26 P,P'-DDD DDD, P,P'- is an isomer of dichlorodiphenyldichloroethane, an organochlorine insecticide. It is a component of commercial mixtures of DDT. DDT was once a widely used pesticide, but today its agricultural use has been banned worldwide due to its toxicity and tendency to bioaccumulate. However, it still has limited use in disease vector control. (L84) 72-54-8 6294 C14H10Cl4 317.953660 White powder. 109.5°C 9e-05 mg/mL at 25 °C [BIGGAR,JW & RIGGS,RI (1974)] Oral (L85) Thyrotropin subunit beta (P01222) Androgen receptor (P10275) Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2 (Q9UL51) Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 (Q9Y3Q4) Sodium/potassium-transporting ATPase subunit alpha-1 (P05023) Sodium/potassium-transporting ATPase subunit alpha-2 (P50993) Sodium/potassium-transporting ATPase subunit alpha-3 (P13637) Sodium/potassium-transporting ATPase subunit alpha-4 (Q13733) Sodium/potassium-transporting ATPase subunit beta-1 (P05026) Sodium/potassium-transporting ATPase subunit beta-2 (P14415) Sodium/potassium-transporting ATPase subunit beta-3 (P54709) Sodium/potassium-transporting ATPase gamma chain (P54710) Calcium-transporting ATPase type 2C member 1 (P98194) Calcium-transporting ATPase type 2C member 2 (O75185) Plasma membrane calcium-transporting ATPase 1 (P20020) Plasma membrane calcium-transporting ATPase 2 (Q01814) Plasma membrane calcium-transporting ATPase 3 (Q16720) Plasma membrane calcium-transporting ATPase 4 (P23634) Sarcoplasmic/endoplasmic reticulum calcium ATPase 1 (O14983) Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (P16615) Sarcoplasmic/endoplasmic reticulum calcium ATPase 3 (Q93084) Calmodulin (P62158) Estrogen receptor (P03372) Estrogen receptor beta (Q92731) Androgen receptor (P10275) (T10) DDD toxicity occurs via at least four mechanisms, possibly all functioning simultaneously. DDD reduces potassium transport across the membrane. DDD inhibits the inactivation of voltaged-gated sodium channels. The channels activate (open) normally but are inactivated (closed) slowly, thus interfering with the active transport of sodium out of the nerve axon during repolarization and resulting in a state of hyperexcitability. DDD inhibits neuronal adenosine triphosphatases (ATPases), particularly Na+K+-ATPase, and Ca2+-ATPase which play vital roles in neuronal repolarization. DDD also inhibits the ability of calmodulin, a calcium mediator in nerves, to transport calcium ions that are essential for the release of neurotransmitters. All these inhibited functions reduce the rate of depolarization and increase the sensitivity of neurons to small stimuli that would not elicit a response in a fully depolarized neuron. DDD is also believed to adversely affect the reproductive system by mimicking endogenous hormones and binding to the estrogen and adrogen receptors. (T10, L85) DDD is absorbed in the stomach and intestine, after which it enters the lymphatic system and is carried throughout the body and incorporated into fatty tissues. Metabolism of DDD occurs mainly via cytochrome P-450 enzymes in the liver and kidney. Its metabolites, mainly DDA (bis(p-chlorophenyl) acetic acid), are excreted in the urine. (L85) LD50: 113 mg/kg (Oral, Rat) (L138) 5 g/kg for an adult human. (L138) Not directly listed by IARC, but carcinogenicity studies of this DDT metabolite are discussed in connection with DDT (L2151). DDD is found in DDT, which is used as a pesticide and in disease vector control. (L84) DDT has been shown to cause mild anemia. Exposure to DDT causes loss of weight and anorexia. DDT poisoning affects CNS function in humans, but pathologic changes are observed in the liver and reproductive organs. Hypertrophy of hepatocytes and subcellular organelles such as mitochondria, proliferation of smooth endoplasmic reticulum, centrolobular necrosis after exposure to high concentrations, and an increase in the incidence of hepatic tumors have been noted. (T10) DDT exposure causes ataxia and abnormal stepping. Acute signs of DDT poisoning include paresthesia after oral ingestion. Studies have shown that a mammal poisoned with DDT-type agents displays periodic persistent tremoring and/or convulsive seizures that are suggestive of repetitive discharges in neurons. These repetitive tremors and seizures can be initiated by tactile and auditory stimuli. (T10) Treatment of DDT exposure should be primarily directed towards decontamination and supportive care, as there is no specific antidote. The use of gastric lavage and activated charcoal for large ingestions may be effective. (L140) 2009-03-06T18:57:56Z 2014-12-24T20:20:55Z Cytochrome P450 2B6 (Q16678) Cytochrome P450 3A4 (P08684) Cytochrome P450 3A5 (P20815) Cytochrome P450 3A7 (P24462) Cytochrome P450 3A43 (Q9HB55) (L85) C06636 27841 CPD-8985 D003632 DDD, P,P'- 379 true Cytochrome P450 2B6 (Q16678) Cytochrome P450 3A4 (P08684) Cytochrome P450 3A5 (P20815) Cytochrome P450 3A7 (P24462) Cytochrome P450 3A43 (Q9HB55) (L85) ClC(Cl)C(C1=CC=C(Cl)C=C1)C1=CC=C(Cl)C=C1 C14H10Cl4 InChI=1S/C14H10Cl4/c15-11-5-1-9(2-6-11)13(14(17)18)10-3-7-12(16)8-4-10/h1-8,13-14H InChIKey=AHJKRLASYNVKDZ-UHFFFAOYSA-N 320.041 317.953661148 Exogenous Solid CHEMBL196590 6057