1. Pesticides were originally developed as chemical weapons and the first major pesticide, DDT, was used during World War 2 to protect soldiers. 2. Pesticide use has increased significantly since the 1940s and exposure can have adverse health effects that may not appear for years. Farmers are at high risk of exposure. 3. Pesticides are classified based on their use, toxicity level, chemical structure, and persistence in the environment. Major types include organochlorines, organophosphates, carbamates, and pyrethroids.

1. Pesticides----an overview-in progress
DrAshok Laddha
Occupational health
physician-

2. Introduction-1
 Synthetic pesticides emerge between 1930 and 1940 as a result of
research aimed at developing chemical weapons that were originally tested
in insects. One of the first compounds, dichlorodiphenyltrichloroethane
(DDT) was synthesized by Zeidler in 1874, and its insecticidal properties
were described by Paul Müller in 1939. DDT was first used during World
War II to protect American soldiers carried diseases / by vector was
marketed in US in 1945

3. Introduction-2
 Since 1940 the production, marketing and ongoing use of various pesticides has
increased to the present day, exposure to pesticides, either during their
development, production or use can have adverse effects on health and the
environment.
 These effects are not always related to immediate and apparent injuries, but can
take even years to manifest (Zuniga and Gomez, 2006). Regardless of its benefits,
it is clear that pesticides are
 Toxic chemicals deliberately created to interfere in any particular biological
system without actual selectivity. Simultaneously affect, and in varying degrees,
both the “target species” as other categories of living beings, particularly
humans. Although the general population is exposed to these compounds,
pesticide exposure to various pollutants is associated with the occupation, farmers
are in a high risk group, thus require bio monitoring studies to assess disease
caused by acute and chronic exposure to pesticides (Castro et al., 2004).

4. Use of Pesticides
 Agriculture
 Industries
 Home
 Public Health
 Maintenance of water reserves
 Maintenance of green areas
 Treatment of structures
 Livestock and domestic animals

5. Health Risk
 Pesticide exposure may pose a potential risk to humans, causing
1. Neuritis, psychiatric manifestations,
2. Hepato-renal disorders, neurological, immunological, metabolic and
endocrine disorders.
3. It has also been linked to increased incidence of leukemia and bladder cancer
in farmers, following genotoxic effects of some pesticides. Results of this type
have led many researchers to evaluate the genetic risk associated with
pesticide exposure

6. Definition
 The United Nations Organization for Food and Agriculture (FAO) defines
pesticides as any substance or mixture of substances intended for preventing,
destroying or controlling any pest, including vectors of human disease or
animal species not unwanted plants or animals that cause damage or
otherwise interfere in the production, processing, storage, transport or
marketing of food, agricultural products, wood and wood products or animal
feeds or which may be administered to animals for the control of insects ,
arachnids or other pests in or on their bodies. Therefore, the purpose of
pesticides is to destroy certain living organisms, as well as constituting a
particular group of biocides that can reach a wide lethality.

7. Classification—As per use
 Due to the large amount of chemicals and pesticides combinations of
compounds have been classified for use in insecticides, miticides, herbicides,
nematicides, fungicides, molluscicides and rodenticides.
 This ranking order from lowest to highest toxicity in numbers I through IV,
being extremely toxic, highly toxic, moderately toxic, slightly toxic,
respectively .

8. WHO Classification
 The World Health Organization proposed classification based on their health
risk, based on their toxic behavior in rats and other laboratory animals by
administering oral and dermal and estimating the median lethal dose (LD50)
that produces death in 50% of exposed animals (WHO 1990).

9. Classification-----Chemical structure
 organ chlorines,
 organophosphates,
 carbamates
 pyrethrins. And
 In addition other pesticides are as triazine herbicides, ureic, hormonal,
amides, nitro compounds, benzimidazoles, ftalamidas, bipyridyl compounds,
 ethylene dibromide, sulfur containing compounds, copper or mercury, among
others.

10. Classification—As per toxicity
 Extremely dangerous,
 highly dangerous,
 moderately dangerous and
 Slightly dangerous.

11. Classification—As per median life
 permanent,
 persistent,
 moderately persistent and
 not persistent.

12. Main source of exposure
 The main sources of pesticide exposure to humans are through the
 food chain
 air
 water
 soil
 flora and fauna.
 While acute poisoning generally affects farmers and industrial workers,
chronic poisoning is more common in the general population.

13. Routes of exposure
 Pesticides are mainly absorbed through dermal, respiratory,eye and oral
pathways.
 Although absorption through the skin is prominent in the work environment.
 The general population are more at risk from ingestion and inhalation.
 Pesticides are distribute to all around the human body through the
bloodstream and are eliminated through urine, faces and exhaled air.
 The main techniques employed in the assessment of pesticides exposure are
the history of exposure, the experts evaluation and environmental and
biological monitoring.

14. Types of effect
 Acute
 Chronic
 Delayed

15. Acute Effect
 Acute effects are illnesses or injuries that may appear immediately after
exposure to a pesticide (usually within 24 hours).
 Studying a pesticide's relative ability to cause acute effects has been the
main way to assess and compare how toxic pesticides are. Acute effects can
be measured more accurately than delayed effects, and they are more easily
diagnosed than effects that do not appear until long after the exposure. acute
effects usually are obvious and often are reversible if appropriate medical
care is given promptly.
 Pesticides cause four types of acute effects:ORAL, INHALATION, SKIN, and
EYE.

16. Organo -chlorine
 Stable compounds are too persistent in the environment and tend to
accumulate in fatty tissue.
 Its main use is in the eradication of disease vectors such as malaria, dengue
and malaria. They are also used in cultivation of grapes, lettuce, tomato,
alfalfa, corn, rice, sorghum, cotton and wood,for preservation
 His way of exposure is mainly on insects by contact or by ingestion (Ferrer
2003). In humans these substances or their metabolites act primarily at the
level of central nervous system altering the electrophysiological properties
and enzymatic neuronal membranes, causing alterations in the kinetics of the
flow of Na +and K + through the membrane of the nerve cell , resulting in the
spread of multiple action potentials for each stimulus , causing symptoms
such as seizures and acute poisoning death from respiratory arrest

17. Organophosphates
 They are esters derived from phosphoric acid. In man act on the central
nervous system by inhibiting acetyl cholinesterase, an enzyme that modulates
the amount and levels of the neurotransmitter acetylcholine, disrupting the
nerve impulse by serine phosphorylation of the hydroxyl group in the active
site of the enzyme
 The symptoms are causing loss of reflexes, headache, dizziness, nausea,
convulsions, coma and even death also described with alkylating properties ,
which from the point of view of mutagenesis is paramount because they act
directly on the deoxyribonucleic acid (DNA) adding alkyl groups
 methyl and ethyl mainly to the nitrogenous bases with nucleophilic groups
capable of reacting with electrophiles . Organo-phosphorus compounds are
most commonly used in agriculture, most are insecticides and miticides, their
way of joining these organizations is by ingestion and contact. They are used
in vegetable crops, grains, cotton, sugarcane,and etc

18. Carbamets
 They are esters derived from acids or dimethyl N-methyl carbamic acid are
used as insecticides, herbicides, fungicides and nematicides. Are less
persistent than organo-chlorines and organophosphates and likewise the latter
inhibit acetyl cholinesterase. How ever, in the case of carbamates action is
fast and the kinetics of blocking is through the carbamylation of the enzyme
by the covalent attachment of electrophilic groups steric carbamoyl sites of
the enzyme

19. Pyrethroids
 They originate from natural insecticide derived from pyrethrum extract
derived from chrysanthemum flowers, known as pyrethrins. Subsequently
were obtained synthetically and are presently manufactured around 100
different commercial products . Your income is the insects by contact or
ingestion. They act on the central nervous system causing changes in the
dynamics of the Na + channels in the membrane of the nerve cell, causing it
to increase its opening time prolonging sodium current across the membrane
in both insects and vertebrates . These events can lead to neuronal hyper
excitation .

20. Medical Management of Organochlorine
poisoning
 The goals of pharmacotherapy are to reduce morbidity and prevent
complications. No specific antidotes are available for organochlorine
poisoning; rather, the medications used in these cases include gastrointestinal
decontaminants, beta-blockers, vasopressors, supportive management and
benzodiazepines and other anticonvulsants

21. Highly toxic organochlorines
 Aldrin
 Dieldrin
 Endrin
 Endosulfan

22. Moderately toxic organochlorines
• Chlordane
• DDT
• Heptachlor
• Kepone
• Lindane
• Mirex
• Toxaphene

23. Epidemiology—International statics
 Although widespread use of organochlorine insecticides has been banned in
North America and Europe, these chemicals are used extensively in many
developing nations. An estimated 3 million cases of severe pesticide poisoning
and 220,000 deaths occur each year worldwide. Organochlorine poisoning
accounts for only a small fraction of pesticide poisoning, but the incidence
varies from 1.8% of all poisonings in South Korea to 13.3% in some parts of
India. A study of contamination in the Brazilian population showed adverse
effects on hematopoietic tissue and the liver.

24. Prognosis
 The prognosis in patients exposed to organochlorine compounds depends on
the amount and type of exposure. Pulmonary fibrosis can occur after
significant aspiration. Acute respiratory distress syndrome (ARDS) may
develop.
 Toxic doses widely vary. The fatal dose in humans is unknown; data from
nonfatal cases suggest that a dose of approximately 10 mg/kg can cause
convulsions. An oral median lethal dose (LD50) is higher than 50 mg/kg in
animal studies. The estimated approximate minimum lethal dose for humans
is 2-7 g.

25. D/D
 Arsenic Toxicity
 Hydrocarbon Toxicity
 Plant Poisoning, Herbs
 Plant Poisoning, Hypoglycemia
 Toluene Toxicity
 Toxicity, Carbon Monoxide
 Toxicity, Hydrogen Sulfide
 Toxicity, Organophosphate and Carbamate
 Toxicity, Rodenticide
 Toxicity, Terpene
 Valproate Toxicity

26. First Aid for Pesticide Poisoning
 First aid is the initial effort to help a victim while medical help is on the way.
If you are alone with the victim, make sure the victim is breathing and is not
being further exposed to the pesticide before you call for emergency help.
Apply artificial respiration if the victim is not breathing. Do not become
exposed to the pesticide yourself while you are trying to help.Look at the
pesticide labeling. It gives specific first aid instructions. Follow those
instructions carefully.
 The best first aid in pesticide emergencies is to stop the source of pesticide
exposure as quickly as possible.

27. Management -Approach Consideration-1
 Supportive treatment
 Decontamination
 Observation and repeated assessment
 Cardiac monitoring
 Use of anticonvulsant drugs-by using traditional anticonvulsant alogrithms-starting
with benzodiazepines and progressing if necessary to phenytoin or fosphenytoin,
propofol, and barbiturates.
 Use beta blockers
 B2 Agonist-Albuterol
 Anticholinergenic-Ipratropium
 If the patient is hypotensive and unresponsive to fluids, intravenous administration
of a pure alpha-adrenergic agonist agent (eg, phenylephrine) is the therapy of
choice.
 Anxiolytics==Lorezepam/Midazolam/Diazepam

28. Management -Approach Consideration-2
 In cases of ingestion, do not induce emesis
 Regardless of the route of exposure, consider multiple-dose activated
charcoal (MDAC) because it may enhance fecal elimination by interrupting the
biliary-enterohepatic and enteroenteric recirculation of the toxin.
 Aqueous-based activated charcoal should be used, as sorbitol-based activated
charcoal may induce vomiting
 Cholestyramine may be used to bind these highly lipophilic agents.
Cholestyramine reduces reabsorption and retains bound agent in the GI tract
for fecal elimination.
 Sucrose polyester (Olestra) has also been shown to increase excretion of fat-
soluble organic chlorine chemicals.
 Psychiatric evaluation, if required

29. Medical management of organo
phosphate poisoning-Goals of treatment
 Reduce absorption of the toxin (xenobiotic)
 Enhance elimination
 Neutralize toxin.

30. Epidemiology--International
 Pesticide poisonings are among the most common modes of poisoning
fatalities. In countries such as India and Nicaragua, organophosphates are
easily accessible and, therefore, a source of both intentional and
unintentional poisonings. The incidence of international organophosphate-
related human exposures appears to be underestimated.

31. Overview
 Examples of organophosphates include the following:
 Insecticides – Malathion, parathion, diazinon, fenthion, dichlorvos,
chlorpyrifos, ethion
 Nerve gases – Soman, sarin, tabun, VX
 Ophthalmic agents – Echothiophate, isoflurophate
 Antihelmintics – Trichlorfon
 Herbicides – Tribufos (DEF), merphos
 Industrial chemical (plasticizer) – Tricresyl phosphate

32. Effect of Poisoning
 Muscarinic effects
 Nicotinic effects
 Central nervous system (CNS) effects

33. Clinical Features--Muscarinic effects
 Bronchospasm
 • Bronchorrhoea
 • Miosis
 • Lachrymation
 • Urination
 • Diarrhoea
 • Hypotension
 • Bradycardia
 • Vomiting
 • Salivation

34. Clinical Features--Nicotinic effects
 Tachycardia
 • Mydriasis
 • Hypertension
 • Sweating

35. Clinical Features---Central nervous system
(CNS) effects
 Confusion
 Agitation
 Coma
 Respiratory failure
 Muscle weakness
 Paralysis
 Fasciculation's

36. Cholinesterase assays
1. Unfortunately, much confusion exists about the use and interpretation of
these assays . Some pesticides inhibit butyrylcholinesterase more effectively
than they inhibit acetylcholinesterase. Butyrylcholinesterase activity does not
relate to severity of poisoning; however, it can be used as a sensitive marker
of exposure to most organophosphorus compounds or other cholinesterase-
inhibiting compounds, and for measuring organophosphorus elimination from
the body
 Diagnosis of organophosphorus poisoning should ideally be confirmed with an
assay to measure butyrylcholinesterase activity in plasma or
 acetylcholinesterase in whole blood .

37. Treatment overview
 Treatment begins with decontamination. Airway control and oxygenation are
paramount.
 The mainstays of pharmacological therapy include atropine, pralidoxime (2-
PAM), and benzodiazepines (eg, diazepam).
 Initial management must focus on adequate use of atropine. Optimizing
oxygenation prior to the use of atropine is recommended to minimize the
potential for dysrhythmias.

38. Steps--Reduce absorption
 Removal from surface of skin, eyes and hair
 • Emesis induction
 • Gastric lavage
 • Activated charcoal administration and cathartics
 • Dilution—milk/other drinks for corrosives
 • Whole bowel irrigation
 • Endoscopic or surgical removal of ingested chemical
 • Skin decontamination—important aspect—not to be neglected:
 – Remove contaminated clothing
 – Wash with soap and water (soaps containing 30% ethanoladvocated).

39. Gastric decontamination
 Gastric lavage
 • Activated charcoal 25 g 2 hourly
 • Sorbitol as cathartic.

40. Medical care
 Airway control
 Adequate Oxygenation
 Cardiac monitoring---------mainstay of treatment
 Atropine
 PAM-2---antidote
 Benzodiazepines
 Supportive Treatment

41. Carbamate Poisoning
 Carbamate poisoning, as well as poisoning with organophosphorus compounds
(OP), have indistinguishable clinical presentation. Both are the same class of
molecules that inhibit acetylcholinesterase causing accumulation of
acetylcholine, consequently overstimulating the neural transmission [
 The medical management of carbamate poisoning consists of supportive
measures and specific antidotal treatment, that is, the anticholinergic
compound atropine.

42. Clinical Manifestation
 Clinical manifestation of carbamate poisoning is highly dependent on the dose,
type of carbamate, route of exposure, and concomitant diseases .
 Excessive stimulation of the sympathetic and parasympathetic system with
carbamates is responsible for deleterious effects on the respiratory system ranging
from difficulty breathing to respiratory failure . The muscular system is also
dependent on acetylcholine (Ach) activation and so signs of fasciculation or brief
contractures of muscles, and incoordination of movements can be observed in
some cases. Additionally, excessive sweating, headache, miosis, cramping in the
abdominal cavity, changes in the cardiovascular system are all signs of possible
carbamate poisoning . Cardiovascular system symptoms include palpitations and
changes in pulse rate, more commonly demonstrating as tachycardias .
 Fortunately, spontaneous recovery is possible within 4 hours of poisoning if the
patient presents only with nausea, vomiting, headache and excessive salivation .

43. Prevention
 The use of multiple OP/CBs and mixing/loading activities were found to be
significant risk factors for butyrylcholinesterase (BuChE) inhibition, and the
use of chemical-resistant boots and lockers for personal protective equipment
(PPE) storage were found to be protective factors. These findings supported
interventions to reduce exposure such as the implementation of engineering
controls for mixing/loading activities, requirements for appropriate footwear,
and the regular use of lockers for PPE storage