Toxicology – Dimercaprol (British Anti-Lewisite, BAL)

Toxicology – Dimercaprol (British Anti-Lewisite, BAL)

Core Concept

Dimercaprol, historically called British Anti-Lewisite (BAL), is a parenteral heavy-metal chelator.

Its modern role is relatively limited because other chelators, particularly succimer (DMSA) and DMPS where available, are often easier to administer and better tolerated.

BAL remains important in selected severe poisonings, especially:

Severe acute arsenic poisoning when oral therapy is unsuitable
Lead encephalopathy, traditionally in combination with calcium disodium EDTA
Selected severe inorganic mercury exposures when alternative chelators cannot be used
Lewisite exposure in specialized settings

Chemical Properties

Dimercaprol contains two sulfhydryl (-SH) groups, making it a dithiol chelating agent.

It is:

Lipid soluble
Poorly water soluble
Administered by deep intramuscular injection
Traditionally formulated in an oil vehicle

Its unpleasant sulfur-like odor reflects its sulfhydryl chemistry.

Mechanism of Action

Many toxic metals bind sulfhydryl groups on enzymes and other cellular proteins.

Dimercaprol provides alternative sulfhydryl binding sites.

The general process is:

Toxic metal + BAL → metal–BAL complex → reduced interaction with critical cellular proteins → enhanced elimination

Chelation is most useful when the metal remains biologically accessible.

Historical Origin

BAL was originally developed during World War II as an antidote to Lewisite, an arsenic-containing chemical warfare vesicant.

The name therefore means:

British Anti-Lewisite

Its ability to bind arsenic subsequently led to use against other heavy metals.

Major Modern Limitation

BAL is not a general-purpose treatment for every elevated metal concentration.

Chelation decisions depend on:

Specific metal
Chemical form
Exposure severity
Symptoms
Blood or urine concentrations when clinically meaningful
Timing
Renal function
Availability of safer chelators

Chelation can itself cause toxicity and should generally involve a medical toxicologist or poison center.

Acute Arsenic Poisoning

Dimercaprol has an established historical role in severe acute inorganic arsenic poisoning.

Clinical manifestations may include:

Severe vomiting and diarrhea
Abdominal pain
Hypotension
QT abnormalities
Dysrhythmias
Encephalopathy
Peripheral neuropathy
Multiorgan dysfunction

Chelation should be considered early in severe symptomatic poisoning rather than waiting for delayed laboratory confirmation when the exposure is strongly supported.

BAL vs Oral Chelators in Arsenic Poisoning

For many patients, modern oral chelators such as:

Succimer (DMSA)
DMPS, where available

are preferred because they are generally easier to administer and better tolerated.

BAL is particularly useful when:

Poisoning is severe
The patient cannot tolerate oral medication
Gastrointestinal toxicity prevents reliable absorption
A parenteral chelator is considered necessary

Once oral treatment becomes appropriate, prolonged BAL therapy is usually unnecessary.

Arsine Gas

Arsine poisoning is fundamentally different from ingestion of inorganic arsenic.

Arsine primarily causes:

Massive intravascular hemolysis
Hemoglobinuria
Acute kidney injury
Anemia

Chelation has not been clearly demonstrated to provide the same benefit in arsine poisoning.

Management focuses heavily on:

Supportive care
Management of hemolysis
Renal support
Extracorporeal therapy when indicated

Lead Poisoning

BAL’s most important traditional lead indication is severe lead poisoning with encephalopathy.

Lead encephalopathy may present with:

Altered mental status
Severe headache
Vomiting
Ataxia
Seizures
Cerebral edema
Coma

This is a medical emergency.

BAL and Calcium Disodium EDTA

Historically, severe lead encephalopathy has been treated with:

Dimercaprol + calcium disodium EDTA (CaNa₂EDTA)

BAL is started before or alongside CaNa₂EDTA according to specialist protocols.

The rationale is to reduce concerns about redistribution of mobilized lead and provide complementary chelation.

Exact regimens should follow current toxicology guidance rather than older fixed schedules.

Critical EDTA Distinction

Do not confuse:

Calcium disodium EDTA

CaNa₂EDTA – a lead chelator.

with:

Disodium EDTA

Na₂EDTA – can produce profound hypocalcemia and has caused fatal medication errors.

This distinction is clinically crucial.

Lead Poisoning Without Encephalopathy

BAL is generally not preferred for routine treatment of elevated blood lead concentrations without encephalopathy.

Depending on severity, alternatives may include:

Succimer
CaNa₂EDTA
Other specialist-directed strategies

Removal from the lead source remains essential.

Mercury Poisoning

BAL has historically been used for selected severe inorganic mercury poisoning when oral chelators cannot be administered.

Modern alternatives commonly include:

Succimer
DMPS where available

The effectiveness of chelation depends strongly on the chemical form of mercury.

Elemental Mercury

Swallowed elemental mercury is poorly absorbed from an intact gastrointestinal tract.

Therefore, simple ingestion usually does not require BAL.

In contrast:

Inhaled mercury vapor → substantial systemic absorption

and may produce:

Cough
Dyspnea
Pneumonitis
Tremor
Neuropsychiatric abnormalities
Renal injury

Chelation decisions are individualized.

Organic Mercury

BAL should not be routinely used for methylmercury poisoning.

Historically, there has been concern that BAL may increase redistribution of mercury toward the CNS.

Modern management of significant organic mercury poisoning generally favors other chelators when chelation is indicated.

Gold Toxicity

BAL was historically used for toxicity caused by therapeutic gold compounds.

Gold therapy could produce:

Bone-marrow toxicity
Dermatitis
Renal injury
Other systemic adverse effects

Because therapeutic gold compounds are now rarely used, this indication has become uncommon.

Other Metals

BAL has historically been proposed for poisoning involving metals such as:

Antimony
Bismuth
Copper
Nickel
Chromium

However, evidence and preferred chelation strategies differ substantially between metals.

BAL should therefore not be assumed to be appropriate simply because an exposure involves a metal.

BAL Must NOT Be Used for Iron Poisoning

This is a major high-yield contraindication.

BAL can form a potentially toxic complex with iron.

Therefore:

Iron poisoning → do not use dimercaprol.

The specific chelator for clinically important systemic iron poisoning is deferoxamine.

Cadmium

BAL should also not be used for cadmium poisoning.

Chelation can potentially increase renal delivery of cadmium and worsen nephrotoxicity.

Management of cadmium toxicity is primarily supportive and exposure-directed.

Selenium

Dimercaprol is also not a routine treatment for selenium poisoning.

Chelation recommendations must always be metal-specific.

Peanut-Oil Formulation

Traditional BAL preparations are formulated in peanut oil.

This historically raised concern regarding use in patients with peanut allergy.

The exact excipients of the available product should be checked because formulations can vary.

For severe life-threatening poisoning, specialist assessment of the actual risk and available alternatives is appropriate rather than treating every historical formulation warning as absolute.

G6PD Deficiency

Dimercaprol may increase the risk of hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency.

This is especially relevant when repeated treatment is contemplated.

The risk must be balanced against the danger of severe metal poisoning.

Renal Function

Metal–chelator complexes often depend partly on renal elimination.

Renal impairment can therefore complicate chelation by allowing:

Metal accumulation
Chelator accumulation
Persistence of metal–chelator complexes

Renal function and urine output should be followed during significant treatment.

Hepatic Disease

Because BAL itself can cause adverse effects and undergoes metabolism, significant hepatic dysfunction requires additional caution.

However, life-threatening metal poisoning may still justify treatment after specialist assessment.

Adverse Effects

BAL is relatively unpleasant compared with newer chelators.

Common adverse effects include:

Painful IM injections
Nausea
Vomiting
Headache
Burning sensations
Paresthesias
Anxiety or restlessness
Lacrimation
Salivation
Rhinorrhea
Sweating
Abdominal discomfort

Symptoms often become more prominent with greater exposure.

Cardiovascular Effects

Dimercaprol may cause:

Tachycardia
Hypertension

These effects can be more concerning in patients who already have:

Severe hypertension
Cardiovascular disease
Significant autonomic instability

Monitoring is appropriate during treatment of severe poisoning.

Injection-Site Complications

Because BAL is administered as an oily intramuscular preparation, treatment may cause:

Significant injection pain
Local inflammation
Sterile abscess formation

This is another reason oral chelators are preferred when clinically appropriate.

Essential Metal Loss

Chelators are not perfectly selective.

BAL can increase elimination of physiologically important metals such as:

Copper
Zinc

This is more relevant with prolonged treatment.

Pregnancy

The older FDA pregnancy letter categories and older animal-data framing should not be used in isolation.

Chelation during pregnancy requires consideration of:

Metal involved
Maternal toxicity
Fetal toxicity from the metal itself
Severity and timing of exposure
Available alternative chelators

In severe life-threatening poisoning, necessary maternal treatment should not be withheld solely because of pregnancy.

Monitoring During BAL Therapy

Important monitoring may include:

Clinical neurologic status
Heart rate and blood pressure
Renal function
Urine output
Liver function when appropriate
CBC
Evidence of hemolysis
Relevant blood or urine metal concentrations
Injection sites

Laboratory concentrations should always be interpreted in the context of the specific metal and timing of chelation.

Transition to Oral Chelation

A common principle is:

Use parenteral BAL during the severe phase when necessary → transition to a better-tolerated oral chelator once clinically appropriate.

Prolonging BAL after the patient can safely receive an effective alternative generally adds toxicity without clear benefit.

Chelation Does Not Replace Supportive Care

Even when BAL is indicated, management may still require treatment of:

Shock
Dysrhythmias
Seizures
Electrolyte disturbances
Hemolysis
Acute kidney injury
Encephalopathy

Chelation is only one component of management.

Important Modernization of the Older Source

Several older recommendations require qualification:

BAL now has a narrower role because succimer and DMPS are often better tolerated.
It remains particularly relevant for severe acute arsenic poisoning when oral treatment is unsuitable and for traditional management of lead encephalopathy with CaNa₂EDTA.
BAL is not recommended for routine treatment of elevated lead levels without encephalopathy.
It should not be routinely used for methylmercury.
BAL should be avoided in iron poisoning.
BAL should be avoided in cadmium poisoning.
The exact available formulation should be checked rather than assuming every product contains identical excipients.
Historical fixed-duration and concentration-based chelation schedules should not replace individualized toxicology guidance.
Hemodialysis is not simply a routine method for removing BAL–metal complexes; extracorporeal therapy depends on the specific metal, clinical syndrome, and renal failure.
Chelation decisions should be based on the specific metal and its chemical form, not merely on the presence of “heavy-metal exposure.”

Key Points

Dimercaprol = BAL = British Anti-Lewisite.
It is a lipid-soluble dithiol chelator administered intramuscularly.
Its sulfhydryl groups bind selected toxic metals.
BAL was originally developed against the arsenical warfare agent Lewisite.
Important modern uses include selected severe acute arsenic poisoning and lead encephalopathy.
Severe lead encephalopathy has traditionally been treated with BAL plus calcium disodium EDTA.
Never confuse CaNa₂EDTA with disodium EDTA.
Succimer or DMPS is often preferred when an effective oral chelator can be used.
BAL is generally not appropriate for chronic methylmercury toxicity.
Do not use BAL for iron poisoning.
Do not use BAL for cadmium poisoning.
Important adverse effects include painful injections, nausea, autonomic symptoms, tachycardia, and hypertension.
G6PD deficiency may increase the risk of hemolysis.
Renal function is important because metal–chelator complexes must be eliminated.
BAL should generally be replaced by a better-tolerated effective oral chelator once the clinical situation permits.
Chelation should be directed by the specific metal, chemical form, severity, symptoms, and appropriate toxicologic testing rather than by a generic diagnosis of heavy-metal exposure.

193. Toxicology – Dimercaprol (British Anti-Lewisite, BAL)