Mercury (Hg)
By Jacqueline Hubbard, PhD, DABCC
The Toxin Spotlight is brought to you by ADLM's
Published in the June 2025 issue of Clinical & Forensic Toxicology News
Elemental mercury (Hg0) is a silver liquid at room temperature and quickly turns to vapor at elevated temperatures. It has an atomic number of 80, an average mass of 200.59, and 7 naturally occurring, stable isotopes. It may be converted to inorganic and methylated forms, which are considered more toxic than its elemental form. Most human exposures occur primarily via inhalation of elemental mercury through occupational exposure or dental amalgam, or ingestion of organic forms of mercury, primarily through seafood. The degree of toxicity after exposure depends largely on its chemical form but may include neurological, renal, hepatic, and/or reproductive damage. Exposure should be regularly monitored for those who work in industrial settings, and methylmercury-contaminated seafood should be avoided. This article reviews the sources of mercury, important pharmacokinetic properties, its toxicity, treatment options, and testing methods.
Trace amounts of Hg0 are present in the earth’s crust, in the form of cinnabar, and are degassed into the atmosphere (1). Anthropogenic activities including industrialization, processing of mercury-rich ores, waste disposal, and combustion of fossil fuels, also significantly contribute to the presence of atmospheric mercury (1, 2). According to the United Nations Global Mercury Assessment, the largest contributing source to global mercury emissions is artisanal and small-scale mining, followed by coal combustion, non-ferrous metals production, and cement production (3). In the United States, stationary coal combustion is by far the largest contributor. Other sources included broken thermometers, barometers, fluorescent light bulbs, certain button cell batteries, lamps, skin lightening creams, and certain vaccines acting as a preservative (2, 4). Improved mercury-free alternatives and restrictions on sales of some of those products have led to the decline of mercury in household products.
Upon entering the atmosphere, mercury deposits into the terrestrial environment. Elemental mercury can combine with other elements, such as chlorine and sulfur, to form inorganic compounds (5). Inorganic mercury may also be present in ayurvedic medicine, skin lightening cosmetic products, other therapeutics, and used as part of ethnic or folk religious or medical practices (5–7). In the sediment at the bottom of lakes, elemental mercury is bioconverted to inorganic and methylated forms of mercury by microorganisms. Biomagnification and bioaccumulation lead to high concentrations of methylmercury in shellfish and predatory fish (8). Commercially available fish are safe for consumption containing <0.3 µg/g mercury, but some game fish contain >2 µg/g. Regular consumption of methylmercury-contaminated seafood accounts for >90% of mercury intake in the United States (2). A 200 g fish that contains high levels (0.5 µg/g) of methylmercury results in uptake of ~100mg methylmercury, whereas a fish with moderate levels (0.05 µg/g) leads to an uptake of ~10 µg (4).
Dental amalgams are created by mixing powdered metal alloy with liquid mercury to form a putty that can be placed into a tooth cavity and shaped appropriately. They contain ~50% mercury. Hg0 is released as a result of chewing. Mercury vapor is absorbed through the gums and pulmonary airways or is quickly converted to methylmercury by oral bacteria (8, 9). The average person with mercury-containing amalgam fillings will uptake the same amount of mercury as moderately mercury- contaminated fish (4). The use of mercury in dental fillings has declined significantly since the UNEP Global Mercury Partnership recommended phasing out its use, and as resin-based and other white fillings have become more popular (10).
Occupational exposure to mercury is most commonly through vapor forms (1). Mining, manufacturing of products such as fluorescent lamps or batteries, as well as dental and health care professionals, are at risk of elemental mercury vapor exposure. Exposure to inorganic mercuric aerosols may occur in chloralkali plants and other chemical industries that use mercuric salts. Other chemical manufacturing facilities that use mercury-based catalysts may expose their employees to organic or inorganic mercury aerosols, which may be converted to methylmercury in the environment.
Elemental mercury vapor is readily absorbed through the lungs, while inorganic salts and methylmercury are primarily absorbed through the GI tract. Mercury is distributed widely throughout the body, but can cross the blood-brain barrier and placental barrier. Mercury is eliminated through both the feces and urine, and accumulates in the kidneys as it is eliminated. It has a half-life (t1/2) of 30- 60 days and can take more than 6 months to reach steady state concentrations in urine in chronically exposed individuals (4, 8). In the brain, ionized mercury has a half-life of ~20 years, likely due to ion trapping and tight binding to proteins (4).
The CNS and kidneys are primarily affected by mercury toxicity. Common symptoms after exposure include fever, cough, tremors, cognitive impairment, hallucinations, reduced motor coordination and reaction time, insomnia, personality changes, and gingivitis (4, 8). However, other organs are also affected. Elevated liver function tests correlate with high blood mercury concentrations, and mercury is an associated risk factor for nonalcoholic fatty liver disease (11). Mercury negatively impacts reproductive health, including abnormal menstrual cycles, infertility, ovarian failure, hormonal disorders, spontaneous abortions, and congenital abnormalities (12). The exact symptoms associated with mercury toxicity will depend on the concentration, route of exposure (inhalation, ingestion, or dermal), and duration of exposure (acute vs. chronic). Importantly, inorganic forms of mercury (elemental or ionized) are relatively less toxic than organic forms:
Relative toxicity: Hg0 <<< Hg2+ < CH3Hg2+ or (CH3)2 Hg
Ingestion of Hg0 is relatively innocuous due to the poor absorption by the GI system, but prolonged exposure may result in GI distress. Dermal absorption can occur, but is uncommon.
Vaporized Hg is considered dangerous because it is odorless and invisible, and is absorbed rapidly in the respiratory tract. Hg vapor is uncharged, highly lipid soluble, and consequently easily passes through the blood-brain barrier and causes neurological impairment (4). Symptoms after acute inhalation are respiratory (cough, dyspnea, and chest pain), GI (nausea and vomiting), and neurological (tremors, irritability, and insomnia). Chronic exposure presents with tremors, irritability, memory loss, delirium, personality changes, and gingivostomatitis. It is believed that bioaccumulation of mercury in the brain may contribute to neurodegenerative disorders such as Parkinson, Alzheimer’s Diseases, or amyotrophic lateral sclerosis with genetically susceptible individuals being at higher risk (4). Once in the cells, elemental mercury is then oxidized it to Hg2+ by the hydrogen peroxidase-catalase pathway in the liver, lungs, erythrocytes, and brain (4).
Ionized mercury readily forms mercury salts, such as mercury chloride or mercuric nitrate. Mercuric nitrite was key to the process of felting, or manufacturing hats from fur, in the seventeenth century (13). This process was often done in poorly ventilated rooms, and hat making quickly became known as a dangerous profession. Many hatters suffered from vapor mercury poisoning that led to neurological damage, including tremors and irrational behavior, and quickly became known as “mad hatter disease.”
Inorganic forms of mercury are readily absorbed from the GI tract and react with chlorine and oxygen. Mercuric chloride (HgCl2) causes cytotoxicity, oxidatitive stress, and increased beta-amyloid secretion (4). Hg2+ is particularly toxic because it has a high affinity for thiols and readily reacts with sulfur in thiol groups of proteins, interfering with their structure, function, and biological activity. Interactions with nucleic acids, enzymes, ion channels, and transporters interfere with cellular function (9). Mercury also depletes glutathione (GSH) and reduces the activity of methionine synthase, an enzyme required for GSH synthesis. Without GSH sequestering free radicals, they cause oxidative damage. Accumulation of reactive oxygen species leads to decreased oxygen consumption, altered electron transport, loss of mitochondrial membrane potential, and apoptosis (9).
Acute exposure to mercury salts may cause severe GI damage and renal failure. Chronic exposure is particularly damaging to the central nervous system (CNS) and kidneys by causing neuropsychiatric symptoms and nephrotic syndrome, respectively. Even low levels of mercury, such as concentrations found in those with dental amalgams, induce neuronal degeneration and disturb excitability (9). As it is cleared, excess Hg2+ accumulates in the kidney and causes significant nephrotoxicity and proteinuria (8). Other effects of exposure to mercury salts include cardiovascular collapse, severe GI damage, and long term exposure may lead to neuropsychiatric symptoms and nephrotic syndrome (4).
Inorganic mercury is methylated by bacteria to form methylmercury (CH3Hg+) and dimethylmercury ((CH3)2Hg). These organic species are soft electrophiles and readily react with protein sulfhydryl and selenohydryl groups and form stable S-Hg and Se-Hg complexes, respectively (9). Very little methylmercury is free in cells because of this high affinity and this interaction damages the catalytic, binding, and transport functions of proteins. Methylmercury forms are readily absorbed and quickly distributed to the liver, kidney, and CNS (8). Organic mercury damages myelin and preferentially distributes into parts of the brain that control sensorimotor functions, leading to problems with coordination, equilibrium, and motor control (4).
In the 1950s, residents living off the west coast of Kyushu Island in Kumamoto Prefecture, Japan, observed strange behavior around Minamata Bay. Fish rotated continuously and floated belly-up to the surface, shellfish decomposed, birds fell midflight, and, most notably, cats salivated, convulsed, exhibited ataxic gaits, and frequently collapsed dead (14). Humans exhibited visual field constriction, dysarthria, auditory disturbances, sensory disturbances, ataxia, and tremors. Since the etiology of the disease was unknown, it was termed Minamata disease in 1956. Of the early diagnosed patients, more than half of them died within 6 months of symptom onset and all shared pathological findings including cerebral and cerebellar cortex necrosis (8). The cause was eventually linked back to a chemical plant owned by Chisso Corporation that dumped industrial waste into the bay for decades. This led to methylmercury-burdened fish, and the local population relied heavily on a seafood diet (9). Unfortunately, the company refused to take responsibility or prevent further contamination until 1965, after the Ministry of International Trade and Industry mandated that they install a closed water system to prevent further contamination (14). Similarly, an epidemic of methylmercury poisoning occurred in Iraq in the early 1970s when residents consumed bread prepared from mercury-based fungicide treated wheat seeds (9). The damage from these events lasted for decades – in utero exposure led to neurodevelopmental delays, symptoms of Minamata disease, increased rates of infantile cerebral palsy, and even death (8, 9, 14). In addition, many thousands of individuals suffered from chronic Minamata disease, fishing was banned in Minamata Bay, the marine life and piscivores suffered from high mercury levels, and the environmental damage was irreversible.
Due to its lipophilic nature, methylmercury readily crosses the placental barrier and leads to fetal concentrations approximately double those of the mother (4). It preferentially accumulates in the CNS and impairs neurological, intellectual, and motor development (15). Breastfeeding with methylmercury contaminated milk was associated with deficits in attention and memory as well as decreased intelligence scores (9, 15). Consumption of contaminated seafood should be avoided while pregnant.
The recommended treatments for mercury toxicity include (a) removal from the source of exposure, (b) supportive care, (c) decontamination, and (d) chelation therapy. Removal from exposure may be difficult if the source is unknown, but treatment may depend on whether the exposure is acute or chronic. Supportive care should focus on maintaining the ABCs (airway, breathing, and circulation), correcting any electrolyte imbalances, and assessing neurological complications. Decontamination strategies depend on the form of mercury, but may involve activated charcoal or chelation therapy with dimercaprol, 2,3-dimercaptosuccinic acid, or D-penicillamine (8).
Analysis to determine mercury body burden may be performed on urine, blood, or hair. Urine is particularly useful to monitor the effectiveness of chelation therapy and is a better indicator of long-term exposure or mercury burden on the kidneys. Urine testing is frequently used to monitor occupational exposure to Hg. In an unexposed individual, urine mercury concentrations are typically <10 µg/ L. Tremors and subclinical neuropsychiatric symptoms may be observed with 24-hour urine concentrations between 30 – 100 µg/L, whereas concentrations >100 µg/L are associated with overt symptoms (8). Therapy may be initiated if methylmercury is >50 µg/L in the urine.
Blood mercury levels are predominantly used to diagnose acute poisoning because mercury concentrations rise sharply after ingestion, but fall over several days. Concentrations in blood rarely exceed 10 µg/L in unexposed persons. Blood concentrations of mercury ranging from 20 – 50 µg/L are associated with dysarthria, ataxia, and constricted visual fields (8). Blood concentrations >50 µg/L after methylmercury exposure or >200 µg/L after Hg2+ exposure are classified as significant and may warrant treatment (8). Umbilical cord blood may help determine methylmercury exposure to the fetus. Hair analysis is used to assess historical exposure.
Several techniques have been used to detect mercury in biological samples, including variations of atomic absorption spectrometry (AAS), atomic fluorescence spectrometry (AFS), inductively coupled plasma mass spectrometry (ICP-MS), direct mercury analyzer (DMA), and modified electrodes (2, 8, 16, 17). However, the most commonly used methods are ICP-MS and AAS.
ICP-MS ionizes the sample and separates ions based on their mass-to-charge ratio. It can detect mercury in clinical specimens down to low ng/mL concentrations. This technique can be combined with high-performance liquid chromatography or gas chromatography to separate mercury species.
There are several variations of AAS used in mercury detection. Cold vapor AAS is a technique that involves mercury reduction to its elemental form, vaporization, and measurement based on UV light absorption. It is highly sensitive, but is primarily used for inorganic mercury. Cold vapor AFS is similar, but uses fluorescence detection and is more common in biological samples. DMA involves the combustion of samples to release mercury vapor that is then directly measured by AAS or AFS. It is rapid but more commonly employed in forensic and environmental labs. Thermal desorption AAS with gold amalgamation (TD-GA-AAS) involves heating the sample to release mercury vapor, which is captured and concentrated on a gold trap. Mercury is then thermally desorbed from the gold and detected using AAS. However, TD-GA-AAS is not inherently suited for Hg speciation but instead is designed to measure total mercury.
Mercury is a pervasive environmental toxin originating from both natural processes and human activities. It undergoes chemical transformations in the environment, forming highly toxic species like methylmercury, which bioaccumulates in aquatic food chains and poses severe health risks through dietary exposure. The toxic effects of mercury, including neurological, renal, and reproductive damage, vary by chemical form and exposure route, with organic mercury being particularly dangerous due to its ability to cross biological barriers. Analytical techniques such as ICP-MS and CVAAS enable precise detection and speciation of mercury, aiding in diagnosis, exposure monitoring, and mitigation efforts. Reducing the biological impact if mercury requires stricter emissions regulations and safer alternatives alongside improved diagnostic methods to guide clinical and public health strategies. Through these efforts, the global burden of mercury on health and the environment can be significantly reduced.
Jacqueline Hubbard, PhD, DABCC, is the co-director of clinical chemistry and director of toxicology at Beth Israel Deaconess Medical Center, department of pathology, Harvard Medical School, in Boston, Mass.
The author has nothing to disclose.
From the humble tuna casserole to artistic displays of sushi, seafood is an integral component of the cuisine of most cultures. As a rich source of the omega-3 fatty acids thought to aid neurological development and cardiovascular health, seafood consumption is recommended by several health organizations, including the American Heart Association. However, reports of toxic chemicals and heavy metals in seafood have led many to question what’s really going in their mouths alongside that wasabi. This article will discuss two well-known toxic metals, mercury (Hg) and arsenic (As), and address common concerns related to their presence in seafood.
Both of these metals are found in multiple forms, with varying degrees of toxicological relevance. Mercury is released from soil, water, volcanic activity, and industrial sources as unionized vapor (Hg0) into the atmosphere. There, it can be converted to the water-soluble ion, Hg2+, and fall back to earth with rainwater. Hg2+, which is also released from industrial sediment, is methylated by aquatic microbes to form methylmercury (MeHg), the primary mercury-containing species in seafood. MeHg and similar compounds (e.g., ethylmercury, dimethylmercury) are referred to as “organic mercury”, while elemental Hg0 or compounds containing ionized Hg2+ (e.g., HgCl2) are referred to as “inorganic mercury”.
All forms of mercury pose risk of toxicity to humans, but MeHg is by far the most concerning when the route of exposure is ingestion. Unlike inorganic mercury, MeHg is well-absorbed (~95%) from the gastrointestinal tract; once absorbed, MeHg distributes extensively to tissues such as kidney, liver, and brain, with a systemic half-life of 6-8 weeks. Inorganic mercury is poorly absorbed and is not methylated by human metabolic enzymes, thus MeHg must be consumed to occur in humans. MeHg can be measured in blood samples, where it accumulates in erythrocytes to roughly 20 times the plasma concentration. However, a preferable analytical matrix may be hair, where MeHg accumulates to over 200 times the level in blood.
Although more toxic mercury species (e.g., dimethylmercury) are present in trace levels in seafood, the primary risk of toxicity arises from MeHg. MeHg is the predominant form of mercury in seafood, is readily absorbed from the digestive tract, and can rapidly cross the blood-brain barrier to exert its neurological effects. Long-lived and predatory fish (e.g., sharks) absorb MeHg from their diets, leading to higher MeHg levels than those present in species lower on the food chain. However, the risk of mercury toxicity from seafood consumption is low for most individuals, with the exception of acute poisonings (e.g., Iraq in 1971, Japan in the 1950’s).
The greatest danger of seafood-derived mercury is posed to the developing fetus: MeHg readily crosses the placenta and blood-brain barrier, thus it can accumulate in fetal tissues to concentrations significantly higher than maternal blood. Sufficient MeHg exposure in utero can lead to neurological deficits and developmental delays, even in infants whose mothers exhibit no mercury toxicity or only mild effects. For this reason, in March 2004, the Food and Drug Administration (FDA) released a safety warning intended to limit mercury exposure in pregnant and nursing mothers, women who may become pregnant, and young children.
The FDA alert recommends those individuals to avoid high-mercury fish (e.g., shark, king mackerel) entirely, and to limit consumption of lower-mercury fish (e.g., shrimp, canned tuna, salmon) to 1-2 meals per week. Fish consumption is still recommended because of the recognized benefits of specific omega-3 fatty acids for fetal neurodevelopment. A 2006 review published in JAMA concurred with these guidelines, finding that the benefits of fish consumption outweigh the risks of mercury and other food-borne toxins, and supporting the recommendation for consumption of two seafood meals per week for women of childbearing age. In May 2014, the FDA released a Quantitative Assessment of the Net Effects on Fetal Neurodevelopment from Eating Commercial Fish (pdf).
In contrast to mercury, the arsenic found in seafood presents minimal risk to humans. Inorganic arsenic (trivalent As[III] or pentavalent As[V]) is ubiquitous in groundwater and seawater; the predominant route of arsenic exposure in humans is through drinking water. Microbial and marine life transforms inorganic arsenic into a variety of organic species. The best-characterized organic forms include monomethylarsenate (MMA), dimethylarsenate (DMA), and arsenobetaine. Arsenic species are readily absorbed, with rapid elimination typically leading to complete clearance within a few days of a single ingestion.
Inorganic arsenic is highly toxic: high levels can cause neurological damage, anemia, leucopenia, and vascular disease, while low-level chronic exposure increases an individual’s risk of developing cancer. MMA and DMA were previously believed to be non-toxic, but have recently been linked to arsenic-induced toxicity. Humans can metabolize inorganic arsenic to MMA and DMA, and it is believed that these metabolites contribute significantly to carcinogenicity and overall toxicity, particularly in their trivalent (As[III]) forms.
However, inorganic arsenic, MMA, and DMA comprise only a very small amount (typically <5% combined) of the total arsenic-containing species in seafood, and generally fall well short of the toxic threshold in humans. The majority of arsenic in marine life takes the form of substituted macromolecules such as sugars. In fish, most arsenic is found as arsenobetaine (an analog of trimethylglycine), whereas other edible sea life, e.g., seaweed, has substantial quantities of arsenosugars. Arsenobetaine, arsenosugars, and their metabolites have shown little to no toxic potential in laboratory studies, suggesting that their consumption by humans is of minimal concern.
Analytical speciation is therefore essential to determine the clinical significance of arsenic levels. Methods coupling high-performance liquid chromatography to various detectors (e.g., atomic absorption spectroscopy, inductively-coupled plasma mass spectrometry) allow separation of highly-toxic inorganic and organic species from non-toxic arsenicals. Arsenobetaine is the major arsenic-containing compound found in human urine when the origin is dietary, whereas DMA and other toxic species can be detected after consumption of arsenic-contaminated water.
In conclusion, the major heavy metal risk posed by seafood consumption is exposure of a developing fetus to MeHg, thus women and children should limit intake of certain fish to minimize MeHg toxicity. Arsenic concentrations in seafood are notable, but the metal is present in the form of non-toxic arsenobetaine and arsenosugars. Laboratory analysis should include speciation to ascertain the source and clinical importance of urinary arsenic.
References
The Toxin Spotlight is brought to you by ADLM's