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Key topic summary. Classification of Pesticides Organophosphorous Pesticides General structure, mechanism of action, clinical signs, treatment. Organophosphates vs. Carbomates Organochlorines Examples, mechanism of action, clinical signs, treatment Herbicides

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Key topic summary
Key topic summary

  • Classification of Pesticides

  • Organophosphorous Pesticides

    General structure, mechanism of action, clinical signs, treatment. Organophosphates vs. Carbomates

  • Organochlorines

    Examples, mechanism of action, clinical signs, treatment

  • Herbicides

    Examples, mechanism of action, clinical signs, treatment

  • Fungicides and Fumigants

    Examples, toxic effects


Pesticides

PESTICIDES

Alexander V. Lyubimov, M.D., Ph.D.

Director

Toxicology Research Laboratory

Department of Pharmacology

University of Illinois at Chicago


Key topic summary

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.


Applicators only
APPLICATORS ONLY?

Are there ANY other populations

(besides occupationally exposed) who can be poisoned by PESTICIDES?


Key topic summary

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


Pesticides classification
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


Key topic summary

* Continued

4. Fungicides

4.1 HCB

4.2 Organomercurials

4.3 PCP

4.4 Phthalimides

4.5 Dithiocarbamates (EBDC)

* Continued


Key topic summary

* Continued

5. Fumigants

5.1 Phosphine

5.2 Ethylene Dibromide / Dibromochloropropane (DBCP)



Key topic summary

OPIDP enzymes – Organophosphate- Induced Delayed Polyneuropathy

  • Distal Sensorimotor axopathy (degeneration of distal axons)

    Symptoms

    Tingling of the hands and feet

    Progressive muscle weakness

    ataxia

  • Mechanism

    Phosphorylation of

    NTE – neuropathy target esterase



Treatment of poisoning
Treatment of Poisoning enzymes

  • 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)


Chlorophenoxy herbicides mechanism of action
Chlorophenoxy Herbicides enzymesMechanism 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


Bipyridyl derivative paraquat
BIPYRIDYL DERIVATIVE enzymesParaquat

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!


Fungicides
FUNGICIDES enzymes

Low acute toxicity

LD50 ~ 800 – 10,000 mg/kg.

Cytotoxic

Mutagenic

(mechanism of action to fungus)

Teratogenic

Carcinogenic ~ 90% in animal models.


Key topic summary
HCB enzymes

Immunosuppression

Hepatic and thyroid tumors (animals)

Teratogen

(transplacental and milk acquisition)


Key topic summary

DITHIOCARBAMATES (EBDC) enzymes

Low toxicity

(Biotransformation  Ethylene Thyourea (ETU)

in animals is well known to produce:

Mutagenicity, Carcinogenicity

Teratogenicity, Embryotoxicity


Key topic summary

FUMIGANTS enzymes

Phosphine

(ALP  PH3)

Ethylene Dibromide / Dibromochloropropane (DBCP)

produce:

gastric carcinomas

DBCP – sterility in humans