ARSENIC POISONING

ARSENIC
Irritant
Cumulative poison
Common environmental toxicant – soil, water air
Exists in three oxidation states
Elemental Form (As3)
Trivalent Arsenic (As3+) – arsenite – more
soluble
Pentavalent (As5+) – arsenate – less soluble
 ARSENIC
Irritant
Cumulative poison
Common environmental toxicant – soil, water air
Exists in three oxidation states
Elemental Form (As3)
Trivalent Arsenic (As3+) – arsenite – more
soluble
Pentavalent (As5+) – arsenate – less soluble
 ARSENIC
Inorganic forms of arsenic more toxic than organic
form
Inorganic – Arsenic trioxide, Sodium, potassium and
calcium salts of pentavalent and trivalent forms of As
Organic arsenic
Trivalent monosodium methanearsonate (MSMA)
Disodium methanearsonate (DSMA)
Thiacetarsamide
Pentavelent arsinilic acid
Sodium arsaniliate
 Arsine gas (Arsenic hydride) – most toxic
 ARSENIC
Order of Toxicity
Organic arsenicals < As5+ <As3+ < Arsine

Trivalent arsenic is 5-10 times more toxic than

pentavalent arsenic
 Sources
Indiscriminate use of arsenic as drugs
 Lead arsenate – ectoparasiticide – dip
 Sodium thioacetarsamide – blood parasites
 Ruminatoric preparations
Excessive use or accidental ingestion of arsenical
pesticides, herbicides, rodenticides, wood
preservatives,
 Copper acetoarsinite or parris green
 Sodium or potassium arsenite or arsenate, Monosodium
methanearsenate
 Arsenic trioxide
 Arsenic pentoxide
Arsenic-contaminated soils or burn piles
Contaminated drinking water
 Sources
Arsenic feed additives in poultry or swine as growth
promoters
 Arsanilic acid, Sodium arsanilate
Burning of wood treated with arsenic preservatives
Smelting of Cu, Zn, Pb – releases As as by-product
Arsine gas and arsenic trioxide – used in manufacture
of computer chips
 Factors Affecting Toxicity
Species
 Herbivore – most common
 Fowl and swine – rarely affected
Oxidation State

Status / Health of animals

Dehydrated, weak, ill animals are more susceptible
 Toxicity
All species are susceptible
 Bovine and Felines– most common
 Fowl and swine – rarely affected
Lethal dose (Arsenic trioxide and Sodium arsenite)
 Horse – 10-45 g and 1-3 g
 Cattle – 5-45 g and 1-4 g
 Sheep and Goats – 3-10 g and 200-500 mg
 Dog – 100-150 mg and 50-150 mg
 Fowls – 50- 300 mg and 10-100 mg

 Cats are highly susceptible

Sodium arsenite – 20 mg/kg

 Toxicokinetics
Readily absorbed from all routes
Distributed throughout the body
Reaches higher concentration in liver, kidneys, heart
and lungs
High concentrations found in hairs and nail – persists
for months – SH in keratin
Arsenic gets deposited in bone and teeth –chemical
similar to phosphorus
 Toxicokinetics
Partly methylated in liver
Excreted rapidlly – urine, faeces, bile, milk, saliva and
sweat
 Toxicokinetics
Conversion of pentavalent to trivalent form in kidney
- nephrotoxicity
Arsenic can cross placental barrier
Movement across BBB is limited
 Toxicodynamics
Trivalent arsenic
Binds with SH groups especially lipoic acid to from
stable compound
Lipioic acis – cofactor in enzymatic decarboxylation of
pyruvate, ketoglutarate, ketobutyrate
Inhibits proteins and enzymes containing SH group
Inhibits formation of acetyl, succinyl and propionyl CoA
Slows or inhibits TCA cycle
Inhibits mitochondrial enzyme and cellular respiration
Intestinal epithelium, kidneys, liver, skin, lungs are
most affected – high oxidative energy requirement
 Toxicodynamics
Trivalent arsenic
Affects Capillary integrity
All capillary beds are affected
 Splanchic area in the GIT – most sensitive
Loss of capillary integrity and dilation in GIT

Transudation of plasma fluids into intestinal mucosa

and lumen

Reduced Blood volume, hypotension, shock

 Toxicodynamics
Trivalent arsenic
Oedema, vesicular and loss of GI mucosa – aggravates
fluid loss and shock
Dilatation and swelling of glomerular capillaries in
kidneys – accompanied by hypotension and
hypovolaemia Decreased renal
perfusion, nephorosis and oliguria

Percutaneous – Capillary dilatation, degeneration –

vesiculation, blistering and edema of skin
 Toxicodynamics
Pentavalent arsenic
Substitutes for phosphate in oxidative
phosphorylation
Uncouples mitochondrial oxidative phosphorylation
Competes with phosphoate in the formation of ATP,
resulting in formation of unstable arsenate ester
which is rapidly hydrolysed – Arsenolysis
Elevated body temperature is not seen with
arsenic
 Toxicodynamics
Pentavalent organic arsenic
Demyelination and axonal degeneration – due to
interference in vitamin B
Peripheral nerve and spinal cord dysfunction in man

Arsine gas
Haemolysis and pulmonary edema
Do not cause typical signs of arsenic poisoning
Arsine combines with haemoglobin and then reacts
with oxygen – haemolysis
Dimercaprol will not have any effect
 Clinical Signs
Trivalent inorganic or organic arsenic
Acute and peracute toxicity
Major action in on GIT and CVS
Peracute – sudden death
Severe colic, staggering gait, collapse, paralysis and death
Acute
Severe gastroenteritis, colic staggering gait, vomiting,
increased thirst, projective watery diarrhoea
Blood in faeces
Fast and weak pulse, hypotension, dehydration,
Oliguria, anuria
Rumen atony, hind limb paralysis, prostration,
Normal or subnormal temperature
Coma and death
 Clinical Signs
Trivalent inorganic or organic arsenic
Subacute toxicity
Similar signs but less pronounced
Colic, anorexia, depression, staggering, weakness
Diarrhoea with blood and/or mucus discharge
Polyuria and then anuria
Dehydration, polydipsia,
Partial paralysis of hind limbs
Cold extremities and hypothermia
Acidosis and azotemia - death
 Clinical Signs
Trivalent inorganic or organic arsenic
Percutaneous toxicity
Edema of skin
Skin eruptions
Secondary skin infections
 Clinical Signs
Trivalent inorganic or organic arsenic
Chronic toxicity
Wasting, poor condition
Thirst
Brick red discolouration of visible mucus membranes
Normal temperature and weak irregular pulse
Swelling of joints, join pains – stiffness and paralysis
Reproductive disorders – sterility and abortion
Percutaneous
 Dry, papery skin
 Skin may crack, bleed
 Secondary bacterial infection
 Clinical Signs
Trivalent inorganic or organic arsenic
Human
Skin blotches – face and body
Hyperpigmentation of the chest and upper arms
Hard patches on palmss and soles
Inability to walk
May cause skin, pulmonary and bladder cancer
 Clinical Signs
Pentavalent organic arsenic

Signs appear 2-4 days after exposure

Ataxia, Incoordination, blindness
Swine – weakness, dog sitting posture, paralyzed,
lateral recumbency

Blindness is characterisitic of arsinilic acid and not

of other arsenicals
 Post Mortem Findings
Peracute – No lesions

Acute
GIT- inflmmataion, edema, rupture of blood vessels,
necrosis and epithelial and subepithelial tissues
Perforation of the gastric or intestinal wall
Gut contents – fluid, often foul smelling, blood tinged,
shreds of epithelial tissue
Diffuse inflammation of the liver and other abdominal
viscera
 Post Mortem Findings
Cutaneous – skin – dry, leathery and peels off

Subacute
Pale Swollen kidneys
Pale Liver
 Histopathology
GIT–
 Intestinal capillary dilatation, mucosal and
submucosal edema , necrosis and sloughing of mucosa
Kidney
Glomerular sclerosis and severe renal tubular
necrosis
Liver
Fatty degeneration and necrosis
 Diagnosis
History
Circumstantial evidences
Clinical signs
Samples to be collected – Urine, vomitus, faeces, hair
PM samples – liver, kidney

Differential Diagnosis
Lead Poisoning
Caustics, irritants, urea
 Treatment

• Dithiol

• Relatively non-toxic

• Also has toxic effects-

Vomiting, tremors,
convulsions
 Treatment

Large Animals:
3 mg/kg, deep IM, repeated every 4 hours for the first 2
days, every 6 hours for the 3rd day and twice a day for next
10 days
Small Animals: 2.5 – 5 mg/kg
 Treatment
Thioctic acid

Considered to be more superior than

BAL but not available commercially

Sodium thiosulphate
Safe antidote

Mesodimercaptosuccinic acid (MDSA) and

Dimercaptosuccinic acid (DMSA, succimer)
Water soluble derivaties of dimercaprol and more
superior
 Supportive Therapy

• Emetics, Gastric Lavage, activated charcoal

• Correction of shock, dehydration, acidosis
• Renal function should be monitored and promoted
using 10% dextrose
• Vitamins, antibiotics and analgesics
• High protein diet – post-exposure period