ANTISEPTICS AND DISINFECTANTS

• Sterilization: destroys or eliminates all forms of life,

especially microorganisms.
• Disinfection: The killing of pathogenic organisms by direct application of
• physical or chemical agents
• Disinfectant: An agent, usually chemical, that frees from infection by
destroying the disease causing microorganism. This refers to substances
applied to inanimate objects.
• Antiseptics: A substance that prevents or arrests the growth or action
of micro organism on living tissue either by inhibiting their activity or by
destroying them.
• Oxidizing agents: H2O2, KMno4, Chlorine, Iodine , Benzoyl peroxide
(Keratolytic)
• Reducing agents - Formaldehyde, Glutaraldehyde, Sulphur dioxide
• Acids and Alkalis - H2SO4, NaOH, Boric acid, Na2Co3, Benzoic
acid, Quick lime, Salicylic Acid
• Alcohols - Ethyl alcohol (70%), Isopropyl alcohol (50%)
• Phenols and cresols
• Phenols: First disinfectant and antiseptic used by Joseph Lister in
1867
• general disinfectant(1-2% solution) and chemical sterilizer (5%)
• standard to measure the effectiveness of other disinfectants and
antiseptics - phenol coefficient.
Dyes - Acriflavine, Gentian violet

Detergents
Anionic - soap
🢝 Sodium lauryl sulphate
🢝 Ca and Ammonium mandelate

Cationic - Quarternary ammonium compounds

🢝 Cetrimide
🢝 Benzalkonium chloride

Chlorhexidine hydrochloride - 0.5% alcoholic or 1% aqueous solution

 INDIGENOUS PLANTS
• Rauwolfia serpentina: Reserpine – Antihypertensive
• Vinca rosea: Vincristine and Vinblastine - Anticancer drug
• Withania somnifera: Somniferine – Immunostimulant
• Leptadenia reticulata: Laptadine – Galactagogue
• Atropa belladona: Atropine – Anticholinergic
• Gingiber officinalis: Gingerol - Carminative and Stomachic
• Ricinus communis: ricin - Purgative
 Anti neoplastic drugs
• ALKYLATING AGENTS:
* Cyclophosphamide: converted to aldophophamide
• Toxicity - Damages the bladder, Necrotising haemorrhagic cystitis
• Treatment : Acetyl cysteine and MESNA
* Melphalan
*Chlorambucil
* Busulfan : Toxicity – lung fibrosis (Busulfan lungs)
* Lomustine
* Mechloethamine
* Streptozocin: mainly treatment for tumours of β cells of pancreas
 ANTIMETABOLITES
•Folic acid analogues – Methotrexate – inhibition of
enzyme Dihydrofolate reductase
• Pyrimidine analogues:
– Cytarabine/Cytosine arabinoside
– 5-Flurouracil[5-FU]
• Purine analogues
– 6-Mercaptopurine - structural analogue of natural purine
hypoxanthine
– thioguanine
 Mitotic Inhibitors
•Vinca alkaloids- vinca rosea/Canthranthus rosea
plant
•Blocks mitosis in metaphase, m-phase specifc
•Vincristine: Dose rate-In Dogs and cats-0.5-
0.75mg/m2, IV bolus 0.025mg/kg
• Possesses immunosuppressant action, neurotoxicity
•Vinblastin: Dose rate-2-2.5mg/m2, I/V
• Taxanes/Inhibitors of microtubule disassembly :
Paclitaxel- Source- Bark of pacific west yew plant-Taxus
brevifolia
• Epipodophyllotoxins-Contains 2 imp. Cytotoxic drugs
• Etoposide, Teniposide
• Prepared from Podophyllotoxin, a toxic extracted from
mandrake plant (Podophyllum peltatum)
• Enzyme: L asparginase – G1 phase specific
Antitumor antibiotics:
Doxorubicin
adverse effects including myelosuppression, Gl disturbances,
cardiotoxicity, hypersensitivity, alopecia and extravasation injuries.
Daunorubicin
Dactinomycin/Actinomycin D

Miscellaneous:
Glycopeptide – Bleomycin – lung toxicity
Platinum compounds: Cisplatin, Carboplatin
• Anti estrogens – tamoxifen - estrogen dependant mammary tumors
• Antiandrogens – flutamide - prostate gland tumour
• Finasteride: 5α-reductase inhibitor
• Estrogens – eg, diethylstilbestrol.
– Uses- prostate gland tumor, testosterone induced prostate gland tumour
• Androgens—eg, testosterone, danazol Uses- mammary tumours
• Progestogens—eg, hydroxyl progesterone
– Uses- endometrial tumour, prostate gland tumour
TOXICOLOGY
• Toxicology is the study of poisons and their effects on living
organisms

• Xenobiotics: substances that are foreign to the body and are

biologically active.

• Poison/ Toxicant: any substance which when taken inwardly in a

very small dose or applied in any kind of manner to a living body
depraves the health or entirely destroys life (M.J.B. Orfila) – father
of toxicology

• “All substances are poisons; there is none which is not a poison. The
right dose differentiates a poison from a remedy” --- Paracelsus.
 Disasters related to toxicology
• Thalidomide in pregnant women – phocomelia

• Minamata disease due to Methyl mercury in Japan

• Itai – itai disease: due to Cadmium toxicity

• Bhopal gas tragedy - methylisocyanate in 1984

• Chernobyl nuclear accident – Ukraine

• Ginger Jake paralysis: OPIDN

 Sources of toxicity
• Plants: Lantana, Bracken fern etc
• Animals: poisonous animals like snake, toad
• Micro-organisms: Toxins produced by certain
fungi and bacteria
• Minerals: Metals and non metals
• Agrochemicals
• Radiations
• Environmental pollutants
 Factors affecting/influencing toxicity
• Solubility: high lipid solubility - more readily
absorbed through the lipid- protein matrix of the
cell membrane. So more toxic than those which are
water soluble.
• Oxidation state of the compound: Trivalent arsenic
is more toxic than the pentavalent arsenic.
- CO is more toxic than CO 2 .
- Nitrates (NO3 - ) are reduced to nitrites (N02 - )
by ruminal and intestinal micro flora and toxicity is
produced by nitrites.
 Species variation
• Atropine is nontoxic to rabbits due to presence of
atropinase
• No glucuronide formation in cat due to lack of enzyme
uridinediphosphate glucuronyl transferase
• No etheteal sulphate in pigs due to lack of enzyme
Phenolsulphotransferase
• Carnivorous animals - glucouronide formation common,
Herbivorous animals – amino acid conjugation common
• Acetylation: dogs do not acetylate due to the presence of a
natural inhibitor in liver of the enzyme arylamine
transacetylase
• Ivermectin is more toxic to Collie breed of dogs as it readily
crosses blood-brain barrier in this breed.
• Greyhound Dog - More susceptible to barbiturate toxicity
• Bedlington Terrier –Genetic predisposition for Cu toxicity

• Sheep - more susceptible to chronic copper poisoning

• Response of horse or rat to Bracken poisoning is clinically and
biochemically different from that of cow or sheep.
• Thiaminase enzyme present in bracken fern destroys Vitamin
B1 essential for horse and rat. In ruminants, the vitamin is
synthesized by ruminal organisms and an exogenous source is
not required.
DIAGNOSIS AND GENERAL TREATMENT OF
POISONING
• History
• Clinical evidence
• Circumstantial evidence
• Pathological evidence:
- Cherry red/pink m.m. : CO, cyanide poisoning;
- Brown/cyanotic m.m.: nitrite poisoning
- Yellow color: nitric acid poisoning
- CN poisoning: Bitter almond smell (it is HCN gas)
- H2S poisoning- rotten egg smell
• Analytical evidence
• Experimental evidence
• Response to treatment
 Analytical evidence: Samples for
Diagnosis
• Quantity of material:
• Blood- 60ml
• Brain- whole (useful for lipid soluble poisons)
• Liver- 500g for large animal and 200g for small animal
• Kidney- 1 kidney
• Stomach/intestine contents- 500-1000 g separately
• Hair- 5 g
• Bone- 1long bone
• Urine- entire quantity (both sides of urinary bladder be tied and send
as such)
• chemical preservative is used, 95% ethyl alcohol
• suspected CN poisoning- 1% mercuric chloride
 Specimens required for specific poisons

1. Liver: Cu, fluoroacetate, thallium, warfarin, Zn, CCl4,

chloroform

2. Kidney: As, OC insecticides, Cu, ethylene glycol,

fluoroacetate, oxalates, thallium, Zn, Hg, sulfonamides.

3. Stomach and intestinal contents: ammonia, ANTU, As , OP and

OC compounds, fluoroacetate, phenols, plant poisons, CN.

4. Whole blood: NH3, Ca (serum), CO, OC, OP (heparinized), Cu,

CN, NO3/NO2, PO4 (serum), chlorate
5. Urine: NH3, As, ethylene glycol, fluoroacetate,
OP compounds, thallium
6. Faeces: Cu
7. Vomitus: Acid/alkalies, As, Pb, NO3/NO2,
chlorate, ANTU, fluoroacetate
8. Bone: Lead, fluoride, selenium
9. Hair: Chronic As poisoning
10. Fat: OC (DDT) about 100 g, OPI about 50 g,
thiobarbiturates
11. Milk: Se, F
 Treatment
(i) To prevent further absorption of poison
(ii) Use of supportive and non-specific agents
(iii) Specific treatment (antidotal treatment)

Use of emetics: In dogs and cats, vomition

may be induced to empty the stomach. e.g.
Apomorphine HCl
 Universal adsorbent mixture (universal
antidote)
• Activated charcoal- 10 g

• Light magnesium oxide- 5 g

• Kaolin- 5 g

• Tannic acid- 5 g
 Therapeutic Index (TI)
• quantifies the safety and efficacy of a drug

• ratio of the dose that produces lethal effect (LD50) to

the dose that produces the desired therapeutic effect
(ED50) in a population

• TI = LD50/ED50

• higher TI - safer drug

 Arsenic Toxicity – King of Poisons
* inorganic and organic arsenical compound. Inorganic form is more
poisonous than organic.

*Order of toxicity is Arsine> As+3 > As+5

* Herbivores are more prone because they are more likely consumed
contaminated forage.

* It is used as rodenticides, herbicide and pesticide.( Lead arsenate is

used as taenicide in sheep and growth promoter in poultry)

* Used in mining operations (for smelting), so in industrialized area air

is polluted with arsenic.
 Toxicokinetic
 route of entry is generally by ingestion

 The highest levels found in liver (primary), kidneys, heart, and

lungs.

 In chronic exposures, arsenic accumulates in skin, nails, hooves, sweat

glands, and hair.

 It does not crosses blood brain barrier (BBB).

 It crosses placental barrier & cause foetal damage.

 The majority of the absorbed arsenic is excreted in the bile, milk,

saliva, sweat urine & faeces by process of methylation.
 Mechanism of action
 Trivalent arsenic compounds : inhibition/slowing of glycolysis
and TCA cycle by interacting with sulfhydryl group of enzymes(
alpha-lipoic acid) , Pyruvate dehydrogenase system
 may combine with SH group of glutathione peroxidase (GSH)

 Pentavalent arsenic - uncouple oxidation phosphorylation.

 may produce demylination and axonal degeneration
(due to interference with vitamin B).

 Arsine gas: hemolytic agent and cause pulmonary oedema

 most toxic form of As and there is no treatment.
 Clinical signs
Acute poisoning :-
 Poisoning is usually acute with major effects on the GI tract and
cardiovascular system.
 watery diarrhoea (rice water diarrhoea)
 severe fall of B.P and hypovolemic shock

 Subacute: staggering gait, paralysis of hind quarter, dehydration etc

 Chronic: brick red mucous membranes, poor condition, animal become

thirsty, pulse weak and irregular, reproductive disorder. Tying up in horse

 Pentavalent As salts: Nervous symptoms like motor incoordination, ataxia,

and blindness. Animal assume dog sitting posture.
 Post-mortem changes
 intense rose-red inflammation of alimentary tract

 Garlic like odor in arsine toxicity

 Diagnosis :
 (a) Liver- most useful material for chemical analysis
 (b) Kidney: considered better in organic As poisoning

 In chronic As poisoning: Levels of As are analyzed in Hair and can be

very high (even µg)

 Marsh Test – to detect As toxicity

 Treatment
Dimercaprol (BAL, British
Antilewsite) - Classical antidote
 Sodium thiosulphate

 Thioctic acid

 MDSA (Meso dimecaptosuccinic acid) and DMSA

(Dimercaptosuccinic acid) - water soluble and
derivative of BAL
 Mercury
 Aristotle named it “Quicksilver”.

 Mercury exists in a variety of chemical forms, including ---

Elemental mercury (Thermometers, light bulbs),
Inorganic mercurial (Mercuric or Mercurous)
Organic mercury called organomercurials, found in 2 forms -
aryl (e.g. phenyl) and short and long chain alkyl ( more
toxic than aryl)
 organic mercurials - more toxic than inorganic mercury
compounds.
* Methyl mercury - can bioaccumulate in certain
edible freshwater and saltwater fish.

* The release of methyl mercury into an ocean bay

(Minamata) in Japan in the 1950s led to a
massive health disaster, and the clinical
syndrome was named Minamata disease.
Thousands of people were poisoned, and
hundreds of them had severe brain damage.
Inorganic mercury :-

 Absorption is poor to the extent of 2- 10%.

 It is distributed non-uniformly after absorption; highest

concentration of mercury is found in kidney where it is retained
for a long period.

 Concentration of mercury are similar in whole blood and placenta.

 Inorganic mercury do not crosses blood brain barrier.

 excreted via urine and stool.

 Continue…
Organic Mercury :-

 It is more completely absorbed from the GIT then

inorganic form. Intestinal absorption of organic mercury
may be as high as 95% of the dose given.

 It crosses the placental barrier and blood brain barrier

hence produce more neurological & teratogenic effect
than inorganic form.

 Major route of excretion is through faeces; they are

also readily excreted via urine.
 Mechanism of Toxicity
Inorganic mercury
due to its interaction
with sulfhydryl/ dithiol (SH) group of
protein and precipitate it, i.e. it interferes with protein
metabolism and their corrosive action directly damage the
GIT mucosa.
organic mercury : similar to inorganic additionally
Methyl Hg inhibits choline acetyl transferase (CAT) enzyme leading to
acetylcholine (Ach) deficiency which leads to motor dysfunction

* easily absorb through GIT

* crosses different cellular membrane
* crosses PB & BBB hence causes harmful teratogenic & neurotoxic effects
 Clinical signs
• Organic mercury: Neurological Signs
• Inorganic mercury:-
 Acute – mainly the effect GIT & Kidney
GIT – The symptoms are metallic taste in mouth, abdominal pain,
diarrhoea with blood in the faeces leading to dehydration
Kidney – Oligouria followed by anuria, albuminuria, and uraemia.

 Chronic – kidney damage is the main symptom. Increase urinary

excretion of alkaline phosphatase is found to be sensitive indicator of
kidney damage
 mercurial ptyalism - to profuse salivation, swelling of gums,
loosening of gum and teeth and necrosis of jaw bones
 Treatment
Specific treatment:-

 BAL (British anti-lewisite ) @ 3 mg/kg, IM, every 4 hr for

the first 2 days, every 6 hr for the third day, and 12 hrly for the next 10 days or until
recovery.

 D-Penicillamine is used as an antidote in the human being

 Non-specific treatment:-
* Gastric lavage for removal of poison from the GIT.
* Administration of proteinous liquid to protect the GIT.
* Selenium and Vitamin E reduces toxicity
Diagnosis: Grunwald test
 Lead Toxicity

 plumbism, colica Pictonum or Saturnism

 most common cause of metallic poisoning in dogs & cattle.

 Goats, swine and chickens are more resistant

 animals ingest lead-based paints

 Vegetation grown in lead smelters areas and near highways

where plants accumulate lead are other important source of
lead poisoning.
 Toxicokinetic
Absorption:-
 GIT & respiratory system

 GIT is very limited (1-2%) and therefore 98% of

lead is eliminated in the faeces

 After absorption a large proportion (85-90% in

sheep & 65-70% in cattle) of lead in blood is
carried to erythrocytes membrane as Lead
phosphate
Distribution:-
majority bound to RBC only small fraction is present in unbound
form & cause toxicity

About 95% of the total body burden of lead is present in the bone
& hence bone is considered to be a “sink” for lead

crosses placental barrier & blood brain barrier

Excretion:-
 Lead is normally excreted via kidney small amount excreted
through bile & sweat.
 excreted in dangerous amount through milk
 Mechanism of toxicity
 Leads depresses aminolevulinic acid(ALA)
dehydratase enzyme ( copper containing enzyme)
 resulting in increase serum level of δ-aminolevulinic
acid and its excretion in urine

 inhibit haem synthetase/ Ferrochelatase, a thiol

containing enzyme which is required to incorporate
iron in the haem molecule.
 prevent entry of iron from cytosol to mitochondria.
 Clinical Sign
gastrointestinal, central nervous system & hematological system.
GIT Symptoms :-
Anorexia, colic, dullness and transient constipation frequently followed by diarrhea
CNS symptoms :-
• In cattle - depression, weakness and ataxia can
progress to more severe clinical signs of muscle
tremors head pressing ,blindness, jaw champing,
muscle tremor and convulsion.

• Horses develop acute lead toxicosis & show clinical

signs of pharyngeal paralysis (roaring) and
dysphagia frequently resulting in aspiration
pneumonia.
• Hematological symptoms:-
Blood capillaries congested with enlarged and
increased endothelial cells.

* Basophilic stippling (the aggregation of ribonucleic

acid) of erythrocytes

* inhibition of hemoglobin synthesis are characteristic

hematological features of lead poisoning.
 Treatment
Specific antidotal therapy

Disodium calcium EDTA(Ethylene

diamine tetra acetate)
Thiamine - treatment lead poisoning in ruminants and is recommended
for other species as well.

Corticosteroids and osmotic diuretics may reduce cerebral oedema in

cattle and horses.

Diazepam and barbiturates may be used to control muscle tremor and

convulsion.
 Copper
 Dietary requirement in ruminants: 8-11 ppm

 Cu poisoning is common in sheep, while cattle & swine are somewhat

resistant, poultry – most resistant

 sheep are affected most often because they accumulate copper in the
liver

 Dog breed like Bedlington terrier breed is highly sensitive to Cu

toxicosis, as genetic defects in breed cause excess storage of
Cu in liver resulting in liver damage.

 Bordeaux mixture (contain 1-3% CuSO4) - fungicide

• Low levels molybdenum and sulphate increase toxicity of
copper. Ideal ratio of Cu-Mo in diet is 6:1

• toxic signs occurs if ratio in excess of 10:1. High SO4

level helps in more excretion of Cu and vice versa

• Prolong ingestion of certain plants which are hepatotoxic with normal

amount of Cu and low level of Mo.
• Cu accumulator plants– Heliotropium Europeum, Senecio sp.,
Trifolium subterraneum
 Toxicokinetic
 absorbed through intestine in cuprous (cu+) form

 absorption Cu in the intestinal epithelial cells binds with

metallothionein a cysteine rich protein

 From intestine Cu is transported to liver by transcuperein (high

affinity to Cu) and albumin (low affinity to Cu)

 In liver Cu combines with metallothionein and is stored in

lysosomes, mitochondria & nucleus for further utilization

 For the transport from liver to peripheral tissues it combines with

blood ceruloplasmin, an α- globulin protein produced in liver
 Mechanism of toxicity
 Excessive accumulation in hepatic mitochondria and lysosome which
cause progressive hepatocyte damage and cellular degenration or
necrosis

 inhibition of dichlorolipoyl dehydrogenase, which leads to inhibition of

pyruvate dehydrogenase system

 causes weakening of erythrocyte membrane increasing there fragility

leading to hemolysis

 Oxidation of hemoglobin by copper leads to methemoglobin

(Hemolytic crisis)

 In swine in addition to the above feature copper inhibit the absorption

Fe from the GIT leading to Fe-Deficiency anaemia (microcytic
hypochromic anaemia)
 Clinical Sign

Acute Toxicity:-

Severe gastroenteritis, abdominal pain , diarrhoea, anorexia,

dehydration and shock

Faeces may appear deep green in colour

due to presence of Cu-chlorophyl
compound
 Chronic Toxicity:-
 Due to hemolytic crisis there will be free hemoglobin –
which causes clogging of renal tubules leading to renal
tubular and glomerular necrosis

 Signs in affected animals include generalised icterus,

hemoglobinuria ,methemoglobinemia, hemoglobinemia

 Faeces & Vomitus- green to bluish in color

 Severe hepatic insufficiency is responsible for death.

 P.M finding

 Pale yellow liver (bronze coloured liver)

 Enlarged pulpy spleen (Black berry jam spleen)

 Bluish black kidney (Gun metal kidney)

 Blood – may be chocolate coloured due to met Hb

 Port wine colored urine

 Diagnosis
•Estimation in body fluids and tissues
•Level in faeces is around 8000-10000 ppm
•Increased values of Liver function test
•Chronic poisoning - 5-20 μg/ml in blood and
>150 ppm in liver

• Liver to be sent for analytical examination

 Treatment
 Ammonium or sodium molybdate (50–500 mg) and sodium
thiosulfate (250 – 1000 mg) should be used daily as a
drench for up to 3 weeks.

 D-Penicillamine or Calcium versenate may be useful if

administered in early stages of toxicosis.

 Molybdenum in the diet can be increased to 5 ppm and zinc

can be supplemented at 100 ppm to reduce copper
absorption.
 Molybdenum Toxicity- PEAT SCOURS, TEART, Alkalied

 Mo: oxygen transfer reactions of aldehyde oxidase, sulfite oxidase,

and xanthine oxidase
 The normal level requirement in Cattle is 5-6 ppm and for Sheep is
10-12 ppm
 ratio of 2 : 1 to 3 : 1 is borderline. The animal show toxic signs if it
is
< 2 : 1.
 Dietary molybdenum of 10 ppm can cause toxicity regardless of
copper intake
 Cattle are most susceptible.
 Toxicokinetic
 inverse relationship with Cu

 High dietary sulphate increases Mo toxicosis by decreasing

copper absorption

 increase in dietary Zn may increase the Mo toxicity

 Water soluble form of Mo (tetramolybdate)- more

toxic than water insoluble from (Mo disulfide)
• absorption and excretion is rapid

• Mainly stored in kidneys and to some extent in

bones

• also excreted in milk and may affect young calves suckling the dams

• eliminated very rapidly via the kidneys (>80%)

and bile
 Mechanism of toxicity
 Mo produces toxicosis as a results of Cu deficiency (Secondary hypocuprosis)

 Thiomolybdates bind to copper in the digestive tract & prevents absorption of

copper

 Microcytic Hypochromic anaemia is characteristic due to inhibition of enzyme

sulfide oxidase

 Cu deficiency produces falling disease in cattle and sheep

 progressive atrophy of myocardium with replacement of fibrous tissue,

weakening the heart and causes sudden death after excitement or exercise
 Teart
 Persistent scouring with passage of liquid faeces full of gas bubbles
(teart)

 due to complex formation between molybdenum and catechols

(bacteriostatic and control the activity of bacteria in the gut)

 excessive activity of bacteria which will cause

diarrhea with liquid feces with lot of gas
bubbles
 Clinical Sign
 severe scouring making a 'parabola’ (shooting
diarrhoea)

 liquid faeces with lot of gas bubbles and

unpleasant odors (called as peat scours or teart)

 Depigmentation of hair coat, noticeable in black animals

specially around eye spectacled appearance
• Hypochromic anemia, Joint pain, Osteoporosis, and
decreased fertility.

• Sheep and young animal show stiffness of the back and legs
with reluctance to rise this condition is called “Enzootic
ataxia” in Australia and “Swayback disease” in the UK.

• In sheep, there is development of pica while Horses are

generally resistant

• Osteoarthritic changes give the animal abnormal look and gait

– called pacing disease
 Treatment
 The two primary mechanisms of treating Mo toxicosis involve removal from
the source of high Mo and copper supplementation

 Scouring can be controlled by daily administration of Copper sulphate 1gm

for calves and 2 gm for cattles.

 Copper glycinate injection S/C @ of 60mg. For calves and 2 0f 120m mg. for
cattle can be given as an adjunct therapy

 ‘Anti-teart cake’ (containing prophylaltic amount of CuSO4)

*Mo level in blood > 0.1 ppm (and less than 0.6 ppm Cu) indicates Mo
toxicity.
*Analysis of Mo in liver > 5 ppm (and less than 10 ppm Cu) indicates Mo
toxicity
Selenium toxicity –
Blind Staggers,
Alkali disease,
DOG MURRAIN
* Obligate indicator plants :
10,000 – 15000 ppm for growth and survival.
accumulate high concentrations of selenium as water-soluble
amino acid analogs of cysteine and methionine.
E.g - Astralagus , Oonopsis & Xylorhiza.

* Facultative indicator plants:

Absorb and tolerate large amounts of selenium (1500 ppm) if
it is present in the soil
E.g - Sideranthus, Aster & Atriplex .

*Passive accumulator plants:

May accumulate selenium if grown on seleniferous soils ( 20 –
60 ppm) E.g - Corn, Wheat & Barley
 Toxicokinetics :-
 Se is readily absorbed from the gut and distributed throughout the body
particularly to the liver kidney and spleen.
 Chronic exposure results in large concentration in hairs and hooves.

 Se can cross the placental barrier in mammals and also enters into avian eggs
causing foetal malformation and embryonic defects.

 natural organo selenium> selenite (+4) = selenate (+6) > selenide (-2) > elemental
selenium

 Se toxicity is most common in areas that have arid or" semi-arid climates (less
than 20 inches annual precipitation)

 Se toxicity is most common in areas that have soils with pH levels above 7.0
 Mechanism of toxicity

 The main mechanism of selenium is due to the incorporation of Se instead

of Sulphur in some amino acids (Cysteine & Methionine) that’s why hoof &
hair defects in chronic Se Toxicosis.

 Se causes depletion of glutathione (GSH, GSH is required for cell

integrity)

 Chronic selenosis depresses ATP formation due to inhibition of –SH

containing enzymes viz. succinic acid dehydrogenase
 Clinical Sign

Subacute (Blind staggers)

In the second stage depression, in-coordination and fore leg

weakness, animal goes down on its knees.

In the third stage colic, subnormal temperature,

emaciation, swollen eyelids, near blindness. Salivation,
lacrimation, severe abdominal pain, inability to swallow,
complete paralysis, collapse and death
rooted to one spot
 Continue…
Chronic (Alkali disease)
 Lameness, hoof and hair abnormalities, partial blindness, paresis, in-
coordination, emaciation and lethargy may be noticed.

 Lameness is due to erosion of the articulate surface of long bones.

 Hoof begins to shed. Shedding is incomplete and old hoof fuses with new hoof
and form abnormally long rocker shaped hoof.

 In horses there will be loss of long hair from the mane and tail will occur

 “bob” tail and “roached” mane appearance, cracking

and sloughing of hoof
 Diagnosis & Treatment

Diagnosis
 Diagnosis is based on clinical signs and estimation of selenium in whole
blood and liver.
 Elevated glutathione peroxidase level in liver and blood suggest Se
poisoning.
 Laboratory analysis of Se in:
 Feed >5 ppm → indicate toxicity.
 Bovine Hoof → 5-20 ppm (in chronic toxicity),
 Bovine Hair → 5-10 ppm (in chronic toxicity)
 Blood → 4-25 ppm – acute toxicity
1-4 ppm – chronic toxicity
 Treatment
• There is no specific antidote for Se toxicosis
symptomatic & supportive care of affected animals
should be started as early as possible.

• Addition of inorganic arsenicals enhances biliary

excretion of selenium and increasing the dietary levels
of sulphur containing proteins is also beneficial.

• CONTRAINDICATIONS:
• BAL (dimercaprol) → alleviates Liver damage but
worsens kidney damage.
• Vit E →Synergistic action with Se
 PHOSPHORUS (P) POISONING
• 4 different forms i.e. white, yellow, red and black.
• Yellow form is most toxic. White form can be converted
into yellow and can cause toxicity
• in the body P circulates first as element and then is
oxidized to phosphate.
• eliminated by lungs and this provides the exhaled air a
smell of phosphorus (garlic-like) and a glow in dark.
• Similarly, the vomitus of GI tract contents may be
luminous and have the same odour.
• Main excretion of phosphorus is in the urine and expired
air
 Mechanism of action
• phosphorus acts as a protoplasmic poison

• direct cardiotoxic effect resulting in cardiovascular

collapse. Phosphate formed in body due to oxidation
of phosphorus causes hepatic necrosis

• On dermal exposure, white phosphorus results in

painful chemical burn injuries by the heat of flame
as phosphorus ignites when comes in contact with air
• gastrointestinal irritation and abdominal pain, colic, profuse
vomiting (occasionally haematemesis), severe diarrhoea (often
haemorrhagic), and a garlic-like odour from the breath

• hepatic failure is followed by convulsions and death

• Pigs vomit profusely and the vomitus show luminous in dark

and gives a characteristic garlic odour

• Luminescence is due to presence of phosphorus trioxide

• In chronic phosphorus poisoning, the main clinical feature is

necrosis of jaw (mandible) called "Phossy jaw" or "Lucifer's jaw".
 Cadmium Toxicity
 impair Vitamin D metabolism in the kidney with deleterious impact on bone

 This effect, coupled with direct Cd impairment of gut absorption of calcium

and derangement of collagen metabolism, can produce osteomalacia and/or
osteoporosis .

 Occupational toxicity due to inhalation of cadmium fumes

 itai-itai disease in Japan

 EDTA significantly increased urinary elimination of cadmium

 Fluorine (F) Poisoning
• non-metallic halogen

• feed-grade phosphates should not contain more than 1 part of fluorine to

100 parts of phosphate

• species susceptibility is as follows: calves, dairy cows, beef cattle, sheep,

horses, pig and poultry ( cattle most sensitive)

• Mainly distributed into calcified tissues like bone and teeth

• Bone is a natural sink for fluoride (like lead) with 96-99

• Normal adult bones contain about 1000-1500 ppm fluoride.

 Acute toxicity
• Gastroenteritis action

• Disrupting ionic balance : interfere with Na+ K+ channels

• Enzyme inhibition: Fluoride impairs utilization of glucose by

inhibiting pre glycolytic and phosphatase enzymes (Enolase)

• Anticoagulant action: Fluoride acts as anticoagulant because it

precipitates the calcium in the form of calcium fluoride
(CaF2).
 Chronic toxicity/ fluorosis
• Dental fluorosis: Excessive amount of fluoride damages ameloblasts and
odontoblasts
• deposition in teeth occurs only during the formative stages
• teeth lesions are the earliest and most severe in young and growing animals.
• Mottling of teeth

• Osteofluorosis: interferes with the osteoclast activity and damage the

osteoblast cells
• Intermittent shifting lameness
• F in Bones – 4000-5000 ppm of ash indicate flurosis
• urine in live animals- Urine levels of F:>15 ppm indicate fluorosis
 SALT POISONING- Water deprivation toxicity
Sodium ion poisoning/ Water deprivation induced sodium chloride toxicosis
• Salt hunger

• Na+ causes an extracellular hyperosmolality resulting in very significant

intracellular dehydration and development of brain or cerebral oedema.

• Dragging of hindfeet while walking & Knucking of fetlock joints

• Eosinophilic meningoencephalitis: Cerebral vascular endothelial

proliferation & distended perivascular space in pigs – is a pathognomonic
lesion of salt poisoning.
 Nitrate and Nitrite Poisoning
• Heavy use of nitrogen fertilizers (e.g. ammonium nitrate, potassium nitrate
and urea) and herbicides (e.g. 2, 4-D)

• cereal grasses (especially oats, millets and rye), corn (maize), sunflower and
sorghum readily accumulate nitrate

• Water: accumulation in water bodies due to increased water run off from
nitrate rich soil, decaying manure, silo pits, and freshly fertilized fields

• toxicity of the nitrate ion is approximately 10 times lower than that of the
nitrite ion
 nitrite
from
Ruminants
feed rumen
Reductase
Ammonia Protein
Rate
Nitrate Reductase limiting
from feed Nitrite

Blood Toxicity
Non Nitrite
from
ruminants feed
X X
Nitrate Nitrite Ammonia
• Ruminants are much more susceptible to nitrate poisoning than
monogastric animals

• Cattle- affected most frequently by nitrates

• Pigs are most susceptible to nitrite poisoning than cattle and

sheep

• cloudy weather or decreased sunlight enhances nitrate levels in

plants due to decreased activity of plant N03-reductase enzymes

• cut hay or green relatively late on sunny days to minimize

concentrations of nitrate
 Mechanism of action
• Nitrite: ingestion of large amount of nitrate or nitrite and this is due
to mainly nitrite ions
• a. Methaemoglobin formation: One nitrite combines with 2 Hb
molecules producing Met-Hb by oxidation

• Normally some Met-Hb (1-2%) is always present which is converted

back to ferrous haemoglobin by two reducing enzymes in blood viz.
NAD-dependent diaphorase I and NADP-dependent diaphorase II

b. Vascular smooth muscle relaxation (Vasodilation): hypotension and

decreased cardiac output
• Nitrate: primary action of large doses of nitrate is
different from nitrite ions and resembles effect of
excess common salt poisoning

• The signs include disturbed osmotic conditions in the

body and death may occur shortly after ingestion of very
large doses of nitrate, even before the nitrite and
methaemoglobin stages are reached

• Dark chocolate brown or coffee brown color of blood (dark tarry

chocolate colored blood) due to methaemoglobin
formation in nitrite poisoning
Methylene blue: antidote for treating methaemoglobinaemia caused by

nitrite/nitrate (chlorate poisoning also)

• After i/v, converted in blood and body tissues to a reducing agent

leucomethylene blue

• Leucomethylene blue also activates Diaphorase I and II systems.

 Cyanogenetic Plants/Prussic acid
poisoning
• poisoning occurs due to ingestion of cyanogenic plants which yield HCN
upon acidic or enzymatic hydrolysis by beta glycosidase and lyase

• Sorghum helepense (Baru grass, Johnson grass), Sorghum vulgare

(Jowar, Millet), Sorghum sudanensis (Sudan grass), Sorghastium nutans
(Indian grass)

• Triglochin maritima (Arrow grass), Zea mays (Maize), Linum

usitatissimum (Linseed, Flax), Prunus laurocerasus (Cherry laurel, Milk
laurel), Lotus spp.,
• Linamarin----------------linseed
• Dhurrin-------------------sorghum (Millet, Jowar, sudan grass etc.)
• Amygdalin---------------bitter almond, wild cherry (Prunus spp.)
• Lotusin or lotaustralin from Lotus spp

• Minimum lethal dose of HCN --- 2mg/Kg

• Plant materials >20mg of HCN per 100gm (200ppm) may have toxic
effects. Highly poisonous plants ---- 6000ppm

• Ruminants are more susceptible ; Among ruminants, cattle are more

susceptible than sheep

• Horses, dogs and pigs - less susceptible to HCN poisoning than

ruminants
• endogenous thiosulphate react with HCN to form thiocyanate
catalyzed by enzyme known as rhodanase

• Small amount of absorbed CN- is eliminated through lungs

(exhaled air has bitter almond smell)

• Cyanide has strong affinity for trivalent iron of the cytochrome

oxidase molecule and inhibits enzymatic activity and hence the
cellular respiration

• death is primarily from tissue anoxia in the brain

• As oxygen of arterial blood cannot be utilised, venous

blood retains the bright colour of oxyhaemoglobin.
 Diagnosis
• In case of suspected CN poisoning, the
liver/muscle/stomach contents should
be preserved with a solution of 1%
mercuric chloride and refrigerated.
• For urine, phenyl mercuric nitrate is
used as preservative. It prevents
enzymatic degradation.
 Post-mortem findings
• Bright cherry red color of venous blood

• Plants containing 200 ppm or more of HCN are potentially toxic

• Rumen contents and liver showing more than 10 ppm and 1.4
ppm of HCN, respectively, are indicative of cyanide poisoning

Sodium nitrite: antidote to cyanide poisoning, often in conjunction with

sodium thiosulphate.
 Oxalate rich plants

The oxalate rich plants

are:
• Amaranthus
retrflexus,
• Atriplex spps.,
• Beta vulgaris,
• Calandrina spp,
• Oxalis spp.,
• Rumexs spp.,
• Setaria spp.
• and Triantema spp.
Atriplex spps.,
 Mechanism of Toxicosis

• Calcium metabolism is upset (oxalates chelate Ca++

causing acute hypocalcaemia), interfering with milk
production in lactation in lactating animals and foetal
bone growth in pregnant animals.

• Blocking of renal tubules by calcium oxalate crystals

– renal injury.

• Failure of blood clotting mechanisms and haemolysis.

• Oxalates also crystallize and cause neuronal damage

in brain – CNS signs and paralysis.
 Treatment

• Shift to oxalate-free pastures.

• Oral administration of dicalcium phosphate (25% in

salt ration) or given as grain or alfalfa hay pellets
containing 10% dicalcium phosphate @ 225
G/animals/day for elimination of oxalates (calcium
oxalate) through faces.

• Prior treatment with dicalcium phosphate before

allowing sheep to graze in oxalate rich pastures, does
not result in oxalate poisoning.
 Plant producing thiamine deficiency
(i) Pteridium aquilinum (Bracken fern)
(ii) Equisetum arvense (Horse tail, bottle brush)
Pteridium plant:
1. Cyanogenetic glycoside - harmless
2. Thiaminase - responsible for poisoning in non-ruminants
3. Aplastic anemia factor (Ptaquiloside): bone marrow suppression in cattle and sheep
4. Haematuria factor: enzootic haematuria and haemorrhages in cattle and sheep
5. A carcinogen (Ptaquilosid (Japanese) / Aquiloside A (Dutch)

Equisetum contains enzyme Thiaminase and alkaloid

Equisetine.
• Chronic poisoning: Chronic enzootic haematuria in cattle
characterised by intermittent haematuria and ultimate death due
to anaemia

• In sheep, a bright blindness may occur due to progressive retinal

atrophy that is characterized by permanent blindness.

a. Administer DL - Butyl alcohol: It stimulates bone marrow

b.Toluidine blue

LANTANA CAMARA
Lantana hepatotoxins -Lantadenes – Lantadene A, B, C, D. (Major)
 Lantadene A is toxic to sheep (ruminants) & guinea pig (most susceptible species)

• causes hepatotoxicity & secondary photosensitization

i) absorbed from whole GIT with max absorption from small intestine and
transported to liver mainly in portal blood. (GIT Phase)

ii) Toxins interact with biomolecules on/in hepatocytes, followed by cascade of

biochemical reactions  cholestasis (hepatic phase)

iii)Cholestasis leads to regurgitation of bile  causes marked increase in levels of

bilirubin & phylloerythrin (biodegradation product of chlorophyll) in blood

undergo phytochemical reaction on exposure to light & causes photosensitization

• Hepatogenous photosensitization:
- Lantana camara
- Blue green algae
- Pithomyces chartarum fungus
 Teratogenic plants
• Veratrum californicum: alkaloids like cyclopamine,
Jervine and Veratrosine
• ‘Cyclopian Disease’ or Cyclopian eye’

• Lupine (Lupinus sericus, L. caudatus): the alkaloid

‘Anagyrine’ LUPININE
• CROOKED CALF DISEASE
Ipomoea carnea (Behaya). I. batata: Sweet Potato, Shakarkhand

Toxic Principles:
Phytotoxins like lysergic acid alkaloids (hallucinogenic), resins (cathartic), toxic
saponins, nitrates etc
SCAMMONIN (JALAPIN) – I. orizabensis
TURPETHIN – I. turpethum (Indian Jalap)
PHARBITISIN – I. hederaceae

Sorghum vulgare (Jowar).

Toxic Principles: HCN
Toxicity:
Cytotoxic anoxia.
Treatment: Sodium nitrite 20mg/kg slow i.v. as 1% solution and sodium
thiosulphate. 500mg/kg
Thevetia peruviana (Yellow Kaner) Nerium oleander (Red Kaner)
Toxic Principles:
N. odorum has one glycoside called ‘Nerin’. Cerebra thevatia (Thevatia nerifolia, yellow
oleander) has two glycosides called Thevitin, Cerberin.

Mechanism of action: oleander glycosides act on heart like digitalis and inhibits
the Na+-K+-ATPase pump.

Datura stramonium, Atropa belladonna (Deadly nightshade)

Toxic Principles: Atropine, Hyoscyamine, Hyoscine- Antimuscarinic action
Animals affected: Cat>Dog>Birds>Horses>Cattle>Sheep>Goat.
Clinical signs: Dryness of mouth & mucous membranes, thirst, anorexia,
mydriasis, visual disturbances, depression, tachycardia.
Treatment: Parasympathomimetic agents, e.g. physostigmine, pilocarpine etc.
Ricinus communis (Redi, Andi).
Toxic Principles: Phytotoxin Ricin I & II (more toxic). Ricin is one of the most
powerful phytotoxins known.
Animals affected: Horses are most susceptible
Toxicity: Cytotoxic (hydrolytic fragmentation of ribosomes and inhibits protein
synthesis, disrupts CM) and Gastrotoxic.
Treatment: Anti-ricin serum. Symptomatic & supportive

Abrus precatorius (Rati) Rosary Pea Poisoning

Toxic Principles: Abrin
Animals affected: All species of animals. Used for Malicious poisoning
Toxicity: A potent cytotoxic phyto protein
Argemona mexicana
Toxic Principles: alkaloid – sanguinarine; berberine; protopine
Animals affected: Poultry
Toxicity &Clinical signs: Drop in egg production, cyanosis of comb,
hemorrhagic enteritis and death in poultry

Gossypol: pigment found in cottonseed cake, occurs in 2 forms i.e.

free form (toxic) and bound form (non toxic)
Young calves, swine and poultry are affected

Supplement feed with iron (Ferrous sulphate) – prevention

Ourecus incana (Oak).
Toxic Principles: Tannins, Gallic and Pyrogallic acids, phenols
Toxicity: Precipitation of proteins and binding of =SH groups of
enzymes

Lathyrus Sativus(Grass Pea).

Toxic Principles:
β-oxalyl aminoalanine (BOAA)--Neurolathyrism
β-N aminopropionitrile (BAPN) –- Osteolathyrism
 Strychnos nuxvomica:
• Strychnine poisoning occurs in farm animals as
a result of accidental ingestion of seeds of
plant or powdered form of nuxvomica used as
bait to kill rats, foxes or dogs.
• Mechanism of toxicity: Main site of action of
strychnine is the recurrent inhibitory inter
neurons (Renshaw cells) of the reflex arc in the
spinal cord and medulla.
• Convulsant action
Oxalate rich plants
The oxalate rich plants are:
• Amaranthus retrflexus,
• Atriplex spps.,
• Beta vulgaris,
• Calandrina spp,
• Oxalis spp.,
• Rumexs spp.,
• Setaria spp.
• and Triantema spp.

Atriplex spps.,
 Mechanism of Toxicosis

• Calcium metabolism is upset (oxalates chelate Ca++ causing acute hypocalcaemia),

interfering with milk production in lactation in lactating animals and foetal bone
growth in pregnant animals.

• Blocking of renal tubules by calcium oxalate crystals – renal injury.

• Failure of blood clotting mechanisms and haemolysis.

• Oxalates also crystallize and cause neuronal damage in brain – CNS signs and
paralysis.
 Treatment
• Shift to oxalate-free pastures.

• Oral administration of dicalcium phosphate (25% in salt ration) or given as grain or

alfalfa hay pellets containing 10% dicalcium phosphate @ 225 G/animals/day for
elimination of oxalates (calcium oxalate) through faces.

• Prior treatment with dicalcium phosphate before allowing sheep to graze in oxalate
rich pastures, does not result in oxalate poisoning.
 Plant producing thiamine deficiency
(i) Pteridium aquilinum (Bracken fern)
(ii) Equisetum arvense (Horse tail, bottle brush)
Pteridium plant:
1. Cyanogenetic glycoside - harmless
2. Thiaminase - responsible for poisoning in non-ruminants
3. Aplastic anemia factor (Ptaquiloside): bone marrow suppression in cattle and sheep
4. Haematuria factor: enzootic haematuria and haemorrhages in cattle and sheep
5. A carcinogen (Ptaquilosid (Japanese) / Aquiloside A (Dutch)

Equisetum contains enzyme Thiaminase and alkaloid

Equisetine.
• Chronic poisoning: Chronic enzootic haematuria in cattle
characterised by intermittent haematuria and ultimate death due to
anaemia

• In sheep, a bright blindness may occur due to progressive retinal

atrophy that is characterized by permanent blindness.

a. Administer DL - Butyl alcohol: It stimulates bone marrow

b.Toluidine blue
 LANTANA CAMARA
 Lantana hepatotoxins -Lantadenes – Lantadene A, B, C, D. (Major)
 Lantadene A is toxic to sheep (ruminants) & guinea pig (most susceptible species)

• causes hepatotoxicity & secondary photosensitization

i) absorbed from whole GIT with max absorption from small intestine and
transported to liver mainly in portal blood. (GIT Phase)

ii) Toxins interact with biomolecules on/in hepatocytes, followed by cascade of

biochemical reactions  cholestasis (hepatic phase)

iii)Cholestasis leads to regurgitation of bile  causes marked increase in levels of

bilirubin & phylloerythrin (biodegradation product of chlorophyll) in blood

undergo phytochemical reaction on exposure to light & causes photosensitization

• Hepatogenous photosensitization:
- Lantana camara
- Blue green algae
- Pithomyces chartarum fungus
 Teratogenic plants
• Veratrum californicum: alkaloids like cyclopamine,
Jervine and Veratrosine
• ‘Cyclopian Disease’ or Cyclopian eye’

• Lupine (Lupinus sericus, L. caudatus): the alkaloid

‘Anagyrine’ LUPININE
• CROOKED CALF DISEASE
Ipomoea carnea (Behaya). I. batata: Sweet Potato, Shakarkhand

Toxic Principles:
Phytotoxins like lysergic acid alkaloids (hallucinogenic), resins (cathartic), toxic
saponins, nitrates etc
SCAMMONIN (JALAPIN) – I. orizabensis
TURPETHIN – I. turpethum (Indian Jalap)
PHARBITISIN – I. hederaceae

Sorghum vulgare (Jowar).

Toxic Principles: HCN
Toxicity:
Cytotoxic anoxia.
Treatment: Sodium nitrite 20mg/kg slow i.v. as 1% solution and sodium
thiosulphate. 500mg/kg
Thevetia peruviana (Yellow Kaner) Nerium oleander (Red Kaner)
Toxic Principles:
N. odorum has one glycoside called ‘Nerin’. Cerebra thevatia (Thevatia nerifolia, yellow
oleander) has two glycosides called Thevitin, Cerberin.

Mechanism of action: oleander glycosides act on heart like digitalis and inhibits
the Na+-K+-ATPase pump.

Datura stramonium, Atropa belladonna (Deadly nightshade)

Toxic Principles: Atropine, Hyoscyamine, Hyoscine- Antimuscarinic action
Animals affected: Cat>Dog>Birds>Horses>Cattle>Sheep>Goat.
Clinical signs: Dryness of mouth & mucous membranes, thirst, anorexia,
mydriasis, visual disturbances, depression, tachycardia.
Treatment: Parasympathomimetic agents, e.g. physostigmine, pilocarpine etc.
Ricinus communis (Redi, Andi).
Toxic Principles: Phytotoxin Ricin I & II (more toxic). Ricin is one of the most
powerful phytotoxins known.
Animals affected: Horses are most susceptible
Toxicity: Cytotoxic (hydrolytic fragmentation of ribosomes and inhibits protein
synthesis, disrupts CM) and Gastrotoxic.
Treatment: Anti-ricin serum. Symptomatic & supportive

Abrus precatorius (Rati) Rosary Pea Poisoning

Toxic Principles: Abrin
Animals affected: All species of animals. Used for Malicious poisoning
Toxicity: A potent cytotoxic phyto protein
Argemona mexicana
Toxic Principles: alkaloid – sanguinarine; berberine; protopine
Animals affected: Poultry
Toxicity &Clinical signs: Drop in egg production, cyanosis of comb,
hemorrhagic enteritis and death in poultry

Gossypol: pigment found in cottonseed cake, occurs in 2 forms i.e.

free form (toxic) and bound form (non toxic)
Young calves, swine and poultry are affected

Supplement feed with iron (Ferrous sulphate) – prevention

Ourecus incana (Oak).
Toxic Principles: Tannins, Gallic and Pyrogallic acids, phenols
Toxicity: Precipitation of proteins and binding of =SH groups of
enzymes

Lathyrus Sativus(Grass Pea).

Toxic Principles:
β-oxalyl aminoalanine (BOAA)--Neurolathyrism
β-N aminopropionitrile (BAPN) –- Osteolathyrism
Strychnos nuxvomica:

• Strychnine poisoning occurs in farm animals as a result of accidental

ingestion of seeds of plant or powdered form of nuxvomica used as
bait to kill rats, foxes or dogs.
• Mechanism of toxicity: Main site of action of strychnine is the
recurrent inhibitory inter neurons (Renshaw cells) of the reflex arc in
the spinal cord and medulla.
• Convulsant action
 Insecticides
Organochlorines- DDT, BHC

Organophosphates- malathion, sarin

Carbamates- Carbaryl, propoxur

Pyrethrins and pyrethroids- allethrin, deltamethrin

Formamidine insecticides- amitraz

Natural products- rotenone, nicotine

Organochlorines
• Organochlorines were the first major class of synthetic
organic chemical to become widely used as insecticides

Diphenyl aliphatic agents - DDT, methoxychlor, perthane, dicofol

Hexachlorocyclohexane – Lindane, mirex, kepone,BHC

Cyclodiene agents – Aldrin, dieldrin, chlordane, endrin, endosulpahan,

toxaphene, heptachlor
 Mechanism of Toxicity
• These drugs are neurotoxic.

• easily enter in the nerve membrane interfere with Na+ Channel

• Prolong the time of sodium channel opening during depolarization.

• Sodium inflow is enhanced and potassium outflow is inhibited

• Results in enhanced action potential and increased neuronal

excitability (seizures).
 Clinical symptoms

• Initial stimulation of CNS followed by depression and death due to

respiratory failure.

 Behavioural symptoms- like anxiety, aggressiveness, abnormal posturing,

jumping over unseen objects, wall climbing and madness syndrome.

• Neurological symptoms - hypersensitivity to external stimuli,

fasciculation and twitching of facial and eyelid muscles, spasm and
twitching of the fore and hind quarter muscles, champing of the jaws,
seizures and hyperthermia.

• Cholinergic symptoms - vomiting, marked salivation, mydriasis, diarrhoea

and micturition are noticed.
Treatment

• Diazepam, phenobarbital or pentobarbital in dogs.

Chloral hydrates, Phenobarbital or pentobarbital in

farm animals.
• Activated charcoal (1-2g/kg).
• If exposure is by dermal suspected, scrubbed
(bathe) the animal with soapy water.
• Supportive and symptomatic therapy.
 Organophosphates
• OP compound are esters of phosphoric, phosphonic,
phosphorothioic or related acids

• which have ability to inhibit cholinesterase enzyme

• 1st OPI - tetraethyl pyrophosphate (TEPP).

 Classification of OPI
Based on chemical structure –
• Phosphate & pyrophosphate- Paraoxon, TEPP, schraden, dichlorvos

• Phosphorothioates - Parathion, fenthion, diazinon, runnel

• Phosphonates - Trichlorphon

• Phosphoramidates- Phospholan, mephospholan

• Phosphorothiolates- Echothiophate, profenophos

• Phosphorohalides- Diisoprophylfluorophosphate (DFP), sarin

• Phosphorocyanides- Tabun
 Based on mode of action
(Classification)

Direct acting OP insecticides Indirect acting OP insecticides

• These insecticides contain P=O • phosphorothioates

group containing P=S groups.

• directly inhibit cholinesterase • Require activation to oxon

enzyme and produce toxicity (conversion of P=S moiety to a
P =O moiety) in the body.
• TEPP, trichlorphon and dichlorvos. • Malathion, parathion and
fenthion.
 Mechanism of action

• OPI owe their toxicity by irreversible inhibition of AChE

enzyme, which is responsible for hydrolytic degradation of
acetylcholine

• This leads to Ach accumulation in nerves and neuro-effector junctions,

which causes excessive synaptic neurotransmitter activity in the
parasympathetic nervous system and at neuromuscular sites and affected
animals show parasympathetic or chlolinergic signs.
• OP compounds interact with only the active esteric site of the
enzyme and the enzyme – OP complex formed is extremely
stable that does not undergo significant spontaneous
hydrolysis.
• However once covalent modification of enzyme occurs and the
phosphorylated enzyme looses one of its alkyl group (called aging), it is
impossible for chemical re activators to break the bond between the
inhibitor and the enzyme.

• Aging is very rapid for nerve gases.

soman (aging half life 2 minutes),
 Delayed Toxicity (delayed neurotoxicity):
• occurs after several days produced by the inhibition of NTE (Neuropathy Target
Esterase),membrane bound enzyme.

• NTE facilitate axonal transport of nutrients

• its inhibition results in demyelination of of axon leading to paralysis called as

organophosphate induced delayed neuropathy (OPIDN) or dying back axonopathy.

• “Hind leg paralysis”/ “Ginger Jake Leg/ Jake Leg Paralysis

• Mipafox is a classical example causing OPIDN

• Charolin’s cattle and SUFFOLK sheep genetically predisposed

 Treatment
• Specific antidotes: a) Muscarinic blockers
b) ChE reactivators
• Atropine SO4:
Dogs and Cats: 0.2-2 mg/kg 1/ iv and rest sc.
Repeat every 3-6 hr as required.
Horse and Pig: 0.1-0.2 mg/kg I/V,
repeat every 10-15 min as needed;
Cattle and sheep: 0.5-1 mg/kg 1/3 iv and rest im or sc,repeat as
needed.
• Oximes/ cholinesterase reactivators : 2-PAM (2-Pyridine aldoxime
methiodide, 2-PAM chloride), DAM, MINA – Binds to anionic site
• @ 20-50 mg/kg as 10% sol im or slow

• ChE activation decreases with time (after exposure), better to use within 24-
48 hr.

• If ingestion: Emetics, purgatives, activated charcoal (3-6 g/kg as slurry in

water.

• If dermal: wash with soap and cool water.

Carbamates
• Naphthyl carbamates- Carbaryl (sevin)

• Phenyl carbamates – Propoxur

• Heterocyclic methyl carbamates-pyrolan and isolan.

• Heterocyclic dimethyl carbamates Carbofuran and

furadan, aldicarb, methomyl and thiodicarb.
 Differences from OP compounds
Carbamates differ from OP compounds in following aspects:

--They are reversible inhibitors of cholinesterase (ChE) enzyme

• They inhibit cholinesterase at both anionic and esteratic sites

• They are selective inhibitors of cholinesterase enzyme

• Decarbamoylation (reactivation) of inhibited ChE enzyme is easier

• Cholinesterase enzyme reactivators like 2-PAM are ineffective

(contraindicated) in the carbamate intoxication.
Mechanism of action
• Carbamate inhibit acetylcholinesterase enzyme, but these insecticides
occupy both anionic and esteratic sites of AChE.

• The inhibition in case of Carbamate results from a chemical reaction

between the carbamoyl moiety of carbamate compound and the
active site serine hydroxyl group of AChE to form carbamoylated
enzyme rather than phosphorylated as with the organophosphate.

• The carbamoylated enzyme is relatively less stable and susceptible

to hydrolysis, although rate of hydrolysis is not very fast as with
acetylcholine.
• Therefore, the decarbamoylation is easier in comparison to
dephosporylation (OPs).

• Because of relatively rapid reactivation of carbamoylated AChE,

the carbamate insecticides are often called reversible
anticholinesterase agents.

• Toxicosis develops when the amount of carbamate pesticide in the

body is so large that the rate of carbamoylation of AChE
exceeds the rate of hydrolysis of pesticide by the enzyme.
Diagnosis:
• History, circumstantial evidence,
• Clinical signs,
• Estimation of blood ChE activity (25% or more decrease in
OPI and carbamate toxicity) and
• Identification of the insecticide in feed, water, ruminal
content or tissues.

Treatment:
• Atropine sulphate only
• Not ChE-reactivators.
 Pyrethrins

• This is a closely related group of naturally occurring

compounds that are the active insecticidal
ingredients of pyrethrum.

• Pyrethrum is extracted from the flowers of

Chrysanthemum cinerariaefolium and has been an
effective insecticide for many years.

• Synergists, such as piperonyl butoxide, sesamex,

piperonyl cyclonene, etc, are added to increase
stability and effectiveness.
Pyrethroids

These are synthetic derivatives of natural pyrethrins and include –

• Allethrin,
• Cypermethrin,
• Decamethrin,
• Fenvalerate,
• Fluvalinate,
• Permethrin
• Type I pyrethroids – Tremors (T syndrome)
• Type II pyrethroids - choreoathetosis-salivation syndrome (CS)
Mechanism of action
• Nerve poisons like DDT.

• Prolonged depolarization (delayed closure of Na channels) and

repetitive discharge.

• Piperonyl butoxide and piperonyl cyclonene potentiate pyrethoid

insecticidal and mammalian toxicity (inhibition of mixed function
microsomal oxidases i.e. by preventing detoxification of pyrethroids).

• Pyrethroids are relatively less toxic in mammals and birds, but highly
toxic to fish.
Herbicides

• Dinitro compound- dinitro ortho cresol (DNOC), dinitrophenol

• Phenoxyacetic acids - 2,4-D, 2,4,5-T etc.

• Bipyridium compounds- diquat, paraquat etc.

• Heterocyclic compounds or triazenes- atrazine, propazine,

simizine.

• Chloroaliphatic acids - dalapon, sodium chloroacetate,

sodium trichoroacetate etc.
• Substituted urea - monouron, diuron, isoproturon etc.

• Substituted dinitroaniline - pendimethalin.

Chlorophenoxy Compounds (Phenoxyacetic acid
compounds): 2,4-D
• The most important and most frequently used
herbicides.

• It can potentiate the toxic effects of some

plants .

• Increases the nitrate content of certain

plants and increases the palatability of certain
toxic plants, thus increases the poisoning risk.

• Dogs are most sensitive animals.

 Bipyridal/Bipyridinium Compounds
• Paraquat

• actively taken up by the alveolar cells via a diamine where it

readily accepts an electron from NADPH to become reduced
paraquat.

• When the reduced paraquat is reoxidized by loss of electron, a

superoxide anion radical O2- is generated.

• The superoxide radical is unstable and spontaneously breaks down

to the reactive singlet oxygen.

• The reactive singlet oxygen attacks the polyunsaturated lipids

associated with cell membranes to form lipid hydroperoxides.
• These lipid hydroperoxides are normally converted to non
toxic lipid alcohols by the selenium – containing enzyme
glutathione peroxidase.

• Selenium deficiency, depletion of glutathione or excess

lipid hydroperoxides allow the lipid hydroperoxides to
form lipid free radicals.

• The action of paraquat in lungs is similar to that produced

by carbon tetrachloride in liver.
Rodenticides
Inorganic rodenticides: Organic rodenticides:
• Arsenic compounds • Anticoagulants- warfarin,
arsenic trioxide and diphacinone, difenacoum and
sodium hydrogen brodifacoum.
arsenite. • Fluoroacetic acid and its
derivatives – sodium fluroacetate
• Elementary and fluroacetamide.
phosphorus • Alphanaphthylthiourea (ANTU)
• Thallium sulphate • Bromothalin
• Zinc phosphide • Strychnine
• Red squill
• Pyriminil
• Norbormide
• Crimidine
• Chloralose
 Zinc phosphide
• It is one of the most widely used rodenticides in developing country
because it is cheap and very effective.

• It is often recommended as the rodenticides of choice because it is

fairly specific for rodents and there is no true secondary poisoning,
except possibly in dog and cat.

• Liberation of phosphine gas in acid pH in stomach – irritates GIT

and causes CVS collapse.
Mechanism of action:
• Acute zinc phosphide toxicosis is due to the phosphine gas. phosphine
gas is said to act as a general protoplasmic poison.
• It causes direct damage to membranes of blood vessels and
erythrocytes leading to cardiovascular collapse.
• Phosphine also causes depression of CNS, irritation of lungs and
damage to liver and kidneys.

Clinical Signs:
• Vomiting, acidosis, abdominal pain, aimless running, howling, ataxia,
dyspnoea, gasping and convulsions.

Treatment:
• Calcium boro-gluconate and fluid therapy to reduce acidosis
(2-4 litres of 5% soda bicarb. PO).
 Warfarin and Congeners
• Pindone, coumafuryl, coumachlor etc. are most commonly used
potentially dangerous compounds.

Mechanism of Toxicosis:
• It is also called as anticoagulant rodenticides.
• It has basic coumarin or indanedione nucleus.
• Act as anti-vitamin K and interfere with synthesis of coagulation-
Factors I, II, VII and X in liver.
• Prothrombin thrombin
(failure of blood clotting)

generalized haemorrhages.
Clinical Signs:
Anaemia, hematomas, hemothorax, epistaxis and hematuria,
weakness ataxia, colic and polypnoea.

Treatment:
•Vitamin K1 @ 2.5-5 mg/kg iv or sc smallest possible needle at several
locations to speed up absorption for 2 – 4 weeks.
•Fresh or frozen plasma @ 9 ml/kg or whole blood 20 ml/kg iv to
replace clotting factors.
•Thoracocentesis to relieve dyspnoea due to hemothorax and
artificial respiration with oxygen.
Alpha Naphthyl Thiourea (ANTU)
Mechanism of Toxicosis: Animal drowned in own fluid

• It interferes with effective uptake of O2 from pulmonary

alveoli by producing massive oedema of lungs due to
increase capillary permeability.

• ANTU undergoes metabolism by microsomal mixed function

oxidases releasing atomic sulphur which damages the
endothelium of alveolar capillaries – leakage of fluid into
alveoli (airways)– pulmonary oedema
• It causes vomiting on empty stomach due to intense local gastric
irritation, but poisoning occurs if ANTU is ingested after feeding.
 Red Squill

• It is the ground bulbs of Urgenia maritime.

• Contain cardiac glycoside- proscillaridin.

• Considered as the safest rodenticide (nontoxic to poultry,

unpalatable to livestock, vomiting if cats/dogs ingest, rats are
incapable of vomiting).
Formamidine insecticides- Amitraz stimulation of alpha2-
adrenoceptors and inhibition of monoamine oxidase (MAO)
enzyme

• NEONICOTINOID INSECTICIDES: IMIDACLOPRID

• Mechanism of action:
acts and binds selectively to nicotinic cholinergic receptors on
the post-synaptic membrane.
- nicotinic receptors of mammals are less sensitive to
imidacloprid than are insect receptors
 Urea Poisoning
• Toxic dose: Cattle, sheep: 1 g/kg (lethal dose), 0.5 g/kg (Toxic), 0.3 g/kg (Mild
toxic)
• Horse: 4 g/kg (Oral LD50)

• rumen pH is elevated to 11, more and more NH3 will be released and present in non-
ionized form (NH3) which is diffusible into systematic circulation

• Toxic conc.: rumen NH3 concentration 80 mg% and BUN 0.84 – 1.3 mg %

• NH3 inhibits TCA (citric acid) cycle. There is decrease in energy production and
cellular respiration.
• presence of urease in soyabean potentiate toxicity

• 5% acetic acid/(vinegar) given (2.5-5 litres) with sufficient cold water

• Bovine bunker syndrome: NPN/ ammonia poisoning
 Carbon tetrachloride
• anti trematodal drug against fascioliasis in ruminants
• reference hepatotoxic agent
• Pigs are most susceptible of all mammals and sheep is quite tolerant

• CCl4 CCl3- CCl3COO -

(trichloromethyl free radical) (trichloromethyl peroxy free radical)

• reactions are catalyzed by cytochrome P450 dependent monooxygenase

 Phenothiazine
• cause photosensitization in animals

• In horses causes hemolysis of RBC (Blood enzyme – lysolecithin is activated)

• Sensitization to sunlight is more frequent problem because of phenothiazine

sulfoxide (metabolite of phenothiazine)

• Hemolysis in horses leading to icteric membranes and presence of Hb in urine

• Calves show photosensitization, keratitis. In sheep, keratitis accompanied by

reddening and thickening of muzzle and ears
 Disease Fungus Crop or Mycotoxin Animals
substrate affected

Aflatoxicosis Aspergillus flavus Ground nut, Afaltoxins B1, Cattle, pig,

Aspergillus maize and nut B2, G1,G2 poultry and dogs
parasiticus crops
Ergotism Claviceps Seed heads of Ergotamine and Cattle, Sheep, Pig,
purpurea many grasses and ergometrine Horse and Poultry
grains
Facial Eczema Pithomyces Pasture, litter Sporidesmin Sheep and Cattle
charatarum

Oestrogenism Fusarium Maize, Barley Zearalenone Pigs

graminareum and cereals
Leukoencephalo Fusarium Maize Fumonisins B1 (A1, Horses and
malacia moniliforme A2, B2) Donkey
Trichothecane Many Fusarium Cereals T-2 toxin, Many species
toxicosis species diacetoxy -
seripenol
Ocharatoxicosis A. ochraceus Barley, wheat Ochratoxin -A Pigs and Poultry
P. viridicatum and Maize
 Species Toxins

A.flavus and A.parasiticus Aflatoxins

A. ocheraceus Ochratoxin

Fusarium roseum Trichothecane (t-2) toxin

Penicillium citrinum Citrinin

Target organs/ tissues Toxins

Vascular system Aflatoxins

Digestive system Aflatoxins

Mucous membrane Trichothecane (t-2) toxin

Urinary system Ochratoxin

Reproductive system Zearalenone

(Fusarium toxin)
Cutaneous system Sporidesmin
 AFLATOXICOSIS
• Afalatoxins produced by A. flavus and A. parasiticus

• Four major aflatoxins are B1, B2, G1 and G2

• B1and B2 produce blue color and G1, G2 gives green fluorescence.

• Aflatoxins M1, M2 are hydroxylated metabolites of B1 and B2 ----

excreted in the milk of lactating animals
· Young animals are highly susceptible

· Aflatoxin B1 produce the most hepatogenic, carcinogenic, teratogenic

and embryotoxic effects

· Calves- blindness, circling, grinding of teeth, diarrhoea, tenesmus &

convulsions
· Ducklings- most susceptible avain species
· In birds over three weeks of age, subcutaneous haemorrhages of
legs and feet
PM Lesions
Principle target organ is liver causes hepatomegaly with necrosis & bile
duct hyperplasia
Chronic toxicity, in additon to liver damage, degenerative changes in the
kidney, thymus cortical aplasia leading to decreased cell mediated
immune response
· Biological assays for toxicity are important confirmatory steps

· Concentration of aflatoxin B1 in excess of 100μg /kg of feed

are considered toxic for cattle

· Thinlayer chromatography and HPLC are more sensitive analytical

methods for determing afaltoxins levels in the food.

· Radio immuno assay & ELISA

· Biological assays- Ducklings are mostly susceptible. Bile duct

proliferation in one-day-old ducklings and chick embryo bioassay
 Erogtism
• Fungal species of the genus Claviceps, notably Claviceps purpurea

· toxic alkaloids - ergotamine and ergometrine

· Two forms of ergotism- gangrenous & convulsive ergotism

· Ergot alkaloids may exert an oxytocin like effects causing abortions

· Gangrenous ergotism - Gangrenous necrosis of the extremities – nose,

ears, tail, teats & limbs

· Tail gangrene
· Estrogenic metabolites – DON, zearalenone (F-2 toxin)
and Trichothecene toxins by Fusiarium graminearum and
other Fusiarium species

·Zearalenone - oestrogenic activity

·Target organ system- reproductive tract of pigs causing

vulvovaginitis, associated with the consumption of moldy
maize by gilts.
 DON and T-2 Toxin

• Deoxynivalenol (DON), also known as vomitoxin

• necrosis and hemorrhage of the digestive tract,

decreased blood production in the bone and spleen, and
changes to reproductive systems.

• In poultry, causes reduced egg production, beak lesions,

and abnormal feathering

• Advisory level of DON/ Vomitoxin is 1 ppm

· Several Aspergillus and Penicillium species, particularly toxigenic strains of
Aspergillus ochraceus, A. alutaceus and Penicillium verrucosum produce
ochratoxins

· Group of related iso coumarin derivatives

· Ochratoxin A is the principal nephrotoxic mycotoxin in this group

· The mycotoxin citrinin, which can also be produced by A. ochraceus as well

as by Penicillium citrinum, P. viridicatum and P. expansum, is nephrotoxic.
 Toxicity caused by poisonous animals
• Zootoxins: Toxins produced by lower animals, e.g. snakes, fish, toads, scorpions, bees,
wasps, spider, ticks etc.

• Venomous animals: Animals capable of producing a poison in a highly

developed secretary gland or group of cells and deliver toxin during a
stinging and biting act

• Spider, scorpions, bees, wasps, ants, beetles, caterpillars etc.

• Venom may be composed of proteins (polypeptides and enzymes) of both

high and low molecular weight.
 Snake Venom Toxicity:
• Snake venom - colloidal solution of toxic components-mainly enzymes and non enzymatic
peptides and amino acids, (in addition to K+, Na+, Ca++, Mg++, Ni++ etc.)

• more than 3500 different species out of which more than 400 are poisonous and dangerous

• 1. Elapidae: Elapids, Cobras, Kraits, Cora snakes, Mombas

• 2. Crotalidae: Crotalids, Pit vipers, rattle snakes, bush master, water moccasins, copper heads

• 3. Viperidae: Viperids, vipers, adders

• 4. Hydrophidae: All sea snakes, water snakes

• 5. Colubridae: Colubrids includes poisonous and non-poisonous snakes – Boomslang, bird snake,
rednecked, keelback snake.
• Active principles of snake venoms:
• Hyaluronidase, Cholinesterase, proteolytic phosphates, phospholipase A
• Protein and amino acids : toxin
• also contain some different fractions like necrotizing, anticoagulant, coagulant,
neurotoxic, cardiotoxic and haemolytic fractions.

• venoms of cobra and krait are mainly neurotoxic while that of vipers and rattles
snakes are haemotoxic

• components which itself are not toxic help to increase toxicity of others e.g.
Hyaluronidase helps in spreading the toxin

• . Horse > Sheep > Cattle > Goat > dog > Pig > Cat

• Antihistaminic are contraindicated as they enhance the action of

venom/potentiate the effect of venom
S.No Viperine Elapine
.
1. Mainly haemotoxic Mainly neurotoxic
2 Local swelling at the site of bite No local swelling. Symptoms take
which develops very rapidly about 1 hr to appear

3 Excitement with anxiety Excitement with convulsions.

Nervous signs – Paralysis, Death –
respiratory paralysis.
4 Coagulability of blood is Coagulability of blood is not
completely lost, therefore affected
haemorrhages
5 Death due to extensive Death due to paralysis of
haemorrhages leading to shock or respiratory centre.
pulmonary thrombosis
 Spider venom toxicity
• Black widow spiders (Latrodectus mactans) Black recluse spider
(Loxoscales reclusa)

• i) Neurotoxin – it affects neuromuscular junctions and cause the release

of ACh from pre-synaptic nerve fibers and enhances depolarization.
ii) Lipoproteins, Hyaluronidase, High content of leucine and isoleucine and
low tyrosine

* neurotoxin of black widow spider is α-latrotoxin

• death occurs in 4 to 6 hrs in acute cases to few days in mild ones. (due to
paralysis of respiratory muscle)
 Scorpion toxicity
• stinger located on the tip of tail.
• Venom causes muscular stimulation and hemorrhage.

• Toxic components: Heterogenous mixture – neurotoxin, cardiotoxin,

nephrotoxin, haemolysin, agglutinins, phospholipases, hyaluronidases,
histamines, serotonin etc. The most potent is the neurotoxins

• Mechanism of action: Neurotoxin interacts with voltage dependent Na+

channel and stabilizes it in the open position, which leads to prolonged and
repetitive firing of somatic, sympathetic and parasympathetic neurons.
 Toads
• Bufo vulgaris (common toad), B. marinus (marine toad), B. alvarius (River toad). Out of these, B.
alvarrius, B. marinus are most toxic and B. vulgaris is least toxic

• Toxins secreted by glands in their skin located above and posterior to eyes (produced in the
parotid glands)

• Different toad toxinsn1. Bufodienolides which include Bufogenins and their derivative
bufotoxins: Bufotalins, Bufotenidin, Bufotenin, Bufoviridin, 2. Serotonin, 3. Catecholamines.

• Bufogenins are cardiac glycosides and effect heart and other smooth muscles.

• toxin binds with specific receptor site on Na+-K+-ATPase pump in cardiac cell membrane and
inhibits its function causing excessive cardiac stimulation and ventricular fibrillation.

• Death occurs rapidly from heart failure.

 Fish toxins (Ichthyotoxins)
• 1. Shellfish toxicity: produces saxitoxin
• Interfere with ionic transport across the axonal membrane. It inhibits inward
current of Na+ across axonal membrane

• 2. Puffer fish toxicity (Fugu fish toxicity): produces Tetrodotoxin

• Mechanism of Action: Tetrodotoxin is a potent neurotoxin that blocks the

inward conduction of Na+ through Na-channels across the cell membranes of
excitable cells.
• direct paralyzing effect on striated muscle and nerve fibers. It also provokes
hypotension and has deleterious effects on respiration.
 Bees and Wasps Toxicity
• Honey bee venom also contains i) hyaluronidase and ii) proteins – melittin, aparmin.

• Hyaluronidase cause hypotension and increased vascular permeability

• Mellitin is antigenic in nature and produce hypersensitivity (allergic) reactions

mainly in human beings and horses.

• Multiple stings result in death due to anaphylactic shock. Allergic responses also
observed.

• Wasp venom also contains a variety of amines and kinins.

 Radiation toxicology
• study of adverse effects of radiation on living organisms.

• Mechanism of action: DNA strands break, point mutation and chromosomal

aberrations, then loss of gene products which leads to cell death. rate of
chromosomal aberrations is directly related to radiation dose.

• Pathogenesis: The rapidly and undifferentiated cells are most sensitive. Skin, GI
tract and haematopoietic system are worst affected (with exception of human
lymphocytes).

• Biological systems irradiated in presence of O2 are more susceptible to injury as

it results in formation of hydroperoxy or H2O2 radicals which damage more due
to their long half-lives. The response is termed as “Oxygen effect”.
• Thyroid: Radioactive isotopes at iodine (131I) are accumulated in the thyroid gland,
which destroy thyroid gland.

• Bones: Nuclides deposited preferentially in bone or on bone are collectively known

as “Bone Seekers”- 89Strontium, 90Strontium, 140Barium, radium isotopes etc. They
suppress bone marrow and result in lymphopenia, leucopenia, anaemia.

• Reproductive organs: Stops cell division of testicular germinal epithelium. Acute

dose of 600 rad in testes produce permanent sterility. But fully developed sperm
cells and primary spermatocytes relatively radio-resistant. Atrophy and
degeneration of ova occurs in ovary. It may cause death of embryo.