1. TOXICITY OF
PESTICIDES

2. • Pesticide is a world that is consisted of 2 parts:
• Pest = unwanted creature or living
• Cide = killing or elimination
• Pesticides include several categories such as
hebicides, insecticides, fungicides, bacteriocides, etc.
• The 3 major groups to be studied in our course are:
Insecticides: organophophates.
Herbicides: paraquat.
Rodenticides: anticoagulants
Dr. TAHAR ABDULAZIZ MD, PhD

3. ORGANOPHOSPHATE
TOXICITY
• Garden and household pesticides, and in
agriculture.
• Formulations include liquids, sprays, and powders.
• In veterinary medicine they are found in
pedicullicide lotions.
• Shampoos, aqueous and alcoholic lotions are also
used as human pedicullicides and scabicides.
• Organophosphate nerve agents may be used as
chemical warfare agents. An example was sarin
used in the Tokyo subway attacks of 1995.
• Parathion is an organophosphate insecticide that is
widely used in agriculture in Libya.
Dr. TAHAR ABDULAZIZ MD, PhD

4. • OP bind ChE and inhibit its function excess of ACh in synapses and NMJ
muscarinic and nicotinic symptoms and signs.
• Excess ACh in the synapse can lead to 3 sets of symptoms and signs:
1) At postganglionic muscarinic synapses lead to SLUDGE/BBB.
2) At nicotinic motor end plates causes persistent depolarization of skeletal muscle
resulting in fasciculations, progressive weakness, and hypotonicity.
3) OP cross the blood-brain barrier, they may cause seizures, respiratory depression,
and CNS depression for reasons not completely understood.
• OP bind to RBC cholinesterase & plasma cholinesterase (pseudocholinesterase)
in the serum.
• The kinetics of the enzyme will reach zero within 10 hours i.e. all enzyme will
be in the form of OP-AchE complex, this situation is called aging phenomenon.
Dr. TAHAR ABDULAZIZ MD, PhD

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7. Causes
Agricultural exposure is the most common cause.
The WHO classifies these poisonings as class I (extremely toxic)
to class III (slightly hazardous).
The WHO advocates banning or strong restrictions on the use of
class I pesticides and a reduction in the use of pesticides to a
minimal number of compounds that are less hazardous than
others.
Organophosphates are used as chemical warfare agents (nerve
agents such as sarin, VX, or soman).
Dr. TAHAR ABDULAZIZ MD, PhD

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9. Ach & AChE
Dr. TAHAR ABDULAZIZ MD, PhD

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12. Clinical Manifestations
• Pesticides can rapidly be absorbed
through the skin, lungs, GI tract, and
mucous membranes.
• Symptoms usually occur within a few
hours after GI ingestion and appear
almost immediately after inhalational
exposure.
Dr. TAHAR ABDULAZIZ MD, PhD

13. cholinergic toxic syndrome
1- Muscarinic effects: SLUDGE/BBB mnemonic
S = Salivation L = Lacrimation U = Urination
D = Defecation G = GI symptoms E = Emesis
B = Bronchorrhea B = Bronchospasm B = Bradycardia
2- Nicotinic effects at neuromuscular junctions and
autonomic ganglia: weakness, fasciculations, and
paralysis.
3- CNS effects may lead to seizures and CNS
depression.
Dr. TAHAR ABDULAZIZ MD, PhD

14. Plasma cholinesterase (pseudocholinesterase) &
RBC cholinesterase levels
• Laboratory evidence of OP poisoning may be
obtained by measuring decreases in:
– Plasma pseudocholinesterase (PChE) and
– RBC acetylcholinesterase (RChE) activities
• Significant depression of enzyme activity may
occur but still fall within the “normal” range.
– It is most helpful if the patient had a pre-exposure
baseline measurement for comparison (eg, as part
of a workplace health surveillance program).
•
TAHAR ABDULAZIZ MD, PhD (tsoleman@yahoo.com)

15. a. The RChE activity provides a more reliable measure of
the toxic effect; a 25% or greater depression in activity
from baseline generally indicates a true exposure effect.
b. PChE activity is a sensitive indicator of exposure but is not
as specific as RChE activity
PChE may be depressed due to
genetic deficiency
medical illness
chronic organophosphate exposure
PChE activity usually recovers within weeks after exposure
RChE may recover after several months
• Carbamate poisoning produces reversible AchE inhibition,
and spontaneous recovery of enzyme activity may occur
within several hours, making these tests less useful.
Dr. TAHAR ABDULAZIZ MD, PhD

16. Treatment
Airway, breathing, and circulation (ABCs):
Decontamination is an important part of the initial care. In general, the
importance of decontamination depends on the route of poisoning.
Patients with dermal and inhalation exposures are more likely to cause
nosocomial poisoning than patients with GI exposure. Patients with GI
exposure should also be decontaminated.
Patients with dermal and inhalation poisonings must be
decontaminated before being brought into the ED.
Case reports have described nosocomial poisoning in staff
members treating patients who have been exposed to OP;
one describes OP toxicity from mouth-to-mouth
resuscitation.
Dr. TAHAR ABDULAZIZ MD, PhD

17. Atropine is a pure muscarinic antagonist that competes with
ACh at the muscarinic receptor.
Atropine is most commonly given in intravenous (IV) form at
the recommended dose of 2-5 mg for adults and 0.05
mg/kg for children with a minimum dose of 0.1 mg to
prevent reflex bradycardia.
Atropine may be repeated every 5-10 minutes.
Severe organophosphate poisonings often require hundreds of
milligrams of atropine.
Observation of 3 major signs:
 dryness of mouth
 flushing of face
 dilatation of pupils.
Dr. TAHAR ABDULAZIZ MD, PhD

18. Oximes {Pralidoxime (2-PAM)}:
Organophosphates bind and phosphorylate one
of the active sites of AChE and inhibit the
functionality of this enzyme. Oximes bind to
the organophosphate, causing the compound
to break its bond with AChE. Most of the
effects are on the peripheral nervous system
because entry into the CNS is limited.
The WHO protocol for oxime therapy is
recommended for any patient with clinically
significant poisoning.
Dr. TAHAR ABDULAZIZ MD, PhD

19. Difference between OP & Carbamates
Dr. TAHAR ABDULAZIZ MD, PhD

20. Complications:
1- Intermediate syndrome (1-4 DAYS AFTER)
sudden respiratory paresis, with weakness in cranial nerves
and proximal-limb and neck flexor muscles.
2- OP-induced delayed neurotoxicity (OPIDN) (9-14
DAYS)
A sensorimotor polyneuropathy with distal motor
weakness and sensory paresthesias in the lower
extremities, which may progress proximally and
eventually affect the upper extremities.
3- Pancreatitis
Pancreatitis has been reported as a rare complication. One
case series reported that 12.76% of OP poisonings were
associated with acute pancreatitis, though this has not
been the experience in other series.
Dr. TAHAR ABDULAZIZ MD, PhD

21. PARAQUAT TOXICITY
• Non-selective, water soluble herbicide (weed
killer).
• It is used since 1962.
• It is available as an aqueous concentrate and in
granular formulations
• In Libya there are 2 compounds:
– Gramaxone (yellowish liquid)
– Weedol (granulation form)
Dr. TAHAR ABDULAZIZ MD, PhD

22. Pathophysiology
• Paraquat is very toxic when ingested. The exact
mechanisms of toxicity is not fully understood.
• The lethal dose is 1-4 grams.
• Lungs are the main target of paraquat due to
active, energy-dependent uptake by alveolar type I
and II cells.
• Skin absorption is poor. Inhalation is a possible
route of toxicity
Dr. TAHAR ABDULAZIZ MD, PhD

23. • Ingestion is the most common route of
toxicity:
• MILD: INGESTION OF LESS THAN 20
MG/KG BODY WEIGHT.
• MODERATE TO SEVERE: INGESTION
OF 20-40 MG/KG. P
• VERY SEVERE: INGESTION OF MORE
THAN 40 MG/KG. DEATH MAY OCCUR
WITHIN 24 HOURS BUT NEVER AFTER
MORE THAN 7 DAYS.
Dr. TAHAR ABDULAZIZ MD, PhD

24. Mechanism of toxicity
• Paraquat may cause lesions in the lung by a mechanism
known as redox cycling. These compounds are reduced by
cytochrome P450 reductase forming a free radical.
• Free radical with tissue macromolecules, one molecule of
oxygen is reduced to superoxide that can then be converted
to other toxic oxygen species.
• These reactive compounds may cause peroxidation of
cellular membranes.
• The specific toxicity of paraquat to the lung results from
the uptake of this compound by lung due to high
pulmonary oxygen tension.
Dr. TAHAR ABDULAZIZ MD, PhD

25. Formatio of superoxide radical
by PQ
Dr. TAHAR ABDULAZIZ MD, PhD

26. • Toxicity may occur through
oxidation/reduction cycle
producing peroxides and free
radicals.
• Free radicals are chemical elements that may
be positively or negatively charged or neutral
but possess a single unpaired electron
Dr. TAHAR ABDULAZIZ MD, PhD

27. Clinical Manifestations
Phase 1: (GIT phase): may start immediately till 72 hours; intense
pain in mouth, pharynx, and stomach due to the corrosive effect of
paraquat. There may be bloody vomiting or diarrhea.
Phase 2: (systemic; renal or hepatic phase): severity depends on the
dose of paraquat, where manifestations of renal and or hepatic
failure appear.
Phase 3: (respiratory phase): in which signs of respiratory illness
appear such as cough or cyanosis
Dr. TAHAR ABDULAZIZ MD, PhD

28. Management
• There is no specific treatment; supportive therapy is
important.
• Gastric lavage with AC
• Gastric lavage with aqueous suspension of clay (Fuller Earth
or Bentonite clay).
• To avoid excessive oxygen administration as this may
aggravate lipid peroxidation reactions in the lungs.
Significant hypoxemia to be treated with supplemental
oxygen; only the lowest oxygen concentration necessary to
achieve a pO2 of about 60 mm.
• Charcoal hemoperfusion
• Hemodialysis anf forced diuresis are not effective
Dr. TAHAR ABDULAZIZ MD, PhD