1. D ichloro D iphenyl T An Organochlorine richloroethane Alan Yanahan CPSC 270, 2009

2. 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…

3. 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 Prize in Medicine in 1948 because of DDT’s role in the control of insect vectored diseases

4. Medical Targets of DDT Anopheles mosquitoes transmit malaria Aedes mosquitoes transmit yellow fever

5. Medical Targets of DDT Oriental rat flea (Xenopsylla cheopis ) transmits plague Human body louse (Pediculus humanus) transmits epidemic typhus

6. 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

7. Agricultural Targets of DDT Colorado Potato Beetle Codling Moth Corn Earworm

8. DDT Today All usage in United States ceased when Environmental Protection Agency banned DDT use on January 1 st, 1973 DDT deemed an environmental hazard Long residual life Biological magnification Particularly harmful to birds

9. 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

10. How Does DDT Work?

11. 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

12. Mode of Action Under normal circumstances, axons carry messages from one nerve cell to another via electrical impulses (action potentials) This occurs as follows…

13. Na + K+K+ K+K+ K+K+ K+K+ K+K+ K+K+ K+K+ K+K+ K+K+ Axon’s interior is negatively charged with respect to the exterior Exterior of the axon is positively charged with respect to the interior 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 + 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

14. 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…

15. Na + K+K+ K+K+ K+K+ K+K+ K+K+ K+K+ K+K+ K+K+ K+K+ 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 + +++++++++++++++++++++++++++++ ____________________ 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 state 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 + 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 +

16. Sources Kreiger, Robert I. Handbook of Pesticide Toxicology 2 nd Edition: Agents. Smith, Andrew G. Chapter 60—DDT and its Analogs. San Diego: Academic Press, 2001. Silverthorn, Dee Unglaub. Human Physiology An Integrated Approach 4 th Edition. San Francisco: Pearson Education Inc., 2007. Ware W., George. Pesticides Theory and Application. New York: W.H. Freeman and Company, 1978.