DDT and its Derivatives

1. Dwight Causey DDT and its Derivatives

2. DDT DDE DDD

3. Chemical Properties

4. History • First synthesized in 1874 • Insecticidal properties discovered in 1939 by Paul Hermann Müller • Won Noble Prize in Physiology and Medicine in 1948 • Used to control insect-borne diseases (i.e. malaria and typhus) • Peak of usage in 1962 • Registered for use on 334 agricultural commodities • 85,000 tons produced • Cumulative estimated world usage is 2 million tons

5. History • Used in homes for mothproofing and lice control • Still used today in developing countries to control malaria and lice • Silent Spring by Rachel Carson in 1962, questioned the widespread use of DDT

7. Mode of Entry into Water • Indirectly • Agricultural runoff • Binds strongly to soil and organic matter • Volatized into the atmosphere • Redistributed through particulate matter • Directly • Water pollution plants (sewer pipes to the ocean) • 1,000,000 kg (~227 tons) from Montrose Chemical Company to Palos Verdes shelf

8. Reactivity • Slightly soluble in water • Very lipophillic • Physical Half-life: 2-15 years • Increases with time • Sequestered in micropores • Biological Half-life: 8 years • Biodegraded into DDE and DDD under aerobic and anaerobic conditions, respectively

10. DDT Derivatives • DDE is the major metabolite • Both resist to biodegradation in aerobic and anaerobic conditions • Very long half-lives in water • Hydrolysis is a minor process in degradation • Photolysis of DDE is a major process • Half-life: 15-26 hours

11. DDD Toxicity • 96 hour LC50: • Glass shrimp: 2.4 µg/L • Rainbow trout: 70 µg/L • Largemouth bass: 42 µg/L • Walleye: 14 µg/L • 48 hour LC50: • Daphnid: 4.5 µg/L

12. DDE Toxicity • 96 hour LC50: • Rainbow trout: 32 µg/L • Atlantic Salmon: 96 µg/L • Bluegill: 240 µg/L • Egg shell thinning • Mallard: 3 µg/g • Brown pelican: 3 µg/g

13. Toxic Effects • Weak estrogenic activities • In the brain: • Inhibition of ATP-based reactions • Hepatic enzyme induction • Disruption of hormonal mechanisms • Inhibition of Na+/K+ ATPases in the gills • Thinning of egg shells in raptors • Reduction in cortisol production

14. Mode of Entry into Organisms • Majority enters through food • Some enters through absorption from water through body surfaces (i.e. gills), not believed to be significant when compared to amount entering through food • Very Lipophillic, bioaccumulates • Some organisms retain 90%+ of ΣDDT in their food source

15. Molecular Mode of Interaction • Egg shell thinning in Raptors, 2 possibilities: • DDE inhibits prostaglandin synthesis in the shell gland mucosa, limiting calcium and bicarbonate transport across the mucosa • Embryonic exposure alters shell gland carbonic anhydrase expression, causing eggshell thinning • In fish, no known molecular mechanism is known • Believed to involve ATPases in the central nervous system and gills • In Insects, causes the irreversible opening of voltage gated Na+ channels along the axon

16. Biochemical Metabolism and Breakdown • DDT metabolized into DDE and DDD by microorganisms • Mixed-function oxidases may induce the dechlorination of DDT to DDE in fishes • In some mammals, DDE is converted to 2-methylsulfonyl-DDE and 3-methylsulfonyl-DDE • Acted on by phase I CYP2B enzymes • Followed by conjugation with glutathione during phase II • Then through the mercapturic acid pathway, 2-SH-DDE and 3-SH-DDE are formed

17. Detoxification • Up-regulation of CYP6G1 gene in Drosophila melanogaster • Secretion through urine, feces, semen, and breast milk • Clams shown to dechlorinate DDE to DDMU under methanogenic or sulfidogenic conditions • Dried and ground seaweed has been shown to increase DDT biodegradation by 80% after 6 weeks, further degradation of DDD also seen

18. Bibliography • Cal/Ecotox Toxicity Data for Brown Pelican (Pelecanusoccidentalis) . Office of Environmental Health Hazard Assessment. 1999. http://www.oehha.ca.gov/cal_ecotox/report/pelectox.pdf • The Comparative Toxicogenomics Database. Mount Desert Island Biological Laboratory. 2008. http://ctd.mdibl.org/ • Denholm I, Devine GJ, Williamson MS (2002). Evolutionary genetics. Insecticide resistance on the move. Science 297 (5590): 2222–3. • Evans, D. H. (1987). The Fish Gill: Site of Action and Model for Toxic Effects of Environmental Pollutants. Environmental Health Perspectives 71, 47-58. • Hazardous Substances Data Bank. National Library of Medicine TOXNET System. 2008. http://toxmap.nlm.nih.gov/toxmap/home/welcome.do • Handbook of Acute Toxicity of Chemicals to Fish and Aquatic Invertebrates. U.S. Fish and Wildlife Services. 1980. • Kantachote D., Naidu R., Williams B., McClure N., Megharaj M., Singleton I. (2004). Bioremediation of DDT-contaminated soil: enhancement by seaweed addition. Journal of Chemical Technology & Biotechnology, 79 , 6, 632-638. • Lacroix M., Hontela A. (2003). The organochlorineo,p’-DDD disrupts the adrenal steroidogenic signaling pathway in rainbow trout (Oncorhynchusmykiss). Toxicology and Applied Pharmacology 190, 197-205. • O’Reilly A.O., Khambay B.P.S., Williamson M.S., Field L.M., Wallace B.A., Emyr Davies T.G. (2006). Modelling insecticide-binding sites in the voltage-gated sodium channel. Biochemical Journal, 396, 255-263. • U.S. Department of Health and Human Services. Toxicological Profile for DDT, DDE, and DDD. Agency for Toxic Substances and Disease Registry. 2002. • World Health Organization. DDT and its Derivatives – Environmental Aspects. Environmental Health Criteria 83. 1989. http://www.inchem.org/documents/ehc/ehc/ehc83.htm • World Health Organization. DDT and its Derivatives. Environmental Health Criteria 9. 1979. http://www.inchem.org/documents/ehc/ehc/ehc009.htm