually without sequela, but pulmonary complications of inhaled toxicity may include interstitial emphysema, pneumatocele, pneumothorax, pneumomediastinum, and interstitial fibrosis. Fatal ARDS has been reported following elemental mercury inhalation.
• Chronic and intense acute exposure causes cutaneous and neurological symptoms. The classic triad found in chronic toxicity is tremors, gingivitis, and erethism (ie, a constellation of neuropsychiatric findings that includes insomnia, shyness, memory loss, emotional instability, depression, anorexia, vasomotor disturbance, uncontrolled perspiration, and blushing).
• Additional findings may include headache, visual disturbance (eg, tunnel vision), peripheral neuropathy, salivation, insomnia, and ataxia.
• Without a complete history, mercury toxicity, especially in elderly individuals, can be misdiagnosed as Parkinson disease, senile dementia, metabolic encephalopathy, depression, or Alzheimer disease.
• Elemental mercury has poor GI absorption and, therefore, oral or rectal exposure to elemental mercury from a thermometer should have no toxic effect. Dental amalgams also contain elemental mercury. Dental professionals who are in contact with amalgam must follow specific guidelines to avoid exposure to toxic amounts of aerosolized elemental mercury. Patients with dental amalgam fillings have slightly elevated levels in their urine, but these findings have not correlated with any systemic disease.
  • In December 2002, the United States Food and Drug Administration (FDA) published a Consumer Update on dental amalgams. It had the following statement to make: "FDA and other organisations of the U.S. Public Health SERVICE (USPHS) * continue to investigate the safety of amalgams used in dental restorations (fillings). However, no valid scientific evidence has shown that amalgams cause harm to patients with dental restorations, except in the rare case of allergy".¹²
  • The FDA has now released final regulations on the use of dental amalgam.¹³
• Inorganic mercury or mercuric salt exposure mainly occurs through the oral and GI tract. Its corrosive properties account for most of the acute signs and symptoms of inorganic mercury or mercuric salt toxicity. The acute presentation can include ashen-gray mucous membranes secondary to precipitation of mercuric salts, hematochezia, vomiting, severe abdominal pain, and hypovolemic shock. Systemic effects usually begin several hours postingestion and may last several days. These effects include metallic taste, stomatitis, gingival irritation, foul breath, loosening of teeth, and renal tubular necrosis leading to oliguria or anuria.
• Batteries contain inorganic mercury but are rarely the cause of systemic symptoms. Ingestion of batteries by pediatric patients is a common problem, and its complications are related to local corrosive complications.
  • Consider chelation therapy in patients who ingest mercury-containing batteries if symptoms of mercury toxicity are present.
  • Use of cathartics and water-soluble enemas is useful for increasing transit time of released mercury, but these treatments are not indicated for intact batteries.
• Chronic exposure usually results from prolonged occupational exposure to elemental mercury that is converted into the inorganic form, topical application of mercurial salves, and the chronic use of diuretics or cathartics.
  • Chronic exposure can present with renal failure, dementia, and acrodynia.
  • Acrodynia, known as Pink disease and considered to be a mercury allergy, presents with erythema of the palms and soles, edema of the hands and feet, desquamating rash, hair loss, pruritus, diaphoresis, tachycardia, hypertension, photophobia, irritability, anorexia, insomnia, poor muscle tone, and constipation or diarrhea.
  • Acrodynia does not present in everyone who is exposed to inorganic mercury, but it is an indicator of widespread disease.
• Organic mercury poisoning usually results from ingestion of contaminated food. The long chain and aryl forms of organic mercury have similar characteristics of inorganic mercury toxicity.
  • The onset of symptoms usually is delayed (days to weeks) after exposure.
  • Organic mercury targets enzymes, and the depletion of these enzymes must occur before the onset of symptoms.
  • Symptoms related to toxicity are typically neurological, such as visual disturbance (eg, scotomata, visual field constriction), ataxia, paresthesias (early signs), hearing loss, dysarthria, mental deterioration, muscle tremor, movement disorders, and, with severe exposure, paralysis, and death.
  • Organic mercury targets specific sites in the brain, including the cerebral cortex (especially visual cortex), motor and sensory centers (precentral and postcentral cortex), auditory center (temporal cortex), and cerebellum.
• All forms of mercury are toxic to the fetus, but methylmercury most readily passes through the placenta. Even with an asymptomatic patient, maternal exposure can lead to spontaneous abortion or retardation.

Physical

Focus the physical examination on the areas most commonly affected.

• Perform a complete neurological examination, including a detailed cerebellar examination. Perform a full visual field evaluation.
• Perform abdominal and rectal examinations, with stool guaiac testing, and include documentation of a skin examination.

Causes

• Causes of elemental mercury toxicity include barometers, batteries, bronzing, calibration instruments, chlor-alkali production, dental amalgams, electroplating, fingerprinting products, fluorescent and mercury lamps, infrared detectors, the jewelry industry, manometers, neon lamps, paints, paper pulp production, photography, silver and gold production, semiconductor cells, and thermometers.
• The causes of inorganic mercury toxicity include antisyphilitic agents, acetaldehyde production, chemical laboratory work, cosmetics, disinfectants, explosives, embalming, fur hat processing, ink manufacturing, mercury vapor lamps, mirror silvering, the perfume industry, photography, spermicidal jellies, tattooing inks, taxidermy production, vinyl chloride production, and wood preservation.
• The causes of organic mercury toxicity include antiseptics, bactericidals, embalming agents, the farming industry, fungicides, germicidal agents, insecticidal products, laundry products, diaper products, paper manufacturing, pathology products, histology products, seed preservation, and wood preservatives.
• Very contraversial source of organic mercury exposure is thimerosal, an additive preservative used in vaccines to prevent bacterial contamination. The most commonly used vaccines that contain thimerosal are for diphtheria-tetanus-whole cell pertussis (DTP), Haemophilus influenzae (HIB), and hepatitis B.

• Search for CME/CE on This Topic »

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