1. PESTICIDES Alexander V. Lyubimov, M.D., Ph.D. Director Toxicology Research Laboratory Department of Pharmacology University of Illinois at Chicago

2. Pesticide is a substance or mixture of substances intended for preventing, destroying, repelling, or mitigating any pest (US EPA). Pest includes harmful, destructive, or troublesome animals, plants, or microorganisms.

5. APPLICATORS ONLY? Are there ANY other populations (besides occupationally exposed) who can be poisoned by PESTICIDES?

9. HOW WE CAN SURVIVE IT? NO-EFFECT-LEVEL (NOEL) in animals is used to determine: Residue Tolerance Limits maximum safe levels of pesticide in food

16. PESTICIDES CLASSIFICATION 1.Insecticides 1.1 Organophosphates (most are actually thiophosphates) 1.2 Carbamates 1.3 Organochlorines 1.4 Botanical compounds 2.Herbicides 2.1 Chlorophenoxy compounds 2.2 Bipyridyl compounds 2.3 Miscellaneous compounds 3. Rodenticides * Continued

17. 4. Fungicides 4.1 HCB 4.2 Organomercurials 4.3 PCP 4.4 Phthalimides 4.5 Dithiocarbamates (EBDC) * Continued

18. 5. Fumigants 5.1 Phosphine 5.2 Ethylene Dibromide / Dibromochloropropane (DBCP)

23. Dealkylation of the intermediate dialkylphosphorylated enzymes

28. Organophosphorus(OP) vs. Carbomates(CB) Esters OPCB Anti-AChE effectYes Pesticide + AChE complex Most stableStable AgingYesNo OPIDINYesNo Treatment with Oximes (pralidoxime & toxogonin) YesNo

33. Treatment of Poisoning Diazepam (0.3 mg/kg IV, max 10 mg) or Phenobarbital (15 mg/kg IV, max 1 g) to control the convulsions Anion-exchange resin, cholestyramine enhanced fecal excretion of chlorodecone (reduced reabsorption of compound excreted with bile)

38. Chlorophenoxy Herbicides Mechanism of action 2,4-D interferes with lipid metabolism enhancing lipid utilization in liver. Induces peroxisome hepatic proliferation Decreases cholesterol Induces myotonia by increasing basic p-NPPase (p-nitrophenylphosphatase) activity

40. BIPYRIDYL DERIVATIVE Paraquat LD 50 ≈ 22 – 262 mg/kg, moderately toxic Target Organ : Lung in all species Mechanism of action : Free Radical  superoxide anion, O 2 -  Lipid peroxidation Treatment : Gastric lavage mineral adsorbents hemoperfusion No hyperbaric oxygen!

44. FUNGICIDES Low acute toxicity LD 50 ~ 800 – 10,000 mg/kg. Cytotoxic Mutagenic (mechanism of action to fungus) Teratogenic Carcinogenic ~ 90% in animal models.

46. HCB Immunosuppression Hepatic and thyroid tumors (animals) Teratogen (transplacental and milk acquisition)

47. DITHIOCARBAMATES (EBDC) Low toxicity (Biotransformation  Ethylene Thyourea (ETU) in animals is well known to produce: Mutagenicity, Carcinogenicity Teratogenicity, Embryotoxicity

48. FUMIGANTS Phosphine (ALP  PH 3 ) Ethylene Dibromide / Dibromochloropropane (DBCP) produce: gastric carcinomas DBCP – sterility in humans