Toxicology of Mercury, Lead, Cadmium, and Arsenic in the Human Body

Toxic metals such as mercury (Hg), lead (Pb), cadmium (Cd), and arsenic (As) are non-essential elements that can bioaccumulate and damage human health. These metals enter the body via inhalation, ingestion, or skin contact, and each has distinct chemical forms and pathways. Mercury exists as elemental (liquid or vapor), inorganic (salts, e.g. HgCl₂), or organic (methylmercury) forms. Lead is found as metallic lead or inorganic salts (Pb²⁺); cadmium mainly as Cd²⁺ salts or fumes; arsenic chiefly as inorganic trivalent (As³⁺) and pentavalent (As⁵⁺) compounds. All four are absorbed to varying extents and distributed to target organs, where they bind cellular proteins (often at sulfhydryl groups) and interfere with normal biochemistry. They are eliminated slowly, often via urine and feces, so that chronic exposure leads to accumulation in body tissues. This report reviews the toxicokinetics (absorption, distribution, metabolism, excretion) and toxicodynamics (organ effects, symptoms) of these metals, and summarizes well-documented human poisoning cases.

Glossary of Key Terms

Absorption – Entry of a substance into the bloodstream after exposure (e.g. through lungs or gut).
Bioaccumulation – Gradual buildup of a substance (e.g. a heavy metal) in tissues over time due to slow elimination.
Biomagnification – Increase in a chemical’s concentration up the food chain (e.g. mercury in fish eaten by humans).
Chelation – Medical use of compounds (e.g. EDTA, DMSA) that bind metals to aid excretion.
Half-life – Time for half of the substance to be eliminated from the body (may be minutes to decades for heavy metals).
Metallothionein – A protein rich in cysteine (–SH groups) that binds metals (e.g. Cd, Zn, Hg) and can sequester them in liver/kidneys.
Nephrotoxicity – Toxic damage to the kidneys (common with Hg, Cd, Pb).
Neurotoxicity – Toxic damage to nervous system (common with Hg, Pb, As).
Porphyrin – Precursors in heme synthesis; lead inhibits key enzymes (e.g. ALA-dehydratase, ferrochelatase), causing buildup of intermediates like protoporphyrin.
Uptake Transporters – Proteins (e.g. DMT1, OATs) that carry metals or their complexes into cells (e.g. Pb and Cd use the DMT1 iron channel; kidney OAT1/3 transport Hg-cysteine conjugates).

Mercury (Hg)

Forms and Exposure: Mercury has three forms with very different toxicology. Elemental mercury (Hg⁰) is liquid at room temperature; its vapor is readily inhaled from broken thermometers or industrial emissions. Inorganic mercury (Hg²⁺) includes water-soluble salts (e.g. mercuric chloride) found in some disinfectants, skin-lightening creams, or gold mining chemicals. Organic mercury such as methylmercury is produced by bacteria in water and concentrates in fish. The main human exposures are inhalation of vapor (Hg⁰), ingestion of contaminated seafood (methylmercury, MeHg), and ingestion or dermal contact with mercury salts. Dental amalgam fillings release small amounts of Hg vapor.

Absorption: Inhaled Hg vapor is highly absorbed – roughly 70–80% of inhaled Hg⁰ enters blood. By contrast, swallowing elemental mercury leads to <0.01% absorption (so an intact mercury spill in the stomach is usually harmless). Inorganic Hg salts are absorbed moderately by mouth (about 7–15% of ingested dose); they can also penetrate skin in mercury-containing ointments. Organic methylmercury is ~95–100% absorbed when eaten in fish. Dermal absorption of metallic Hg or salts is limited (except prolonged contact with some salts).

Distribution and Metabolism: Absorbed mercury circulates bound to proteins or in red blood cells. Elemental Hg⁰ vapor dissolves in blood, diffuses widely, and crosses cell membranes easily because it is uncharged and lipid-soluble. Within tissues (especially red blood cells and brain), Hg⁰ is oxidized to mercuric Hg²⁺ over minutes. Methylmercury also penetrates cells (entering via amino acid transporters) and is oxidized in cells to Hg²⁺. In contrast, inorganic Hg²⁺ (from salts) is not lipid-soluble and stays mostly in extracellular fluid and kidneys; it does not cross the blood–brain or placental barriers appreciably. Mercury has high affinity for sulfhydryl groups, so it binds to many enzymes and structural proteins. Mercuric mercury accumulates primarily in the kidneys (proximal tubule cells) and liver. Elemental/organic mercury deposits strongly in the brain and kidneys; MeHg causes severe brain damage in fetuses and adults. Some inorganic Hg can be found in placenta and breast milk, indicating fetal transfer.

Excretion: Mercury is eliminated slowly. Elemental Hg⁰ that remains unmetabolized is partly exhaled in breath, accounting for fast initial loss. Most absorbed mercury is oxidized to Hg²⁺ and excreted via urine and feces. Excretion is biphasic: a rapid initial phase (days to weeks) followed by a prolonged slow phase. The overall body half-life of mercury (reflecting urinary/fecal excretion of Hg²⁺) is on the order of 30–90 days (longer for those with high burden). For long-term exposure, urine mercury concentration is the best biomarker of total body burden, whereas blood mercury reflects only recent inhalation. Hair mercury reflects methylmercury exposure more than elemental/inorganic Hg. Mercury stored in kidneys and brain may remain for months or years.

Toxic Effects: Mercury’s toxicity depends on its form and target organs. Elemental and inorganic mercury predominantly damage the central nervous system and kidneys. Chronic exposure to Hg vapor causes a classic syndrome of tremor, excitability, and behavioral changes (“erethism”: irritability, memory loss, shyness, insomnia), along with gingivitis and excessive salivation. Tremors of the hands and limbs are common, as is proteinuria (kidney damage). Inorganic salts (if ingested) primarily irritate the GI tract (causing vomiting, diarrhea, and sometimes severe ulceration) and then injure the kidneys (acute tubular necrosis, proteinuria). Organic methylmercury causes delayed neurotoxicity: patients develop sensory disturbances (“glove-and-stocking” numbness), ataxia (loss of coordination), dysarthria (slurred speech), constricted visual field and hearing impairment. These symptoms are due to widespread neuronal loss. High-level exposure to any mercury form can cause acute encephalopathy, coma, and death. Developing fetuses and infants are especially susceptible: women exposed to MeHg gave birth to babies with microcephaly, cerebral palsy–like deficits, and severe intellectual disability (called congenital Minamata disease).

Medical Case Studies: The classic case is Minamata disease (1950s Japan), in which factory discharges of methylmercury contaminated seafood. Over 2,000 people were affected, with symptoms as above. A similar incident in Iraq (1971) poisoned thousands via bread made from MeHg-treated grain. More recent reports include episodic mercury spills or occupational inhalation leading to tremor, personality change and renal dysfunction. (For example, mercury vapor released during paint removal has caused childhood acrodynia with pink discolored extremities, but full cases are rare now.) Dental amalgam exposure is debated: urine Hg correlates with number of amalgam surfaces, but widespread poisoning from fillings has not been proven. Overall, overt mercury poisoning is now uncommon in modern settings, but environmental methylmercury and artisanal gold mining remain public health concerns.

Lead (Pb)

Sources and Exposure: Lead is widely found in old paint, plumbing, solder, batteries, and some industrial processes. Historically, leaded gasoline and paint caused pervasive exposure; today the main risks are renovating old buildings, manufacturing (smelting, battery factories), and hobbies (bullets, fishing weights, ceramics). Children are especially at risk through ingestion of lead paint chips or contaminated dust (pica behavior), and adults through inhalation of lead fumes or dust.

Absorption and Distribution: Lead is absorbed via lungs and gut. Inhalation of fine lead particles is very efficient (small particles deposit deeply). Ingested inorganic lead is partly absorbed in the duodenum; adults absorb ~10%, but children (especially if iron-deficient) absorb up to 50% of ingested lead. Lead in blood is mostly bound in red cells (~99%) where it inhibits heme enzymes (ALAD). Some lead remains in plasma bound to proteins. Lead crosses the placenta and enters fetal blood.

In the body, lead is distributed to bone and teeth (≈90–95% of the total body burden in adults), and to soft tissues (liver, kidney, brain). It deposits especially in growing bone (trabecular in children). The skeletal stores act as a long-term reservoir: lead has a half-life in bone of years to decades. Under conditions like pregnancy, osteoporosis, or hyperthyroidism, bone lead can be mobilized back to blood. These bone reserves explain why blood lead can remain elevated long after external exposure stops.

Excretion: Lead is eliminated slowly via urine and feces; urine excretion is about twice that of feces. Minor amounts appear in saliva, sweat, and breast milk. The blood half-life is about 30 days (in adults), whereas lead in bone may persist for years. Lead has no known biological role, so any accumulation is potentially toxic.

Toxic Effects: Lead interferes with many cellular processes, most notably heme synthesis and neuronal function. By inhibiting enzymes such as δ-aminolevulinic acid dehydratase (ALAD) and ferrochelatase, lead causes microcytic anemia with basophilic stippling of red cells (due to accumulation of lead–RNA complexes). Lead also mimics calcium and can perturb neurotransmitter release and synapse formation. Thus, neurological effects are prominent: children exposed to lead show reduced IQ, learning disabilities, attention deficits, and hearing loss (even at low blood levels). Adults may develop headache, memory loss, and peripheral neuropathy (wrist-drop or foot-drop due to motor nerve damage). Lead also affects other organs: it can cause abdominal pain and constipation (“lead colic”), kidney tubular injury (especially with chronic high exposure), and hypertension. Lead lines (blue-black bands on gums or wrist) are historic clinical signs but not always seen.

Symptoms: Acute high-dose lead poisoning (rare today) causes severe abdominal pain, vomiting, constipation, headache, and encephalopathy (coma, seizures). Chronic lower-level exposure yields more subtle effects: in children, developmental delay, behavioral issues (irritability, hyperactivity), and anemia; in adults, anemia, mild cognitive changes, and neuropathy. A classic picture (erethism) includes fatigue, irritability, and loss of concentration. Laboratory clues include elevated blood lead, increased erythrocyte protoporphyrin (ZPP), and anemia.

Case Studies: Lead poisoning from old paint and renovation remains common. For example, a case series of three painters exposed to 19th-century lead paint reported malaise, abdominal cramps, nausea, and mild confusion. All had high blood lead (≈84–85 μg/dL) and anemia; two required chelation therapy. Despite treatment and source removal, bone-lead stores caused prolonged elevated blood levels. In children, notable outbreaks included Devonshire colic in 17th-century England (lead-lined cider presses) and modern incidents in developing countries. In 2014–2016, Flint, Michigan water poisoning highlighted how lead in old pipes can leach and cause widespread exposure. These cases underscore that even “hidden” sources of lead (pipes, paint, toys) can have serious health impacts.

Cadmium (Cd)

Sources and Exposure: Cadmium occurs in metal ores and is released by mining, smelting, and refining of zinc and lead. It is used in nickel–cadmium batteries, pigments, and solders. Tobacco smoke is a major source of cadmium exposure for smokers. Food (rice, leafy greens) and contaminated water may contain Cd, especially near industrial areas or phosphate fertilizers.

Absorption and Distribution: Inhaled cadmium (as dust or fumes) is absorbed into blood depending on particle size and solubility: about 10–50% of inhaled Cd may be taken up. In contrast, only ~5–6% of ingested cadmium is absorbed in the gut (higher if nutritional deficiencies exist). Smokers absorb more cadmium because cigarette particles are tiny and lung deposition is high. Dermal absorption is negligible (~0.5%).

Absorbed Cd initially binds to albumin in plasma and is carried to the liver, where it induces metallothionein (MT) synthesis; cadmium–MT complexes circulate and are filtered by the kidneys. Storage: Cadmium accumulates predominantly in the kidneys (especially renal cortex) and liver, where it binds MT. It also deposits in bone (interfering with calcium metabolism). The biologic half-life of cadmium in kidney is very long (~10–30+ years) and in liver ~4–19 years. Thus, body burden rises over a lifetime: adults may carry 10–50 mg of Cd in tissues, whereas neonates have essentially none.

Excretion: Elimination of cadmium is very slow because it is tightly bound by proteins. The main route is urinary excretion of cadmium and cadmium–metallothionein complexes. Under normal conditions, only about 0.01–1% of body Cd is excreted per day. Biomarkers: Blood cadmium reflects recent exposure; urine cadmium (especially with low-molecular-weight proteinuria) indicates long-term body burden. However, once kidney damage occurs, cadmium is lost more rapidly (so urine Cd may rise even as body burden is fixed).

Toxic Effects: Cadmium’s hallmark toxicity is renal. Chronic low-level exposure causes progressive damage to the proximal renal tubules. Early signs are tubular proteinuria (elevated β2-microglobulin in urine). Higher doses cause glucosuria, phosphate wasting, and declining glomerular filtration. Ultimately, cadmium nephropathy can lead to kidney failure. Because damaged tubules fail to reabsorb calcium and phosphate, bone is affected: osteomalacia and osteoporosis (softening and fragility) can result, exemplified by Japan’s itai-itai disease. This syndrome (“ouch-ouch disease”) occurred in women who drank rice paddies’ water contaminated by Cd-contaminated mining waste. They suffered severe back pain, multiple bone fractures, and kidney failure simultaneously. Cadmium can also damage the lungs: inhalation of high Cd fume causes acute pulmonary edema and chronic obstructive lung disease (workplace pneumonitis). Itai-itai patients also had anemia and low blood pressure. Other reported effects of chronic Cd include hypertension and potential risk for prostate and breast cancer, although kidney and bone are the primary targets.

Symptoms: Acute cadmium inhalation produces flu-like “metal fume fever” (chills, cough, chest tightness), and high-level inhalation leads to severe pneumonitis. Oral cadmium ingestion (rare) causes nausea, vomiting, and liver injury. Chronic poisoning presents with fatigue, anemia, proteinuria, and bone pain. In itai-itai disease, patients walked with difficulty due to fractures. Occupational case reports from battery and smelter workers often describe weakness, loss of appetite, anemia, and kidney abnormalities. Cadmium is also carcinogenic (IARC Group 1) – linked to lung and prostate cancer in industrial exposures, but this is beyond the usual clinical syndrome.

Case Studies: The term “itai-itai” (Japanese for “it hurts”) arises from a real endemic. In Toyama Prefecture (1950s–60s), mining activity released cadmium that accumulated in rice fields. Many post-menopausal women developed the disease. Epidemiologic studies confirmed they had extremely high urinary cadmium (20–30 μg/g creatinine) and showed severe osteoporosis/osteomalacia with renal failure. Treatment was largely supportive (rehabilitation and chelation in some cases). Other cases come from occupational outbreaks: in Japan and Europe, battery plant workers with blood Cd >100 μg/L developed kidney dysfunction and early bone disease. There are no analogous “mass poisoning” incidents like Minamata for Cd, but surveys in polluted areas (e.g. Belgium, US Appalachia) show subclinical kidney changes in populations with elevated Cd. Because cadmium smelting is now regulated, most new cases are sporadic (e.g. someone eating contaminated shellfish or smoking heavily).

Arsenic (As)

Sources and Exposure: Arsenic is a ubiquitous metalloid in the earth’s crust. Inorganic arsenic compounds (arsenites and arsenates) are used industrially (pesticides, wood preservatives, semiconductors, mining). Naturally, arsenic leaches into groundwater in some regions (Bangladesh, West Bengal, Taiwan, parts of the US and Chile). People are exposed by drinking contaminated water, eating food grown with arsenic-rich water (rice is a well-known example), or inhaling dusts/fumes (smelting, coal burning). Organic arsenic (arsenobetaine in seafood) is less toxic and excreted rapidly.

Absorption and Metabolism: Ingested inorganic arsenic is very well absorbed (>90%) through the GI tract. Inhaled arsenic is also readily taken up. In the body, inorganic arsenic is metabolized in the liver via methylation reactions (using arsenic methyltransferase) to mono- and dimethylated species (MMA, DMA). This biotransformation generally enhances excretion and was long considered detoxification. Some arsenic remains in red blood cells briefly, but most is processed by the liver. Very little arsenic is stored long-term; most undergoes clearance.

Excretion: Over half of an acute arsenic dose is excreted in urine within days. Ingested arsenic is eliminated mostly as methylated metabolites: about 80% excreted as dimethylarsinic acid (DMA) and ~10% as monomethylarsinic acid (MMA). Only a small fraction remains as inorganic As in urine. The half-life of inorganic arsenic in the body is ~3–5 days. Because elimination is rapid, urinary arsenic levels (measured within days) reflect recent exposure. Blood arsenic is cleared within hours, so it is useful only in acute poisoning. Hair and nail arsenic levels can indicate exposure weeks to months past, but they accumulate organic arsenic too (e.g. from seafood) so they require careful interpretation.

Toxic Effects: Arsenic’s toxicity stems from its binding to sulfhydryl groups of enzymes and substituting for phosphate in biochemical reactions. Acute arsenic poisoning (massive intake) produces severe gastrointestinal and cardiovascular collapse. Within hours of ingestion, victims develop intense vomiting, diarrhea (often bloody), and abdominal pain. Hypotension and shock follow, and multi-organ failure (renal, liver, respiratory distress) can be fatal. Peripheral neuropathy (sensory loss and motor weakness) may appear after a delay. Chronic exposure (lower doses over years) leads to more insidious outcomes. The earliest sign is dermatologic: diffuse skin hyperpigmentation and hyperkeratosis (especially on palms and soles). Mee’s lines (white bands) can appear on nails. Over time, chronic arsenic causes characteristic skin changes and increases risk of skin cancer. Systemically, it induces vascular disease: endemic “blackfoot disease” (gangrene of lower limbs) was documented in Taiwan’s arsenic-poisoned wells. Arsenic also causes peripheral neuropathy and impaired intellectual development in children exposed before age 10. Importantly, arsenic is a known carcinogen: chronic high-level exposure is linked to cancers of the skin, lung, and bladder. Even at moderate exposure, studies show elevated liver and lung cancer rates. Other reported effects include QT prolongation (heart rhythm), and in utero exposure has been associated with increased infant mortality and possibly fetal anomalies (though evidence is mixed).

Symptoms: Chronic arsenic toxicity manifests gradually. Patients may complain of weakness, abdominal discomfort, and numbness in hands/feet. Skin findings (dark freckles and hard patches) are hallmark clues. Laboratory tests show high urinary DMA and MMA, and elevated liver enzymes in some cases. In arsenic-endemic areas, coordination of dermatologic, neurologic, and vascular symptoms often clinches the diagnosis.

Case Studies: The most cited human case is Bangladesh (and West Bengal, India), where up to 50 million people have been exposed to arsenic in well water. Surveys have found that ~20 million people in Bangladesh are drinking water above the WHO limit (50 μg/L). Many of these individuals show skin lesions of arsenicosis and have increased rates of lung, bladder and skin cancers. One analysis estimated that up to 1 in 10 of the exposed population may eventually develop an arsenic-related cancer. Another famous incident occurred in Taiwan (“blackfoot disease”) where drinking artesian well water led to peripheral vascular disease and gangrene. Industrial exposures have also produced case clusters: for example, in a Chinese factory, workers exposed to inorganic arsenic fumes developed peripheral neuropathy and skin cancer over time. In all these cases, biopsies and nail arsenic levels corroborated the diagnosis. Overall, arsenic poisoning remains a global public health issue, and its late effects (cancer, vascular disease) are well documented in population studies.

Comparison and Treatment

All four metals share the property of binding to vital enzymes and producing oxidative stress, but their organ targets differ. Mercury and arsenic primarily injure the nervous system; lead and cadmium target blood-forming and renal systems. Chronic effects often relate to the slow release from tissue stores (bone for lead, kidney for cadmium, brain/kidney for mercury). Diagnosis relies on history (e.g. work or diet), clinical signs, and blood/urine metal levels or biomarkers (e.g. urinary NAG for cadmium, zinc protoporphyrin for lead). Treatment focuses first on removing exposure. Chelating agents (e.g. EDTA for Pb, dimercaprol or DMSA for Hg/Cd/As) can enhance urinary excretion of some heavy metals, but timing and choice are critical. For example, dimercaprol is used in acute arsenic or inorganic mercury poisoning, while succimer (DMSA) is used for lead and mercury. Folate and calcium supplementation may also be considered (e.g. Ca can reduce lead release from bone). Unfortunately, much of the damage (neuronal death, kidney scarring) is irreversible, so early detection and prevention are paramount.

Sources: Authoritative toxicological reviews and case series were used to compile this report. Absorption, distribution, and excretion data come from ATSDR and scientific reviews. Clinical effects and case details are documented in toxicology texts and reports of incidents (e.g. Minamata, itai-itai). The Bangladesh arsenic data are from epidemiological studies. Wherever possible, quantitative values and mechanisms are cited from these sources.