IN VIVO & IN VITRO STUDIES IN RATS HAVE REVEALED TWO ROUTES OF BIOTRANSFORMATION OF CHLORDANE & SHOWN THAT THE METABOLITES INCLUDE: TRANS-CHLORDANE, 1,2-DICHLOROCHLORDENE, OXYCHLORDANE, 1-HYDROXY-2-CHLOROCHLORDENE, 1-HYDROXY-2-CHLORO-2,3-EPOXY CHLORDENE, CHLORDENE CHLOROHYDRIN, & 1,2-TRANS-DIHYDROXY DIHYDROCHLORDENE, AS WELL AS METABOLITES OF HEPTACHLOR. IN VITRO STUDIES SHOWED THAT THE LIVER OF RAT & MAN HAVE ALMOST IDENTICAL CAPACITY TO DEGRADE CHLORDANE EXCEPT THAT HUMAN LIVER HAS LITTLE CAPACITY TO CONVERT TRANS-NONACHLOR TO TRANS-CHLORDANE.
... AFTER 15 DAYS ON DIET CONTAINING PURE TRANS-CHLORDANE, RATS OF BOTH SEXES STORED MORE OXYCHLORDANE THAN WHEN FED CIS-ISOMER. ... STORAGE IN FEMALES WAS HIGHER THAN IN MALES. ... 1-EXO-2-ENDO-DICHLOROCHLORDENE WAS ALSO FORMED & DATA INDICATED THAT THIS WAS AN INTERMEDIATE IN OXYCHLORDANE PATHWAY.
GROWING CULTURES OF ACTINOMYCETE (NOCARDIOPSIS SPECIES), WHICH HAD BEEN ISOLATED FROM THE SOIL, METABOLIZED PURE CIS- OR TRANS-CHLORDANE TO AT LEAST 8 SOLVENT-SOL SUBSTANCES INCL DICHLOROCHLORDANE, OXYCHLORDANE, HEPTACHLOR, HEPTACHLOR ENDO-EPOXIDE, CHLORDANE CHLOROHYDRIN, & 3-HYDROXY-TRANS-CHLORDANE. OXYCHLORDANE WAS METABOLICALLY INERT, & ACCUMULATED IN MYCELIUM AS A TERMINAL RESIDUE.
TROPICAL FRESHWATER CICHILDS, CICHLASOMA SPECIES, WEIGHING 300 G EACH, WERE INDIVIDUALLY PLACED IN 16 L OF WATER WITH 80 UG OF CIS-(14)C-CHLORDANE FOR 72 HR. DICHLOROCHLORDENE, OXYCHLORDANE, CHLORDENE CHLOROHYDRIN, DIHYDROXY HEPTACHLOR, DIHYDROXYL DIHYDROCHLORDENE PLUS 4 UNIDENTIFIED COMPOUNDS ACCOUNTED FOR 12.5% OF RADIOCARBON RECOVERED FROM FISH & WATER. REMAINDER WAS UNCHANGED CIS-CHLORDANE.
Treatment is symptomatic and supportive. Oils should not be used as either cathartics or dermal cleansing agents, as they increase absorption. Gastric lavage and use of activated charcoal and sodium sulfate are indicated for ingestion. If dermal exposure occurred, contaminated clothes should be removed, and the skin should be thoroughly cleansed with soap and water. Management of seizures in both children and adults is with valium or phenobarbital. Respiratory depression and even respiratory arrest, especially with concomitant use of valium and phenobarbital in children, may occur. These drugs preferably should be used only in critical care areas where emergency endotracheal intubation can be performed. /It is recommended/ that epinephrine not be utilized in patients with organochlorine poisoning, as the organochlorines induce myocardial irritability and ventricular arrhythmias may occur. However, dopamine may be necessary in the event of hypotension unresponsive to fluid administration, and epinephrine may be necessary in the event of cardiopulmonary arrest. /Organochlorine insecticides/
In cases of ingestion, emesis is indicated unless the patient is comatose, is convulsing, or has administration of activated charcoal and saline cathartics. Oil-based cathartics such as castor oil or other substances including fats or oils should be avoided since these compounds may tend to enhance the absorption of the chlorinated hydrocarbon from the gastrointestinal tract. Epinephrine is contraindicated since it may induce ventricular fibrillation due to the sensition of the myocardium by the chlorinated hydrocarbons. Convulsions may be treated with diazepam in a dose of 0.1 mg/kg, administered intravenously, to a maximum of 10 mg. Methods to enhance elimination have not been successful other than as a supportive measure for hepatic and renal failure. /Chlorinated hydrocarbon insecticides/
Seizures, hypoxemia, and resultant acidosis are the immediate life-threatening emergencies. Diazepam is the anticonvulsant of choice. Moderately to severely poisoned patients should have intravenous lines and a cardiac monitor. The usual measures of gut decontamination (ipecac/lavage, charcoal, cathartics) are recommended within the first several hours after exposure. Experimental animal studies suggest that chlorinated hydrocarbon pesticide absorption by charcoal is highly variable. Most organochlorine inseticides contain organic solvents, which are severe aspiration hazards. Skin decontamination (removal of contaminated clothes, washing of area with water and green or mild soap) is necessary to prevent continued dermal absorption. Be careful not to cross-contaminate health personnel. The use of cholestyramine(3-8 g four times a day) increased fecal excretion of chlordecone by seven times and reduced the mean blood half-life from 165 to 80 days. In organochlorine exposures to compounds that have substantial enterohepatic recirculation, activated charcoal also may reduce the half-life and should be considered in serial doses for moderate to severe acute poisonings. Dialysis, diuresis, and hemoperfusion are ineffective because of extensive tissue binding and large volumes of distribution. /Organochlorines/
1. WASH CONTAMINATED SKIN WITH SOAP & WATER. 2. FLUSH CONTAMINATED EYES WITH COPIOUS AMOUNTS OF FRESH WATER FOR 15 MINUTES. 3. INGESTIONS OF SMALL AMOUNTS (LESS THAN 10 MG/KG BODY WEIGHT) OCCURRING LESS THAN AN HOUR BEFORE TREATMENT, ARE PROBABLY BEST TREATED BY: A. SYRUP OF IPECAC, FOLLOWED BY 1-2 GLASSES OF WATER. DOSE FOR ADULTS & CHILDREN OVER 12 YEARS: 30 ML. DOSE FOR CHILDREN UNDER 12 YEARS: 15 ML. B. ACTIVATED CHARCOAL: /SRP: 30 G ACTIVATED CHARCOAL IN 3-4 OZ WATER (CHILDREN), 100 G IN 8-10 OZ WATER (ADULT)/ ... AFTER VOMITING STOPS. C. SODIUM OR MAGNESIUM SULFATE, 0.25 G/KG IN TAP WATER, AS A CATHARTIC. /PESTICIDES OF LOW OR MODERATE TOXICITY/
The two isomers of chlordane (including its metabolite oxychlordane) accumulate in body fat of animals. The propensity for storage is low. Ratio of storage level in fat to feeding level is about 0.1 in a 30 day feeding trial of chlordane and roughly approaches unity for a chronic 2 year feeding ... .
The chief route of excretion is biliary, althugh nearly all organochlorines yield measurable urinary metabolites. ... Many of the unmetabolized pesticides are efficiently reabsorbed by the intestine (enterohepatic circulation) substantially retarding fecal excretion. /Solid organochlorine insecticides/
