DichloroDiphenylTAn Organochlorine

richloroethane

Alan YanahanCPSC 270, 2009

History

First synthesized by Othmar Zeidler in 1874 German graduate student in chemistry Interested in the compound’s structure

and was unaware of its insecticidal properties

His creation was later put on a shelf and forgotten until…

History …its rediscovery in 1939 by Paul Müller

Swiss entomologist working for J.R. Geigy AG in Basel, Switzerland

Wanted a long-lasting pesticide for use against the clothes moth

Awarded Nobel Prizein Medicine in 1948because of DDT’s role in the control of insect vectored diseases

Medical Targets of DDT Anopheles

mosquitoes transmit malaria

Aedes mosquitoes transmit yellow fever

Medical Targets of DDT Oriental rat flea

(Xenopsylla cheopis ) transmits plague

Human body louse (Pediculus humanus) transmits epidemic typhus

DDT during WWII The United States

sprayed DDT in military installations, ports, and transportation centers to control malaria

Soldiers were dusted with DDT to control epidemic typhus

Agricultural Targets of DDT

Colorado Potato Beetle

Codling Moth

Corn Earworm

DDT Today All usage in United

States ceased when Environmental Protection Agency banned DDT use on January 1st, 1973

DDT deemed an environmental hazard

Long residual life Biological

magnification Particularly harmful

to birds

DDT Today Still used in some

developing countries in Africa and Asia to control malaria Sprayed sparingly

on interior and exterior of walls to deter and kill mosquitoes

How Does DDT Work?

Mode of Action DDT is thought to

interact with voltage-gated sodium channels that line the axon of nerve cells

However, the mode of action is not entirely worked out

Mode of Action Under normal

circumstances, axons carry messages from one nerve cell to another via electrical impulses (action potentials)

This occurs as follows…

Na+

Na+ Na+

Na+

Na+

Na+

Na+

Na+

K+K+

K+

K+K+

K+

K+ K+

K+

Na+Na+

Na+

Axon’s interior is negatively charged with respect to the exterior

Exterior of the axon is positively charged with respect to the interior

Na+

Na+Na+

Na+

Na+

+ + + + + + + + + + + ++ + + + + + + + + + + ++ + + + +

____________________

Voltage gated sodium channel opens when the nerve cell receives a stimulus

Sodium ions (Na+) enter the axon

This causes a region of the axon to depolarize

___________

+ + + + + + + + + + ++ + + + +

Voltage gated sodium channel closes

Voltage gated potassium channel opens

Potassium ions (K+) exit the axon

This causes that region of the axon to repolarize

+ + + + + + + + + + ++ + + + +

___________

Voltage gated potassium channel closes

Na+Na+

But during that time, the sodium ions have migrated further down the axon

This causes the neighboring region of the axon to depolarize

+ + + + + + + + + + + ++

_________

Another voltage gated sodium channel opens

More sodium ions enter the axon to further depolarize neighboring regions

Voltage gated sodium channel closes

Voltage gated potassium channel opens

More potassium ions exit the axon

This region of the axon repolarizes

+ + + + + + + + + + + + ++

_ _________

Voltage gated potassium channel closes

Mode of Action When DDT is

present, it causes the voltage-gated sodium channel to remain open longer Spontaneous nerve

impulses are generated

Leads to muscle twitch, convulsion, and death

Occurs as follows…

Na+

Na+ Na+

Na+

Na+

Na+

Na+

Na+

K+K+

K+

K+K+

K+

K+ K+

K+

Na+Na+

Na+

The axon’s interior is negatively charged with respect to the exterior

The exterior of the axon is positively charged with respect to the interior

Na+

Na+Na+

Na+

Na+

+ + + + + + + + + + + ++ + + + + + + + + + + ++ + + + +

____________________

Voltage gated sodium channel opens when the nerve cell receives a stimulus

Sodium ions (Na+) enter the axon

This causes a region of the axon to depolarize

___________

+ + + + + + + + + + ++ + + + +

DDT interacts with the voltage gated sodium channel stabilizing it in the open stateVoltage gated potassium

channel opens

Potassium ions (K+) exit the axon

This causes that region of the axon to repolarize

+ + + + + + + + + + ++ + + + +

___________

Voltage gated potassium channel closes

Na+Na+

But during that time, the sodium ions have migrated further down the axon and more sodium ions have entered the axon

As this region is depolarizing and repolarizing…

+ + + + + + + + + + + ++

_________+ + + + + + + + + + + ++

_________

…this region is depolarizing and repolarizing…

___________

+ + + + + + + + + + ++ + + + +

+ + + + + + + + + + ++ + + + +

___________

…while sodium ions continue leaking into the axon to generate false action potentials

Na+Na+

Sources Kreiger, Robert I. Handbook of Pesticide

Toxicology 2nd Edition: Agents. Smith, Andrew G. Chapter 60—DDT and its Analogs. San Diego: Academic Press, 2001.

Silverthorn, Dee Unglaub. Human Physiology An Integrated Approach 4th Edition. San Francisco: Pearson Education Inc., 2007.

Ware W., George. Pesticides Theory and Application. New York: W.H. Freeman and Company, 1978.