Background
Toxaphene and related organochlorine compounds (eg, endrin, dieldrin, aldrin, endosulfan, chlordane, heptachlor, dichlorodiphenyltrichloroethane [DDT], lindane, chlordecone) have been manufactured since the 1940s for use as pesticides. They are prepared commercially as dusts, sprays, and wettable powders and are used alone or in combination with other pesticides (eg, organophosphorous compounds) for use on cotton and food crops. Their use between the 1940s and 1970s revolutionized modern agriculture, allowing a massive increase in crop output. DDT was also used in public health measures for control of typhus and eradication of malaria in the United States. They are not safe for household application. Organochlorines persist in the environment long after their initial use.
Toxaphene (ie, chlorinated camphene, camphechlor) is a complex mixture of chlorinated derivatives of camphene (ie, polychlorinated 10-carbon cyclic compounds), which are obtained by isomerization of alpha-pinene, a byproduct of turpentine distillation. A major toxic component identified is heptachlorobornane. Toxaphene is identified as CAS#8001-35-2 and by its United Nations Department of Transportation number, UN#2761.
Toxaphene is a tasteless, pleasant-smelling mixture that is fat soluble, possessing low molecular weight and low volatility. It is amber to yellow in color and waxy in consistency; it has an odor similar to turpentine. Toxaphene is not very biodegradable (ie, slow biotransformation and degradation); it persists in the environment and accumulates in biological systems (eg, food chain of fish, poultry, cattle).
Pathophysiology
Toxaphene is absorbed through intact skin, by inhalation, and by ingestion. Because toxaphene is slowly biodegradable and highly lipid-soluble, it accumulates with repetitive exposures and duration of toxicity may be prolonged. Toxaphene acts as a neurotoxin by interfering with transmission of nerve impulses, especially in the brain, resulting in CNS stimulation.
Toxaphene lowers the normal neural excitation threshold with stimulation of sensory and motor nerve fibers and the motor cortex. Toxaphene alters movement of sodium (Na+) and potassium (K+) across neuronal membranes and adversely effects membrane-related enzymatic reactions. This may antagonize GABA-mediated inhibition in the CNS.
Toxaphene can also induce hepatic enzyme induction (cytochrome P-450 mixed function oxidases), increasing metabolism of therapeutic drugs and reducing their efficacy.
Epidemiology
Frequency
United States
Acute poisoning and fatality caused by organochlorine exposure is rare. DDT was banned by the US Environmental Protection Agency (EPA) in 1972. The EPA and manufacturers of organochlorine pesticides agreed to halt sales of organochlorine pesticides in 1987 after a partial ban in 1976. All use of toxaphene was banned in 1990. Despite a ban on sales, organochlorines may still be found in storage in the United States; thus, exposure is still possible. Toxaphene can be transported in the air at long distances and can persist in air, soil, and water for years.
The 1998 annual report of the American Association of Poison Control Centers' Toxic Exposure Surveillance System documented 2782 exposures to chlorinated hydrocarbon pesticides, with 1144 occurring in children younger than 6 years.[1] Although 22 major adverse outcomes were reported, no deaths were noted.
International
Widespread use of organochlorine insecticides has been banned in North America and Europe. In contrast, these chemicals are used extensively in many developing nations.
Mortality/Morbidity
Toxic doses widely vary. The fatal dose in humans is unknown; data from nonfatal cases suggest that a dose of approximately 10 mg/kg can cause convulsions. An oral median lethal dose (LD50) is higher than 50 mg/kg in animal studies.
The estimated approximate minimum lethal dose for humans is 2-7 g.
Race
No scientific data indicate that outcomes of exposure to organochlorine pesticides depend on race.
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