Insecticides poisoning

Pesticides:
• Pesticides can be defined as
any substance or mixture of
substances intended for
preventing, destroying,
repelling, or mitigating pests
that can be insects, rodents,
weeds, and a host of other
unwanted organisms.
(Ecobichon, 2001).
Cont..
• Most pesticides are not highly selective, but
are generally toxic to many non target species,
including humans.
 Organophosphate
and
Carbamate insecticides
• Groups of chemicals share a common
mechanism of cholinesterase inhibition and
hence can cause similar symptoms.
• Toxicodynamic:
– Inhibition of the acetylcholinesterase (AChE) at nerve
endings.
– Loss of available AChE results accumulation of
acetylcholine at receptor sites and effector organ to
become over stimulated by the excess acetylcholine.
 Mechanism of toxicity, cont..:
• Organophosphates phosphorylate
acetylcholinesteras and carbamates
carbamoylate it .
• Both mechanisms lead to inhibition of
acetylcholinestrase and prevent hydrolysis of
acetylcholine ,hence accumulation and
increase stimulation of cholinergic receptors.
 Clinical features:
• Clinical Features are based on excessive
cholinergic stimulation.
• Unlike organophosphate poisoning,
carbamate poisoning tend to be of shorter
duration because the inhibition of nerve tissue
AChE is reversible (no aging of the complex
compound).
Site of action and clinical features:
 Routes of exposure and clinical features:

• Eye contact: Irritation or pain, lacrimation,

swelling, blurring of vision.
• Inhalation: Cough, difficulty in breathing,
bronchitis, pneumonia.
• Ingestion: Nausea, vomiting, diarrhoea,
sweating, salivation, small or pin point pupils,
muscle twitching, fasciculation.
Organophosphate compounds:

• Based on chemical
differences, OPs can be
divided into several
subclasses, which include
phosphates,
phosphorothioates,
phosphoramidates,
phosphonates, and others.
Sarin Gas Attack in Japan

• June 1994,
Matsumoto (614)
• March 1995, Tokyo
subway (5510)
 Sarin toxicology

Isopropyl methylphosphonofluoridate
High potency organophosphate ester
Clear, colorless liquid with a vapor pressure of
2.1 mm Hg
Liquid: rapidly penetrate skin and clothing
Vapor: rapidly penetrate mucous membranes
of the eye or inhaled in to the lung
Diagnosis of Organophosphate or Carbamate
Poisoning:

• Clinical Diagnosis
• Laboratory
– Red cell cholinesterase
(Adults and Children: 12.5 ± 1.3 units/mL
packed RBC)
– Plasma (Pseudo, Butyryl (Bu)) cholinesterase
(8 -18 units per milliliter (U/mL).
 Management:

1. Basic life support

• Decontamination.
• Airway stabilization.
• Activated charcoal.
ANTIDOTES

TOXIC
 Atropine
(1-2 mg ,iv)
Muscarinic Effects
Heart rate
Sweating
Secretion
Pupils

The dose is repeated every 5 to 10 min, depending on improvement of respiration.

Organochlorine insecticides
• OC insecticides are low-molecular-weight, fat-
soluble compounds with greater selectivity for
lipid storage in insects.
• Very few organochlorines are used now as
pesticides.
• Organochlorines are very toxic if ingested or
inhaled. Some are readily absorbed through
the intact skin.
 Toxicodynamic:
• OCs alter membrane chloride ion permeability
and interfere with normal GABAergic (γ-
aminobutyric acid) neuronal transmission.
• The loss of this inhibitory neurotransmitter
translates into the neurotoxic sequelae.
Classification of Organochlorine

Dichlorodiphenylethanes
DDT Methoxychlor
Hexachlorocyclohexane
Lindane
Cyclodienes
Aldrin Chlordane Dieldrin
Endrin Endosulphan Hepatochlor
Chlordecone (kepone)
Mirex
 Acute Organochlorine Poisoning
• Prodomal symptoms:
– tremor, ataxia, quick involuntary jerk (myoclonus)
– dizziness, confusion
– nausea, vomiting
 Acute Organochlorine Poisoning
• The typical presentation: Status epilepticus

• Followed by:
– Respiratory failure
– Cardiac arrhythmias
– Rhabdomyolysis & acute renal failure
Acute Organochlorine Poisoning

• Treatment:
– Control seizure as the same way as “Status
epilepticus”
• Benzodiazepines
• Phenobarbital
• Phenytoin

– control arrhythmia by an anti-arrhythmic like

lidocaine
Diagnosis of Organocholine Poisoning

• Clinical Diagnosis
– History of exposure
– Clinical features of repeated seizure
• Laboratory Test
– Plasma level
– Subcutaneous fat level
Subacute Organochlorine Poisoning

• Hyperexcitability stage:
– Tachycardia
– Tremor
– Hyperreflexia
• Treatment
– Symptomatic : Anxiolytic
– Enhance Elimination : Cholestyramine
Chronic Organochlorine Poisoning

– Organochlorine insecticides interfere with

endocrine and reproductive systems.
– People who working with the insecticides
have low sperm count and motility,
infertility and abortion.
– The insecticides have also been reported
to be carcinogenic to animals.
Pyrethroid insecticides
 Pyrethroid esters:
• Pyrethrum flowers have been used as insecticides for
centuries.
• Pyrethrins are noted for their quick “knock-down” effect of
flying insects, particularly flies and mosquitoes.
• The compounds (0.17 to 0.33%) are combined with
piperonyl butoxide or n-octyl-dicycloheptane dicarboximide
(2 to 4%) in therapeutic nonprescription pediculicide
preparations for the treatment of lice, tick, and mite
infestation.
• The products are available in lotions, sprays, and shampoos
for skin or scalp applications, as well as for removal from
furniture and bedding material.
 Toxicodynamic:
• Type I pyrethrins (allethrine, permethrin, cismethrin )
produce repetitive depolarization of axons by inhibiting
inactivation of sodium channels.

• Type II pyrethrins (fenvalerate, deltamethrin, cypermethrin)

have a similar mechanism, but longer duration of action,
and also affect GABA receptor-mediated chloride channels.
 Pyrethroid poisoning
• Most poisonings, are benign and limited to:
1. contact irritant dermatitis
2. allergic dermatitis
3. rhinitis
4. Pulmonary asthmatic reactions may occur in sensitive
individuals

• Severe poisoning have been reported from

massive oral ingestion that resulted in coma,
convulsions, and death.
Treatment of pyrethrins toxicity

• Treatment is symptomatic and limited to

alleviation of the inflammatory response.
• Oral or topical corticosteroids and H1-
antihistamine may be of use.
Nicotine
• Nicotine is a pyridine alkaloid obtained from
the cured and dried leaves of the tobacco
plant, Nicotiana sp.
• Early American settlers in the nineteenth
century recognized the insecticidal properties
of nicotine as they dusted their vegetable crops
with finely powdered tobacco leaves.
• The demand for nicotine as an insecticide
declined with the advent of the
organophosphate compounds.
 Toxicodynamics :
• Toxic effects of nicotine as a contact insecticide are
identical to ingestion of large amounts of the
compound in other commercial products.
• Nicotine stimulates nicotinic receptors of all
sympathetic and parasympathetic ganglia,
neuromuscular junction innervating skeletal muscle,
and CNS pathways.
• The most significant target organs affected by
nicotine is the cardiovascular system. Hence it
produces a characteristic bradycardia or tachycardia.
 Nicotine action on CNS:
• Nicotine’s action on the CNS results in stimulation,
followed by predominance of parasympathetic
overtone, i.e., salivation, lacrimation, urination,
defecation, and vomiting.
• Continued exposure progresses to muscular
weakness, tremors, hypotension, and dyspnea.
• Convulsions and respiratory paralysis are advanced
complications of unattended nicotine toxicity.
Treatment of nicotine poisoning

• Treatment is primarily symptomatic and

involves:
1. decontamination
2. induction of emesis (depending on the time
of onset of symptoms)
3. maintenance of vital signs
Rotenone
• Rotenone (tubotoxin, derrin) is a colorless-
to-red, odorless insecticidal principle derived
from the Derris plant genus.
• Rotenone, and the chemically related
rotenoids (toxicarol, tephrosin, sumatrol),
are a series of naturally occurring cyclic
aromatic hydrocarbons.
• The agents are widely employed in
agriculture for controlling chewing and
sucking insects, and are dusted or sprayed on
garden plants and crops as well.
 Mechanism of toxicity:

• Rotenone blocks electron transport in mitochondria

by inhibiting oxidation linked to NADH2, resulting in
nerve conduction blockade.

• It is considered to possess generally low toxicity.

• Respiratory, dermal, oral, or ocular exposure results

in symptoms that mimic the chemical irritants.
 Poisoning and Management:
• Acute poisoning is characterized by an initial
respiratory stimulation followed by respiratory
depression, ataxia, convulsions, seizures, coma have
been reported and death from respiratory arrest.
• Rotenone dust is highly irritating to:
– eyes : causing conjunctivitis
– skin : causing contact dermatitis
– upper respiratory tract :causing rhinitis
– throat : linked with pharyngitis
• Management of poisoning is supportive and
symptomatic.
Diethyltluamide
(DEET)
 DEET
• DEET (m-isomer of N,N-diethyl-3-
methylbenzamide) is a popular insect repellant
available in topical preparations at 5 to 100%
concentrations (OFF® Insect Repellant).
• About 5 to 10% of a dermal application is
absorbed, due to its high lipid solubility, and
stored in lipid compartments, resulting in a
prolonged plasma half-life (2.5 h).
• It is considered a chemical with low toxicity,
dermal reactions reflect excessive topical
application of sprays, creams, lotions.
 Toxicodynamics:
• Ocular or dermal irritation is generally limited to allergic
reactions and is the most frequent complaint.
• Prolonged dermal contact with significant absorption, or
oral ingestion, has precipitated CNS toxicity.
• This is manifested by the development of:
– headache
– lethargy
– confusion
– tremors
– Hypotension, seizures, and coma are rare.
 Treatment of Toxicity

 Treatment is largely symptomatic and

supportive and involves:
– Decontamination
– Gastric lavage
– Maintenance of vital signs
– Washing the contaminated area with soap and
water
– Induction of emesis is recommended if needed.