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important human diseases such as malaria. It is thus monitored in the FDA
food surveillance programs.
The chlorinated hydrocarbons can be classified into four distinct chemical
classes:
1. Dichlorodiphenylethanes: DDT, which includes DDD, DDE, and
TDE; dicofol; chlorobenzilate; methoxychlor; and chloropropylate
2. Hexachlorocyclohexane: lindane; benzene hexachloride
3. Cyclodienes: aldrin; chlordane; dieldrin; endosulfan; endrin; hep-
tachlor; photochlordane; toxaphene
4. Miscellaneous chemicals: mirex and chlordecone (kepone)
Hexachlorobenzene (HCB) and pentachlorophenol (PCP) have similar tox-
icological properties to the chlorinated hydrocarbons and often are discussed
in the same breath.
TOXICOLOGY PRIMER 169
As with any pesticide, there are acute and chronic manifestations of poi-
soning. A major manifestation of chlorinated hydrocarbon toxicity, which
may have ecological implications, are the estrogenic and enzyme-inducing
properties, which are especially pronounced with the dichlorodiphenyleth-
anes. This interaction with steroid hormone metabolism at very high doses,
such as that seen only after point contamination or environmental spills, may
adversely affect reproduction. This is not believed to be a concern at residual or
trace levels encountered in the diet. Although DDT and other members of this
class have been weakly implicated to be carcinogenic in mice, they are not in
the rat, dog, monkey, or hamster. Similarly, they are not listed as official
human carcinogens. Therefore, even with the prototypical evil DDT, there is
no hard evidence of serious human disease.
There are few recorded fatalities associated with the use of DDT-like pesti-
cides, an attribute not shared with the other classes of chlorinated hydrocar-
bons, such as the cyclodienes. Most symptoms of acute dichlorodiphe-
nylethane poisoning are related to oral ingestion (they are not well absorbed
through the skin), and are manifested by signs related to the nervous system.
An oral dose of 10 mg/kg may produce effects. For a normal 70 kg person,
this is 700 mg or .7 of one gram! These signs include paresthesia (which is a
prickling or tingling sensation), ataxia, dizziness, nausea, vomiting, fatigue,
and peripheral tremors. In contrast, chronic signs are more diffuse and
include weight loss, anorexia, anemia, tremors, muscle weakness, nervous
tension, anxiety, and hyperexcitability. These changes are associated with
damage to the sensory arm of the peripheral nervous system. Pathology at
these doses may also be seen in the liver and reproductive organs.
The cyclodienes are significantly more toxic after high-dose acute exposure
and do direct damage to the central nervous system. Convulsions and seizures
may be the first signs of acute toxicity. This is also associated with gastroin-
testinal symptoms, dizziness, headaches, general motor hyperexcitability,
and hyperreflexia. Chronic signs are an extension of these and, in addition to
muscle twitching, myoclonic jerking (muscle spasms), hyperexcitability, and
headaches, there are psychological disorders and ultimately loss of con-
sciousness and epileptic-like convulsions. In contrast to the DDT-like com-
pounds, the cyclodienes are readily absorbed through the skin and thus are
an occupational hazard to workers. This is the focus of toxicologic concern.
Aldrin and dieldrin are also known reproductive toxicants at high doses.
Mirex is a nervous system stimulant and also produces skin and ocular
manifestations.
It must be recalled that lindane is a member of this class of compounds. It
is used extensively in humans, including children, as an over-the-counter
treatment for head lice. In veterinary medicine, it is widely used in sheep.
When used at approved doses, this is an extremely safe product and has not
170 APPENDIX A
been associated with any serious problems. The prolonged biological half-life
associated with chlorinated hydrocarbons is shared by lindane, and thus
results in long withdrawal times before sheep can be marketed for food.
Hexachlorobenzene and pentachlorophenol are chlorinated hydrocarbon
fungicides that have been widely used in agriculture. HCB was associated with
a classic case of mass poisoning in Turkey in the 1950s. Effects included pho-
tosensitization (sunlight-induced skin damage), hyperpigmentation (skin dis-
coloring), alopecia (hair loss) and skin blistering. This compound is also a car-
cinogen as well as an immunosuppressant and alters porphyrin (a breakdown
product of blood cells) metabolism. It is no longer produced in the United
States. Pentachlorophenol, another chemical studied in my laboratory, is a
widely used fungicide and wood preservative which is easily absorbed across
skin. At very high doses, PCP has been shown to uncouple oxidative phos-
phorylation, resulting in hyperthermia, profuse sweating, dehydration, dysp-
nea, and ultimately coma and death. It has not been shown to be carcinogenic.
One problem with PCP is that commercial exposures are often associated with
chlorinated dibenzodioxins and dibenzofurans, as manufacturing contami-
nants, which produces signs of hepatic toxicity. Purified PCP alone is not
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