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

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

Director
Toxicology Research Laboratory
Department of Pharmacology
University of Illinois at Chicago
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?

Are there ANY other populations

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

4. Fungicides

4.1 HCB
4.2 Organomercurials
4.3 PCP
4.4 Phthalimides
4.5 Dithiocarbamates (EBDC)

* Continued
* Continued

5. Fumigants

5.1 Phosphine

5.2 Ethylene Dibromide / Dibromochloropropane (DBCP)

Dealkylation of the intermediate dialkylphosphorylated enzymes
OPIDP – 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
 Organophosphorus(OP) vs.
Carbomates(CB) Esters
OP CB
Anti-AChE effect Yes Yes
Pesticide + AChE Most stable Stable
complex
Aging Yes No
OPIDP Yes No
Treatment with Yes No
Oximes
(pralidoxime &
toxogonin)
 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)
 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
 BIPYRIDYL DERIVATIVE
Paraquat
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
Low acute toxicity
LD50 ~ 800 – 10,000 mg/kg.
Cytotoxic
Mutagenic
(mechanism of action to fungus)
Teratogenic
Carcinogenic ~ 90% in animal models.
 HCB
Immunosuppression

Hepatic and thyroid tumors (animals)

Teratogen
(transplacental and milk acquisition)
 DITHIOCARBAMATES (EBDC)

Low toxicity

(Biotransformation  Ethylene Thyourea (ETU)

in animals is well known to produce:

Mutagenicity, Carcinogenicity

Teratogenicity, Embryotoxicity
 FUMIGANTS

Phosphine

(ALP  PH3)

Ethylene Dibromide / Dibromochloropropane (DBCP)

produce:
gastric carcinomas

DBCP – sterility in humans