PRINCIPLES OF TOXICOLOGY

352 PROPERTIES AND EFFECTS OF PESTICIDES
15.2 ORGANOCHLORINE INSECTICIDES
Introduction, Use, and History of Organophosphates and Carbamates
While organochlorine insecticides had widespread use in the 1940s through the mid-1960s in
agricultural and malarial control programs, their use has become almost completely discontinued
because of their environment effects. Examples of organochlorine insecticides that were commonly
used in the past include toxaphene (Toxakil), endrin (Hexadrin), aldrin (Aldrite), endosulfan (Thiodan),
BHC (hexachlorocyclohexane), dienoclor (Pentac), heptachlor (Heptagran), dicofol, mirex (Declorane),
chlordane, and DDT. One organochlorine compound that is still in use today is lindane, which
is used in the medicinal product Kwell for human ectoparasite disease (as well as in products for use
in the home and garden and on animals, e.g., Acitox, Gammex). In additional to their use as insecticides
in agricultural and forestry settings, organochlorine compounds were also widely used as structural
protection against termites in the past. Some of these compounds are still commonly used in some
developing countries.
Physical and Chemical Properties
The physical and chemical properties of the organochlorine compounds—their lipophilicity, low vapor
pressures, and slow rate of degradation—not only made them effective pesticides, but these same
qualities also resulted in their persistence in the environment and their bioaccumulation in the food
chain leading to the eventual discontinuance of their use.
Mechanisms of Action
Organochlorine compound chemicals act on the nervous system to produce adverse effects. This class
of chemicals is thought to act by the interference with cation exchange across the nerve cell membranes
resulting in hyperactivity of the nerves.
Benzene hexachloride compounds (BHCs) (lindane and related compounds) are examples of
isomers that produce different effects on the nervous system. The γ isomer, also referred to as lindane,
causes severe convulsions with rapid onset, while other isomers of BHC, generally cause central
nervous system depression. The relative contribution of each of the isomers may explain toxicological
differences between formulations of these products. The effect of the cyclodiene organochlorine
compounds (e.g., dieldrin) is on the central nervous system.
Pharmacokinetics
Organochlorine compounds are lipophilic and can be absorbed not only through the intestines but also
across the lung and skin. Some of these compounds (e.g., lindane, endrin, and chlordane) are more
readily absorbed dermally than other compounds in this class, such as DDT or toxaphene.
This class of insecticides (e.g., DDT) can also be stored in fatty tissues in the body. Organochlorine
compounds can be detected in adipose tissue, serum, and in milk. Some compounds (e.g., DDT) are
mainly stored unchanged in adipose tissue (some DDE is stored in adipose tissue), while others (e.g.,
endrin) are stored in a metabolized form, aldrin metabolized to endrin (this transformation also occurs
in the environment) or heptachlor metabolized to heptachlor epoxide. Organochlorine insecticides are
eliminated primarily via the feces.
Acute and Chronic Health Effects of Organochlorine Insecticides
The principal adverse effect associated with over-exposure to organochlorine insecticides is nervous
system hyperactivity (e.g., headache, dizziness, paresthesias, tremor, incoordination, or convulsions).
Early symptoms seen in chlorinated insecticide intoxications, such as with DDT, include hyperesthe-