ORGANOCHLORINE PESTICIDE - PowerPoint Presentation

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ORGANOCHLORINE PESTICIDE POISONING IN ANIMALSVPP 609 Unit II 18/11/2020

Dr.

Sanjiv

Kumar,

Assistant Professor,

Department of Veterinary Pathology,

BVC, Patna

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Organochlorines (OC) are a group of chlorinated compounds widely used as synthetic pesticides. These chemicals belong to the class of persistent organic pollutants (POPs) with high persistence in the environment. 

These

compounds are known for their high toxicity, slow degradation and bioaccumulation.

Even

though many of the compounds which belong to OC were banned in developed countries, the use of these agents has been rising.

This

concerns particularly abuse of these chemicals which is in practice across the continents

.

Though

pesticides have been developed with the concept of target organism toxicity, often non-target species are affected badly by their application

.

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Natural occurrenceMany organochlorine compounds have been isolated from natural sources ranging from bacteria to humans.

Chlorinated

organic compounds are found in nearly every class of biomolecules including 

alkaloids

, 

terpenes

, 

amino acids

, 

flavonoids

, 

steroids

, and 

fatty acids

.

Organochlorides

, including 

dioxins

, are produced in the high temperature environment of forest fires, and dioxins have been found in the preserved ashes of lightning-ignited fires that predate synthetic

dioxins.

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PesticidesThe two main groups of organochlorine insecticides are the DDT

-type compounds and the chlorinated 

alicyclics

. Their mechanism of action differs slightly.

The DDT like compounds work on the 

peripheral nervous system

. At the axon's 

sodium channel

, they prevent gate closure after activation and membrane 

depolarization

. Sodium ions leak through the nerve membrane and create a destabilizing negative "

afterpotential

" with

hyperexcitability

of the nerve. This leakage causes repeated discharges in the neuron either spontaneously or after a single stimulus

.

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Chlorinated cyclodienes include aldrin

, 

dieldrin

, 

endrin

, 

heptachlor

, 

chlordane

 and 

endosulfan

. A 2- to 8-hour exposure leads to depressed 

central nervous system

 (CNS) activity, followed by

hyperexcitability

, tremors, and then seizures. The mechanism of action is the insecticide binding at the GABA site in the 

gamma-Aminobutyric acid

 (GABA) chloride

ionophore

complex, which inhibits chloride flow into the nerve.

Other examples include 

dicofol

, 

mirex

, 

kepone

, and 

pentachlorophenol

. These can be either 

hydrophilic

 or 

hydrophobic

, depending on their molecular structure.

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Examples

Chemical names

DDT

, DDD

,

Dicofol

, Eldrin,

Dieldrin

,

Chlorobenziate

,

Lindane

, BHC,

Methoxychloro

Aldrin, Chlordane,

Heptaclor

,

Endosufan

,

Isodrin

,

Isobenzan

,

Toxaphene

,

Chloro

propylate

Organochlorines

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Chemical structure

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Pesticides

Toxicity LD

50

Use

Persistence in environment

WHO classification based on rat oral LD

50

Dichlorodiphenyltrichloro

ethane (DDT) C

14

H

9

Cl

5RatOral: 113–130 mg/kgDermal: 2510 mg/kgMiceOral: 150–300 mg/kgGunia PigsOral: 300 mg/kgRabbitOral: 400 mg/kgAcaricide InsecticideHigh Persistence Half life: 2–15 yearsModerately hazardous

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1,1-dichloro-2,2bis (p-

chlorophenyl

)ethane (DDD)

Rat

Oral: 4000 mg/kg

Insecticide

High Persistence Half life: 5–10 years

Acute hazard is unlikely

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Endrin C

12

H

8

Cl

6

O

Rat

Oral: 3 mg/kg

Dermal: 15 mg/kg

Mouse

Oral: 1.37g/kg

Intravenous: 2300 g/kg

GoatOral: 50 mg/kgRabbitOral: 60–94 mg/kgAvicideinsecticideModerate Persistence Half life: 1Day to 12 YearsHighly hazardous

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Methoxychlor

C

16

H

15

Cl

3

O

2

Rat

Oral: 5000–6000 mg/kg

Mice

Oral: 2000 mg/kg

MonkeyOral: 2500 mg/kgInsecticideHigh Persistence Half life:< 120 DaysAcute hazard is unlikely

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Lindane C

6

H

6

Cl

6

Rat

Oral: 88 – 270 mg/kg

Mouse

Oral: 59–246 mg/kg

Acaricide

Insecticide

Rodenticide

High Persistence Half life: 15 monthsModerately hazardous

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Aldrin C

12

H

8

Cl

6

Oral: 39 to 60 mg/kg

Dermal: 100 mg/kg

Mouse

Oral: 44 mg/kg

Dog

Oral: 65–95 mg/kg

Insecticide

Moderate Persistence Half life: 4–7 yearsHighly hazardous

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Biochemical toxicityOrganochlorine toxicity is mainly due to stimulation of the central nervous system. Cyclodines, such as the GABA antagonists endosulphan and lindane, inhibit the calcium ion influx and Ca- and Mg-ATPase causing release of neurotransmittors

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Biochemical effects

Sl.No

Chemical name

Organism

Biochemical effects

1

Aldrin and

Dieldrin

Human

Neurotoxic, reproductive,

developmental,immunological

, genotoxic,

tumerogenic

effects, nausea, vomiting, muscle twitching and aplastic anemiaMouse, rat, guniea pig, rabbit and dogConvulsions, loss in body weight, depression, increased irritability, salivation, hyperexitability, prostration and death2ChlordaneHumanConvulsions, tremor, mental confusion and incoordinationMiceReduced fertility, liver cancer

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BHC/ DDE

Human

Cyst in hands, itching, psoriasis, eczema,

leucoderma

, skin rashes

DDT

Human

Prickling sensation of the mouth, nausea, dizziness, confusion, headache, lethargy, incoordination, vomiting, fatigue, tremors in the extremities, anorexia,

anemia

, muscular weakness,

hyperexcitability

, anxiety, and nervous tension

Mice

Liver tumors, liver changes including hepatocellular hypertrophy, margination and formation of lipospheres.BirdsEgg shell thinning

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Lindane

Human

Damage human liver, kidney, neural and immune systems, and induces birth defects cancer, cause neurotoxicity, reproductive toxicity and hepatotoxicity

Rats

Alters gene expression of liver and hepatotoxicity

Methoxychlor

Rats

Reduced fertility

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SignsThe organochlorines most commonly stimulate the CNS, and symptoms can range from paresthesias to seizures. With large exposures and severe toxicity, status epilepticus with respiratory failure and death can ensue. In addition, nonspecific neurologic symptoms such as nausea, vomiting, headaches, and dizziness can also be seen. Myoclonus, increased deep tendon reflexes and tremors are also reported following toxic exposures.Some of these agents can cause sudden seizures, without any prodromal symptoms. These include

lindane

,

cyclodienes

and

toxaphene

. These sudden seizures can happen from 1 to 6 hours post-exposure, and the effects can last for days in severe cases.

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DiagnosisThe nervous system manifestations, signs, and symptoms described above are the most common clinical effects demonstrable after acute exposure to these agents. The differential diagnosis of this presentation includes other causes of seizures such as CNS infection and proconvulsant toxins such as theophylline, amphetamine derivatives, cocaine, camphor, INH and tricyclic antidepressants.

A noxious, turpentine-like odor is described with

toxaphene

.

Endosulfan

imparts the smell of rotten eggs due to its high sulfur content.

Many

of the organochlorine agents are radio-opaque, so a plain radiograph of the GI tract may be helpful in estimating the dose ingested in select cases where organochlorine oral exposure is suspected

.

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Definitive laboratory confirmation of the presence of organochlorines in the serum, urine or tissues can be done using gas chromatography, but this process typically takes days and is not useful in the acute management of these agents. Where lindane

is suspected as a toxin, serum concentrations can help to guide management and prognosis. A level of 0.02 to 0.20 mg/L is indicative of a toxic exposure with higher levels at greater risk for seizures.

It is important to note that specialized testing is not readily available so test results may be delayed for days to weeks after specimens are collected and sent; clinical signs and symptoms are therefore paramount for diagnosis and management of these ingestions.

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TreatmentNo specific antidotes are available for organochlorine poisoning. Decontamination may be indicated to prevent continued absorption, as well as exposure.

Close attention must be paid to the airway and respirations of any patients in whom organochlorine toxicity is suspected.

Oral exposures are difficult to manage because the risk of seizures and subsequent CNS depression precludes the use of activated charcoal in many cases. However, in cases that present within an hour of ingestion and in which the patient is still asymptomatic, a dose of activated charcoal may help prevent absorption from the intestines and enhance elimination from the GI tract

.

The

enteral use of resins or lipophilic compounds that can sequester the toxin in the GI tract. Cholestyramine and olestra (a non-absorbed fat substitute) have both been utilized for this purpose

.

Although these agents may theoretically enhance the elimination of organochlorines after chronic exposures, they have not been studied in acute poisonings.

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When seizures occur from organochlorine compound toxicity they should be managed using standard care procedures for protecting the airway and maintaining oxygenation. General anticonvulsants such as benzodiazepines (with barbiturates or propofol

as second line agents) should be used in cases of status epilepticus.

It

is important to monitor for and recognize the

dysrhythmogenic

effects of organochlorine agents

.

Instead of epinephrine as first line therapy, beta-adrenergic blocking agents and magnesium are administered

initially.

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