Physical and chemical properties of DDT

and organocarbamate insecticides. The oral LD50 in male rats for a number of

organochlorines ranges from 18 mg/kg for endrin to 5,000 to 7,000 mg/kg for

methoxychlor, while the dermal LD50 ranges from 18 mg/kg for endrin to

2,510 mg/kg for DDT (Klaassen, Amdur, and Doull 1986). Acute hazard

potential may be ranked approximately from highest to lowest as endrin, aldrin,

dieldrin, chlordane, toxaphene, kepone, heptachlor, DDT, and methoxychlor

Hazardous Substances Database (HSDB 1997).

Organochlorine insecticides are classified as neurotoxins; however, their

mechanism of action is not the same as that of the organophosphates and

organocarbamates. DDT is believed to act on the sensory and motor nerve fibers

and the motor cortex, inducing repetitive firing in the presynaptic nerve

membrane (Klaassen, Amdur, and Doull 1986). Signs and symptoms of acute

DDT poisoning include paresthesia of the tongue, lips, and face, apprehension,

hypersusceptibility to stimuli, irritability, dizziness, disturbed equilibrium,

tremor, and tonic and clonic convulsions. Although the central nervous system

(CNS) is the primary site of toxic action, primary pathologic changes resulting

from subacute or chronic feeding are observed in the liver. Large doses of DDT

in animal studies result in centrolobular necrosis of the liver, while smaller doses

result in liver enlargement. Histologic changes in the livers of male rats fed diets

containing 5 to 15 mg/kg or more for 6 months include hypertrophy, inclusion

bodies, and cytoplasmic granulation (Klaassen, Amdur, and Doull 1986). DDT

and related compounds induce mixed-function oxidase enzymes of the liver in

several species, including humans and increases the incidence of liver tumors in

rodent diet studies (Klaassen, Amdur, and Doull 1986).

Methoxychlor and lindane have low CNS toxicity. However, there have been

a number of fatalities resulting from acute poisoning by the cyclodiene

insecticides, considered CNS stimulants. The precise site and mechanism of

toxic action for these compounds are unknown. Acute, subacute, and chronic

toxicity studies of aldrin and dieldrin in experimental animals have shown the

critical effects to be increased liver/body weight ratios and histologic changes in

the liver, occurring at 0.5 mg/kg of dieldrin and 2 to 2.5 mg/kg of aldrin in rats

(Klaassen, Amdur, and Doull 1986). Like DDT, all of the chlorinated cyclodiene

insecticides are capable of inducing hepatic microsomal drug-biotransformation

enzymes. Lindane and alpha-BHC are convulsants, while beta and delta-BHC are

CNS depressants. The mechanism of neurotoxic action of these compounds has

not been demonstrated.

There is a growing body of evidence which suggests that environmental

chemicals, including many of the organochlorine insecticides, can disrupt the

endocrine system by exhibiting estrogenic function, causing a cascade of

biological effects. Endocrine disrupters interfere with the role of natural

hormones in the body. Organochlorine insecticides considered to be estrogenic

include DDT, DDE, kepone, heptachlor, chlordane, dieldrin, lindane, and

toxaphene. Observed effects in animal studies have included disruption of

female and male reproductive functions, including disruption of normal sexual

differentiation, ovarian function, sperm production, and pregnancy as well as

effects on the thyroid gland (USEPA 1997). Rats given DDT exhibited

estrogenic effects. A contaminant of DDT (o,p'-DDT) was shown to compete

D58

Appendix D Toxicological Profiles