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Pharmacology and Toxicology
PHAR 100
Hisham Elbatarny

Environmental Toxicants - Part 2 Pesticides Used for intentionally killing organisms 1) Insecticides 2) Herbicides Organoclorine Insecticides • act by increasing the sensitivity of neurons • increased CNS stimulation, seen as tremors and convulsions ◦ normally have to reach threshold → don't need as much of a signal to have an effect • example is DDT: 1945, for malaria control • 1970’s, use stopped because: 1. Insects developing resistance 2. ↑ soil/water concentrations (chemically stable) 3. ↓ bird/fish populations 4. ↑ levels in food/meat Organoclorine Insecticides DDT Toxicity: • acute: CNS stimulation – tremors convulsions • chronic ◦ carcinogenic ◦ developmental and reproductive effects ◦ neurological problems • organochlorines largely phased out Organophosphorous Insecticides • first synthesized in WWII – nerve gases • example is Sarin gas (Syria) • selective organophosphorus insecticides: ◦ Malathion, Parathion ◦ metabolically activated, occurs rapidly in insects • very toxic to humans • absorbed through skin • leading cause of poisoning in agricultural sector Organophosphorous Insecticides Sheepdipping:(organo phosphates) liquid • toxicity formulationofinsecticide and fungicide used ◦ inhibits acetylcholinersterase (irreversible) to protect sheep frominfestationagainst ◦ increased ACh in nervous tissue externalparasites suchas itchmite, blow-fly, ticks and lice ◦ increased parasympthetic effects → now have to wear lots ofprotective ◦ generally death due to respiratory • treatment: pralixodime clothing ◦ reverses inhibition Carbamate Insecticides • e.g. carbaryl • works like organophosphorus insecticides • reversibly inhibit acetylcholinesterase ◦ less toxic Herbicides • Chlorophenoxy compounds • 2,4-D and 2,4,5-T (Agent Orange – used in Vietnam War to get rid of forests) ◦ mimic plant growth hormones ▪ uncontrolled, unsustainable growth leading to plant death ◦ contaminated with 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) • 2,4-D Toxicity ◦ large doses: vomiting, diarrhea, convulsions, coma Toxicity of Dioxins • 75 chlorinated dioxins exist ◦ 2,3,7,8-TCDD is most toxic • contaminant from herbicide production, formed during burning of wastes, wood • huge species differences in susceptibility • animals show liver toxicity, liver cancer and lung cancer Human Toxicity of TCDD • binds to the aryl hydrocarbon receptor ◦ involved in expression of many genes • Seveso, Italy, 1976 ◦ 2 kg TCDD released in chemical
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