1) The document presents several theories on the mode of action of the insecticide DDT, including Mullin's theory that DDT acts as a wedge in nerve cell membranes, keeping sodium channels open and disrupting ion flow. 2) Additional theories discussed are that DDT may cause dehydrochlorination and release of HCl at the site of action, or that it has both a conductophore group to carry a toxophore group to the target site. 3) The document also summarizes classical symptoms of DDT poisoning in insects and references several textbooks on insecticide toxicology.

1. welcome
Prajwal Gowda MA
RAM/2020-50
1st year, Msc Entomology

2. PRESENTATION ON: Different
Theories of DDT Mode
of Action.
COURSE: Toxicology of Insecticides. 3(2+1)
Course No: ENT-508
Presented to:
Dr. S Upendhar.
Associate Professor
Dept. of Entomology.

3. DDT:
• Dichlorodiphenyltrichloroethane (C14H9Cl5), commonly
known as DDT, is a colorless, tasteless organochloride.
Originally developed as an insecticide, it became infamous
for its environmental impacts.
• DDT was first synthesized in 1874 by Othmar Zeidler.
DDT's insecticidal action was discovered by the Paul
Muller in 1939.
• DDT was used in the second half of World War II to limit
the spread of the insect-borne diseases malaria and typhus.
• Muller was awarded the Nobel Prize in Physiology or
Medicine in 1948 "for his discovery of the high efficiency
of DDT as a contact poison against several arthropods".

4. HISTORY
• In 1945, DDT was made available to farmers as an
agricultural insecticide.
• In 1947, the first cases of DDT resistance occurred in Aedes
(Brown).
• First insect showing resistance to DDT in India is Anapheles
mosquito-1952.
• First Agriculture Pest showing resistance to DDT in India
1963- Singhara beetle.
• In 1972, DDT was first banned from agricultural use in the
United States.
• In 1989, DDT was banned in India for agricultural usage.

5. COMPOSITION OF DDT:
• Technical grade DDT contains 5 isomers. The p,p’ isomer, which
accounts for about 70 percent of the total weight, is the toxic form of
DDT and is usually called DDT.

6. IRAC Group 3B: DDT
• Sodium channel modulators are neurotoxins that act on the action
potential of sodium channel. They slow the closing and
inactivation of the channel, causing it to remain open longer than
normal, which has the effect of prolonging the action potential.
• When the action potential is not terminated, it can re-excite the
same area of membrane, leading to repetitive firing. Because
nerve axons occur throughout the insect’s body.
• DDT cause symptoms as soon as they enter the body and are
considered extremely fast-acting, causing immediate
“knockdown”.
• It shows a negative temperature correlation that means the
lower the surrounding temperature the more toxic it becomes to
insects.

7. • It acts on sodium channel to cause leakage of sodium ions. So the
neurons fire impulses spontaneously, causing the muscles to twitch
causing symptom called as “ DDT Jitters ”- followed by
convulsions and death.
Metabolism of DDT:
• DDT in rats and man converted to Dichloro diphenyl acetic acid
(DDA).
• DDT in Drosophila to Dicofol.
• DDT in Cockroaches and fruit fly larvae to Dichloro
benzophenone (DBP).
• DDT in plants to Dichloro diphenyl dichloro ethane (DDD).
• DDT in resistant insects to Dichloro diphenyl dichloro ethylene
(DDE).

8. 1. Mullin’s Theory.
• Mullin proposed that the activity of DDT comes from its
physical shape, which is such that it can fit into the
intermolecular spaces within the cylindrical lipoprotein lattice.
• DDT acts as a wedge in the outer covering of nerve which keeps
the sodium gate open.
• A foreign substance entering the interspace in axonic membrane
can temporarily hinder its permeability to ions and have a
narcotic effect.
• Permanent damage can be done if this substance is firmly
attached to the surrounding lipoprotein molecules.
• So it brings some distortion of interspace causing leakage of ions.
• Holan revised this, and explained the structure-activity
relationships among cyclopropane analogues of DDT by
proposing fitting of DDT molecules in the Na and K channels.

9. Here DDT enters the interspace from trichlorocarbon group, which brings
attractive forces of the halogen atoms into a very favourable position to be
effective. The di carbon group spreads enough to make a triangle so that p-
chlorophenyl group constitutes two stable feet.
In order to make this arrangement, benzene rings should rotate. Thus a
compound like DDE, which posses a double bond, cannot fit into the
interspaces.

10. 2.Dehydrochlorination Theory:
• Proposed by Martin and Wain.
• They said that HCl was released at the site of action by
dehydrochlorination of the CHCCl3 group.
• So the nature of ring substituents affected insecticidal
properties either because of electronic affect or because
of solubility factors.
Drawback is,
• Insecticidal properties of DDT analogues, which do not
contain chlorine, cannot be explained on the basis of this
theory.

11. 3. CONDUCTOPHORE AND TOXOPHORE THEORY.
• Lauger defined that the role of CCl3 group was only that
of a conductophore to bear the toxophore group to the site.
• The combination in one molecule of both these moieties
renders DDT as an effective insecticide.
• Like the previous theory, this also fails to explain the
insecticidal properties of DDT analogues that do not
contain chlorine.
• Examples are prolan, bulan.

12. 4.Blood Toxin Theory:
• Given by Sternburg and Kearns.
• They stated that blood of DDT poisoned insects contains
a toxic factor other than DDT. These produces similar
effects like DDT only.
• Later it has been concluded that variety of stresses,
electrical imbalance produces similar toxic factors in
insects blood.
• This factor is called as autotoxin, which is possibly
released from the nerve as a result of hyperactivity of
nervous tissue.

13. 5. BUTTERFLY CONFIGURATION THEORY.
• Rogers explained the high activity of prolan over other DDT
analogues. They considered the optimal stereochemical
configuration of DDT.
• They considered CCl3 group as bulk which interacts with p-
chlorophenyl groups to impart to the aryl rings the position
of maximum clearance and provide the butterfly
configuration to DDT.

14. • If substituents on the methylene group are small, the phenyl
group rotates freely around their bond to the methylene. But
if a bulky substituent is inserted on the methylene, such a
rotation is inhibited.
DRAWBACK IS,
• The replacement of chlorine atoms with other substituents
of equal or larger size does not always increase the toxicity
of resulting compound.

15. 6. ROTATABILITY OF BENZENE RINGS.
• Reimschneider and Otto on the basis of relationship between
toxicity and structure of various DDT analogues and isosteres
given a theory for the toxic action of DDT.
• Free rotation of the two phenyl groups and of the trichloro
carbon group is the most important factor in deciding the toxicity
of DDT.
• This theory relates toxicity of such chemicals to rotatability of
benzene rings about the alkyl carbon or alpha carbon to
which they are attached.
• When the auxophoric groups are attached in the p,p’ positions
the rotatability of the benzene rings is the greatest, hence p,p’
DDT shows maximum inseciticidal activity.

16. • The movement of these chlorines to ortho or meta positions
creates a steric hinderance, thus interfering with the free
rotation of the rings.
• DRAWBACK IS,
• In case of o,p’- DDT, the rings are also non rotatable, but it
is nearly as potent an insecticide as DDT.

17. 7. VANDER WAAL FORCES.
• Gunther discovered that the toxicity of a series of DDT
analogues was parallel with the sum of the logarithms of
van der waals attractive forces of the substituent group.
• Lines of similar slope were obtained for those DDT
analogues that were insecticidally active.
• The role of bonding energies and similar van der waals
radii of Cl (1.85 A) and CH3 (2 A) and suggested a close fit
into a receptive protein cavity such as an apoenzyme, of
isosteres possessing comparing dimensions.
• They summarized that closely fitting molecules would
provide optimal insecticidal activity.

18. Classical Symptoms of DDT Poisoning.
• Tobias et al., (1946) gave the sequence of symptoms in cockroach.
Hyperextension of legs and uncoordinated movement.
General trembleness and convulsions.
Ataxia and hyperactivity.
Repetitive falling on the back.
Two separate leg movements - a high frequency tremors.
Disappearance of fast tremors, with the only symptom left being
isolated motion of tarsi, palpi, cerci and antenna.
Complete stillness with the heartbeat being the only sign of life.

19. References
• Toxicology of Insecticides by Fumio Matsumura.
• Insecticides: Toxicology and Uses by H.C.L Gupta.
• The Toxicology and Biochemistry of Insecticides by Simon
J. Yu.
• Toxicology of Insecticides by Dileep K. Singh.

20. THANK YOU.