Metals are a unique class of toxicants that occur and persist in nature, mainly dispersed in rocks,

ores, soil, water and air. Metals can assume different chemical forms because of their
physicochemical, biological and anthropogenic activities. Most of them are widely used in
industry, agriculture and medicine. Some metals are essential elements, while others only pose
health hazards to humans and animals.
1. Arsenic
Arsenic (As) is an irritant and cumulative poison that is found mainly in soil, water and air as a
common environmental toxicant. Arsenic was described and used more than 2400 years ago in
Greece and Rome as a therapeutic agent and a poison and its preparations are found in
Paracelsus writings (1520 A.D.). The element is usually not mined as such but is recovered as a
by-product from the smelting of copper, lead, zinc and other ores.
Arsenic poisoning is caused by different types of inorganic and organic arsenical compounds.
Properties: Arsenic is a metalloid which belongs to the group V of the periodic chart of
elements and has some properties similar to phosphorus, antimony and bismuth. The arsenic
atom exists in three oxidation forms i.c. elemental (As'), trivalent (As3* or arsenite) and
pentavalent (As* or arsenate). The organic arsenical compounds contain arsenic linked to a
carbon atom by a covalent bond, where it exists in the trivalent or pentavalent states. Trivalent
arsenic compounds, known as arsenites, are more soluble and, therefore, more toxic (5-10 times)
than pentavalent or'arsenate compounds.
Inorganic forms of arsenic (i.e. arsenic trioxide) and pentavalent and trivalent forms of sodium,
potassium and calcium salts (arsenates and arsenites, respectively) are more toxic than the
organic forms e.g. trivalent monosodium methanearsonate
(MSMA), disodium
methanearsonate (DSMA), thiacetarsamide, and pentavalent arsanilic acid and sodium arsanilate.
Arsine (arsenic hydride) gas, which may come from charging of storage batteries or by the action
of water on pyritic ores, is most toxic arsenic compound. In general, toxicity increases in the
sequence of organic arsenicals < AsS+ < As3+ < Arsine (AsH3).
Sources of toxicity: Arsenic was a common poison used for homicidal or suicidal purposes in
ancient times. Accidental arsenic poisoning was also common a few years ago because it was
often used in ant and roach baits. Arsenic is less common cause of poisoning in livestock
nowadays because of its displacement from almost all phases of farming activity. Still arsenic is
an important poison and its toxicosis in animal may occur from following sources:
●
● preparations, skin tonics and for control of ectoparasites (e.g. lead arsenate as dip) and
blood parasites (c.g. sodium thiacetarsamide).
● Excessive use or accidental ingestion of arsenical pesticides i.e. insecticides (e.g.
copper acctoarsenite or Paris green), defoliants/herbicides (e.g. sodium or potassium
arsenite or arsenate, monosodium methanearsonate),
rodenticides (c.g. arsenic trioxide), wood preservatives (e.g. arsenic pentoxide) and ant
baits (e.g. sodium or potassium arsenate).
● Arsenic-contaminated soils or burn piles, which are often licked by animals that crave for
salt or minerals.
 ● Contaminated drinking water especially well water containing high concentrations of
arsenic. Underground water having ligh arsenic may result in widespread poisoning in
human beings and livestock.
● Overdosage or extended use of organic arsenical feed additives in poultry or swine as
growth promoters (e.g. arsanilic acid and sodium arsanilate).
Burning of wood products treated with arsenical preservatives or coals which have variable
concentration of arsenic. Arsenic is released into the environment during combustion.
● Smelting of copper, zinc, lead and other ores can release arsenic as a by-product into
the environment.
● Arsine gas and arsenic trioxide used in the manufacture of most computer chips using
silicon-based technology. These may cause occupational toxicosis.
● Litter from poultry fed phenylarsonic compounds.
● Pastures and crops near smelters contaminated with arsenic,
● Dyes and paints containing arsenic (much rarer, now).
1. Malicious poisoning with arsenic trioxide (very common).
Factor affecting toxicity: Toxicity of arsenic in animals varies with several factors such as

species, oxidation slate, sortery and duration of

exposure.
● Species: Herbivores are commonly poisoned due to ingestion of contaminated forages.
Cats and dogs are poisoned less. while fowl and swine are rarely effected due to their
limited exposure to arsenic.
● Oxidation state: Inorganic arsenic in the trivalent state is more toxic (up to ten times)
than the inorganic pentavalent form (as pentavalent form has less affinity for thiol group),
which in turn is more toxic than organic form. Toxicity of pentavalent arsenicals is largely
due to their conversion in vivo to trivalent state.
● Solubility / Form: Finely divided soluble arsenic compounds are more toxic than coarse
and poorly soluble ones because the insoluble compounds áre poorly absorbed.
● Status / Health of animal: Dehydrated, weak, ill and poor conditioned animals are more
susceptible to arsenic toxicity due to slow renal excretion of arsenic.
● Tolerance: Constant exposure to arsenic may confer some degree of tolerance to its
toxicity.
Toxicity: All species are susceptible to arsenic poisoning, but it is most commonly observed in
bovine and feline animals followed by horses and sheep. Incidence of arsenic poisoning is less
common in dogs and rare in swine and poultry. The single dose lethal toxicity of sodium arsenite
for most species is in range of 1-25 mg/kg body wt. with arsenic trioxide being 3-10 times less
toxic.
The average total lethal dose of arsenic trioxide and sodium arsenite, respectively is: horses
10-45 g and 1-3 g; cattle 15-45 g and 1-4 g; sheep and goals
30.050 mg: 204500/5 50 300m 3 and 10-100 mg
Cats are highly susceptible to arsenicals and may succumb to sodium arsenite at a dose rate of
20 mg/kg. Chronic poisoning is not often seen and not well described in domestic animals as
arscnic is rapidly excreted from the body.
Toxicokinetics: Soluble arsenicals (both trivalent and pentavalent) are readily absorbed from all
body surfaces including GI tract and skin. Percutaneous toxic dose, however, is much lower
(probably one-tenth of) than the oral toxic dose.
The absorption is more if the animals are dipped in hot weather, if the fleece is long and if they
are crowded 100 tightly in draining yard. Absorption of poorly water-soluble arsenicals such as
AszO3 greatly depends on the physical state of the compound; coarsely powdered material is
climinated in faeces before it dissolves. After absorption, arsenic is distribuled throughout the
body but tends to reach higher concentration in liver, kidneys, heart and lungs. Because of high
sulphydryl contents in keratin, high concentrations of arsenic are found in hair and nails where it
stays for months. Because of its chemical similarity to phosphorus, arsenic is deposited in bone
and teeth and retained there for long period. Deposition in the keratinised tissues primarily
occurs after the continuous intake of arsenic.
In domestic animals, arsenic does not stay in tissues for very long and is partly methylated
(detoxification) in the liver and rapidly excreted in the urine, faeces, bile, milk, saliva and sweat.
Some portion of pentavalent arsenic (arsenate) is reduced to the more toxic trivalent arsenic. In
this process, the pentavalent arsenic is coupled to the oxidation of glutathione (GSH) to its
disulphide (GSSG) to form trivalent arsenic (arsenite) which is further methylated to form
monomethyl arsenite and then dimethylarsenite (Figure 11.1) which is readily eliminated from the
body. This conversion from pentavalent arsenic to trivalent arsenic in the kidneys may also
account for nephrotoxicity Arsenic crosses placental barrier in significant amount but its passage
to CNS through blood brain barrier is limited. Excretion of arsenic in domestic animals is rapid
and nearly complete within a few days.
Mechanism of action: Regardless of the form of arsenic entering the body (pentavalent or
livalent), the major effects are believed to be attributable to the trivalent form.
a. Trivalent arsenic:
i. Trivalent arsenic binds primarily to sulphydryl compounds especially lipoic (thioctic) acid to
form stable compounds that subsequently disrupt enzymes involved in cellular respiration
(Figure 11.2). As such, trivalent arsenicals inhibit many proteins and enzymes by reacting with
biological ligands containing available
-SH groups.
The pyruvate
dehydrogenase system is especially sensitive because interaction of arsenic with two sulphydryl
groups of lipoic acid results in a stable six-membered ring. Lipoic acid is an essential cofactor for
the enzymatic decarboxylation of keto acids such as pyruvate, ketoglutarate and ketobutyrate.
By inactivating lipoic acid, arsenic inhibits formation of acetyl, succinyl; and propionyl
coenzymes-A. Other oxidative decarboxylations that use lipoic acid are probably also inhibited
The major effect of lipoic acid inhibition is slowing or inhibition of glycolysis and TCA cycle.
Inhibition of mitochondrial •enzymes and impairment of tissue respiration seems to. be related to
the cellular toxicity of arsenic. Tissues with high oxidative energy requirement (e.g. actively
dividing cells such as intestinal epithelium, kidneys, liver, skin, lungs etc.) are most affected
ii. Trivalent arsenic affects capillary integrity by an unknown mechanism.
Although all capillary beds are affected, the splanchnic area in the GI tract is the most sensitive.
Loss of capillary integrity and dilation in GI tract allows transudation of plasma fluids into the
intestinal mucosa and lumen with reduced blood volume, hypotension,
shock and circulatory loss. Oedema,
vesiculation and eventual loss of GI
mucosa also occur that further
aggravate fluid loss and shock.
Dilatation and swelling of glomerular
capillaries in kidneys accompanied by
hypotension and hypovolaemia lead to
decreased renal perfusion, nephrosis
and oliguria (Figure 11.3). Following
percutaneous absorption, capillary
dilation and degeneration cause
vesiculation, blistering and oedema of
skin.
b. Pentavalent inorganic arsenicals: The
arsenate (pentavalent) ion appears to
substitute for phosphate in oxidative
phosphorylation. Arsenate is a well-known
uncoupler of mitochondrial oxidative
- phosphorylation. There is competitive substitution of arsenate for inorganic
phosphate in the formation of adenosine
Liphosphate, with subsequent formation of
an unstable arsenate ester that is rapidly
hydrolysed. This process is called
arsenolysis. However, elevated body
temperature is not a characteristic of
arsenate as seen with other oxidative
uncouplers (e.g. nitrophenols).
c. Pentavalent organic arsenicals feed
additives): They act by an unknown
mechanism. They produce demyelination
and axonal degeneration, which perhaps
is due to interference with the B vitamins
required for maintenance of nervous tissue.
This effect of arsenic has been associated
with peripheral nerve and spinal cord
dysfunction in man.
d. Arsine gas (AsH3): Arsine is a gaseous
hydride of trivalent arsenic. Arsine does
not cause typical signs of arsenic
poisoning. It causes haemolysis and
pulmonary ocdema by mechanisms which
are not clearly understood. Rapid and fatal
haemolysis results probably from arsine
combining with haemoglobin and then
reacting with oxygen to cause haemolysis.
This effect of arsenic does not apparently
depend on sulphydryl inhibition and hence
dimercaprol has no effect on the
haemolysis.
Clinical signs :
«. Trivalent inorgunic or orgunic arsenicals
A cule and Peracute toxicity: Acute or peracute
poisoning with arscnic is common with high
morbidity and mortality. Major action of acute or
peracute toxicosis is on the GI tract and
cardiovascular system. In peracute cases, there are
no signs and the animal is found dead. Alternately,
there may be sudden and severe colic, staggering
gait, collapse, paralysis and death.
In acute cases, the signs include severe
gastroenteritis, colic, staggering gait, extreme
weakness, trembling, salivation, vomiting (in dogs,
cats and pigs), increased thirst, projectile watery
diarrhoea, possible blood in faeces, fast and weak
pulse, hypotension, dehydration, oliguria or anuria,
rumen atony, hind limbs paralysis, prostration,
normal or subnormal temperature, coma and death
in 1-3 days. Severity of clinical signs in cattle
correlates with hacmoconcentration as indicated by
105
the PCV. Animals inadvertently sprayed with
soluble arsenites may exhibit vesicles, pustules,
ulcers and skin necrosis.
Subacute toxicity: In subacute cases, the
animal may live several days with same clinical
signs as mentioned for acute toxicity, but generally
less pronounced. The important signs include colic,
anorexia, depression, staggering, weakness,
diarrhoea with blood and/or mucous discharge,
polyuria and then anuria, dehydration, polydipsia,
partial paralysis of rear limbs, cold extremities, and
hypothermia. Convulsions rarely occur. Acidosis
and azotemia may cause death. Percutaneous
absorption of arsenic may cause oedema of skin,
skin eruptions and secondary skin infections.
Chronic toxicity: Chronic cases are rarely seen
in domestic animals, but are well documented in
man. Chronic arsenic poisoning in animals is
characterised by wasting, poor condition, thirst,
brick red discolouration of visible mucous
membranes, normal temperature and weak
irregular pulse. Swelling of the joints, joint pains
with stiffness and paralysis have also been reported.
Following percutancous absorption, the skin
becomes dry, papery, and may crack, bleed and
develop secondary infection. Disorders of
reproduction (sterility, abortion) have been
associated with chronic arsenic exposure. Chronic
arsenic poisoning in animals is generally
encountered in industrial regions following
ingestion of forage contaminated by industrial
pollutants. Deliberate or criminal poisoning is often
referred to but is rarely seen in veterinary medicine.
In human medicine, arsenicosis is recognized
by the skin blotches that arise all over face and
body with hyper-pigmentation of the chest and
upper arms, hard patches on palis and soles,
inability to walk accompanied with debilitating pain
and watery eyes. Arsenic is carcinogenic and its
chronic exposure can result in skin, pulmonary and
bladder cancers.
b. Pentavalent organic arsenical feed
additives: Early signs are apparent after 2-4 days
and include nervous derangement such as ataxia,
incoordination and blindness. Affected animals
(mostly swine) become weak, assume a sitting dog
posture, and eventually become paralysed in lateral
recumbency. Appetite remains normal and animal
is alert. Blindness is characteristic of arsinilic acid
poisoning and not of other arsenicals.
Post-mortem findings: In peracute arsenic
toxicosis, no icsions may be seen. Necropsy lesions
in acute poisoning include inflamination of GI tract,
ocdema, rupture of blood vessels, and necrosis of
epithchal and subepithelial tissues. The necrosis
may progress to perforation of the gastric or
intestinal wall. Contents of the gut are fluid, often
foul smclling and blood tinged and may contain
shreds of epithelial tissue. There may be diffuse
inflammation of the liver and other abdominal
viscera. Occasionally haemorrhages may occur on
all surfaces of the heart. Skin is dry, leathery and
peeling following cutaneous exposure. In subacute
cases, there are pale swollen kidneys, pale liver,
petechial haemorrhages of intestinal serosa and
inucosa.
Microscopic lesions in the GI tract include
intestinal capillary dilatation, mucosal and
submucosal ocdema, and necrosis and sloughing
of mucosa. In kidneys, all portions of nephron are
affected with glomerular sclerosis and severe renal
tubular necrosis. Hepatic fatty degeneration and
necrosis may be observed in liver. Capillary
degencration is observcd in various organs
including gut, skin, lungs and kidncys.
Diagnosis: Diagnosis is made from history,
circumstantial evidences, clinical signs and lesions.
A sudden onset of severe colic, bloody or watery
diarrhoca containing mucosal shreds, and post-
mortem findings of haemorrhagic gastroenteritis
and degene ative changes in liver and kidneys
should always be interpreted as possible arsenic
poisoning. No other metal or metalloid, with the
possibl exception of thallium, causes such a speedy
onset of severe GI damage. Chemical determination
of arsenic in tissues and ingesta provides
confirmation. Antemortem samples include urine,
vomitus, faeces and hair. After death, hepatic, renal
and nervous tissues (organic pentavalent toxicosis)
may be taken. Analysis of feed, plant, soil should
also be done. Liver and kidney tissues of healthy
animal rarely contain > 1 ppm arsenic (wet wt.),
whercas toxicity is associated with concentrations
> 3 ppm. Urinalysis reveals high arsenic content
for many days, proteinuria, increased specific
gravity and casts.
Arscnic poisoning has to be differentiated
from:
a. Lead poisoning: Lead poisoning, if severe
cnough, can mimic various aspects of
arsenic poisoning but with lead there are
nervous and behavioural signs.
TEXTBOOK OF VETERINARY TOXICOLOGY
b. Caustics, irritants, urea: These also show
GI signs like diarrhoea and colic and
require careful identification. The nervous
syndrome in pigs poisoned by organic
arsenicals may be confused with organic
mercury poisoning, salt poisoning and
encephalitis, but the mildness of signs,
lack of effect on appetite and absence of
fever differentiate it from others.
Treatment and management:
Specific therapy: Specific therapy is aimed at
the known affinity of arsenic for sulphydryl groups,
particularly dithiols.
a. Dimercaprol/British Anti-Lewisite (BAL)
: It is a dithiol-containing chelating agent
that can form a relatively non-toxic and
easily excretable complex with arsenic.
However, it is relatively ineffective unless
given prior to a set of clinical signs as
enzymes that have been inhibited for long
time are not easily regenerated by
dimercaprol. Further, if arsenic is present
in large excess, neither dimercaprol nor
any other chelator can be expected to work
very well to regenerate enzyme activity
Dimercaprol also has toxic effects
(vomiting, tremors, and convulsions)
which limit its dosage and frequency of
administration.
Large animals: 3 mg/kg (5% sol. in 10%
sol. of benzyl benzoate in arachis oil) by
deep I.M. injection. The injection should
be repeated every 4 hours for the first 2
days, every 6 hours the 3rd day and twice
a day for next 10 days until recovery. Renal
function should be monitored during
therapy.
Small animals: 2.5-5 mg/kg (10% sol. in
oil). Dose intervals are same as in.large
animals. Dosage and frequency of BAL is highly
specific i.e. if administered 1o0 late or in
insufficient doses at infrequent intervals
the animal may die of arsenic poisoning,
and if administered in excess or at too
frequent intervals the animal may die of
BAL poisoning. This is also true for other
specific chelating agents uscd in, metal
toxicosis

b. Thioctic acid: Thioctic acid (a-Lipoic

acid) is considered more effective than
dimercaprol for arsenic poisoned cattle,
however, it is not available in a commercial
dosage form. Thioctic acid is used alone
or in combination with dimercaprol.
Cattle: 50 mg/kg body wt., I.M., thrice a
day as 20% solution (50 g of di -6, 8-
thioctic acid dissolved in 100 ml of warm
SN NaOH, cooled, then adjusted to ph
neutrality with IN HCl and brought to
volume with distilled water).
c. Sodium thiosulphate: Sodium thiosulphate
is a safe antidote to arsenic poisoning. The
sulphur of thiosulphate probably reacts
with arsenic and immobilises it.
Horses and cattle: 8-10 g (total dose) I.V
as 10-20% solution plus 20-30 g orally in
about 300 ml water.
Sheep and goats: One fourth of above dose.
d. Mesodimercaptosuccinic acid (MDSA)
and Dimercaptosuccinic acid (DMSA,
succimer): These are water soluble
derivatives of dimercaprol and said to be
superior to dimercaprol, but efficacy is not
wel tested against arsenic poisoning
Supportive therapy and maintenance
a. Emetics, gastric lavage and activated
charcoal may be employed i f the arsenic
ingestion is recent. Emesis and vigorous
lavage is contraindicated after clinical
signs have developed, due to possibility
of increasing the likelihood of perforation
and shock.
b. Correction of shock, dehydration and
acidosis with extracellular electrolyte
solutions may be done. Blood may be
given, if necessary.
c. Renal function should be monitored and
urinary flow may be promoted using 10%
dextrose solution.
d. Animal should be kept warm and
comfortable.
e. Sufficient vitamins, antibiotics, analgesics
and other symptomatic care may be
instituted.
f. A high protein diet is recommended
during the post-exposure period.
107
Prognosis: The prognosis of arsenic poisoning
is grave if the animal is not treated promptly or if
there has been extensive organ damage and animal
is prostrate. The mortality rate is high among
acutely poisoned animals with inorganic trivalent
arsenicals. With organic pentavalent arsenicals, the
mortality is low but morbidity is high and recovery
may take 2-4 weeks with good nursing and
supportive care.
Public health concerns: All arsenicals should
be treated as poison. Their containers must bear a
warning label 'poison' and must be kept out of
general reach. These may be used only by trained
workers and any use must be strictly recorded. In
domestic animals, arsenic does not stay in tissues
for very long. Milk from poisoned cows can be toxic
for humans, but the flesh of surviving animals is
said to be safe for human consumption.
Some important compounds of arsenic:
Inorganic arsenic compounds
a. Hydrogen arsenide (Arsine): Hydrogen
arsenide (AsH or arsine) is a colourless
gas with garlic odour. It is generated under
the effect of hydrogen on arsenic
compounds. It is a very strong poison (10
to 20 times as toxic as CO); 10 ppm is toxic
within a min. It has MAC of 0.05 ppm.
b. Arsenic trioxide: Arsenic trioxide
(Arsenious oxide, AszO3, Sankhya) is
commonly called white arsenic or simply
arsenic. It is white amorphous, vitreous or
crystalline matter, slightly soluble in cold
water (1-2 mg/ml) but highly soluble on
boiling (0.2 - 0.3 g/ml). The solution
formed is acidic and is called arsenious
acid. Arsenic trioxide has a property of
floating on water as a white film. It is
largely used as principal ingredient of fly
papers, rodenticides, anthelmintic, ctc.
c. Potassium arsenite and Sodium arsenite:
Potassium arsenite (K3AsO3) and sodium
arsenite (Na2AsO3) are white powders,
soluble in water. Both are poisonous and
are used in manufacturing of fly papers,
insecticides, herbicides, sheep dips,
rodenticides, etc.
d. Sodium arsenate and Potassium arsenate:
Arsenic acid (H3AsO4, obtained by
warming arsenious oxide with nitric acid)
combines with metals to form salts called
arsenates. The arsenates of the alkali metals are soluble in water. Both sodium arsenate
(NazAsO,) and Potassium arsenate (K3AsO4) are poisonous and are used for homicidal and
malicious poisoning of cattle.
Organic arsenic compounds
e. Acetarsone: Acetarsone (3-acetylamino-4-hydroxy phenyl arsonic acid, acetarsol) is an
organic compound of arsenic used in veterinary medicine as antihistomonad in turkeys and
spirochetocide in poultry. It has also been used as a tonic. It occurs as colourless crystals and
contains 27% of arsenic.
§. Thiacetarsamide: Thiacetarsamide
(Arsenamide) is an organic arsenic compound used in the treatment of heartworm infection in
dogs, especially the adult stages.
g. Copper acetoarsenite:
Copper
acetoarsenite (Paris green) is an insecticide, but is less used nowadays due to high toxicity.