Toxicity of Organochlorines

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Toxicity of Organochlorines
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A Decreasing Hazard in the US

• The USEPA deregistered most organochlorines in
  the US
• Lindane and endosulfan, two remaining
  organochlorines both are likely to be cancelled
  in the near future
• Methoxychlor remains on the market
• Organochlorines may be imported illegally and are
  still in use internationally

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Absorption

• Lindane and Endosulfan are generally well
  absorbed across the skin
• Damaged skin facilitates absorption
• DDT, Mirex, dicofol, marlate and toxophene are
  less well absorbed across the skin
• GI absorption enhanced by fat or solvents
• Aerosols may be deposited in airways, coughed and
  swallowed

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Storage and Excretion

• Many organochlorines stored in fat
• Most can be measured in the lipid fraction of
  blood either as the based chemical or a
  metabolite
• Most are dechlorinated, congugated and excreted
  to some degree
• Biliary is the chief route of excretion and
  chemical may be reabsorbed (enterohepatic
  circulation), slowing excretion

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Storage and Excretion

• DDT and its isomers, hexachlorocyclohexane,
  dieldrin, heptachlor epoxide and mirex tend to
  store in body fat
• Lindane, endosulfan, methoxychlor, dienochlor,
  endrine, chlorobenzilate dicofol perthane and
  toxaphene are metabolized more quickly

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Toxic Action

• Organochlorines bind to sodium channels in
  neurons increasing permeability to sodium
• This increased permeability facilitates
  uncoordinated discharge of neurons
• This uncoordinated discharge can lead to CNS
  alterations including myoclonus and seizures
• Cyclodienes (dieldrin, heptaclor mirex, aldrin)
  may induce seizures for days after over exposure

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Other Effects

• High organochlorine levels may cause myocardial
  instability and arrythmias
• Organochlorines may induce microsomal activity
  and increase drug metabolism
• Hexachlorobenzene has been responsible for
  porphyria cutanea tarda
• Organochlorines may interact with endocrine
  receptors which may affect reproductive processes

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Organochlorine Overexposure Symptoms

• Early symptoms
• Altered sensorium, parastesias headache,
  dizziness, nausea and vomitting, incoordination
  tremor
• Severe symptoms
• Myoclonic jerking, tonic-clonic seizures
• Cyclodienes may cause seizures without warning
  and may occur as late as 48 hours after exposure

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Status Epilepticus

• Severe organochlorine poisoning may lead to
  status epilepticus
• Cardiac monitoring should be initiated given the
  myocardial irritability caused by organochlorines
• Phenobarbital can be used to control seizures

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Special Populations

• Children are particularly vulnerable due to their
  surface area to body weight ratio
• Lindane, long used for scabies is absorbed
  rapidly and levels peak about 6 hours after
  application
• Levels of 24-28 ng/mL were seen after scabies
  treatment with lindane
• One child with abraded skin who suffered seizures
  showed a level of 54 ng/mL on day three after
  treatment