Ashley Watts Aquatic Toxicology Physical & Chemical Properties • 1,1,1-trichloro-2,2-bis-(p-chlorophenyl) ethane • Technical grade DDT – – – – 65–80% was the active ingredient, 4,4’-DDT 15–21% of the nearly inactive 2,4’-DDT 4% of 4,4’-DDD 1.5% of 1-(p-chlorophenyl)-2,2,2-trichloroethanol • Degrades into 2,4’-DDE, and 2,4’-DDD 4,4’-DDE Physical & Chemical Properties Physical & Chemical Properties Half-life 3-10 years • Discovered in 1939 • U.S. used in WWII – Control vectors of malaria and typhus • 1945 - Agricultural pesticide for 30 years – 1.3 billion pounds used • 1959 – use declined greatly • 1974 – banned DDT Timeline Degradation Pathway DDT DDE DDD Environmental/Organismal Entry • Introduced as a powder, emulsion, encapsulation • Long term persistence in soil – Dispersed via runoff – Erosion – Volatilization • Solubility in lipids results in concentrated amounts in aquatic organisms • Biomagnification results in all levels of the food chain being affected Biomagnification DDT and DDE are readily stored in fats of vertebrates Toxic Effects • Insects – Death • Fish – Reproductive effects – Neurotoxin effects • Birds – Eggshell thinning • Mammals – – – – Localized liver and kidney damage Neurotoxin effects Teratogenic effects (mice) Carcinogenic effects are likely Molecular Interactions • How it kills insects – Na ion channels stay open, resulting in random neuron fire and death “DDT Jitters” – Those with a mutation or up-regulated CYP-450 genes are resistant • DDE mimics the action of estradiol causing a decline in androgen synthesis in some vertebrates • DDE inhibits the Ca2+ -ATPase or Ca2+-Mg2+ ATPase activity in the eggshell gland Biochemical Breakdown and Removal • DDE and DDD formed – In the presence of NADPH and NADH – In anaerobic conditions • Dechlorination is catalyzed enzymatically by cytochrome P450 • DDT and DDE are further oxidized to form DDA which is the major excreted product in animals. Detoxification • Insects – DDTase can render the compound more water soluble. DDT -> DDE • Mammals – DDT is dehalogenated to DDD and DDE is produced also in small amounts – DDD is produced and stored in liver – DDE found excreted in milk • Fish – DDT is highly resistant to metabolism and very little is excreted References • Agency for Toxic Substances & Disease Registry http://www.atsdr.cdc.gov/toxprofiles/tp35-c4.pdf • DDT Regulatory History: A Brief Survey (to 1975) http://www.epa.gov/history/topics/ddt/02.htm • Davies, T. Field, L., Usherwood, P., Williamson, M. 2007. DDT, Pyrethrins, Pyrethroids and Insect Sodium Channels. Life, 59(3): 151 – 162. • Lundholm, C. 1997. DDE-Induced Eggshell Thinning in Birds:Effects of p,p’-DDE on the Calcium and Prostaglandin Metabolism of the Eggshell Gland. Comp. Biol. Physiol. Vol. 118C, No. 2, pp. 113128. • Kitamura, S. Shimizu, Y., Shiraga, Y., Yoshida, M., Sugihara, K.,Ohta,S. 2002. Reductive Metabolism ofp,p′-DDT ando,p′-DDT by Rat Liver Cytochrome P450. DMD,30.2.113. • Low, W.Y. et al. Recognition and Detoxification of the Insecticide DDT by Drosophila melanogaster Glutathione S-Transferase D1. J. Mol. Biol. (2010) 399, 358–366, • Whiting, F. Et al. 1968. Detoxification of DDT by the Perfused Bovine Liver. Journal of Dairy Science. 51.10, 1612-1615. • Wang, X., Wang, W. Uptake, absorption efficiency and elimination of DDT in marine phytoplankton, copepods and fish. Environmental Pollution 136 (2005) 453e464. • Loomis &Thomas. Effects of Estrogens and Xenoestrogens on Androgen Production by Atlantic Croaker Testes In Vitro: Evidence for a Nongenomic Action Mediated by an Estrogen Membrane Receptor.. April 1, 2000 vol. 62 no. 4995-1004.