Metals

Mohamed Yehia, Ph.D.

Lecturer of Toxicology and Forensic Medicine
Veterinary College
Cairo University
Metals or their salts are
therapeutically used.

Certain metal salts such as

mercurial diuretics, lithium Background
carbonate and bisthmus are
essential for life.
Metals released to the environment
may be bioconcentrated and thus
enter the food chain.
 Common Characters of Metallic Poisons

 Have double action

Local action produce gastrointestinal irritation (Irritants) causing diarrhea

except lead produce constipation
Remote selective action on certain organs Bind to SH group containing
enzymes
 Common Characters of Metallic Poisons
 Symptoms start after a latent period depends on:-

Type of stomach and its health state

Content of the stomach (Lipid delays the absorption of As)

Nature and amount of the metal

 Have acute and chronic forms (dose, period, nature)

 Common Characters of Metallic Poisons
 Re-excreted after absorption through the wall of GIT into its lumen

Lead in the biliary cycle

Arsenic through the descending colon

Mercury through the caecum

 Excreted in urine after short period of exposure and persist for days or months

(depending on the dose and rout of administration)

 Common Characters of Metallic Poisons

 Have general treatment

Charcoal and tannins are general antidote

Sod. thiosulphate to increase urinary excretion

Stomach tube is permissible except in cases of barium chloride and antimony

trichloride

 Most of theme are not affected by putrefaction (can be detected after long time

of death in bone, hair)

 Arsenic
 Arsenic is a toxic and carcinogenic metalloid, distributed in ores of most metals

 Arsenic is one of the more common causes of poisoning in Livestock

 The morbidity rate is variable, but the mortality rate usually approximates 100%

except for poisoning by organic compounds

 Arsenicals have been used since ancient times as drugs and even today are very

effective against acute promyelocytic leukemia

 The maximum permissible limit of Arsenic in drinking water is 10 µg/L(ppb).

 Inorganic

Arsenic trioxide Arsenic sulphide Arsenic sulphite

Arsine gas (AsH3)
(white arsenic) (yellow arsenic) (red arsenic)

Na, K arsenites

Copper arsenite
(Paris green)

- Weed killer, wood preservative ,grain dressing

Na, Ca and Pb - Eradication of flies and mosquitoes and animal
arsenate
dipping
 Forms and Occurrence
 Arsenic compounds are widely distributed in nature and the area of most metals

contains small quantities

 Naturally occurring arsenic is pentavalent while that added to the environment is

trivalent.
 Organic Salts ( Medicinal Forms of Arsenic)

 They are less toxic e.g. salversan, new salversan , atoxil.

 They are used as general tonics treatment of some diseases e.g. black head

disease in turkeys and skin cancer, antidotes to selenium poisoning and as

growth promoting factors.
 Toxicokinetic

Absorption
 From the GIT depending on the solubility and stomach content

 Through skin (intact or abraded)

 From respiratory tract

Distribution and Storage

 After absorption accumulate in liver

 Then slowly released and stored in

Bone, Skin, keratinized tissues (e.g. hair and hoof)

 It is irremovable from hair while disappear from soft tissues
 Toxicokinetic

 Withdrawal time from soft tissues:

2 weeks after treatment of poisoned animal

6 weeks after stoppage administration of arsenical drugs
Excretion
 Absorbed part in Urine, sweat, milk
 Unabsorbed part in feces
 Toxicity
 Toxic dose varies according to

Animal age and species (cat, pig, horse , cattle , sheep)

Nature, solubility & affinity to SH gp

 Inorganic is more toxic than organic (high affinity to SH gp)

 Arsenites (trivalent) are more toxic (more soluble) than arsenates (pentavalent)

 Arsine gas (the most toxic)

 Tolerance
 Habitual use of small doses causes tolerance to large dose

 The mechanism is due to increase the expression of gene which coded to

Arsenite methyl transferase (AS3MT) to improves metabolism and flushes out the
toxin faster.
 Routs of Exposure

 Using unclean utensils of arsenic dips, weed killer, insecticides, foot-rot bath and
dips
 Contaminated herbage by arsenical preparations

 Contamination of water near the metals melting works

 Licking wood preserved with arsenicals

 Routs of Exposure

 Misuse consumption of arsenicals (resemble to other preparations)

 - Lead arsenate is fed to dairy cattle in mistake for lime

 - White arsenic as mistaken by wheat flour
 Careless of shearing rams before dipping (percutaneous dose is lower than oral)

 Dosing animals with arsenical tonics after dipping

 Ingestion of arsenical rat poisons

 Mode of Action
It disrupts ATP production by :-
 Binds to SH-group containing enzyme; inhibits pyruvate dehydrogenase of the
citric acid cycle
 Uncoupler of mitochondrial oxidative phosphorylation, by Competitive substitution
of arsenic for phosphate; it inhibits oxidative phosphorylation, and energy-linked
reduction of NAD
 Increases hydrogen peroxide production (H2O2 reacts with iron or manganese
producing reactive oxygen species) inducing oxidative stress, chromosomal
break and teratogenicity
 Attaches to glutathione (SH-group) of RBCs producing hemolysis
 Symptom of Peracute Toxicity
Ingestion of large dose of inorganic salt (mainly) or arsine gas in short period
 May cause sudden death without illness

If symptoms appear showing:-

 Severe abdominal pain

 Staggering gait
 Collapse

 Paralysis
 Symptom of Acute Toxicity

Symptoms appear after a latent period

 ½ - 10 hr in mono- gastric animals , 1 - 2 day in ruminants

Depending on :-

 Type of stomach and its health state

 Content of the stomach (Lipid delays absorption)

 Symptom of Acute Toxicity
 Bloody Rice watery diarrhea (differentiated from cholera)

 Vomiting even in cattle

 Salivation and thirst

 Severe abdominal pain & Violent colic

 Increased respiratory and heart rates

 Symptom of Sub-Acute Toxicity
Animals live for several days and Symptoms are mainly gastroenteritis manifested by:-
 Vomiting

 Diarrhea and sometimes dysentery

 Depression & Loss of appetite

Nervous signs including:-

Muscle tremors & Inco-ordination

Staggering gait & Paralysis of hind limbs

 Rapid heartbeat rates

 Subnormal temperature

 Proteinuria and haematuria

 Symptom of Chronic Toxicity (Cumulative)

Animals are long exposed to small doses of organic or inorganic compounds

Skin lesions

 Dry bright coat

 Brick red coloration of the visible mucous membrane

 Symptom of Chronic Toxicity (Cumulative)

Animals are long exposed to small doses of organic or inorganic compounds

Skin lesions

 Muco-cutaneous junctions are red and cracked

 Produces characteristic transverse white bands across fingernails (Mees’ line),

which appear about 6 weeks after the onset of symptoms of arsenic toxicity.
 Symptom of Chronic Toxicity
 Ulceration & perforation of nasal septum

Nervous manifestations
 Incoordination & Paresis
 Blindness

GIT- Manifestations
 Thirst & Indigestion
 Loss of appetite and body weight (poor growth)

 Anemia

(Massive hemolysis of RBCs and it appears as subcutaneous hemorrhage)

 renal failure du to oliguria
 Milk yield is reduced in dairy cattle
 Abortion and stillborn may occur
 Organic Arsenical Toxicity
Nervous manifestations
 Incoordination & Paresis

 Blindness

GIT- Manifestations
 Thirst & Indigestion

 Loss of appetite and body weight (poor growth)

 Severe pain in teeth and gums

 Skin disturbances
 Necropsy Findings (PM)
 Rose-red inflammation of GIT especially the stomach

 Swollen of mucous membrane and detached epithelium

 Gut contains fluid mucous and threads of mucosa

 Cloudy swelling and fatty degeneration of liver, kidneys and heart

Degeneration, Cloudy swelling and Fatty liver

fatty change of pig liver
 Laboratory Findings
 Arsenic determination in living animals in urine faces, hoof

 After death is mainly performed in liver kidney hair hoof and tissues

 Increased blood urea nitrogen (BUN), proteinuria, increased urine specific

gravity, and urinary casts have been reported as a result of renal damage.

 Laboratory Analysis by Reinch’s test

 Treatment

Peracute and Acute cases of little value because of :-

1- The ingestion of large amounts
2- Short period between ingestion and appearance of symptoms
Subacute and Chronic cases treatment is consists of:-
 General treatment
 Specific treatment
 Treatment
General treatment
 Remove the cause

 Provide a high caloric ration with plenty of fluids

 Symptomatic treatment

 Remove residual arsenic from the gut by:-

Induction of emesis even in animals which are vomit

Gastric wash with warm water

Rectal irrigation with warm soapy water (in carnivorous)

Saline purgative (large dose) in ruminants

Oil demulcents (GIT coater)

 Treatment
Specific treatment
 Ferric hydroxide solution

It is classical oral antidote (doubtful effect)

Freshly prepared (3 parts Ferri perchloride + 1part Mg oxide (manesia) + 7 parts

water)
 Sodium thiosulphate (Hypo)

Increases urinary excretion (orally or IV)

Horses and cattle: 10 gm 10-20% solution IV, followed by 30 gm orally every 6
hour until recovery (3-4 days)
Sheep and goat receive ¼ of the dose
 Treatment
 Dimercaprol (BAL)

For man and pets for acute and chronic

Limited effect in large animals and sheep

Ineffective orally, given I/M

3 mg/kg 5% in 10% benzyl benzoate in arachis oil

Given every 4 hr for 2 days, every 6 hr on the 3rd day, and twice/ day for the next
10 days or until recovery
 Pencillamin & Ca-EDTA

more efficient and safer chelators for oral or parenteral

 Prognosis

 The mortality rate is high among animals acutely poisoned with inorganic
arsenicals.
 Animals poisoned with pentavalent organic arsenicals can experience a high
morbidity rate, but with good nursing care a low mortality rate.
 Recovery may require 2 to 4 weeks.
Antimony
Poisoning
 Forms and Occurrence
Antimony is used with lead alloys, in batteries, rubber, ceramics, enamels and paints

It contaminates food, water and air of urban areas

Inorganic compounds
 Antimony oxide was used in feeding geese in Europe to produce enlarged liver
(voagra)
 Antimony trichloride (butter of antimony) used in dehorning, canker of hoof in horse
and foot-rot in sheep
 Antimony trioxide is used as a fire retardation in plastics, textiles, rubber, and paper

 Antimony trisulphide (black antimony) sulphide (orange) are used in paints

 Stibine gas (SbH3)

 Forms and Occurrence
Organic compounds
 Antimony barium tartarate was used by inhalation for treatment of lung worms

 Antimony K tartarate (Tartar emetic) is used as emetic, expectorant and

vermicide
 Antimosan, Fouadin, Stibophen were used for treatment of schistosomiasis
 Toxicokinetic
Absorption
 Mainly from the Lung and Slowly from GIT

Distribution
 In all organs; mainly in liver and lung in case of inhalation

 Trivalent salts are concentrated in RBCs and liver

 Pentavalent are found in the plasma

Metabolism
 Pentavalent is reduced in the cells to the trivalent

 Trivalent is taken up by RBCs and interact with SH- group of glutathione

Excretion
 Mainly in feces, also in urine and through skin
 Mode of Action
 It inhibits phospho-fructokinase thus reduces the cell ability to utilize glucose

(source of energy) leading to exhaustion

 Lipid peroxidation in cardiac myocyte
 Symptoms of Acute Toxicity
 Ruminants are more resistant

 In carnivorous, symptoms are similar to GIT manifestations of arsenic subacute

toxicity
 Vomiting may absent in large animals in case of poisoning with inorganic salts
(not for organic forms)
 Weakness and exhaustion

 Irregular respiration , Cardiac depression and death

 Dogs lose smell sensation after treatment with stibophen

 Eye irritation occurs if applied directly (not toxic)

 Symptoms of Chronic Toxicity
 Severe depression, Vomiting and Loss of appetite

 Aphthous patches “antimony spots” on mucous membrane of the buccal cavity

(differentiate from FMD)
 Skin inflammatory rashes consisting of pustules around sweat and sebaceous
glands “antimony spots”
 Post-mortem lesions
Acute form
 Inflammation of the mucous membrane of GIT

Chronic form
 Aphthous patches on the buccal cavity

 Toxic myocarditis
 Fatty degeneration and necrosis of liver and kidney

 Laboratory Analysis by Reinch’s test

Stomach wash and a purgative given by a stomach tube
except in case of butter of antimony

Precipitate antimony in the stomach by tannic acid, calcium

hydroxide (lime milk or lime water) and MgO (milk of
magnesia)

Stimulants
Treatment
Keep the animal warm with high fluid intake

BAL as in treatment of arsenic

DMPS (2,3 dimercapto-1 propane sulfonic acid)

 Hhydrargy
rum

hydrargyrum
 Forms and Occurrence

Metallic mercury Inorganic salts Organic salts

•Mercurochrome
•Fungicides
•Purgative powder •Hg chloride - Methyl Hg chloride
• Parasiticidal (Corresive sublimate) - Methyl Hg acetate
• Counter irritant •Mercurous chloride -Ethyl Hg
ointments (calomel) • Dimethyl Hg
• improper disposal •Red Hg iodide • Ethyl Hg
of fluorescent lamps •Hg cyanide •Diuretics
- Mersalyl
- Salyrgan
 Mercury Toxicity
 Hg2+ (mercuric II) are more toxic than Hg22+ (mercurous I) because its solubility in
water is greater (more absorbed from GIT)
 Dimethyl mercury, is the most dangerous mercury compound (few microliters
spilled on the skin, or even a latex glove can cause death)
 Mercury vapor emitted from amalgam tooth fillings
 Methyl mercury in edible tissues of fish
Methylation of Mercury
 Biomagnification: Methyl Hg is bio-concentrated it in the food chain of the human,
large carnivorous and fish. High species on the food chain accumulate mercury
ten times higher than the species they consume (Minamata disease)
 Mechanism of action

 Hg irreversibly inhibits selenoenzymes as thioredoxin reductase.

 Thioredoxin reductase restores vitamins C and E and antioxidant molecules,

back into their reduced forms, enabling them to counteract oxidative damage
 Methyl (CH3Hg+) is the most hazardous form because it sticks within sediment
and dissolves in membrane lipids. This reaction enables the Hg to penetrate cell
membranes more rapidly and accumulate in the cells by binding with essential
proteins, enzymes, and nucleic acids
 Methyl mercury cross the placenta and blood-brain barrier

 Mercurial diuretics cause diuresis by reducing the reabsorption of sodium in the

ascending loop of henle, thus causing more water delivered to distal convoluted
tubule.
 Toxicokinetic
Absorption
 Vapor metallic mercury from respiratory tract

 A significant portion of mercury vapor crosses the blood–brain barrier and placenta before it
is oxidized by erythrocytes, and thus shows more neurotoxicity and developmental toxicity.
 Liquid element & inorganic salts are slightly absorbed from GIT and skin

 Organic salts (MeHg & di MeHg) from the GIT, lung and dermal even from intact skin

 Dogs and cats are most susceptible to poisoning from mercurial ointments (absorption from
skin and licking of the applied part)
Distribution
 All over the body

 Depends on its form and the route of entry

 Toxicokinetic
Metabolism
 Once inhaled, elemental mercury is mostly converted to an inorganic divalent
(mercuric) form by catalase in RBCs. This inorganic form has similar properties to
inorganic mercury (poor lipid solubility, limited permeability to BBB and excretion
in feces)
 Methylmercury combines with cysteine forming methylmercuric-cysteinyl
complex. This complex is transported throughout the body including across BBB
and placenta
 Toxicokinetic
Storage
 mainly in the kidney and liver

Excretion
 Inorganic mercury: mainly in urine and some in feces, saliva, sweat and milk

 Organic mercury: mainly in feces

Radiograph in abdominal, a patient
ingested elemental mercury. mercury beads deposited in lung
mercury outlines the large intestine
from ascending to descending
 Symptoms of Acute Toxicity
 Death occurs within few hours or days from shock and dehydration

 Renal manifestations for inorganic mercury

 Neurological singes sensory impairment (vision, hearing, speech) for methyl

mercury
 Vapor produces neuropsychiatry symptoms
 Symptoms of Acute Toxicity
Gastroenteritis
 Inorganic compounds have caustic action (coagulation) of the alimentary mucosa
lead to:-
 Bloody vomiting

 Severe diarrhea
 Anorexia

 Colitis

 Stomatitis, gingivitis, salivation with fetid breath and dermatitis

 Symptoms of Acute Toxicity

Renal signs
 Rare in inorganic toxicity, common in chronic (acute nephritis)
 Oliguria may progress to anuria and ended with death

Respiratory signs (due to inhalation)

 Nasal discharge
 Bleeding from nose and mouth

 Cough ,Dyspnea ,Fever

 Pneumonia and collapse

 Symptoms of Acute Toxicity

Nervous signs
 Weakness, Stiff stilted or staggering gait, incoordination progress to paresis and
paralysis and mental disturbance
 Pigs showed blindness, inability to eat and continuous walking

 Cattle standing on tiptoes

 Symptoms of Chronic Toxicity (Mercurialism)

 Occurred due to chronic industrial exposure or mercurial diuretics

 Clinical signs may delayed until 30 days

 Depression, weakness, lethargy and coma

 Anorexia and Emaciation

 Chronic diarrhea and dehydration

 Alopecia, scabby lesions around anus and vulva skin rashes and dermatitis

 Mercurial ptyalism (mainly in man and pigs)

excessive secretion of saliva

Pruritis, petechiation and tenderness of the gums

Loose teeth & Necrosis of the jaw bones

 Symptoms of Chronic Toxicity (Mercurialism)

Renal signs
 Anuria due to

 Tubular obstruction
 Increased back diffusion of tubular filtrate

 Preglomerular vasoconstriction

 Progressed polyuria due to decreased renal concentration reducing the

reabsorption sodium in the ascending loop of Henle
 Urine contains blood, casts and albumin (Proteinuria)
 Post-mortem Findings
 Ingested mercury
Severe gastroenteritis

Acute parenchymatous nephritis (degenerative changes of renal tubules)

 Inhaled mercury vapor

Edema and congestion of lung

Hydrothorax, pericardium & endocardium

 Degenerative changes in brain and peripheral nerves

 Treatment
General treatment
 Ingestion of mercury thermometers is a minimal risk because elemental mercury is so
poorly absorbed via the gastrointestinal tract. Dogs can be given a high-fiber diet for 2 to 3
days to aid passage of ingested glass
 Precipitate Hg in GIT by raw egg white , skimmed milk as insoluble Hg albuminate,
followed by purgative to remove it from the gut before digestion and absorption
 Administration of Leishica solution

500 ml skimmed milk + 50 g glucose + 20 g Na bicarbonate + 3 egg white + barley water

50 g glucose, 20 g Na bicarbonate and barely water (diuretics)

 Injection of morphine every 4-6 hours for pain

 IV injection of saline for dehydration

 Na thiosulphate IV or orally
 Treatment
 Alkaline diuretics as K nitrate or Na gluconate 10%
 In case of skin absorption, wash with soap and water

In case of urine retention

 Inject Novocain 10% between thoracic & lumbar vertebrae

Specific treatment (Delay treatment is fatal)

 BAL as in arsenic poisoning

(not effective for alkyl mercury (not cross BBB))

 D- Penicillamine, acts as a chelator, may be given orally
 DMPS (2,3 dimercapto-1 propane sulfonic acid)
 DMSA (Dimercaptosuccinic acid) can cross BBB of mice but not of humans, it is used
to extract heavy metals from parts of the body other than CNS
 In which meaning 1070 = 1110 ?
Reward
 The Answer
 10 hours 70 minutes equals 11 hours 10 minutes
Plumbu
m
 Lead Compounds

Inorganic Organic Metallic

•Red lead (Pb3 O4) (Salakon)
• Lead acetate
lead shots
•Lead oxide (Pb O) litherage Batteries
•lead carbonate (White lead ) (Sugar of lead)
Oil fields
•Lead sulphate
•Lead nitrate • Lead alkyl Water pipes
•Pb arsenate , arsenite Pb tetramethyl
Pb tetraethyl
(parasiticide )
• Lead halides
Pb tetra fluoride
Pb tetra chloride
 Contamination Sources

 Contamination of water supply passing through lead pipes (water rich in nitrates)
or contaminated pasture and soil near lead works (Run off water via pipes before
drinking)
 Wild Birds ingest the spent lead shots or bullets

 Carnivorous animals or birds eat lead shot animals

Fence is paint with sump Brocken batteries are attractive

to animales
oil
 Toxicokinetic
Absorption
 GIT:

10% is absorbed

Greater in infants and during fasting

Influenced by dietary levels of Ca, iron, vit.D, proteins

 Respiratory system

More rapid than GIT

Depends on the chemical form and particle size

 Skin (intact or abraded)

Insignificant for inorganic salts

Important for alkyl lead

 Toxicokinetic
Distribution
 Mainly attached to the RBCs

 Small amount bound to serum albumin

 Less amount stay free (induce toxic effect)

 Free Pb is in equilibrium with the bound

Storage
 Acute toxicity in soft tissues, kidneys & liver

 Chronic toxicity bones, teeth (detoxification)

Excretion
 Feces (Bile)

 Urine, milk, sweat

 Mode of action
 Inorganic lead act directly
 Alkyl lead is de-ethylated in liver to trialkyl, then to inorganic
 Pb ion replaces Ca ion and altering the hormonal regulation of the calcium and
the osteoblast function
 On nervous system
 Pass through the endothelial cells (BBB) it substitute calcium ions and up taken
by Calcium-ATPase pumps
 Structural and functional disorders loss of structural integrity of the nerve cells
 Demyelination and axonal degeneration
 Degeneration & atrophy of optic nerve
 Increase intracranial pressure (increase CSF pressure)
 Mode of action
On haemobiotic system
 Microcytic Hypochromic Anemia (acute & chronic) due to 2 defects

I- Shortening erythrocyte life span due to:-

Affect the developing red cell in the Bone Marrow
Decrease the integrity of red cell membrane
 Mode of action
II- Decrease Hb concentration through:
A- Inhibits 2 enzymes essential for haem synthesis
1- Delta-amino-levulenic acid dehydratase (δ -ALAD)
Aminolevulenic acid Porpho-bilinogen
2- Ferrochelatase
Protoporphyrin + Fe⁺² Haem
B- Impairs globin formation: inhibits incorporation of glycine into globin
 Mode of action
 Cause erythrocytic basophilic stippling

 Basophilic granules appear in the RBCs due to disturbed erythropoiesis

 Mode of action
On reproductive system
 Sterility in males (abnormal sperm shape)

 Abortion in pregnant females (indirect effect on uterus, direct effect on embryo)

 Chromosomal aberrations (gap, break, adhesion)

 Symptoms of Acute and Subacute Toxicity

 Due to ingestion of large amount of lead paints in short period

 Common in calves, in farm animals, especially cattle and sheep with high mortality rate
uncommon in horses
 Sudden onset of signs and a short course (12-24 h) or death without signs

 Stagger and muscle tremor in head and neck

 Champing of the jaws and froth from mouth

 Snapping of eye lids, rolling of eyes, pupil dilatation and blindness with circling movement

 Colonic convulsions continue till death due to respiratory failure

 Opisthotonus and Muscle tremor persist between the convulsive episodes

 Hyperesthesia to touch and sound

 Symptoms of Acute and Subacute Toxicity

Cattle
 Mania, charging into fences, climb walls, circling move and pressing the head
against fixed objects
 Ruminal atony, constipation then offensive diarrhea.
 Symptoms of Acute and Subacute Toxicity
Horses
 Inspiratory dyspnea due to paralysis of the recurrent pharyngeal nerve

 Aspiration pneumonia

Dogs
 GI disturbance in old while nervous disturbance in the young

Poultry
 Depression

 Loss of appetite, emaciation

 Excessive thirst

 Drop in egg production

 Muscular weakness and inability to stand

 Sudden death in young birds

 Symptoms of Chronic poisoning (Plumbism)
 Common in man, cats, dogs, horses

 Loss of weight & Anemia

 Swelling of knees and paralysis of hindlegs

 After long exposure blue-black line band on gums

 Blue-black line or lead line on gum in horses, man and carnivores, due to the presence of
lead sulphide, not occur in cattle due to the failure to form tartar
Long bone Radiograph of knee “lead lines” with blood lead
level of 10.6 µg/dL. Notice the increased density on the
metaphysis growth plate of the knee, especially in the femur
 PM Findings

 GIT inflammation (abomasitis, enteritis)

 Congestion of meningeal and cerebral BVs

 Blue-black line band on gum

 Lead shots in gizzard

 Laboratory Diagnosis
 Detection of lead in blood, urine, feces, milk and tissues

 Porphrin content of the RBCs (decreased)

 Blood film for detection of stippling

 Urinary aminolevulenic acid content is increased

 Activity of δ-ALAD enzyme in blood is decreased

 Increased R/F ratio in blood (more than 3 indicate toxicity, less than 1 the species is
resistant as pig, rabbit, chickens)
Blood incubated with δ-ALA; the formed porphobilinogen is measured (E1) indicating
free (F) δ-ALAD.
Addition of glutathione to the sample reactivates the blocked part of the enzyme by
lead. Total enzyme activity is measured again (E2).
Reactivated (R) =E2 - E1
 Treatment
 Acute lead poisoning in cattle always fatal

General treatment
 Remove lead from the GIT by:

Rumenotomy

Oral Saline purgatives

Bowel irrigation with polythylene glycol

Emetics

 Sedative (IV injection of Na pentobarbital in calves & chloral hydrate in adults)

 Precipitating antidotes

 Na sulphate, Mg sulphate, milk, egg white and tannic acid (ppt Pb as insoluble sulphate,
albuminates or tannate)
 Immobilization of lead in a harmless form in bone by Ca and vit D
 Treatment
 Increase lead elimination from the body by K citrate & Na thiosulphate (urinary
alkalinizers)
Specific treatment
 Calcium versenate (Ca Na2EDTA)

(Calcium disodium ethylene diamine tetra-acetate)

100 mg/kg Bwt for 4-5 days, then 2 days rest, then repeat for 3 days or until
disappearance of signs
Given IV and SC (2.5% solution not exceed 3%,painful)

Over dose cause toxic nephritis and death

 Injection a mixture of Ca versenate + BAL

 Injection of D. pencillamine
 A milkman has an 8-liter container full of
milk, and also two empty containers that
measure 5 liters and 3 liters. He needs to
deliver 4 liters of milk to a customer.
Reward
The milkman has no other spare containers
and no way to mark any containers. He
does not want to pour milk away. How will
he measure the 4 liters of milk?
 The Answer
1. Fill the 5-liter container.

2. Pour out from the 5-liter container to the 3-liter one until it's full. The 5-liter
container now has 2 liters left.
3. Pour all the milk from the 3-liter container back to the 8-liter container.
4. Pour the 2 liters from the 5-liter container to the 3-liter container. It has therefore
just one liter of space left!
5. Fill the 5-liter container.

6. Pour out from the 5-liter container enough milk to fill the 3-liter container (which
already has 2 liters). You will have 4 liters left in the 5-liter container.
POISONING
 Forms and Occurrence
 Has long biological half life and cumulative effect

 Transmitted by air, water and food (rice, meat, fish)

 Found in zinc, lead ores (by-product of mining & smelting)

 Soluble salts Cd. Nitrate, Chloride, Sulphate, Acetate

 Insoluble salts (silver polishing) Cd. Sulphide, Carbonate, Oxide

 Used as:-

 Coloring pigment for paints, plastics, glass, porcelain and in photography

 Cathode for rechargeable Ni-Cd battery

 As a contaminant in phosphate fertilizers

 Sprayed on tobacco plant as a fungicide

 In medicine (anthelmintic e.g. Ascaris in pigs)

 Toxicokinetic
Absorption:
 Respiratory tract 90%

 Dermal exposure is insignificant

 GIT poorly absorbed (90% is bound to intestinal MT)

 Increasing of Cd absorption in case of dietary containing low level of Ca

Distribution:
 Bound to RBCs and serum albumen then to soft tissues in kidney & liver forming
Cd. metallothionine
 Stored in association with metallothionein for long time in liver &kidney (Cd-
metallothionein complex has protective effect)
 Toxicokinetic
Excretion
 The unabsorbed Cd (95% ) in feces

 In sweat (during sauna) and milk

 Poorly excreted in urine (long biological half life)

 Mechanism of Action
 Attach to the SH group
 Interference with Zn-mediated metabolic processes

 Mutagenic, produce free radicals (DNA damage)

 Carcinogenic, increases prostatic acid phosphatase enzyme leading to carcinoma

of prostate gland
 Increases Ca excretion from kidneys (calciuria)
 Decrease bone mineral density (osteoporosis and oesteomalacia) through:-

stimulate the formation and activity of osteoclasts

 Symptoms of Acute Toxicity
 Liver is the target organ of acute toxicity
 hepatotoxicity is the major cause of death
 Depends on route of entry
 Ingestion route:
 Nausea, vomiting abdominal pain, diarrhea, salivation and gastroenteritis.
 testicular injury (swollen, congestion and hemorrhage)
 Pulmonary route:
 Acute chemical pneumonia and edema
 Nasopharyngeal irritation, cough, chest pain
 Vomiting, nausea and diarrhea
 Symptoms of Chronic Toxicity
 Low doses of Cd causes tolerance to acute toxicity (induces MT production)

 Kidney is a major target following chronic Cd exposure

 Tubular interstitial nephritis and tubular necrosis

 Renal calculi (Ca excretion)

 Nephrotoxicity is due to Cd-MT complex. This because Cd-MT formed in the liver
is released to the blood from damaged hepatocytes then filtered by the kidney
and taken up into proximal tubule cells, where it is degraded, releasing high
levels of “free” Cd which binds to high molecular protein in kidney producing
tubular injury
 It was thought that increased excretion of renal Cd increases its toxicity, however
it was due to chelating agent
 Symptoms of Chronic Toxicity
Respiratory Signs (in case of inhalation)
 Alveolar damage, bronchitis and emphysema

 Skeletal disturbance due to increased Ca excretion

 Bone pain, oesteomalacia and oesteoperosis

(Itai Itai, ouch ouch disease)

 Other symptoms: hypertension, carcinogenicity and teratogenicity
 Laboratory Analysis

Urine contains:-
 High amounts of Cd & Calcium

 Low molecular weight proteins, e.g.

Globulin - B2 microglobulin - Retinol-binding protein - Metallothionein

PM Finding (not specific)
 Tubular degeneration, interstitial inflammation and fibrosis
 Treatment

General treatment
 Prevent more exposure to Cd

 Induction of metallothionein production by: Zn, Cobalt & Selenium

 Vit D & anabolic steroids

Specific treatment
 BAL alone is not preferable

 Ca Na2 EDTA & BAL.

The efficacy of EDTA is improved with concomitant use of glutathione (protects against
nephrotoxicity) and antioxidants as thiamine, zinc or methionine
 D-pencillamine

 DMSA (dimercapto- succinic acid) (Succimer)

Poisoning
 Forms and Occurrence
 It is a halogen

 Naturally in animal tissues (bones and teeth)

 Occurs in rocks (phosphate lime stones), associated with

phosphate
 As a contaminant in aluminum industry an fertilizers (super
phosphate)
 Fluorine is used in:

Fungicides
Wood preservatives
Rodenticide
 Toxicokinetic
Absorption
 GIT
 Respiration
 Skin

Distribution
 Absorbed F is transported to liver then to bone and teeth (90%), to placenta and soft
tissues
Storage
 in teeth and bones

Excretion
 Mainly in urine then faeces, milk and saliva
 Mode of Action

Stomach HCl + fluorine hydrofluoric acid

GIT irritation

Absorbed F + blood Ca CaF 2 (inert Ca)

interfere with

Cardiovascular kidneys
Ca & P blood
Anti Nervous system
Hyperesthesia
Myocarditis
excretion coagulant Tetani
 Mode of Action
Enzymes inhibition
AChE

Aconitaze enzyme

Fluorocitrate Citric acid cycle

Decrease Glucose production

Affect cell respiration Lowering energy production

 Bones are composed of Ca carbonated
hydroxyapatite (Ca10(PO4)6(OH)

Ca²⁺ ions and HF forms an insoluble

salt (CaF2)

This salt is cleared by the body and

Mode of
decrease calcium from the bone matrix. Action
Bone is hardened and less elastic due to
high fluorine concentration , resulting in
an increased frequency of fractures.

This process results in increased

density, but decreased strength in
bones.
 Mode of Action
Fluorine & Phosphate deposition

Bone Teeth

Replace periostium OH gp Bone fragility

(Osteosclerosis, exostosis & osteoporosis)

Small dose Large dose

Fight caries Pigment spots, horizontal bands
Increase Ca deposition Enamel hypoplasia (mottling)
 Mode of Action

Crosses the placental barrier

Teratogenic action

Protoplasmic poisonous

Destructs protein hydrogen bond

 Symptoms
Acute form
 Sever GIT disturbance (vomiting, colic and diarrhea)

 Nervous signs (tremors and hyperesthesia)

 Death from cardiac or respiratory failure

Chronic form (Fluorosis)

 Exposure to small repeated doses for long period (years)

 Top dressing of pasture with phosphate limestone (North Africa)

 Characterized by bone & teeth lesions
 Symptoms
Chronic form (Fluorosis)
 Other symptoms include thickening of the bone structure leading to impaired joint
mobility
 Ligaments and cartilage can become ossified

 In advanced cases, skeletal fluorosis causes pain and damage to bones and
joints
 Osteosclerosis elevation in bone density detected on a radiograph as an area of
increased opacity where more mineral is present
 with/without osteoporosis (decrease in bone mass and density)
 Skeletal fluorosis

Bone exostosis Narrowing of

Painful bones
calcification of joints BM cavity

Moving lameness Aplastic

(form posterior to anterior) anaemia
 Symptoms

Dental fluorosis
 May occur in permanent teeth before
eruption
 Mottling, pigmented spots or bands
(yellow to brown)
 Excessive and irregular erosion
 Painful teeth & loss of body weight
 Eruption of abnormal teeth
 Hypoplasia of enamel and dentine
 Enlarged lower jaw
 Gum damage
 PM Findings

Acute poisoning shows non specific lesions

 Hemorrhage in GIT

 Hepatitis and nephritis

Chronic poisoning
 Chalky Bones (white appearance and brittle)
 Bone exostosis

 Narrowing of BM cavity
 Mottling of teeth

 Degenerative changes in kidney, liver, heart, adrenal gland and CNS

 Laboratory Diagnosis
Determination of fluorine content in:-
 Urine

 blood

 Bone biopsy (ribs and tail)

 Using fluorine ion detector or atomic absorption

Skeletal fluorosis Osteosclerosis of

diaphysis of forearm and
calcification of inter osseous
membrane
 Treatment
 Acute poisoning
 Remove the source of fluorine
 Gastrointestinal sedatives
 Precipitate the residual F by aluminum sulphate
 IV Ca till disappearing of nervous signs
 Skin, wash by 5% Ca salt (avoid local damage &
absorption)
 On eyes, 1% Ca salt irrigation
 IV glucose (reduce glucose metabolism)
 Vit. C

 Treatment of dental fluorosis is hopeless

 Treatment
Acute poisoning
 Remove the source of fluorine

 Gastrointestinal sedatives

 Precipitate the residual F by aluminum sulphate

 IV Ca till disappearing of nervous signs

 Skin, wash by 5% Ca salt

 On eyes, 1% Ca salt irrigation

 IV glucose (reduce glucose metabolism)

 Vit. C

Treatment of dental fluorosis is hopeless

 Farmer Brown and Farmer Green were
ruminating one day on the fence between
their farms. Farmer Brown says, "You know
I was just thinking. If you gave me one of
your cows, then we would have the same
Reward number of cows." Farmer Green replies, "If
you gave me one of your cows, then I would
have twice as many as you!"

How many cows does Farmer Brown have

and how many cows does Farmer Green
have?
Farmer Brown has ANSW
five and Farmer ER
Green has seven
cows