Toxicology of agro-chemicals

Organochlorides:

 Three main categories of OCs based on chemical structure:

 Diphenyl aliphatic compounds: DDT, Methoxychlor, Perthane, & Dicofol

 Aryl hydrocarbons: Lindane (BHC), Mirex, Kepone, & Paradichlorobenzene

  Cyclodiene: Aldrin, Dieldrin, Endrin, Chlordane, Heptachlor, and Toxaphene

Sources  of poisoning:

• Environmental residues are a source of chlorinated hydrocarbon poisoning. Contaminated soils or leakage from old dump sites occasionally leads to residues.
• The organochlorine insecticides that are present already in the environment are slowly degraded and low levels of residues may persist in select areas. The highly lipid soluble nature of these agents, combined with their environmental persistence, favour bioaccumulation upward in food chains from environment to animal or human hosts.

      Stress- Increased epinephrine- Increased lipolysis- Increased release of stored CHC

• Accidental exposure to these products may lead to toxicity.  Improper dilution of organochlorines in sprays and dips may cause toxicity.
• Lindane toxicosis is common in cats and dogs. It was never approved for cats, it is used for dogs (fleas, ticks, sarcoptic mange) and also for human beings (for scabies).
• Small animals- Cats especially susceptible.

Toxcokinetics:

• Well absorbed through most exposure routes.
• Blood concentrations initially increase following absorption, but then they decline rapidly as distribution takes place to liver, kidney, brain, and lipid – rich tissues such as adipose where OCs are stored.
• Body fat may serve as a source of OC poisoning if weight loss occurs and stored OCs are released into the general circulation. Because of their lipophilicityOCs will be secreted into milk and eliminated from the body via this route.
•  Some OCs are excreted through the bile and reabsorbed (enterohepatic recirculation), contributing to persistence in the body.

Mechanism of toxicity:

• Two main mechanisms:

✓ In general, the diphenyl aliphatics interfere with sodium channel kinetics, resulting in partial depolarization.

 ✓ The aryl hydrocarbons and cyclodienes act to inhibit the binding of GABA (an inhibitory neurotransmitter) to GABA receptors. 

• For both mechanisms, clinical signs reflect nervous stimulation.
• DDT metabolites also cause selective necrosis of the adrenal gland zona fasciculata and zona reticularis.
• The OCs have demonstrated potent estrogenic and enzyme – inducing properties, which interfere with fertility and reproduction in wildlife and laboratory animals.

Clinical symptoms :

• Initial stimulation of CNS followed by depression and death due to respiratory failure.
•  Behavioural changes like anxiety, aggressiveness, abnormal posturing, jumping over unseen objects, wall climbing and madness syndrome, neurological symptoms like 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, pivoting on one foot, fall over backwards and hyperthermia and chloinergic symptoms like vomiting, marked salivation, mydriasis, diarrhoea and micturition are noticed. o In birds there will be sudden death after depression, disorientation, abnormal posture and apparent blindness.
•  Lesions o Large doses may sometimes cause centrolobular necrosis of liver and smaller doses cause liver enlargement.

Diagnosis:

• History
• Clinical Signs
• Lab: Levels in blood, serum or urine from live animals
• Postmortem: Absence of specific lesions
• Ppm of CHC in liver and brain tissue .

Treatment:

• No specific antidote
• Symptomatic treatment:

Dermal: wash in soap & cold water

 Oral: Lavage & purgative, heavy mineral oil, activated charcoal

• Barbiturates, chloralhydrate or Valium, if excitatory CS
• Remove stress from environment
• IV fluids or gastric tube

 Prognosis

• Guarded to good with early diagnosis and treatment
• Weeks to recover

DDX :

• Any agent or disease process causing neurological stimulation:

 Infectious encephalitis

 Lead poisoning

 Rabies

Eclampsia

Canine distemper

Strychnine

Metaldehyde