Inorganic Metallic Irritant Poisons

Source: P C Dikshit - Textbook of Forensic Medicine and Toxicology; Katzung's Basic and Clinical Pharmacology, 16th Ed.

1. ARSENIC (As)

Sources / Forms

• Arsenic trioxide (most common), copper arsenite (Paris green), lead arsenate, calcium arsenate
• Found in insecticides, pesticides, weed killers, paints, dyes, cosmetics, smelting industries

Fatal Dose & Period

• Fatal dose: Arsenic trioxide - 180 mg (as low as 30 mg can be fatal; tolerance varies widely)
• Fatal period: 12-48 hours (may be fatal within 2-3 hours)

Mechanism of Action

1. Reversible combination with sulphydryl (-SH) groups in tissue proteins
2. Inhibition of enzyme systems essential for cellular metabolism
3. Acts as a capillary poison - dilates capillaries
4. Causes fatty degeneration of liver
5. Hyperemia and hemorrhages in the intestine
6. Renal tubular necrosis
7. Peripheral nerves - disintegration of axis cylinder (axonal neuropathy) with fragmentation and resorption of myelin

Signs & Symptoms - ACUTE

1. Metallic taste in mouth, slight garlicky odour in breath, xerostomia (dry mouth), dysphagia
2. Severe nausea and vomiting, colicky abdominal pain, profuse diarrhea - sometimes bloody with rice water stools (due to vasodilation, mucosal vesicle formation and sloughing)
3. Progressive cardiovascular collapse, renal failure
4. Peripheral neuropathy in survivors

Signs & Symptoms - CHRONIC (4 Stages)

• Mee's lines - transverse white streaks 1-2 mm wide appearing above base of each fingernail (after ~5 weeks)
• Symmetrical sensorimotor polyneuropathy resembling Guillain-Barre syndrome
• Bowen's disease (squamous cell carcinoma in situ) - long-term complication
• Hematologic: normochromic normocytic anemia, leukopenia, thrombocytopenia, mild eosinophilia, karyorrhexis on bone marrow

Diagnosis

• Hair analysis (arsenic deposited in hair; can time exposure by segmental analysis - 1 cm of hair = ~1 month)
• Urine arsenic levels
• Reinsch test, Marsh test, Gutzeit test (forensic)

Treatment

1. Remove patient from source of poison
2. BAL (British Anti-Lewisite / Dimercaprol) - 6 hourly for 2-3 days, then once daily (also used for acute: 3.5 mg/kg 4-hourly for 2 days)
3. Vitamin B1 injection for peripheral neuritis
4. General supportive care

Medico-legal Importance

• Ideal homicidal poison - tasteless, odorless, easily available, small doses required
• Can be mixed with food, drinks, sweets; mass poisoning simulates cholera
• Detected even in charred/decomposed bodies and bones/hair years after poisoning
• Delays putrefaction

2. COPPER (Cu) - Copper Sulphate Poisoning

Fatal Dose & Period

• Fatal dose: 15-30 g (small repeated doses are MORE fatal than a single large dose)
• Fatal period: 1-3 days

Signs & Symptoms - ACUTE

1. Metallic taste in mouth and constriction in throat
2. Burning pain in mouth, throat, esophagus, and stomach
3. Repeated, violent, profuse vomiting - vomitus is bluish or greenish-blue in color (becomes bluer on adding ammonium hydroxide; does NOT change color if bilious)
4. Intense thirst, salivation, nausea, gaseous eructions
5. Gums and tongue stained bluish
6. Repeated diarrhea - liquid, brown motions with tenesmus and colicky pain
7. Oliguria, anuria, albuminuria leading to uremia
8. Hemolytic tendencies - increased copper in erythrocytes → hematemesis and melena
9. Jaundice may develop
10. Muscular cramps, paralysis of limbs, convulsions, dyspnea, weak pulse, BP fall, cold clammy skin, coma, death
11. Liver biopsy shows centrilobular necrosis and biliary stasis

Chronic Copper Sulphate Poisoning

Chemical Test

Treatment

1. No emetics (copper sulphate itself causes emesis)
2. Gastric lavage with 1% freshly prepared potassium ferrocyanide (antidote - converts copper sulphate to insoluble cupric ferrocyanide)
3. Demulcents: milk and egg albumin (convert copper sulphate to insoluble cupric albuminate)
4. IV 5% dextrose saline with Vitamin C and amino acids (fluid/electrolyte maintenance)
5. Morphine for pain
6. Chelating agents:
   • Penicillamine 2 g/day orally in divided doses for 5-7 days (or 30 mg/kg parenterally)
   • BAL 300 mg IM stat, then 150 mg 4-hourly for 6-7 days
   • Calcium EDTA as an alternative chelator

3. LEAD (Pb)

Sources / Forms

• Lead acetate ("sugar of lead"), lead carbonate, lead tetraethyl
• Exposure via paints, petrol, printing, plumbing, smelting

Fatal Dose & Period

• Fatal dose: Lead acetate - 20 g; Lead carbonate - 30 g
• Fatal period: Uncertain; usually 2-3 days

Mechanism of Action

Signs & Symptoms - ACUTE

1. Metallic taste
2. Burning sensation, dryness of throat, intense thirst
3. Vomiting within 30 minutes - vomitus mixed with blood
4. Colicky pain - comes in intervals, relieved by pressure
5. Constipation (constant feature)
6. Urine scanty; coated tongue; foul offensive breath
7. Nervous symptoms: drowsiness, insomnia, headache, vertigo, muscle cramps, convulsions, paralysis of lower limbs
8. Wasting; death from exhaustion

Acute Lead Encephalopathy

• Rare in adults, more common in children
• Features: anemia, mild colic, vomiting, apathy, drowsiness, stupor, ataxia, hyperactivity
• Blood lead normally 0.03 mg/100 mL; in poisoning: 0.1-0.6 mg/100 mL

Chronic / Subacute Lead Poisoning (Plumbism / Saturnism)

• Burton's line (Burtonian line) - bluish line along the gums (lead sulphide deposits)
• Neurological: reduced IQ, hyperactivity, insomnia, irritability, extreme learning disability in children
• GI: constipation, diarrhea, abdominal pain, vomiting, poor appetite, weight loss
• Lead colic - severe colicky abdominal pain
• Anemia (microcytic hypochromic with basophilic stippling)
• Kidney problems (lead nephropathy)
• Reproductive problems
• CNS: seizures, coma (in extreme cases)

Treatment

1. Stomach wash with 1% magnesium sulphate or sodium sulphate
2. Magnesium sulphate (1 oz) orally to remove lead from GI tract
3. Demulcents - milk, egg white
4. Calcium gluconate IV for abdominal colic
5. Morphine or atropine for severe pain

• Calcium EDTA (Calcium Disodium Versenate) - first-line chelating agent
• DMSA (Dimercaptosuccinic acid / Succimer) - oral chelator; preferred in children
• BAL (Dimercaprol) - used with Calcium EDTA in severe encephalopathy
• D-Penicillamine - oral chelation

• First create alkalosis (high calcium diet, milk) to fix lead in bones and relieve symptoms
• Then induce mild acidosis (ammonium chloride 8-12 g/day + dilute phosphoric acid) to mobilize lead
• Then chelate and excrete

4. MERCURY (Hg)

Sources / Forms

• Corrosive sublimate (mercuric chloride HgCl₂) - most common cause of acute inorganic mercury poisoning
• Mercury vapors (industrial), calomel (HgCl), red oxide of mercury

Fatal Dose & Period

• Fatal dose: 15 g (smallest recorded fatal dose: 2 g)
• Fatal period: 3-5 days

Signs & Symptoms - ACUTE

1. Acrid metallic taste in mouth
2. Constriction or choking sensation; hoarseness of voice
3. Difficulty in breathing
4. Mouth and tongue corroded and swollen with gray-white coating
5. Hot burning pain in mouth, stomach, abdomen
6. Stools blood-stained
7. Urine suppressed/scanty, contains blood and albumin; necrosis of renal tubules and damage to glomeruli
8. Pulse quick, small, irregular; circulatory collapse
9. Thrombocytopenia and bone marrow depression
10. When vapors inhaled: salivation, gingivitis, loosening of teeth
11. When injected IV: dyspnea, cyanosis, hypotension, convulsions
12. Death from anaphylactic shock or ventricular fibrillation

• Symptoms appear sooner
• Acrid (not garlicky) taste
• Throat constriction more marked
• Vomitus more often contains blood and mucus
• Kidneys more severely affected
• Urine contains >500 mcg mercury

Signs & Symptoms - CHRONIC

1. Nausea, vomiting, diarrhea; indigestion, colicky pain
2. Excessive salivation, swollen and painful salivary glands
3. Foul smelling breath
4. Inflamed and ulcerated gums with brownish-blue line (differentiate from phosphorus poisoning by context)
5. Loosening of teeth; necrosis of jaw
6. Mercuria lentis - brownish reflex from anterior lens capsule (seen on slit-lamp examination); bilateral; no effect on visual acuity
7. Erythematous, eczematous, papular skin lesions on hands and feet with skin thickening
8. Mercurial tremors (Hatter's shake / Glass blower's shake) - coarse tremors, worst with voluntary movement, absent during sleep; involve fingers, tongue, face, arms, legs; incoordination, increased deep reflexes, paresis, peripheral neuritis
9. Erethism (mental symptoms) - shyness, timidity, irritability, loss of confidence, mental depression, loss of memory, insomnia, hallucinations, delusions (features of insanity)

Treatment

1. Stomach wash with warm water and magnesium carbonate
2. Egg albumin, skimmed milk, or vegetable gluten (forms insoluble albuminate of mercury)
3. Demulcent drinks to protect stomach wall
4. Activated charcoal + magnesium sulphate
5. BAL (Dimercaprol):
   • 3.5 mg/kg 4-hourly × 2 days
   • 2.5 mg/kg 6-hourly × 1 day
   • 2.5 mg/kg twice daily per severity
6. Penicillamine

1. Remove from source of exposure
2. Plenty of milk
3. Mouthwash with borax
4. Saline purgative
5. Sodium thiosulphate IV
6. One course of BAL
7. Symptomatic treatment for paralysis
8. Prophylactic: proper ventilation, periodic medical checkups

Comparative Quick Reference

• P C Dikshit Textbook of Forensic Medicine and Toxicology, Chapter on Irritant Metallic Poisons
• Katzung's Basic and Clinical Pharmacology, 16th Ed., Chapter on Heavy Metal Toxicology