Special Veterinary Pathology

ORGANOCHLORINE INSECTICIDES

• The organochlorines are the first generation insecticides.
• They are also known as chlorinated hydrocarbons.
• These compounds are mainly used as contact insecticides and ectoparasiticides.

Sources of poisoning

• Ingestion of organochlorine contaminated feeds and water by the animals.
• Inhalation or absorption from the skin during topical application as ectoparasiticides.

Absorption and fate of chlorinated hydrocarbons

• Organochlorine insecticides are water insoluble but soluble in oil and organic solvents.
• These are rapidly absorbed from the oily preparations and are capable of penetrating the intact skin when applied in oily solution or emulsion.
• Dieldrin is an exception which may be absorbed even from dry powder form.
• However, all the compounds, in powder form, can easily penetrate the cuticle of insects compared to mammalian skin and intestinal mucosa which explains its greater toxicity to insects than in mammals.
• Biotransformation of DDT in animals and plants involves dehydrochlorination catalysed by DDT dehydrochlorinase which converts DDT into non-polar and persistent metabolite DDE and the resultant conjugates are the major metabolites which are excreted in urine.
• The major metabolic path-way for methoxychlor is o-demethylation and subsequent conjugation and excretion.
• In mammals, methoxychlor is rapidly degraded by liver and the non-toxic metabolite(s) come to the intestines and get excreted through faeces.
• Its low toxicity and tissue accumulation is due to rapid detoxification and slow gastrointestinal absorption.
• Aldrin is metabolized by microsomal enzymes to dieldrin which are more toxic than the parent compound.
• Except methoxychlor, other organochlorine insecticides are stored in the body fat.
• However, none of these agent are known to accumulate in other vital organs.

Mechanism of toxicity

• The chlorinated hydrocarbons are neuro-poisons.
• By virtue of their high lipid solubility, these agents can enter the neural membrane with ease and interfere with normal functioning of the nerve membrane sodium channels.
• DDT acts by
• reducing the potassium transport through pores:
• inactivating sodium channel closure
• inhibiting Na+-K+ and Ca2 – Mg2+ AT Pases and
• inhibiting calmodulin- Ca2+ binding with release of neurotransmitter.
• The cyclodiene compounds act on the chloride ion (CI-) transport by antagonizing the gamma amino butyric acid (GABA) receptors in the CI- channels and also inhibit the Ca2+-Mg2+ ATPase.
• However, the relative importance of these two mechanisms (GABA blockade and indibition of Ca2+-Mg2+ ATPase) in chlorinated cyclodiene neurotoxicity is yet to be understood.
• Lindane, an isomer of HCH binds to the GABA receptors thereby producing an inhibition of GABA- dependent chloride influx into the neuron.
• However, lindane is less potent than the cyclodienes in inhibiting the GABA-dependent Cl^- influx and is less toxic.

Clinical symptoms

• Dichlorodiphenylethanes poisoning cause intial stimulation of CNS followed by depression and death due to respiratory failure.
• In chronic poisoning, liver damage, hypoglycemia, fall in liver glycogen concentration, blood lactacidemia and hyperkalemia may be noted.
• Symptoms of cyclodiene compound poisoning are similar to DDT poisoning but more severe in nature and are characterized by grinding of teeth, difficult respiration, snapping of the eyelids and frequent urination.
• Other signs include walking backwards, wall climbing, aimless jumping and violent frenzied behaviour.

Salient clinical features observed in chlorinated hydrocarbon poisoning may be categorized as:

1. Behavioural changes

• Initial anxiety
• Aggressiveness
• Abnormal posturing
• Jumping over unseen objects
• Wall climbing
• Madness syndrome.

2. Neurological symptoms

• Hypersensitivity to external stimuli
• Fasciculation and twitching of the facial and eyelid muscles
• Spasm and twitching of the of the fore- and hind quarter muscles
• Champing of the jaw
• Hyperthermia.

If death does not takes places at this stage, the anim als may go into coma state.

3. Cholinergic manifestations

• Vomiting
• Marked salvation
• Mydriasis
• Diarrhoea and
• Micturations may also be observed

Post-mortem lesions

• There are no specific lesions in the nervous system.
• However, acute aldrin poisoning may cause hepatitis and acute tubular nephrosis.
• Chronic DDT and methoxychlor toxicoses may produce focal centrilobular necrosis of the liver.

Diagnosis

Diagnosis of organochlorine insecticides poisoning may be made based on:

• History of exposure to the insecticide.
• Clinical symptoms and post- mortem lesions.
• Analysis of feeds and\or biological samples like liver and kidneys in dead animals and blood and milk samples in living animals for the presence of organochlorine compounds.