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

DDT Timeline• 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

Degradation Pathway

DDT

DDEDDD

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 Registryhttp://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. 113-128.• 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.