PESTICIDES

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PESTICIDES

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

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• 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.

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APPLICATORS ONLY?

• Are there ANY other populations
• (besides occupationally exposed) who can be
  poisoned by PESTICIDES?

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• 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

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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

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

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

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Dealkylation of the intermediate
dialkylphosphorylated enzymes
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Organophosphorus(OP) vs. Carbomates(CB) Esters
OP CB
Anti-AChE effect Yes Yes
Pesticide AChE complex Most stable Stable
Aging Yes No
OPIDIN Yes No
Treatment with Oximes (pralidoxime toxogonin) Yes No
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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)

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Chlorophenoxy HerbicidesMechanism 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

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BIPYRIDYL DERIVATIVEParaquat

• LD50 22 262 mg/kg, moderately toxic
• Target Organ Lung in all species
• Mechanism of action
• Free Radical ? superoxide anion, O2-
• ? Lipid peroxidation
• Treatment
• Gastric lavage
• mineral adsorbents
• hemoperfusion
• No hyperbaric oxygen!

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FUNGICIDES

• Low acute toxicity
• LD50 800 10,000 mg/kg.
• Cytotoxic
• Mutagenic
• (mechanism of action to fungus)
• Teratogenic
• Carcinogenic 90 in animal models.

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HCB

• Immunosuppression
• Hepatic and thyroid tumors (animals)
• Teratogen
• (transplacental and milk acquisition)

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• DITHIOCARBAMATES (EBDC)
• Low toxicity
• (Biotransformation ? Ethylene Thyourea (ETU)
• in animals is well known to produce
• Mutagenicity, Carcinogenicity
• Teratogenicity, Embryotoxicity

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• FUMIGANTS
• Phosphine
• (ALP ? PH3)
• Ethylene Dibromide / Dibromochloropropane (DBCP)
• produce
• gastric carcinomas
• DBCP sterility in humans

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