Toxicology

Arsenic & Arsenicals

History

• Arsenic is known to mankind since 3000 BC (Partington, 1935) as a drug and a poison.
• Theophrastus of Erebus (370-287 B.C.) mentions of arsenic.
• An early use for arsenic was in decoration of Egyptian tombs
• Aristotle makes reference to in the 4th century B.C .
• In the 1st century AD Pliny the elder stated that sandarach is found in Gold & Silver mines and arsenic (arsenic trioxide) is composed of the same matter as sandarach.
• Arsenic was obtained during the melting of copper & tin

History

• By the 11th century three species of arsenic were known, the white, yellow and red - since then recognized as arsenic trioxide, arsenic trisulfide (orpiment) and arsenic disulfide (realgar), respectively.
• Albertus Magnus is reputed in the 13th century to be the discoverer of metallic arsenic
• In 1649 J. Schroder reported the preparation of metallic arsenic by reducing arsenic trioxide with charcoal.
• Thirty-four years later, N. Lemery also observed that metallic arsenic was produced by heating arsenic trioxide with soap and potash.

History

• Many folk lores are associated with arsenic, & it is alleged that King George III , & Napoleon died due to arsenic.Great painters like Cezanne, Monet' & Van Gogh also suffered from arsenic poisoning
• Ehrlich’s land mark work with organic arsenicals laid the some of modern concepts of chemotherapy.
• Arsenicals are even now used in treatment of African trypanosomiasis.
• The metal is not mined as such but recovered as a by-product from the smelting of copper, lead, zinc and other ores and pollutes the environment.
• Mineral spring waters and the effluent from geothermal power plants also release arsenic from soils and rocks.

Arsenic

• Metallic arsenic is non-poisonous as not absorbed from alimentary canal being insoluble in water.
• Readily oxidizes in air and oxide is poisonous and absorbed.
• Compounds
• Inorganic
• Arsenious oxide or Arsenic trioxide(Sankhya/ Somalkhar/ white arsenic) White crystalline powder or solid mass initially transparent but later becomes porcelain like, tasteless, odourless.
• Arsenious acid- Soln. Of arsenious oxide in water which is odourless and tasteless
• Arsenites- Arsenious acid compounds- Paris green
• Arsenic acid- On warming arsenious oxide with nitric acid
• Arsenates- Combination of arsenic with other metals
• Arsine- A gas encountered in industry can kill out right.
• Organic- Salvarsan, & others were used as drug

Main Sources of Poisoning

• It is an uncanny thought that this lurking poison (arsenic) is everywhere about us,  ready to gain unsuspected entrance to our bodies from the food we eat, the water we drink and the air we breathe"  Karl Vogel, 1928.
• Arsenic exposure from natural contamination of shallow tube wells as well as deep tube wells is found in many parts of world including West Bengal & Bangladesh
• Smelting, microelectronics industries, wood preservatives,
• Paints, Calico-printing, taxidermy, wallpaper, artificial flowers,

Main Sources of Poisoning

• Pesticides, herbicides, fungicides, rodenticide, fly killing paper
• "Fowler's solution", Folk remedies, medicines by Hakims & Vaidyas
• Incineration of these products
• Daily average human intake is 10 µg in food & water

Metabolism

• Organic arsenicals (arsenobentaine & arsenocholine) are consumed with sea food and fish but are non-toxic
• Inorganic arsenical readily absorbed through G.I. Tract & Lungs
• Sequesters are- Liver, spleen, kidneys, heart, lungs & G.I.Tract
• highest concentration in skin, hair & nails
• Biomethylation results in detoxification but this process saturates easily
• Passes the placental barrier
• Urinary excretion of arsenic-half life 3-5 days

Clinical Picture

• Acute Poisoning- Usually by white arsenic,
• Onset of symptoms between ½ to several hours (up to 12 hrs)
• Depending on route of entry and other conditions Ex. Full or empty stomach, Given orally or rectum / vagina / skin ( healthy or abraded)
• Mechanism of action-
• All arsenicals inhibit sulfhydryl enzyme systems necessary for cellular metabolism.
• Arsenicals are also the most potent capillary poison and dilate it
• If given in very large dose- Death due to shock without any symptoms or
• Poison expelled due to vomiting and patient survives.

Acute poisoning by Arsenic

• Clinical picture
• Acute poisoning results in necrosis of mucosa of G.I.Tract due to haemorrhagic gastroenteritis.
• Pt. First complains of burning lips constriction in throat & difficulty in swallowing
• Feeling of faintness, depression, and nausea.
• Severe burning pain in abdomen which increases on pressure. Salivation and stomatitis
• Projectile vomiting, & intense thirst
• Vomitus later contains blood in streaks / spots
• Purging with tenesmus, pain irritation around anus,

Acute Poisoning

• Stool dark coloured, foetid, & bloody.
• Later on colourless, odourless,watery “ Rice water stool of Cholera”
• Cramps in the calf muscles & other muscles due to dehydration.
• Skin Cold & clammy, eyes sunken
• Urine- suppressed, scanty, and contains albumen, RBC, & casts
• Pain on micturition
• Pulse feeble, features of shock, delirium, there may be terminal hypoxic convulsion, coma & death
• With prompt treatment of acute poisoning survival usually with residual abnormality.

Other Forms of Acute Poisoning

• Inhalation of Arsenic Dust
• Cough, frothy sputum, breathless, cyanotic, restless, and acute pulmonary oedema
• Narcotic form
• Gastrointestinal symptoms mild,
• Pupil dilated, giddiness, precordial distress, formication, muscle tenderness, delirium, coma and death
• Sometimes complete paralysis of extremities
• Arsine poisoning –Rapid and often fatal haemolysis
• Classic triad- haemolysis, abdominal pain, and haematuria
• Jaundice appears after 24 hrs
• A coppery skin pigmentation frequently present
• Death from renal failure if survives haemolysis

Subacute Poisoning

• Sublethal dose repeated at intervals
• To hide poisoning. Usually homicidal
• Sign & symptoms
• Dyspepsia, cough, tingling in the throat, followed by vomiting, purging with abdominal pain, and tenesmus, foul tongue, dry and congested throat and a feeling of depression & languor. The stools are bloody. Cramps & tenderness of muscles, neuritis, collapse & death. With treatment may survive with persistent peripheral neuritis.
• Unusual picture includes convulsion, lockjaw, maniacal delirium painful joints, muscular atrophy,

Difference between Arsenic Poisoning & Cholera

Difference between Arsenic Poisoning & Cholera

Chronic Poisoning

• 1^st stage
• Insidious onset- Loss of wt. Dyspepsia,alternate diarrhoea & constipation, occasional vomiting, oedema ankle, and lower eyelids. Garlic odour of breath & sweat
• 2^nd stage (Skin effect)
• Chronic coryza. Silver white fur on tongue underlying surface red & raw. Stomatitis,& excessive salivation
• Yellow brown pigmentation finely mottled diffuse/ raindrop of neck, eyelids, nipples, & axillae more marked on flexures, and lower abdomen,
• Hyperkeratosis- Epithelial hyperplasia with discrete, multiple, hard wart like keratoses of palm and soles
• Mee’s lines on nails

Chronic Arsenic Poisoning

• Third stage (sensory symptoms)
• Headache, hyperaesthesia skin, tingling & numbness of extremities, cramps and tenderness of muscles, arthralgia, knee jerks usually lost, impotence common, evidence of bone marrow depression, aplastic anaemia, folic acid absorption affected
• Painless perforation of nasal septum

Chronic Arsenic Poisoning

• Fourth Stage (Peripheral neuritis & muscle atrophy)
• Muscle weakness, ataxia, wrist drop, foot drop, interossei and intercostal muscles frequently affected
• Diabetes. Peripheral neuropathy
• QRS broadening, QT prolongation, ST depression, T wave flattening
• Vasospasm, peripheral vascular insufficiency, and gangrene
• And cancer of skin, lung, liver, (angiosarcoma), bladder, kidney

Treatment

• Induce vomiting if not started- Not given tartar emetics or copper sulphate
• Gastric lavage with warm milk/ water/ 1% sod. thiosulphate soln.
• Administer freshly prepared hydrated ferric oxide in water
• Activated Charcoal large doses continuously with mag.sulph.to adsorb and expel out arsenic
• Hypovolumia & hypotension- Fluid + Dopamine
• Chelation Therapy-
• Dimercaprol-3 to 4 mg/kg I.M. 4 to 12 hrsly- till G.I. Symptoms subside
• Then give Penicillamine orally 1gm to 2 gm in four divided doses
• Succimer
• Supportive Care in ICU

Arsenic Poisoning

• Fatal dose- 120-200 mg(Adults)
• 2 mg /kg (Children)
• Fatal period Death can occur within 1 hr. But usually in 24 -48hrs
• 24-h urinary arsenic > 50µg/ daily(no sea food for previous 24 hrs)
• Serum arsenic recent exposure >7µg/dL

Post-Mortem Findings

• Body shrunken,eye balls sunken,
• Rigor mortis lasts longer
• Mucosa of stomach congested, inflamed denuded at places and covered with blood streaks. Sandy, gritty arsenic particles may be embedded in thick mucus over it
• All organs congested. Liver shows fatty changes. Kidneys show acute tubular necrosis.Lungs may be oedematous. Cardiomyopathy with subendocardial haemorrhage seen in heart.
• Hair, part of bone, nails and a piece of skin also preserved for chemical examination.

Medico- Legal Aspects

• Was considered ideal homicidal poison till its detection even years after death became possible in hair /bone/ nails
• Suicidal sometimes specially among people handling arsenic
• Accidental – Considered third most hazardous substance in occupational and environmental poisoning.

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