Organochlorines

organochlorines toxicity and classification,use,mechanisam of action,clinical manifestations,diagnosis,Treatment

1. Organochlorines Mr.P.Srinu Asst.proff.Pharmacology Dept Vignan institute of pharmaceutical technology Duvvada, Visakhapatnam

2. Organochlorine  pesticides are chlorinated hydrocarbons used extensively from the 1940s through the 1960s in agriculture and mosquito control. 1. DDT and analogues—for example, DDT (dichlorodiphenyltrichloroethane), and methoxychlor. 2. Benzene hexachloride group—for example, benzene hexachloride (BHC), and gamma- hexachlorocyclohexane (lindane). 3. Cyclodienes and related compounds—for example, aldrin, dieldrin , endosulfan (thiodan), endrin, isobenzan, chlordane, chlordecone (kepone), heptachlor, mirex (dechlorane). 4. Toxaphene and related compounds—for example, toxaphene. Organochlorines

3. These compounds are available as dusting powders, wettable powders, emulsions, granules and solutions. Uses : ■ Insecticide. ■ Gamma benzene hexachloride is used as a scabicide (treatment of scabies), and a pediculocide (eradication of head lice). It is available as topical ointment, cream, or lotion. Some Indian brand names include Bexarid (Shalaks), Gab (Gufic), Gamaric (Euphonic), Scaboma (Glenmark), and Ultrascab (Perch). Physical Appearance & Uses

4. ■ DDT, lindane: 15 to 30 grams. ■ Aldrin, dieldrin , endrin : 2 to 6 grams. Toxicity Rating: Dieldrin is placed in the “extremely toxic” category (LD50: 1 to 50 mg/kg), while DDT, endosulfan, and lindane are considered “highly toxic”(LD50: 51 to 500 mg/kg) In addition, the following are extremely toxic: endrin, aldrin, chlordane, and toxaphene, while these are highly toxic: kepone, heptachlor, mirex. Usual Fatal Dose

5. organ chlorines are commonly dissolved in petroleum distillates which form emulsions when added to water. All the organochlorines can be absorbed transdermally, orally, and by inhalation. Gastrointestinal absorption of these agents is generally efficient, particularly in the presence of absorbable lipid (animal or vegetable) fat. DDT is the least well absorbed transdermally, while dieldrin is very well absorbed Toxicokinetics

6. DDT and analogues affect the sodium channel and sodium conductance across the neuronal membrane Mode of Action

7. 1. Acute Poisoning: a. GIT: nausea, vomiting, abdominal pain, hyperaesthesia or paraesthesia of the mouth and face. b. CNS: headache, vertigo, myoclonus, tremor, ataxia, nervousness, amnesia, rapid and dysrhythmic eye movements, mydriasis, weakness, agitation, confusion, and convulsions . c. Other systems: fever, aspiration pneumonitis, renal failure. Coronary spasm, hypotension, and sinus tachycardia may occur following exposure. Dieldrin, endrin, chlordane, toxaphene, DDT are direct respiratory depressants . DDT pass through the placenta. They can also be found in breast milk. Clinical Features

8. 2. Chronic Poisoning : Long-term exposure to some of these compounds (chlordecone, chlordane, heptachlor) results in cumulative toxicity with manifestations such as weight loss, tremor, weakness, opsoclonus, ataxia, pseudotumour cerebri, abnormal mental changes, oligospermia, and increased tendency to leukaemias, thrombocytopenic purpura, aplastic anaemia, hepatomegaly, centrilobular hepatic necrosis and liver cancer.

9. Abdominal radiograph Organochlorines can be detected in serum, adipose tissue, and urine by gas chromatography . Blood chlorinated hydrocarbon levels Measurement of organic halogen compounds in urine Diagnosis

10. 1. Decontamination Do NOT give oils by mouth. They tend to increase intestinal absorption of these lipophilic toxicants. Seizures should be controlled with benzodiazepines, phenytoin, or phenobarbitone in the usual way. Monitor for respiratory depression, hypotension, arrhythmias, and the need for end tracheal intubation. Evaluate for hypoxia, electrolyte disturbances, and hypoglycaemia (if present, treat with intravenous dextrose: 50 ml IV (adult), or 2 ml/kg (child) of 25% dextrose ). Cholestyramine, a non-absorbable bile acid binding anion exchange resin is effective in enhancing the faecal excretion of organochlorine compounds, particularly chlordecone. It is administered at a dose of 16 gm/day for several days Treatment

11. Hyperthermia should be managed aggressively with cooling . . Supportive measures—special attention must be paid to the airway and breathing, and adequate circulation should be maintained . The following are contraindicated—oil-based cathartics, adrenaline, and atropine. Do NOT administer adrenergic amines, which further increase myocardial irritability and produce refractory ventricular arrhythmias . . Haemodialysis and haemoperfusion have not been proven effective.