org rodenticide

ORGANIC RODENTICIDES

To be effective, yet safe, rodenticides must satisfy several criteria:

• The poison must be very effective in the target species once incorporated into bait in small quantity;• Baits containing the poison must not excite bait shyness, so that the

animal will continue to eat.• Species-specific, with considerable lower toxicity to other animals

What are organic rodenticides ?• Rodenticides are pesticides that kill rodents.

• Rodenticides have the same effect when eaten by any mammal.

• Rodenticides are usually formulated as baits, which are designed to attract animals.

• These may be attractive to children and pets, so they should never be used or stored within their reach.

1. ANTICOAGULANTSINTRODUCTION

• Most commonly used organic rodenticides Eg : Warfarin, Anti- Vit. K compounds.

• Discovered in 20th century during the search for Sweet Clover Disease (DICOUMAROL) in cattle in North America.

• In 1948, a more potent synthetic congener was introduced as an extremely effective rodenticide.• The compound was named warfarin, derived from

the name of the patent holder: Wisconsin Alumni Research Foundation.

• Potential and common source of poisoning for pets.

• ROUTE: Directly from baits or by consumption of poisoned rats.

Chemistry and Classification

• Derivatives of 4-Hydroxycoumarin (or) indan-1,3-dione.• Placed into two groups : a) Hydroxycoumarins : eg. warfarin, coumafuryl,

coumatetralyl, bromadiolone

b) Indanediones : eg. pindone, chlorophacinone, diphacinone

Anticoagulants contd …1. First generation anticoagulant rodenticides : • Potency as vit. K antagonist is low. Hence multiple

doses only produce toxicity.

• Have short half life due to rapid excretion.

• Eg : Warfarin , Dicoumarol, Pindone (PIVAL), Coumatetralyl (ENDOX) .

• Therapeutic use : Rx and prevention of venous thrombosis and aortic or pulmonary thromboembolism.

2. Second generation anticoagulant rodenticides:

• Highly potent and are able to kill warfarin resistant rats. Pose a threat to non target species !!

• High potency as Vit. K antagonists.

• Long retention time in tissues ( long acting) .

• Eg: Brodifacoum, bromadiolone (RADIONE) , diphacinone (Diphacin).

Properties :

• Odourless and tasteless.• Due to slow action, bait is carried to nesting places

where other rodents may eat.• Conc. in 1st gen. is 0.02 to 1 % and in 2nd gen. is 0.005 to

2 %.

• Available forms in market : Powder, bait packs, concentrates, pellets, tablets and capsules.

Factors affecting toxicity :• Ruminants less susceptible.• Horses are resistant.• Dogs and cats are mostly involved.• Renal insufficiency.• Liver abnormalities or other lesions.• More toxic when consumed continuously for long

period than the equal dose consumed at a time.• Animals with inborn error of deficit clotting mechanism

are more susceceptible.

• Other poisons in the body that increase capillary permeability or cause clotting disorders.

• Admin. of ACTH or ELTROXIN may inc. the receptor site affinity for the anticoagulant.

• Drugs like Sulphomamides increase the anticoagulant rodenticide toxicity.

• Aspirin and phenylbutazone increase the toxicity too.

TOXICITY :• Single dose of warfarin @ 20-50 mg/kg is fatal to DOGS.• Repeated dose of 1 mg/kg for 7days is lethal to dogs and

cats.

• Diphacinone @ 3 mg/kg is the LD50 dose for dogs.

• Warfarin @ 30 mg/kg single dose and 0.05mg/kg/day for 7days is LD50 in PIGS.

• Brodifacoum @ 29 mg/ kg is LD50 in RUMINANTS.

TOXICOKINETICS :Absorption, distribution, metabolism and excretion.

• Absorbed slowly, 90% from GI tract.• PPC may reach in 12 hrs.• Distribution in plasma is prolonged due to strong

binding by PP ( 90-95% for warfarin ).• These rodenticides may be metabolised by

microsomal mixed function oxidases to inactive form which are excreted in urine.• Half life = warfarin- 15 hrs , Diphacinone- 5 days ,

Brodifacoum – 24 days in serum.

MECHANISM OF ACTION

(A) INHIBITION OF SYNTHESIS OF

CLOTTING FACTORS

(B) DAMAGE TO CAPILLARIES

MECHANISM OF ACTION : (A)

Carboxylation

Oxidation

Reduction

Precursors of clotting factors

Active clotting factors

FIGURE :• Reduced vitamin K (hydroquinone) serves as cofactor for the

conversion of glutamic acid to γ-carboxyglutamic acid in the peptide chains of coagulation factors II, VII, IX, and X.

• During this reaction, vitamin K is oxidized to an epoxide that is then reduced to quinone and hydroquinone by vitamin K epoxide reductase, which is inhibited by warfarin

Mechanism of action contd. . . All anticoagulant rodenticide block Vit

K epoxide reductase. This interferes with regeneration of active form of

Vit. K , thereby inhibiting synthesis of :

a) Factor II - Prothrombin b) Factor VII - Proconvertin c) Factor IX - Thromboplastin d) Factor X - Stuart factor

• This results in 50 % reduction in clotting mechanism factors. • Animal dies of TISSUE HYPOXIA due to MASSIVE

INTERNAL BLEEDING.

Mechanism of action : (B)• Warfarin containing rodenticides cause direct

damage to capillaries.• Exact cause unknown.• Benzalacetone moiety of warfarin.• This leads to bleeding upon slightest trauma.

CLINICAL SIGNS :• Seen after 1-3 days because the clotting facors present

at the time of ingestion of anticoagulant rodenticide should be utilized.

LETHARGYPALLOR

WEAKNESSDYSPNOEA

SHOCK

MASSIVE HAEMORRHAGEBlood discharge from orifices

HEMATOMASHYPOXIA

DEATH

• Premonitory signs of death go unnoticed and thought to be natural because of old age .

• Sudden internal haemorrhage can lead to ACUTE ANAEMIA, shock, cyanosis & DEATH !!

• PME = Hges on mm, S/C bleeding, internal hges. UNCLOTTED BLOOD .

DIAGNOSIS1. H/O consuming any baits observed by owner.2. Clinical signs and external lesions (small

incision is made with BP blade which leads to profuse uncontrollable bleeding)

3. Persistent bleeding during surgery.4. Lab. Diagnosis : Inc. clotting time Inc. activated prothrombin time5. Radiography.

Differential Diagnosis (DD)1. Inherited bleeding disorders (Haemophilia-A, Von

Willebrands disease, Clotting factors deficiency)

2. Medicinal warfarin overdose

3. Vitamin K deficiency

Rx and Management

SPECIFIC THERAPY

SUPPORTIVE THERAPY

Specific antidote : Vitamin K1 ( PHYTOMENADIONE ) Dose : Dogs= 2.5-5 mg/kg b.w./day I/M or S/C H/C/S/G = 0.5 – 1 mg/ kg b.w. I/M or S/C in divided doses

•Blood transfusion @ 20ml/ kg bw•Emetics must be given to expel the poison.•Sedation of animal•Oxygen therapy•Thoracocentesis

Contraindication:• Sulphonamides• Aspirin (NSAID’s)• Antihistamins

COMMERCIAL PREPARATIONS :• Warfarin as 0.25 – 1% as pellet or powder• Pindone as 0.005-0.05% active ingredient.• Brodifacoum as 0.005% pellet formulation and wax

blocks/

2. FLUOROACETIC ACID & DERIVATIVES

• Sodium fluoroacetate (Compound 1080) and fluoroacetamide are the main representatives of this class of rodenticides.

• The name "1080" refers to the catalogue number of the poison, which became its brand name.

• Both compounds have indeed high acute toxicity.

• The main targets of toxicity are the central nervous system and the heart.

Chemistry and Properties• They are fluorinated derivatves of acetic acid.• Available as stable sodium salts.• Colourless , tasteless and water soluble.• No bait shyness due to long lag period after ingestion. • Concentratin used : 0.08-0.5 %

Sodium fluoracetate > Sodium fluoroacetamide

Toxicity• Oral LD50 is 0.1 – 8 mg/kg hence highly toxic to domestic pets. • Preparation containing fluoroacetate have WARNING black color

(Nigrosine) !!• As a rodenticide LD50 values are :

Rats- 15 mg/kg bw Mice- 30 mg/kg bw

Toxicokinetics :• Readily absorbed from gut ,lungs, open wounds.• Concentration more in brain than other tissues. • In chronic drunkards the compound in alcohol is

Fluoroethanol . How is it metabolized ??

ALCOHOL DEHYROGENASE

Mechanism of action• The main targets of toxicity are the CNS and the

heart.

• Inhibition of the Krebs cycle, leading to lowered energy production,reduced oxygen consumption, and reduced cellular concentration of ATP.

MOA

FLUOROCITRATE

Fluoroacetate : A Suicide Substrate

Fluoroacetate ( harmless)

Fluoroacetyl CoA

Fluorocitrate ACONITASE

The conversion of fluoroacetate to Fluorocitrate is called LETHAL SYNTHESIS.

Acetyl CoA

Oxaloacetate

___

CLINICAL SIGNS :• Seen after half to two hours of ingestion

RestlessnessAnxiety

HyperirritabilityVOMITING

REPETITIVE URINATIONDEFECATIONTENESMUSFROTHING

HYPERTHERMIAA

Diagnosis

1. Detailed history2. Clinical signs and external lesions3. Lab. Diagnosis : Kidney tissues can be tested for INCREASE CITRATE levels.

Differential Diagnosis (DD)1. Encephalitic disease2. Hypomagnesemic tetany3. Hypocalcemia4. Strychnine poisoning etc…

Rx and management• Specific treatment - NO

• Supportive therapy :

1. Adsorbents like activated charcoal are recommended.

2. Glyceryl monoacetate (monoacetin) Competitive antagonist of fluoroacetate at dose

rate of 0.5 mg/kg/ hour till 2-4 mg/kg wt is reached.

3. Ethanol (50%) and acetic acid (5%) at a dose rate of 8 ml/kg PO .

4. Calcium borogluconate @ 0.25-0.5 mg/kg of 5% solution should be given slow IV

Contraindications

• Emetics are contraindicated, if clinical signs are present.

BROMETHALINIntroduction

• It is a diphenylamine rodenticide.

• Developed in 1980 as an alternative to warfarin against warfarin-resistant rats and mice.

• However, it is less frequently used than anticoagulant rodenticides due to high toxicity.

• Secondary bromethalin poisoning can occur in dogs or cats that eat killed rodents.

Chemistry and Properties :• Bromethalin is N-methyl-2, 4- dinitro-N-(2, 4, 6-tribromophenyl)-6-

(trifluoro methyl) benzeneamine.

• It is a yellow crystalline solid, insoluble in water but soluble is acetone and chloroform.

• Bromethalin is used in baits in concentration of 0.005% or 0.01 % and is usually pelleted or dyed green.

Toxicity:• Cats are more than 3 times as sensitive as dogs.• The acute oral LD5o 1.5 to 5 mg/kg body weight Rats 2.0-4.0 mg/kg, Mice 2-3 mg/kg, Cats 1.8 mg/kg, Dogs 4.7 mg/kg and Pigs 0.25 mg/kg

• In guinea pigs the LD5o is more than 100 mg/kg.

Toxicokinetics:• Peak plasma conc. reaches in 4 hours.

• However, its absorption from skin is poor.

• After absorption, bromethalin circulates through blood to most tissues.

• Metabolised to a active form called as Desmethyl bromethalin .

• Excretion is mainly through the bile. The half-life of bromethalin in rats is 5-6 days.

MOA

Mechanism of action : Uncoupling of oxidative phosphorylation

Decreased ATP synthesis

Na/K ATPase pumps offline

Intracellular swelling

Cellular membrane damage via lipid peroxidation

MOA contd …• Fluid filled vacuoles between myelin sheaths, cell

swelling and degeneration.

• Accumulation of fluid and cerebral oedema may result in increased CSF pressure and increased pressure on nerve axons resulting in decreased nerve impulse conduction, paralysis and death.

• Bromethalin may also induce cerebral lipid

peroxidation.

Clinical signs:• It is a slow acting, progressive neurotoxin.

Two neurological syndromes

At Sublethal dose (< 2.5mg/kg)

• Termors, Depression• Ataxia ,Hind limb

weakness• Vomiting• Lateral recumbency

Note : Effects are reversible

At Lethal dose ( > 5 mg/kg)

•Hyperexitability•Muscle tremors•Hind limb hyprereflexia•Grand Mal seizures•CNS depression•Death

•Note : Signs are Irreversible

Post-mortem findings• The gross lesions seen on PME are cerebral oedema (brain swelling). • Mild pulmonary congestion may be seen in some cases.

• Histological change : Spongy degeneration occurs in the optic nerve and in the white

matter of brain and spinal cord.

Diagnosis :1. Detailed history

2. Clinical signs and external lesions

3. Clinical Diagnosis : EEG may reveal marked depressed voltage

and abnormal high voltage short wave activity.

4. Laboratory diagnostic procedures are sophisticated and tiresome, not performed usually

Treatment and management :• Specific antidote to bromethalin is not available.

• Aim of Rx : Blocking the absorption of toxicant from gut and

reducing the cerebral oedema.

• Repeated oral administration of activated charcoal /sorbitol mixture decreases absorption of bromethalin and is considered useful in early stages of poisoning.

Rx contd…• Use of Mannitol (250 mg/kg, I. V. every 6 hour) as

an osmotic diuretic and corticosteroids have been suggested, but these have shown variable responses. • Fluid balance should be maintained with oral

fluids. • Seizures and hyperexcitability can be controlled

with diazepam or phenobarbitone sodium. • Prognosis: Prognosis is guarded, if signs are

severe or advanced.

STRYCHNINE

Strychnine

Introduction

• Strychnine is an alkaloid extract obtained from the dried ripe seeds of Indian tree Strychnos nux vomica.

• Strychnine was isolated in pure form in 1818 and since then it is used for control of rodents, birds and stray dogs.

Properties:• Strychnine forms colourless and odourless crystals,

very bitter in taste and almost insoluble in water .

• Readily soluble in ethanol and other organic solvents.

• It is relatively stable agent and persists in food or environment when used as bait.

• The baits are usually Red- or green-coloured grains that contain 0.5% to 1 % strychnine sulphate.

Contd…• Due to its bitter taste, strychnine readily produces bait shyness.

• Therapeutic value :

It has been used in lower concentrations as a tonic and stimulant in veterinary and human medicine.

Toxicity:• Strychnine is extremely toxic mainly in birds and small

animals, particularly dogs.

• The female rats are more susceptible due to inefficiency of hepatic metabolism .

• The oral lethal dose of strychnine in various animal species is:

Dogs and cattle 0.5 mg/kg, Horses and pigs 0.5-l.0 mg/kg, Cats 2.0 mg/kg, Rats 3.0 mg/kg and Poultry 5.0 mg/kg.

ToxicokineticsAbsorption, distribution, metabolism and excretion.

• Rapidly absorbed from the GIT and nasal mucosa, but not through the skin.

• In blood, it is widely distributed with significant amounts found in the liver and kidneys.

• Some portion of strychnine reaches CNS, but it does not accumulate in nervous tissues.

• It is readily metabolized in liver by microsomal mixed function oxidases to several non-toxic polar metabolites including strychnine-N-oxide.

Contd …• Both parent compound (5-20%) and metabolites arc excreted rapidly

in the urine.

• The t1/2 of strychnine is approximately 10 hours.

• Acidic urine fastens excretion of strychnine by causing ionization and ion trapping.

Mechanism of action• Strychnine is a strong convulsant.

• strychnINe antagonises the action of INhibitory neurotransmitter glycINe in the central nervous system.

• Glycine normally interacts with glycine receptors at post-synaptic neuronal sites in the spinal cord and medulla and opens CC channels, which hyperpolarizes neurons and thus decreases likelihood of depolarization.

• Inhibition of glycine receptors by strychnine results in loss of inhibitory effects leading to unchecked reflex stimulation and hence uncontrolled excitation of the spinal cord.

• Stimulation of extensor muscles, which predominates, results in extensor rigidity and tonic seizures.

• The major site of strychnine action is the recurrent inhibitory interneuron (Renshaw cells) of the reflex arc in spinal cord and medulla.

Clinical signs• Signs appear after half to 2 hours of ingestion.

• Initial signs : Restlessness Anxiety MUSCULAR TWITCHING NECK STIFFNESS CONVULSIONS Labored and irregular breat

Advanced Clinical Signs :

• Spontaneous and nearly continuous tetanic seizures

• Marked rigidity sometimes known as a ‘Saw Horse stance' (opisthotonos

condition).

• There is no salivation, masticatory activity, paddling or running movement.

• Vomiting is rare and poisoned animals are in full consciousness until near death.

• Death mainly occurs from suffocation due to spasms of the respiratory muscles or paralysis of the respiratory centre.

• Birds affected by strychnine poisoning exhibit ataxia, wing drop, tremors, muscle tenseness, feathers fluffed or held tightly against the body and convulsions.

Post-mortem findings:• Subcutaneous or intramuscular haemorrhages may result from

trauma.

• Animal may have food or bait in stomach and cyanosis results from asphyxia.

• The onset of rigor mortis is rapid.

Diagnosis:1. History2. Clinical Signs and lesions3. Chemical analysis :• Strychnine can be detected in the

carcass for several months after death. • Urine from live and dead animal are the samples of choice for

laboratory analysis of strychnine.

Differential Diagnosis :• Rabies• Tetanus• Canine distemper• Aujesky's disease• Epilepsy• Hypoglycaemia• Phosphide poisoning and• Ethylene glycol poisoning.

Treatment• There is no specific antidote to strychnine.• Therapy includes symptomatic and supportive

care with primary goal to prevent asphyxia. 1. Sedatives: Sedation of the poisoned animal

to prevent seizures .

Eg : Pentobarbitone Dogs & cats: 5 - 15 mg/kg, IV to effect.

Dose may be repeated in 4 - 8 hours.

• Chloral hydrate may be useful in large animals.

• Diazepam is normally the DOC for animals having seizure.

2. Muscles Relaxants :• It decreases the central respiratory depression.• These may include : Glyceryl guaiacolate (110 mg/kg) or Methocarbamol (55-220 mg/kg, IV,

followed by 90 mg/kg, if required).

3. Gastric lavage with potassium permanganate or tannins .

4. Fluid diuretics : 5% Mannitol in 0.9% normal saline should be

initiated to stimulate urine flow and excretion of strychnine.

5. Acidification of urine :

• Ammonium chloride (100 mglkg, PO, twice daily) Useful for ion-trapping and urinary excretion of strychnine.

Contraindications:• Ketamine and morphine are contraindicated WHY ???

Answer : Due to their motor stimulatory effect and respiratory depression effect.

• Emesis is contraindicated due to potential for development of seizures.

ALPHANAPHTHYL THIOUREA (ANTU)

Introduction• It is a less commonly used thiourea rodenticide.

• It was introduced as rodenticide in 1945, but presently has been withdrawn from use in several countries because of the carcinogenicity of a -naphthylamines present as impurities.

• Although dogs, cats and pigs are susceptible, most domestic animals are resistant to ANTU.

Properties :• Pure form is colorless , insoluble in water and no detectable smell.• Do not get deteriorated on long storage.• Baits are prepared as 2% ANTU in cerea;ls, bread, meat .

Toxicity• It is a selective poison for rats with LD5o of

3-5 mg/kg body weight.

• Susceptibility of other species to ANTU is variable with oral LD50:

Dogs 40 mg/kg, Cats 75-100 mg/kg, and Poultry 2500-5000 mg/kg bw.

• In empty stomach dogs, it induces vomiting which many times save the animal

Toxicokinetics:• It is rapidly absorbed from the gut and can cause

illness in dogs in less than 1 hour. • Death can occur within 6-48 hours; however,

survival for 12 hours may indicate possible recovery. • It is rapidly metabolised and quickly eliminated

from the body.

NOTE : Tolerance develops after ingestion of sublethal doses of ANTU.

Mechanism of action:• It has selective action on lung capillaries caused by widening of

pores between endothelial cells and formation of BLEBS on endothelial cell membranes.

• This leads to massive pulmonary oedema and leakage of fluid into air passages.

• Thus, the animal literally drowns in its own fluid .

• Death occurs due to marked hydrothorax and pulmonary oedema.

• The exact mechanism by which ANTU damages lung capillaries endothelial cells and pneumocytes is not clear.

Clinical signs :Vomiting, occurring a few minutes I to a few hours following ingestion.

Irregular breathing (short jerky inspiration) Cough.

Animal becomes inactive Respiratory distress, Laboured breathing

Cyanosis

Clinical signs contd…• Auscultation of chest reveals bubbly respiratory

sounds.

• Animal continues to vomit as the disease progresses and the vomitus may consist entirely of blood.

• In later stages, white foam is discharged from nostrils and oral cavity.

Contd. . .• The pulse is usually accelerated and hydropericardium.

• The affected animal initially remains standing, then sits on its-haunches to relieve thoracic pressure and finally assumes a position of sternal recumbency.

• As asphyxiation proceeds, coma ensues and terminal clonic convulsions may occur.

• Pulmonary oedema and circulatory failure usually kill the animal within 12 hours.

Treatment and management :• There is no specific antidote to ANTU poisoning.

• Supportive and detoxification therapy may be used. 1. Emetic and gastric lavage may be tried to

remove the toxicant in the early stages. 2. Animal may be sedated or anaesthetised

with barbiturates to reduce struggling, dyspnoea and production of foam.

3. The animal may be placed on an inclined surface so that fluid escapes from the bronchi. The chest may be periodically compressed to facilitate drainage.

4. Silicone aerosols might be of some value in preventing fatal foaming in bronchioles.

5. Competitive ANTU antagonist :

Ethylenethiourea

RED SQUILL

Red squill • It is one of the oldest rodenticides with

selective action on rats and mice.• It is obtained from the bulbs of the

Mediterranean Sea onion Urginea (Scilla) maritima, a plant with large bulbs.

Properties:• Red squill contains a mixture of glycosides of which

scilliroside is most toxic.

• Scilliroside is a potent emetic and bitter tasting compound whose concentration is high in the bulbs.

• Red squill is bitter in taste, so rodents quickly learn to avoid the baits.

• The squill is mixed in meat, fish and cereals or other

type of baits mostly at a concentration of 10%.

Toxicity:• Red squill is highly toxic to rats ( absence of vomiting mechanism)

and nontoxic to other warm-blooded animals. • Rats LD50 values Male 490 mg/kg Female 200-250 mg/kg

Pigs, Dogs and Cats 5 - 16 mg/kg Ruminants 250 mg/kg

Mechanism of action:• Scilliroside is a cardioactivc glycoside which in

higher dose produces digitalis-like action and cardiac arrest.

• It also acts on CNS, but the mechanism of neurotoxicity is not clear because it does not cross BBB.

• Scilliroside is metabolized by the gut microflora to its aglycone scillirosidin, which is equally toxic and produces some of the toxic effects of red squill.

Clinical signs:• Vomiting, abdominal pain, diarrhoea, ataxia,

cardiac irregularities, and hypraesthesia followed by paralysis, depression or convulsions.

• Bradycardia and cardiac arrhythmias may end in cardiac arrest.

• The initial signs of poisoning occur within 12 hours

and death usually follows within 3 days.

Post-mortem findings:• Enlargement and congestion of abdominal and thoracic organs.

• Gastritis and enteritis (due to strong irritant action).

• Kidneys, liver, lungs and myocardium show signs of congestion and swelling.

• Histopathological studies may reveal degenerative changes

Treatment and management:• No specific antidote is available for red squill poisoning.

a) Gastric lavage and saline cathartic may be used to remove the toxicant from digestive tract.

b) Atropine sulphate given subcutaneously at 6-8 hours intervals may prevent cardiac arrest.

c) Phenytoin (35 mg/kg, PO, thrice daily) is given to dogs to suppress arrhythmias.

CRIMIDINE

• Crimidine (2-Chloro-4-dimethyl amino-G- methyl pyrimidine) is an old rodenticide having limited use nowadays due to its non-selectivity.

• Oral LD50 of crimidine in various species is: Rats 1.2-1.5 mg/kg, Rabbits 5 mg/kg, Dogs 0.5-1.0 mg/kg and Poultry 5 mg/kg bw.

• In body it acts as an antagonist of vitamin B6 (pyridoxine).

• Clinical signs in animals appear 1 to 3 hours after ingestion and include staggering gait, bellowing, barking or howling, followed by hypersalivation, prostration, open mouth breathing, acute convulsive seizures and hyperthermia.

• Death occurs mainly due to asphyxia.

• Animal may recover quickly when treated with Pyridoxine hydrochloride (20 mg/kg, 1. V. or 25 mg/ kg, S.C.).• Diazepam or barbiturates can be used to control

convulsive seizures.

NORBORAMIDE• It is a selective rodenticide lethal to rats but not to

other rodents (mice) .

• Oral LD50 in rat is about 5–10 mg/kg, whereas in dog and monkey 1000 mg/kg produces no effect.

• Such species difference in toxicity seems to be

accounted for by differences in response of the peripheral blood vessels to norboramide- induced vasoconstriction.

• The exact mechanisms of this effect are not known.

CHLORALOSE• Chloralose (Alpha-chloralose) is a fast acting

narcotic agent used as rodenticide .

• The oral LD5o value of chloralose in different species is :

Rats and mice 300-400 mg/kg, Cats 100 mg/kg, and

Dogs 600-1000 mg/kg.

• It acts by slowing down several metabolic processes in body causing hypothermia and virtually death.

• Important clinical signs of poisoning include incoordination, disorientation, hypnosis, hypothermia and hyperaesthesia.

• Death may occur due to respiratory failure.

• Rx : Administration of analeptics such as

Methylamphetamine «(}5-4 rug/kg, orally or intramuscularly) or ephedrine (2. 5 mg/kg,

PYRIMINIL :• Pyriminil (-3-pyridylmethyl~N'-p nitrophcnylurca; Vacor; PNU) is

a substituted urea rodenticide.• Effective against rodents resistant to warfarin.

Toxicity:• It is highly toxic to rats (oral LD5o 4.5 rug/kg) and

humans (lethal dose 5 mg/kg), and moderately toxic to cats (oral LD5o 62 mg/kg) and dogs (LD5o 500 mg/kg).

• It is sold for indoor use only as prepared bait containing 2% active ingredient and as 10% tracking powder.

Mechanism of action :• The exact mechanism of action of pyriminil is not clear.

• It is suggested that pyriminil selectively inhibits the NADH: ubiquinone reductase (Complex I) activity in mammalian mitochondria.

• It produces peripheral neuropathy, encephalopathy and diabetes mellitus.

• Inhibition of complex I activity also correlates well with the inhibition of insulin release from pancreatic islets, an action responsible for development of hyperglycaemia and diabetes mellitus.

Diagnosis and Rx :• Clinical pathological findings may include

glycosuria, hyperglycaemia and ketosis.

Rx: • There is no specific antidote .• Emetics, gastric lavage, activated charcoal may be

used to remove the recently ingested poison. • Blood glucose should be closely monitored

for development of diabetes mellitus.