These agents are usually classified into four groups: DDT (chlorophenothane) and its analogs, benzene hexachlorides, cyclodienes, and toxaphenes (Table 56–2). They are aryl, carbocyclic, or heterocyclic compounds containing chlorine substituents. The individual compounds differ widely in their biotransformation and capacity for storage in tissues; toxicity and storage are not always correlated. They can be absorbed through the skin as well as by inhalation or oral ingestion. There are, however, important quantitative differences between the various derivatives; DDT in solution is poorly absorbed through the skin, whereas dieldrin absorption from the skin is very efficient. Organochlorine pesticides have largely been abandoned because they cause severe environmental damage. They are now known to be endocrine disrupters in animals and humans. DDT continues to have very restricted use for domestic mosquito elimination in malaria-infested areas of Africa. This use is controversial, but it is very effective and is likely to remain in place for the foreseeable future. Organochlorine pesticide residues in humans, animals, and the environment present long-term problems that are not yet fully understood.
1. Human toxicology—The acute toxic properties of all the organochlorine pesticides in humans are qualitatively similar. These agents interfere with inactivation of the sodium channel in excitable membranes and cause rapid repetitive firing in most neurons. Calcium ion transport is inhibited. These events affect repolarization and enhance the excitability of neurons. The major effect is CNS stimulation. With DDT, tremor may be the first manifestation, possibly continuing to convulsions, whereas with the other compounds convulsions often appear as the first sign of intoxication. There is no specific treatment for the acute intoxicated state, and management is symptomatic.
The potential carcinogenic properties of organochlorine pesticides have been extensively studied, and results indicate that 1Toxicity rating: Probable human oral lethal dosage for class 3 = 500−5000 mg/kg, class 4 = 50−500 mg/kg, and class 5 = 5−50 mg/kg. (See Gosselin et al, 1984.) 2ADI, acceptable daily intake (mg/kg/d).
chronic administration to laboratory animals over long periods results in enhanced carcinogenesis. Endocrine pathway disruption is the postulated mechanism. Numerous mechanisms for xenoestrogen (estrogen-like) carcinogenesis have been postulated. To date, however, several large epidemiologic studies in humans have not found a significant association between the risk of cancer and specific compounds or serum levels of organochlorine pesticide metabolites. The results of a case-control study conducted to investigate the relation between dichlorodiphenyldichloroethylene (DDE, the primary metabolite of DDT) and DDT breast adipose tissue levels and breast cancer risk did not confirm a positive association. In contrast, recent work supports an association between prepubertal exposure to DDT and brain cancer. Recent studies also suggest that the risk of testicular cancer and non-Hodgkin’s lymphoma is increased in persons with elevated organochlorine levels. Noncancer end points are also of concern. Recent work associates cryptorchidism and hypospadias in newborns with maternal adipose levels of chlordane metabolites. These residues are also linked to testicular cancer.