the presentation talks about the insecticides used in public health and its impact on human health. Ways of insecticide exposure to human health and clinical manifestations due to insecticide exposure.

1. Insecticides and Human Health

2. Insecticides: these are chemicals used to control insects by killing them preventing them
from engaging in undesirable or destructive behaviours.
- US EPA
Chemical nature of Insecticides: Organic, Inorganic, Synthetic, Biological (biopesticide).
Toxicity: It is the ability of a insecticide to injure/kill a living organism.
Human health related toxicity: It is based on acute risk to human health (that is the risk
of single or multiple exposure over a relative short period of time)
- WHO

3. Toxicity can be two types based on the dosage, exposure length and exposure area;
• Acute toxicity- It refers to those adverse effects occurring following oral or dermal
administration of substance, or multiple doses given within 24 hours, or an inhalation
exposure of 4 hours.
• Chronic toxicity- It is the ability of a substance to cause adverse health effects
resulting from long-term exposure to a substance.
#Note-
The toxicity of a insecticide can’t be changed but risk of exposure can be reduced with
the use of proper Personal Protective Equipment’s (PPE), proper handling and
application procedure.

4. Acute toxicity hazard categories and approx. LD50/LC60
values defining the respective categories
Exposure Rate Category 1 Category 2 Category 3 Category 4 Category 5
Oral (mg/kg) 5 50 300 2000
5000
Dermal (mg/kg) 50 200 1000 2000
Gases (ppm) 100 500 2500 5000
Vapours (mg/l) 0.5 2.0 10 20
Dusts & Mists
(mg/l)
0.05 0.5 1.0 5

5. Depiction
Colour of lower
triangle
Bright red Bright yellow Bright blue Bright green
Toxicity class Extremely toxic Highly toxic Moderate toxic Slightly toxic
LD50 (mg/kg) <50 51-500 501-5000 >5000
Signal Word
POISON
(in red)
POISON
(in red)
DANGER CAUTION
Warning word
Keep out of reach of
children. If swallowed or
symptoms of poisoning,
call doctor.
Keep out of the
reach of children
Keep out of the
reach of children
------------
Categorisation of pesticides

6. Human Pesticide Exposure
Routes of pesticides exposure to human:
• Inhalation
• Dermal absorption
• Ingestion
• Injection

7. Respiratory Exposure
• Due to presence of volatile components of pesticides, potential for
respiratory exposure is more.
• Inhalation of sufficient amount of insecticide may cause serious damage
to nose, throat and lung tissues.
• Low volume equipment (ULV or fogging) pose more threat to respiratory
exposure due to production of smaller droplets and the risk increases
with the concentration dosage of insecticide.
• Working with wettable powders can be hazardous because the powder
may be inhaled during the process of mixing.
• Increase in temperature leads to increased vapour level of many
insecticides which worsen such exposure.
• It is recommended that insecticides should not be applied at air
temperature above 30°C.
• Insecticides with high vapour hazards should be applied with sufficient
equipment for respiratory protection.

8. Dermal exposure
• It is the most common route of pesticide
poisoning.
• Absorption will continue as long as the pesticide
remains in contact with the skin.
• Pesticide formulation vary broadly in
physicochemical properties and in their capacity
to be absorbed through the skin.
• The rate of absorption is different for each part of
the body.
• The head (especially the scalp and ear canal) and
the genital areas are particularly vulnerable.
• Applicators are more vulnerable to exposure of
residues on application equipment, protective
clothing or treated surfaces after pesticide
application.
• A cut or skin abrasion can greatly increase
pesticide absorption.

9. Eye exposure
The tissues of the eyes are particularly absorbent. Enough pesticide can be
absorbed through the eyes to result in serious or fatal poisoning. Granular
pesticides pose a particular hazard to the eye depending upon the size and weight
of the individual particle. Eye protection is needed when measuring or mixing
concentrated or highly toxic pesticides.
Protect yourself from eye exposure. Follow these guidelines:
1. Always wear eye protection when you measure or mix pesticides.
2. Always wear eye protection when pesticide sprays or dusts may contact
your eyes.
3. Do Not wipe your eyes with contaminated gloves or hands.
4. Be prepared to respond to accidental eye exposure quickly.
5. Protective face shields or goggles should be worn whenever there is a
chance that pesticide sprays or dusts may come in contact with the eyes.

10. Ingestion (oral exposure)
Pesticides taken through the mouth result in the most severe poisoning, compared to
other types of exposure. Pesticides can be ingested by accident, through carelessness, or
intentionally. The most frequent cases of accidental oral exposure are those in which
pesticides have been stored in an unlabelled bottle or food container. There are many
cases where people, especially children, have been poisoned by drinking pesticides from
a soft drink bottle. People have also been poisoned by drinking water stored in
contaminated containers. Workers handling pesticides or application equipment can also
consume excessive levels of pesticides if they do not wash their hands before eating or
smoking.
Protect yourself from oral exposure. Follow these guidelines:
1. Always store pesticides in their original labeled containers.
2. Never put pesticides in an unlabelled bottle or food container.
3. Never use your mouth to clear a spray hose or nozzle, or to begin siphoning a
pesticide.
4. Always wash after handling pesticides and before eating, drinking, smoking, or
using the toilet.
5. Never leave pesticides unattended.
6. Avoid splashes or dusts when mixing pesticides.
7. Label your pesticide measuring containers.

11. Injection
• Substances may enter the body if the skin is penetrated or
punctured by contaminated objects.
• Effects can then occur as the substance is circulated in the blood
and deposited in the target organs.

12. There are four different class of insecticides:
• Organophosphates
• Carbamates
• Organochlorines
• Synthetic Pyrethroid

13. Organophosphates & Carbamates
• It has been used as insecticide worldwide for more than 50 years
• It is estimated to be 30,00,000 people exposed to organophosphate or carbamate
agents each year with upto 3,00,000 fatalities.
• Toxicity generally results from accidental or intentional ingestion of, or exposure to,
insecticide/pesticide.
• Other potential causes of toxicity includes ingestion of contaminated fruit, flour, or
cooking oil, and wearing contaminated clothing.
• OP and Carbamates exhibit similar clinical manifestations with toxicity and require similar
management

14. Mechanism of Toxicity
• Inhibition of Ach-Esterase enzyme
• OP phosphorylate serine hydroxyl group at the site of action of
acetylcholine.
• Once OP binds to AChE, the enzyme can undergo one of the
following:
Endogenous hydrolysis of the phosphorylated enzyme by esterase's
or paraoxonases
Reactivation by antidote pralidoxime (2-PAM)
Irreversible binding and permanent enzyme inactivation (aging
phenomenon)
• Accumulated Ach activate muscarinic, nicotinic, CNS receptors

15. Mechanism of Toxicity
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
skeleton 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 binds to RBC cholinesterase & plasma cholinesterase
(pseudocholinesterase) in the serum.
The kinetics of the enzyme will reach zero within 10 hours with
formation of OP-AchE complex.

16. 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 inhalation exposure.
• The clinical presentation of acute cholinergic toxicity include
 Bradycardia, miosis, lacrimation, salivation, bronchorrhea,
bronchospasm, urination, emesis and diarrhoea.
• Diaphoresis may occur because sweat occur because sweat glands are
regulated through sympathetic activation of postganglionic muscarinic
receptors.
• At times, however, mydriasis and tachycardia may be observed, as
sympathetic ganglia also contain nicotinic receptors.

17. Clinical Manifestations
Cardiac-
• It includes heart block and QTc prolongation are occasionally
observed in OP agent poisoning.
Respiratory-
• Fatalities from acute OP agent poisoning generally result from
respiratory failure due to a combination of:
 depression of the CNS respiratory center
 neuromuscular weakness
 excessive respiratory secretions
 bronchoconstriction

18. Clinical Manifestations
Neurological (Intermediate)-
• 10-40 per cent of patients poisoned with OP develop a distinct
neurologic disorder 24 to 96 hours after exposure.
• Consists of characteristic neurological findings including
• Neck flexion weakness
• Decreased deep tendon reflexes
• Cranial nerve abnormalities
• Proximal muscle weakness, and
• Respiratory insufficiency
Delayed neurotoxicity-
• OP induced delayed neuropathy (OPIDN) typically occurs 1-3 weeks
after ingestion of one of a small number of specific OP agents.

19. Laboratory Evidence of OP poisoning
• Laboratory evidence of OP poisoning may be obtained by measuring
decrease 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 patients has a pre-exposure baseline
measurement for comparison (eg, as part of a workplace health
surveillance program)
• 25 per cent or greater depression in activity of RBC cholinesterase
shows a reliable measure of the toxic effect.

20. Carbamate Poisoning
It poisoning produces reversible AchE inhibition, and spontaneous
recovery of enzyme activity may occur within several hours,
making these tests less useful.

21. Pyrethroids
• They act as ion channel toxins
• They delay the closure of voltage-sensitive sodium channels & to
prolong neuronal excitation (action potential)
• They have low mammalian toxicity

22. Modes of exposure
• Occupational exposure
• Household/ indoor exposure (low risk)
• Use of permethrin as a topical treatment or sampoo for head
lice or scabies (low risk)

23. Clinical Manifestations
Mild Moderate Severe
Paraesthesia CNS depression Seizures
Nausea Increased salivation Coma
Headache Fasciculations Pulmonary oedema
Vomiting Fever Respiratory failure
Dizziness Diaphoresis
Fatigue Blurred vision
Anorexia

24. Organochlorines
• The most widely known organochlorine insecticide is DDT.
• DDT is mainly stored in the fat.
• There is also evidence that DDT and its metabolite p,p
dichlorodiphenyldichloroethylene (DDE) may have endocrine-
disrupting potential and carcinogenic action.
• In utero exposure to both DDT and DDE has been associated with
neurodevelopmental effects in children.
• The general class of organochlorine insecticides has been
associated with health effects, such as endocrine disorders,
effects on embryonic development, lipid metabolism, and
hematological and hepatic alterations.

25. Treatment
• Airway, breathing and circulation (ABC)
• Patients with dermal and inhalation exposure are more likely to cause
nosocomial poisoning then patients with GI exposure. Patients with GI
exposure should also be decontaminated.
• Case reports have described nosocomial poisoning in clinicians treating
patients who have been exposed to OP;
• Case report also describes OP toxicity from mouth-to-mouth resuscitation.
• Atropine is most commonly given intravenous (IV) form at the
recommended dose of 2-5 mg for adults and 0.05 mg/kg for children on
observation of following signs-
- Dryness of mouth
- Flushing of face
- Dilation of pupils

26. Treatment
• WHO recommends oxime therapy for any patients with clinical
significant poisoning.
• Decontamination, supportive care, aggressive antimuscarinic
therapy, seizure control and administration of oximes are
cornerstones of management
• Irrespective of class of insecticide oxime and atropine can be
used regardless of the nature of the toxic compound.

27. Dose-response
• A given amount of a toxic agent will elicit a given type and intensity of
response.
• A dose-response relationship is defined as a consistent mathematical
and biologically plausible correlation between the number of
individuals responding on a given dose over a period of exposure.
• A dose-response relationship is represented
by dose-response curve.
• Dose-response curve is represented by
plotting the dose of the chemical versus the
response in the test population.
• Dose-response curve provides information
regarding the potency of the compound. Dose-response curve

28. Limitations of dose-response terms
• It is difficult to select a test species that will closely duplicate
the human response to a specific chemical.
• Most lethal and toxic dose data are derived from acute (single
dose, short term) exposures rather than chronic (continuous,
long term) exposures,
• The LD50 or LC50 is a single value and does not indicate the toxic
effects that may occur at different dose levels.

29. Thanks