2. INTRODUCTION
• Most common heavy metals toxicity:
• Lead (Pb),
• Mercury (Hg),
• Arsenic (As) •
• mainly produced by industrial activities, and deposit slowly in the
surrounding water and soil
• Toxicity may occur through
• ingestion,
• inhalation or
• dermal exposure
• Toxicity is either acute or chronic
• Metallic taste if ingested except arsenic which is tasteless
• Can cause both local & systemic effects
• Most metals cause diarrhea except lead which causes
constipation
• The antidotes are called chelators
3. Arsenic
• Toxic principles
• Inorganic arsenicals
• Arsenic trioxide
• Arsenic penta-oxide
• Sodium and potassium arsenate
• Sodium and potassium arsenite
• Calcium and lead arsenate
4. SOURCES
• Pasture near smelters
• Paints
• Strong solutions of lead arsenate for animal dipping
• a drug for control of ectoparasites,
• Blood parasites and
• skin tonics
• Water, herbage contamination
• Animals licking wood preserved in arsenical preparations
• Overdose of arsenical feed additives
• Milk from arsenic poisoned animal
• Rodenticides
• Weedicides
• Baits and insecticides
• Use of lead arsenate as taenicide
5. animal Arsenic triioxide Sodium arsenite
Horse 10-45 gm 1-3 gm
cow 15-45 gm 1-4 gm
Sheep and goat 3-10 gm 200-500 mg
Swine 500-1000 mg 50-100 mg
Dog 100-150 50-150 mg
fowl 50-300 mg 10-100 mg
• Arsenic
cumulative poison
Stored in liver skin and hair
Oral lethal dose of sodium arsenate 1-25 mg/kg in most animals
Sodium arsenite is 10 times poisonous than arsenic trioxide
6. Factors influencing Toxicity:
• Species:
• Herbivores commonly poisoned
• Dog maliciously poisoned
• Cats are occasionally poisoned
• fowl, and swine rarely poisoned
• Oxidation state:
• Inorganic trivalent arsenic is more potent than inorganic pentavalent
• Organic arsenicals are less toxic than inorganic arsenicals
• Pentavalent arsenicals converted in-vivo to trivalent and becomes
toxic
• Solubility/Form:
• Finely divided and soluble form -more toxic than coarse and poorly
soluble
• Status of animals:
• Dehydrated, weak, Ill and poor body condition- more susceptible
• Tolerance: constant exposure increased toxicity
7. Toxicokinetics
• Distributed
• in almost all biological fluid of the body
• Higher concentration
• liver kidney spleen
• Does not stay in the body for longer time
• in domestic animals
• Rapidly excreted in
• urine feces, bile, milk and saliva
• Half life is 1.5 days in animals
• Does not cross BBB but readily cross placental
barrier
8. Mechanism of Toxicity:
• Trivalent arsenic binds with sulfahydril groups of lipoic acids ( essential
cofactor for enzymatic decarboxylation or keto acid such as pyruvate,
ketoglutamate and ketopyruvate)
• Arsenic acid inactivates lipoic acid and inhibits formation of acetyl
succinyl and propanyl co-enzymes A
• other oxidative decarboxylation used by lipoic acid is also inhibited
• Thus glycolysis or TCA cycle is inhibited
• As produce local corrosive action on gut mucosa
• GI damage due to route of absorption
• Liver kidney intestine-rich in oxidative enzymes and As has special affinity to
them
• As increases capillary permeability and capillary endothelial cells of those organs
are very much susceptible
• The wall of blood vessels and smooth muscles are dilated
9.
10. Clinical signs:
• Peracute
• Animals found dead showing no symptoms
• Severe colic, staggering, collapse, paralysis and death
• Acute:
• Severe colic, staggering, weakness trembling,
salivationvomitting,thrist,projectile watery diarrhea, blood tinged
feces, fast and weak pulse, hind limb paralysis , normal or subnormal
temperature and death 1-3 days
• Subacute:
• Colic anorexia, blood mixed diarrhea, muscle threads in feces,
polyuria followed by anuria, dehydration thrust, partial paralysis
of hind limbs, trembling, stupor, cold extremities, subnormal
temperature, hematuria, convulsion
• Chronic
• Wasting, poor condition, thirst, brick red coloration of mucus
membrane,, normal body temperature, weak and irregular pulse
11. PM FINDINGS
• Cattle
• Reddened abomasal or duodenal mucosa
• Sub-mucosal edema
• Hemorrhage in the abomasum and duodenum
• Perforation of the gut wall
• Intestinal content foul smell
• Liver soft and yellow
• Lungs edematous and congested
• Swine
• Larynx and trachea edematous
• Fowl
• Proventriculus and gizzard inflamed
• Gelatinous exudates beneath the horny line of gizzard causes
sloughing of the gizzard horny layer
13. TREATMENT
• Non specific treatment
• Emetics, Gastric Lavage
• Specific antidote
• Dimercaprol / British Anti-Lewisite (BAL):
• Large animals-3 mg/kg i.v. until recovery
• Small animals- 2.5 mg/kg i.v. until recovery
• Sodium Thiosulphate:
• Horse & cattle: 20-30 mg; PO + 300 ml water twice daily till recovery
• Sheep goat 8-10 g orally
• Supportive therapy
• Good nursing care, animal should be kept in warm
• Should be treated symptomatically with Antibiotic and analgesic
• Rehydration Therapy
• High protein diet
14. • Prognosis- grave
• If the treatment started late
• Extensive organ damage
• Analysis
• Stomach
• Intestine(feces or vomitus)
• Liver and kidneys
• Blood milk urine
• More than 3 ppm arsenic concentration in these
organs confirms the arsenic poisoning in the
animals
16. Mercury
• Occurs in three forms
• elemental, inorganic salts, and
• organic compounds
• Contamination results from
• mining, smelting, and
• industrial discharges.
• Mercury in water can be converted by bacteria
to organic mercury (more toxic) in fish.
• Can also be found in
17. Mercury
• thermometers, dental amalgams,
• fluorescent light bulbs,
• disc batteries, electrical switches,
• folk remedies, chemistry sets and vaccines.
• some medications,
• drinking water, and
• many other things.
• Young are more susceptible to getting
mercury poisoning than adults.
• The vapor form of mercury is the most toxic.
18. Mercury - Exposure
• Elemental
• liquid at room temperature that volatizes readily
• rapid distribution in body by vapor, poor in GI tract
• Inorganic
• poorly absorbed in GI tract, but can be caustic
• dermal exposure has resulted in toxicity
• Organic
• lipid soluble and well absorbed via GI, lungs and
skin
• can cross placenta and into breast milk
19. Elemental Mercury
• At high concentrations,
• vapor inhalation produces acute necrotizing
bronchitis, pneumonitis, and death.
• Long term exposure affects CNS.
• Early: insomnia, forgetfulness, anorexia, mild
tremor
• Late: progressive tremor and erythrism (red
palms, emotional labiality, and memory
impairment)
• Salivation, excessive sweating, renal toxicity
(proteinuria, or nephrotic syndrome)
• Dental amalgams do not pose a health risk.
20. Inorganic Mercury
• Gastrointestinal ulceration or perforation and
• hemorrhage are rapidly produced, followed by
circulatory collapse.
• Breakdown of mucosal barriers leads to increased
absorption and distribution to kidneys (proximal
tubular necrosis and anuria).
• Acrodynia (Pink disease) usually from dermal
exposure
– maculopapular rash, swollen and painful
extremities, peripheral neuropathy,
hypertension, and renal tubular dysfunction.
21. Organic Mercury
• Toxicity occurs with long term exposure and effects
the CNS.
• Signs progress from paresthesias to ataxia, followed
by generalized weakness, visual and hearing
impairment, tremor and muscle spasticity, and
then coma and death.
• Teratogen with large chronic exposure
• Asymptomatic mothers with severely affected
infants
• Infants appeared normal at birth, but psychomotor
retardation, blindness, deafness, and seizures
developed over time.
22. Diagnosis and Treatment
• Diagnosis made by
• history and physical and lab analysis.
• Inorganic mercury
• can be measured in 24 hour urine collection;
• organic mercury
• is measured in whole blood.
• The most important and effective treatment
• is to identify the source and end the exposure
• Chelating agents (DMSA) may
• enhance inorganic mercury elimination.
• Dimercaprol may increase mercury
concentration in the brain.
23. Mercury - Prevention
• Elemental mercury spills:
–Roll onto a sheet of paper and place in
airtight container
–Use of a vacuum cleaner should be avoided
because it causes mercury to vaporize
(unless it is a Hg Vac)
–Consultation with environmental cleaning
company is advised with large spills.
• avoid consumption of certain fish from specific
bodies of water.
24.
25. Absorption
• Most commonly by breathing contaminated air.
• Can also be absorbed by drinking water or
• eating contaminated food
• (usually fish, especially those that eat other fish).
• There about 2 ppm of mercury in one billion
parts of drinking water.
26. Distribution
• Mercury is distributed
– to the bloodstream from the lungs, then the blood
carries it to the central nervous system.
• This is especially harmful to young, because their
nervous systems are still developing.
29. Excretion
• Mercury is excreted from the body through urine
and feces. It can take the body several months
to excrete it.
• Chelation therapy can also be used to help get
rid of the toxin. This is where a substance that
binds to the mercury is injected into the body, for
easier removal.
30.
31. Acute exposure
• Can lead to lung damage, vomiting, diarrhea, high blood
pressure, eye and skin irritation.
• Mercury can cause damage to the body even before
effects are noticed!!
• Some effects include:
• Tremors
• Shyness
• Irritability
• Insomnia
• Changes in hearing or vision
• Difficulty with memory
32. Chronic exposure
• A few drops can raise the surrounding air to those of high
contamination!!
• When mercury is inhaled it can lead to
• Acute necrotizing bronchitis
• Chemical pneumontis
• Death due to respiratory failure
• Damage to the kidneys, lungs, brain.
• Symptoms can be passed from child to fetus through the
placenta, resulting in birth defects;
• Mental retardation
• Blindness
• Seizures
• Problems with the nervous and digestive systems
33. References
• http://www.atsdr.cdc.gov/cabs/arsenic/
• http://www.epa.gov/safewater/arsenic/
• http://www.emedicine.com/neuro/topic20.htm
• http://physchem.ox.ac.uk/msds/AR/arsenic.html
• Chattopadhyay, S ; Bhaumik, S ; Purkayastha, M ; Basu, S ; Chaudhuri, AN ; Das
Gupta, S. 2002. Apoptosis and necrosis in developing brain cells due to arsenic
toxicity and protection with antioxidants. Toxicology Letters. v.136, no.1, p.65-
76.
• Santra, A; Maiti, A; Das, S; Lahiri, S; Charkaborty, SK; Mazumder, DNG. 2000.
Hepatic damage caused by chronic arsenic toxicity in experimental animals.
Journal of Toxicology. v.38, no.4, p.395-405.
• http://www.atsdr.cdc.gov/tfacts46.html
• http://www.atsdr.cdc.gov/alerts/970626.html
• http://www.mercuryinschools.uwex.edu/
• http://www.fda.gov/cder/fdama/mercury300.htm
• http://www.epa.gov/mercury/exposure.htm
• http://www.vaccinationnews.com/DailyNews/July2001/AutismUniqueMercPoi
son.htm
• http://www.tuberose.com/Mercury.html
• http://en.wikipedia.org/wiki/Mercury_poisoning
• http://enhs.unm.edu/5200/mercury/metabolism.html
34. Toxicokinetics:
• Absorption- Readily absorbed from all body
• surfaces
• Distribution- Throughout the body
• High concentration in liver,kidney,heart & lungs
• High concentration in nails & hair because of
• high sulphydryl contents
• Cross placental barrier
• • Partly methylated in liver
• • Excreted in urine, feces, bile,milk,saliva & sweat
• • Lethal oral dose of sodium arsenite in most
• species 1–25 mg/kg. Cats more sensitive. In
• livestock, arsenates are 5–10 times less toxic
• than arsenites.
36. • SOURCES
• Paint and paint cans
• Greases, linoleum, leaded gasoline,
• solid lead, solder, roofing materials and
• industrial effluents
• Grass near busy streets
• Licking of discarded batteries, paints,
• Milk secreted from lead-poisoned animals
• Agricultural use of fertilizers,
• fungicides, herbicides
• Drinking water from old lead pipes
• Lead parasiticide sprays particularly those containing lead
arsenate
37. • Acute toxicity
• The acute single oral lethal dose in animal
• Calves 50-600 mg/kg (leadd or lead salts)
• Cattle 50-100 gm)
• 600-800 mg/kg lead salt
• Horse and goats
• 20-40 gm( lead acetate)
• 600-800 mg/kg (lead salts)
• Swine 10-25 gm ( lead acetate)
• Dogs 1—25 gm ( lead acetate)
• Fowl 16-600 mg/kg (lead salts)
38. Factors influencing Toxicity:
• Age: Young animals more susceptible
• Species: Goats, swine, chicken are more
• resistant
• Reproductive state: Pregnant ewe more
• susceptible than nonpregnant
• Rate of ingestion: large amount within short
• time is more toxic
• Undernutrition and presence of other
• debilitating factors
• Presence of food or ingesta in stomach or
• intestine delays absorption and thereby
• reduces toxicity
39. Absorption and Fate:
Almost lead enters
through ingestion
—Absorption from
gut (only 1 or 2 %)
—85-90% binds to
Hb in erythrocyte
—Remainder bind
to serum albumin
—Less than 1%
actually free
40. CNTD….
Distribution of
unbound fraction
to various parts of
body
—Mainly sink in
bone (90-98%)
—Via portal
circulation reaches
to liver and then to
duodenum via bile
—Excretion via milk,
urine and feces.
—Can cross Blood
Brain Barrier and
Placental Barrier
—Concentrations of
lead in the blood at
0.35 ppm, liver at
10 ppm, or kidney
cortex at 10 ppm in
most species
—lead
concentrations in
blood >0.05–0.10
ppm to be a
notifiable disease
in food-producing
animals
41. Mechanism Of Toxicty:
• Toxicity mainly by inhibiting sulfhydryl
groups of essential enzymes of cellular
metabolism.
42. A. Neurotoxic mechanism:
lead
Enter into brain cells
Disturbs the function
of cellular calcium
Damage to capillary
endothelium
Inactivates BBB
Cerebral edema &
hemorrhages
43. B. Gastro-Intestinal toxicity:
• Specific mechanism-not understood
• Could be secondary to neurological
• mechanisms
• Lead causing
• Contraction of smooth m/s of intestinal wall
• -gastroenteritis
• -anorexia
• -Vomition
• -Colic
44. C. Haematopoietic toxicity:
• Inhibition of Haeme synthesis by inhibiting
key enzymes involved in synthesis eg. ∂-
ALAS,∂-ALAD, HS
• Inhibits Na+/K+ ATPase pump Which Attach
to RBC membrane and causing Lysis of RBC
45. CNTD…
• D. Immunotoxicity:
• Decreased production of Antibodies
• E. Nephrotoxicity:
• Inhibition of cellular respiration
• Generalized dysfunction of renal tubular &
energy dependent function
46. CNTD..
• F. Endocrine toxicity:
• Decreased release of GH & insulin growth
factors
• G. Reproductive toxicity:
• Gametotoxocity (both male and female)
47. Clinical Symptoms:
• Acute or Chronic
• IN Acute:
• common in cattle
• Bellowing, rolling eyes and frothy mouth
• Excitation followed by quiscient phase
• Muscular spasm, tetany and death
48. CHRONIC
• IN Chronic:
• Anorexia, constipation, recumbency and
death
• (cattle and sheep)
• Paralysis of limbs, anorexia, jaundice, nasal
• discharge, Roaring due to laryngeal muscle
• paralysis (Horse)
49. • Pigs- considerably resistant
• Dog- i) Gastrointestinal symptoms
• (anorexia, vomiting, colic, diarrhoea)
• ii) Nervous symptoms (anxiety,
• hysterical barking, salivation,
• convulsions)
• Cats- not very common
• Birds- anorexia, ataxia, excitement,
• loss of condition;decrease in fertility,
• hatchability and egg production; High
mortality
50. Post-Mortem Lesions:
• No observable gross lesions
• Stomach and intestine may present
ingested lead
• Brain edema, gastritis, hyperemia and
• petechiae on various organs
51. DIAGNOSIS
• History, Clinical signs, PM lesions,
• lead content in body inclusions
• Measurement of ALA dehyratase in
• blood
• Urine ALA is increased
• Level of lead >4 ppm in liver , 0.2 ppm
• in whole blood indicates lead
• poisoning
53. Treatment:
• Calcium Ethylenediamine tetra acetate (EDTA) as an
• antidote
• Cattle and horses:110 mg/kg i/v or s/c two doses @
• 6hrs. Interval every other day for three treatments
• Dogs: 110 mg/kg s/c as 1% solution diluted with
• 0.9%saline divided into four doses every other day for
• three treatments
• BAL increases lead excretion in urine
• Intestinal lavage or a cathartic to eliminate the
• unabsorbed lead
• Vit.D and Ca-borogluconate give additional support
• MagSulf will prevent further absorption of lead by
• reducing lead solubilty
• Cerebral oedema can be controlled using
• dexamethasone and mannitol
• Broad spectrum antibiotics to control secondary
• bacterial infection
63. Diagnosis of Mercury poisoning
• Blood mercury:
– only really useful acutely
- normal <10µg/l
- symptoms with blood mercury >150-200µg/l
• Urine mercury
– probably the most reliable indicator
- normal <10µg/l
- symptoms with urine mercury >100-150µg/l
• U&E
• Radiology: for elemental ingestion/aspiration/injection
64. Treatment of Mercury poisoning
• Remove from source
• Supportive care
– particularly important with inhalation
• DMPS Chelation (2,3-Dimercapto-1-propanesulphonate)
- Chelation therapy of choice for mercury
- For both acute and chronic mercury poisoning
- For all forms of Hg (inorganic > metallic >> organic)
- Indications:
- symptomatic patients
- blood/urine mercury persistently > 100 - 150mg/l
