Toxicology – Arsenic Poisoning

Core Concept

Arsenic is a naturally occurring metalloid with important environmental, occupational, medicinal, and toxicologic relevance.

Toxicity depends strongly on its chemical form:

• Inorganic arsenic — most important in classic systemic poisoning
• Organic arsenic compounds — often considerably less toxic
• Arsine gas — produces a distinct syndrome dominated by massive intravascular hemolysis and should be considered separately

Acute inorganic arsenic poisoning classically causes:

Severe GI injury → capillary leak/hypovolemia → cardiovascular instability → multiorgan dysfunction

Delayed effects may include:

• Bone-marrow suppression
• Painful peripheral neuropathy
• Skin/nail changes

Chronic inorganic arsenic exposure is associated with:

• Skin abnormalities
• Peripheral neuropathy
• Cardiovascular and metabolic effects
• Increased cancer risk

Sources of Exposure

Potential sources include:

• Contaminated groundwater
• Mining and smelting
• Semiconductor manufacturing
• Glass and metal industries
• Historical pesticides and rodenticides
• Historical arsenic-containing wood preservatives
• Contaminated traditional or folk remedies
• Certain occupational processes

Many household applications described in older references are now obsolete or heavily restricted.

Seafood and Arsenic

Seafood, particularly some shellfish and seaweed, can contain substantial amounts of organic arsenic compounds.

These forms are generally much less toxic than inorganic arsenic.

However, recent seafood ingestion can markedly increase total urinary arsenic, potentially creating a misleading laboratory result.

Therefore arsenic speciation is often preferable to simply assuming an elevated total urinary arsenic concentration represents toxic inorganic exposure.

Mechanism of Toxicity

Arsenic disrupts several fundamental cellular processes.

Trivalent arsenic binds sulfhydryl groups and inhibits important enzymes.

Arsenic also interferes with:

• Cellular respiration
• Pyruvate metabolism
• Oxidative phosphorylation
• ATP generation
• Redox regulation

The result is widespread cellular dysfunction affecting:

• GI tract
• Cardiovascular system
• Nervous system
• Bone marrow
• Liver
• Kidneys

The older description of arsenic simply “uncoupling oxidative phosphorylation” is an oversimplification.

Toxic Dose

Historical texts provide specific lethal-dose ranges, but these are unreliable for bedside risk assessment.

Toxicity varies with:

• Arsenic species
• Solubility
• Formulation
• Route
• Absorbed amount
• Timing
• Patient factors
• Treatment delay

A credible significant inorganic arsenic ingestion should therefore be assessed according to the clinical syndrome and exposure circumstances, rather than relying on a single dose threshold.

Acute Arsenic Poisoning

Severe acute poisoning may evolve through several stages.

Early manifestations are predominantly:

• Burning GI discomfort
• Nausea
• Profuse vomiting
• Severe abdominal pain
• Watery diarrhea

Severe cases can resemble fulminant gastroenteritis or cholera-like illness.

Severe Gastrointestinal Toxicity

Profuse GI fluid loss can cause:

• Dehydration
• Hypovolemia
• Electrolyte abnormalities
• Metabolic acidosis
• Hypotension
• Shock

Hemorrhagic gastroenteritis can occur in severe poisoning.

This early GI syndrome may be mistaken for infectious gastroenteritis, delaying recognition of arsenic exposure.

Cardiovascular Toxicity

Severe acute arsenic poisoning can produce:

• Tachycardia
• Hypotension
• Shock
• Myocardial dysfunction
• Nonspecific ST-T abnormalities
• QT prolongation
• Ventricular dysrhythmias

Torsades de pointes has been reported.

Cardiovascular collapse may result from several mechanisms simultaneously:

GI fluid loss + capillary leak + vasodilation + direct myocardial toxicity

ECG Monitoring

Significant acute poisoning warrants:

• Initial ECG
• Continuous cardiac monitoring
• Serial ECG assessment when abnormalities are present

Particular attention should be given to:

• QRS
• QT/QTc
• Ventricular ectopy
• Rhythm

Electrolyte abnormalities can further increase dysrhythmia risk.

Pulmonary Toxicity

Severe systemic poisoning may cause:

• Dyspnea
• Hypoxemia
• Pulmonary edema
• Acute respiratory failure

Pulmonary edema may be related to systemic endothelial injury and severe shock rather than isolated primary cardiac failure.

Neurologic Toxicity – Acute

Severe poisoning can produce:

• Headache
• Weakness
• Confusion
• Delirium
• Encephalopathy
• Seizures
• Coma

These findings usually indicate substantial systemic toxicity.

Delayed Peripheral Neuropathy

One of the most characteristic delayed complications is a painful symmetric sensorimotor polyneuropathy.

It may begin days to weeks after the acute illness.

Typical pattern:

Distal symmetric “stocking-glove” neuropathy

Symptoms include:

• Burning pain
• Paresthesias
• Numbness
• Weakness
• Reduced reflexes
• Gait difficulty

Severe cases can resemble Guillain–Barré syndrome.

Arsenic Neuropathy vs Guillain–Barré Syndrome

Arsenic should be considered when a rapidly progressive neuropathy follows:

• Severe unexplained gastroenteritis
• Hypotension
• QT abnormalities
• Cytopenias
• Known environmental/occupational exposure

Electrodiagnostic studies may help characterize the neuropathy.

Recovery may require months and can be incomplete.

Hematologic Toxicity

Acute systemic poisoning can cause delayed:

• Anemia
• Leukopenia
• Neutropenia
• Thrombocytopenia
• Pancytopenia

Bone-marrow suppression may become more apparent several days after exposure.

Therefore a normal initial CBC does not exclude subsequent hematologic toxicity.

Renal Toxicity

Severe arsenic poisoning can cause AKI through several mechanisms:

• Shock/hypoperfusion
• Acute tubular injury
• Systemic toxicity
• Hemolysis in specific arsenic-related exposures such as arsine

Monitor:

• Creatinine
• Electrolytes
• Urine output
• Urinalysis

Hepatic Toxicity

Possible findings include:

• Elevated transaminases
• Hepatic dysfunction
• Rare severe hepatic injury

Liver abnormalities are generally part of severe multisystem poisoning rather than the dominant acute feature.

Dermatologic Findings – Chronic Exposure

Chronic inorganic arsenic exposure can produce characteristic skin abnormalities.

These include:

• Mottled hyperpigmentation
• Areas of hypopigmentation
• Palmar hyperkeratosis
• Plantar hyperkeratosis

A classic description is a mottled or “raindrop” pigmentation pattern.

These findings develop over time and are not useful for diagnosing a very recent ingestion.

Mees Lines

Transverse white nail bands—Mees lines—may appear weeks after substantial arsenic exposure.

Important limitation:

Mees lines are not specific for arsenic.

They can occur after other systemic illnesses or toxic exposures.

Their position as the nail grows may provide rough historical timing but should not replace exposure testing.

Garlic Odor – Poor Diagnostic Sign

A garlic-like odor has historically been associated with arsenic poisoning.

However:

• It is inconsistent
• It is subjective
• Other chemicals can produce similar odors

Its absence does not exclude arsenic poisoning, and its presence does not confirm it.

Chronic Arsenic Toxicity

Long-term inorganic arsenic exposure can produce:

• Fatigue
• Weakness
• GI complaints
• Peripheral neuropathy
• Skin pigmentation changes
• Palmar/plantar hyperkeratosis
• Hematologic abnormalities
• Cardiovascular effects

Exposure assessment is essential because these findings are individually nonspecific.

Carcinogenicity

Chronic inorganic arsenic exposure is a well-established human carcinogenic exposure.

Strong associations include increased risk of:

• Skin cancer
• Lung cancer
• Bladder cancer

Associations with additional internal malignancies have also been reported, but strength of evidence varies by cancer site and exposure setting.

The risk relates primarily to chronic inorganic arsenic exposure rather than ordinary dietary organic arsenic from seafood.

Arsine Gas – Important Distinction

Arsine is a gaseous arsenic compound encountered mainly in industrial settings.

Its defining acute toxicity is:

Massive intravascular hemolysis

Possible consequences include:

• Rapid anemia
• Hemoglobinuria
• Jaundice
• AKI
• Hyperkalemia
• Cardiovascular instability

This syndrome differs substantially from classic inorganic arsenic ingestion.

Diagnosis

Ask specifically about:

• Contaminated drinking water
• Well-water use
• Occupation
• Mining/smelting
• Semiconductor work
• Pesticides
• Traditional remedies
• Supplements
• Recent intentional or accidental exposure
• Other exposed household/workplace members

A careful environmental and occupational history is particularly important in chronic toxicity.

Urine Arsenic – Preferred Exposure Test

For many suspected exposures, urinary arsenic is more useful than blood arsenic because arsenic clears relatively rapidly from blood.

A timed urine collection or appropriately interpreted spot urine may be used depending on the clinical setting.

However, interpretation requires attention to arsenic species.

Arsenic Speciation

When total urine arsenic is elevated, speciation can distinguish toxicologically important inorganic arsenic and its metabolites from less-toxic seafood-derived organic species.

This is especially useful when the patient has recently eaten seafood.

A high total urinary arsenic result should therefore not automatically trigger a diagnosis of inorganic arsenic poisoning.

Seafood Before Testing

Older teaching recommended avoiding seafood for several days before urinary testing.

That can still help reduce dietary interference when testing is nonurgent.

However, in a clinically significant suspected poisoning:

Do not delay necessary testing or treatment simply to wait for seafood-derived arsenic to clear.

Instead, obtain appropriate samples and request speciation when available.

Blood Arsenic

Blood arsenic can be elevated soon after a substantial exposure but falls relatively rapidly.

Therefore:

• It may support a recent exposure
• A normal later blood concentration does not exclude poisoning
• It is generally less useful than urine testing for many exposure investigations

Other Laboratory Evaluation

In significant acute poisoning, consider:

• CBC with differential
• Electrolytes
• Glucose
• Bicarbonate
• BUN/creatinine
• Magnesium
• Calcium
• Liver tests
• Urinalysis

For severe illness:

• Blood gas
• Lactate
• Coagulation studies
• CK

Serial CBC and renal/electrolyte testing may be necessary because toxicity can evolve.

Imaging

Some arsenic-containing compounds can be radiopaque.

Abdominal imaging may occasionally identify retained radiopaque material after a substantial ingestion.

However:

• A normal radiograph does not exclude arsenic ingestion
• Imaging is not required for every exposure

It should be used when the formulation and exposure circumstances make retained material plausible.

Initial Management

For significant acute poisoning:

Airway/breathing → circulation → aggressive treatment of fluid loss/shock → ECG/electrolytes → confirm exposure → consider GI decontamination when appropriate → early toxicology consultation → chelation when indicated

Treatment should not be delayed while waiting for confirmatory arsenic concentrations in a severely symptomatic patient with a convincing exposure.

Fluid Resuscitation

Severe vomiting and diarrhea can cause profound intravascular depletion.

Management includes:

• Appropriate isotonic crystalloid
• Frequent reassessment of perfusion
• Electrolyte correction
• Monitoring urine output

Persistent shock requires vasopressor support according to hemodynamic physiology.

For persistent vasodilatory shock, norepinephrine is generally preferred.

Trendelenburg positioning and routine dopamine-first therapy are outdated.

GI Decontamination

Do not induce vomiting.

Ipecac is obsolete.

Routine gastric lavage is not recommended.

Activated charcoal has limited and uncertain effectiveness for metals/metalloids such as arsenic and should not be assumed to provide reliable adsorption.

Management should prioritize resuscitation and toxicology-directed care.

Whole-Bowel Irrigation

Whole-bowel irrigation may occasionally be considered after a substantial ingestion when:

• Radiopaque arsenic-containing material remains in the GI tract
• A poorly soluble preparation is suspected
• There is concern for continued GI absorption

It is not routine treatment for every arsenic exposure.

Contraindications include situations such as bowel obstruction, ileus, perforation, severe hemodynamic instability, or an unprotected airway.

Chelation

Chelation is considered for significant inorganic arsenic poisoning, especially when the patient is symptomatic or has evidence of substantial systemic exposure.

Important agents include:

• Dimercaprol (BAL)
• Succimer (DMSA)
• DMPS where available

Selection depends on:

• Clinical severity
• Ability to tolerate oral medication
• Arsenic species
• Timing
• Availability
• Toxicology expertise

Dimercaprol – BAL

Dimercaprol has historically been used for severe acute arsenic poisoning, particularly in critically ill patients who cannot take oral therapy.

Important adverse effects include:

• Hypertension
• Tachycardia
• Nausea/vomiting
• Headache
• Fever
• Pain with IM administration

It can also cause hemolysis in susceptible patients, including those with G6PD deficiency.

Because administration and toxicity are significant, its use should be guided by a medical toxicologist.

Succimer – DMSA

Succimer is an orally administered chelator that can bind arsenic.

It may be considered in selected patients who:

• Have clinically significant inorganic arsenic poisoning
• Are stable enough for oral therapy

It is generally better tolerated than BAL.

Potential adverse effects include:

• GI upset
• Rash
• Mild transaminase elevation

DMPS

DMPS is another sulfhydryl-containing chelator with activity against arsenic.

It is used in some countries and specialist settings.

Availability varies geographically.

Evidence and regulatory status differ by jurisdiction, so use should be coordinated with a poison center or medical toxicologist.

Chelation Should Not Be Based on a Number Alone

Modern management should not automatically continue chelation until urine arsenic falls below a single historical cutoff.

Decisions should integrate:

• Clinical improvement
• Exposure source
• Arsenic speciation
• Serial urinary measurements when useful
• Organ injury
• Toxicologist recommendations

This is especially important because total urinary arsenic may be distorted by dietary organic arsenic.

Timing of Chelation

In severe symptomatic poisoning with a credible exposure:

Do not wait for laboratory confirmation before obtaining specialist advice and initiating appropriate chelation.

Chelation is most useful when started early in substantial poisoning.

However, unnecessary chelation should also be avoided when exposure evidence is weak or the elevated laboratory result represents nontoxic organic arsenic.

Seizures

For toxicologic seizures:

Benzodiazepines are first-line.

Persistent seizures may require additional benzodiazepines, phenobarbital, or appropriate anesthetic therapy.

Correct:

• Hypoglycemia
• Hypoxia
• Electrolyte abnormalities
• Severe acid–base disturbances

QT Prolongation and Ventricular Dysrhythmia

Management includes:

• Continuous ECG monitoring
• Correction of potassium and magnesium abnormalities
• Treatment of shock and hypoxia
• IV magnesium for torsades when indicated
• Electrical therapy for unstable malignant rhythms

Avoid adding unnecessary QT-prolonging medications.

Hemodialysis

Hemodialysis is not a substitute for chelation in ordinary arsenic poisoning.

Its role in removing arsenic is limited and depends on factors such as:

• Renal function
• Timing
• Arsenic species
• Whether chelation has altered circulating complexes

Dialysis may nevertheless be required for conventional indications such as:

• Severe AKI
• Refractory electrolyte abnormalities
• Severe acid–base disturbance

Specialist guidance is appropriate.

Monitoring

Significant acute arsenic poisoning may require serial monitoring of:

• Hemodynamics
• ECG
• Electrolytes
• Renal function
• CBC
• Liver function
• Neurologic status
• Urine output

Remember that:

GI/cardiovascular toxicity may be early, while marrow suppression and neuropathy may appear later.

Admission

Hospital admission is appropriate for patients with:

• Significant symptomatic acute exposure
• Severe vomiting or diarrhea
• Dehydration
• Hypotension/shock
• ECG abnormalities
• Significant electrolyte disturbance
• AKI
• Encephalopathy
• Seizures
• Cytopenias
• Need for chelation
• Significant uncertainty about an ongoing exposure source

ICU care is appropriate for:

• Shock
• Respiratory failure
• Malignant dysrhythmia
• Severe encephalopathy
• Status epilepticus
• Multiorgan failure

Chronic Exposure Management

The most important intervention is:

Identify and eliminate the arsenic source.

This may require:

• Testing drinking water
• Occupational investigation
• Removing contaminated remedies/supplements
• Public-health involvement
• Assessment of other exposed people

Chelation is not automatically indicated for every chronically exposed asymptomatic person and should be individualized.

Safeguarding

Historical rules assigning intentional poisoning or neglect according to rigid childhood age cutoffs are outdated.

Assess:

• Developmental capability
• Access to the substance
• Exposure environment
• Consistency of the history
• Recurrent unexplained illness
• Whether other household members are affected
• Broader safeguarding concerns

Prognosis

Mild exposures can resolve completely.

Severe acute poisoning can cause:

• Refractory shock
• Dysrhythmias
• Multiorgan failure
• Encephalopathy
• Death

Delayed complications may include:

• Persistent painful polyneuropathy
• Weakness
• Hematologic abnormalities
• Residual neurologic impairment

Neuropathy can take months to improve and may not resolve completely.

Important Modernization of the Older Source

• Arsenic is a metalloid, although often grouped clinically with heavy-metal poisonings.
• Toxicity depends strongly on arsenic species; inorganic arsenic is much more clinically important than most seafood-derived organic forms.
• Seafood can markedly elevate total urine arsenic without representing dangerous inorganic arsenic exposure.
• Arsenic speciation is therefore important when interpreting elevated urinary concentrations.
• Blood arsenic falls relatively rapidly and is less useful than urine for many exposure assessments.
• Garlic odor is neither sensitive nor specific.
• Mees lines are delayed and not specific for arsenic.
• Acute poisoning classically produces severe GI toxicity, shock, QT abnormalities, and multiorgan dysfunction.
• Painful sensorimotor peripheral neuropathy may emerge days to weeks later and can mimic Guillain–Barré syndrome.
• Serial CBC monitoring may be necessary because marrow suppression can be delayed.
• Chronic inorganic arsenic exposure is strongly associated with skin, lung, and bladder cancers.
• Arsine gas is a separate syndrome characterized primarily by massive intravascular hemolysis.
• Activated charcoal does not reliably adsorb arsenic and should not be considered standard metal decontamination.
• Ipecac and routine gastric lavage are obsolete.
• Whole-bowel irrigation is reserved for selected substantial exposures with retained GI material.
• BAL, succimer, and DMPS are potential chelators depending on severity and availability.
• Severe symptomatic poisoning may justify chelation before laboratory confirmation after specialist consultation.
• Chelation should not be started or stopped solely according to one historical urinary arsenic threshold.
• Trendelenburg and routine dopamine-first shock management are outdated.
• Hemodialysis is not a routine substitute for chelation.
• Chronic poisoning requires source identification and removal, often involving occupational or public-health assessment.
• Rigid age-based assumptions about intentional poisoning or neglect are obsolete.

Key Points

• Acute inorganic arsenic → severe gastroenteritis + fluid loss/shock + cardiac toxicity.
• QT prolongation and ventricular dysrhythmias can occur in severe poisoning.
• Delayed painful stocking-glove sensorimotor neuropathy is characteristic.
• Bone-marrow suppression may appear several days after acute poisoning.
• Chronic exposure can cause mottled pigmentation, palmar/plantar hyperkeratosis, neuropathy, and increased cancer risk.
• Urinary arsenic with speciation is generally more informative than relying on blood arsenic alone.
• Recent seafood can falsely suggest toxic exposure if only total urine arsenic is measured.
• BAL, DMSA, or DMPS may be used for clinically significant inorganic arsenic poisoning with specialist guidance.
• Do not delay appropriate chelation in a severely symptomatic patient solely while awaiting arsenic levels.
• Arsine gas poisoning is different: think intravascular hemolysis and AKI.