Transcript Mechanism of action and toxicity of organochlorines

Toxicity of
Organochlorines
A Decreasing Hazard in
the US
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The USEPA deregistered most
organochlorines in the US
Lindane and endosulfan, the two remaining
organochlorines are both a likely to be
cancelled in the near future
Methoxychlor remains on the market
Organochlorines may be imported illegally
and are still in use internationally
Absorption
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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
Storage and Excretion
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Many organochlorines stored in fat body
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
Storage and Excretion
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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
Toxic Action
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Organochlorines bind to sodium channels in
neurons increasing permeability to sodium
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This increased permeability facilitates
uncoordinated discharge of neurons
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This uncoordinated discharge can lead to CNS
alterations including myoclonus and seizures
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Cyclodienes (dieldrin, heptaclor mirex, aldrin)
may induce seizures for days after over
exposure
Other effects
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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
Symptoms of Organochlorine
Overexposure
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Early symptoms:
– Altered sensorium, parastesias headache,
dizziness, nausea and vomitting, incoordination
tremor
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Severe symptoms:
– Myoclonic jerking, tonic-clonic seizures
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Cyclodienes may cause seizures without
warning and may occur as late as 48 hours
after exposure
Status Epilepticus
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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
Special Populations
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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