Toxicity of Organochlorines

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

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

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

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

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

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

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

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

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