ORGANOCHLORINE COMPOUDS TOXICITY

ORGANOCHLORINE COMPOUNDS TOXICITYINTRODUCTIONIt is classified under Pesticides. Used in Agricultural field food production

Sources of Toxicity1. Accidental / Unintensional poisoning Common Storage tanks Consumption of freshly sprayed crops-LA Inhalation

Ingestion of contaminated concentrates.Drinking of water from pesticide treated paddy field .Mosquito fogging, Aerial spray.Consumption of intoxicated dairy products.Spillage of pesticide.Secondary poisoning (Dog-rat, Lawn ; Birds-Seeds )Contaminated watering & feeding vesselsExposure to SprayFaulty storageHigher concentration of pesticides2. Malicious /Intensional poisoning a. Intensional mixing in feed & fodder b. Homicidal/Suicidal

3.Occupational poisoning a. Pesticide industries b. Faulty operation-leakage, naked hand handling c.Spraying by untrained workers PesticidesInsecticides- OPC , OCC, carbamate, PyrethrinsHerbicide Inorganic & OrganicFungicides - CaptanFumigants Alliminium phosphideRodenticides - WarfarinMolluscide Metaldehyde , CuSO4Acaricides AmitrazAvicides Chloralose , EndrinNematicide AcetoproleAlgicides DichloneBird repellants GuazathineMammal repellants - Ziram

CLASSIFICATION OF INSECTICIDE

OCC - DDT, BHC, MethoxychlorOPC Malathion , DichlorovosCarbamate- Carbaryl, PropoxurPyrethroid Allethrin , DeltamethrinFormamidine AmitrazNeonicotinoid - ImidaclopridNatural products Avermectins , Nicotine

Organochlorine Insecticideare chlorinated hydrocarbonsFirst generation insecticide OC TOXICOSIS

Used in Agriculture Malarial control programsEctoparasiticide Used as Dusts, Wettable powder, Emulsions ,Suspe..

DDT - First synthesized by a German graduate student Othmar Zeidler in 1873 Rediscovered by Paul Mueller, a Swiss entomologist, in 1939

World War II, Use of DDT to control typhus and malaria.January 1, 1973 (EPA)Rachael Carson canceled all uses of DDT in the US

Further classified on properties and Degree of Toxicity

Diphenyl aliphatic compounds or DDT group- DDT, DicofolAryl hydrocarbons BHC, Mirex Cyclodiene Endosulfan, Endrin, Aldrin

PropertiesLipid Soluble poor Soluble in waterhighly volatile exptn endosulfan and perthane

OC compounds-less toxic-when small dose absorbed from gut or skinHighly stable in enviroment because they resist chemical or microbial decomposition in soil(1-12 yrs) DDT; 3-10 yrs Toxaphene; 10yrs

OCC+ Enviromental persistence = Bioaccumulation

DDTGAMMA BHCMethoxychlorFactor affecting ToxicityYoung animals adultFemale-maleFatty and lactating animal- Emaciated non lactatingStress or iIlness- seOC in oily vehicle than suspension & dry powder-ToxicCyclodiene group more toxic( DDT is least)Cats more susceptible than other domestic animalFishes > Mammals > Birds

Toxicity

Depends on , Type of compound Aliphatic , Aryl Formulation - Oily,Dry Species of animal Route Ingestion, Inhalation, dermal Toxicokinetics:Absorption It is lipid soluble absorbed through skin,oral respiratory routes. Intestinal absorption influenced by Fibre &fat diet.DDT-poorly absorption from skin & GIT except oily preparation

Entry into blood stream

Bind to Serum lipoproteins- Stored in body fat

Accumulate in Liver ,Kidney , Brain , Adrenal

Metabolism Liver microsomal Cytochrome p-450 systemConjugation with Glutathione / formation of glucouronides Cyclodiene Epoxides Diphenyl Aliphatics DechlorinatedDistributionMFOExcretionBile, Milk, Urine, Faeces-Unchanged

Half life Days to weeks

Elimination Two Compartment modelFirst phase - Rapid , 40-50% , 3-4 daysSecond phase- Slow phase-Storage fat, MonthsMechanism of actionNonspecific stimulants to CNSNo Stereo receptorsNo Known Competative AntagonistPrimary action - Interfere with Sodium Channel kinetics in Nerve membranes

Diphenyl aliphatic OC- Lipid soluble enter nerve membrane alters electrophysiological & Enzymatic properties of nerve membrane Change in Na+ & K+ flow (slowing down the Closure of Na+ by inhibiting opening of K+ - AP increaseNa+ Inflow - Increased K+ Outflow Decreased

Ion ImbalanceTransmembrane resting Potential - seAction Potential - seNeuronal excitabilitySenory nerves than Motor nervesDepolarization of medullary neuronsSeizures, Respiratory failure Primary target for Cyclodiene - GABA receptorsCyclodiene & Aryl hydrocarbons- bind to site close to or in the Cl- channel on GABA receptor

Inhibition of GABA depedent opening Cl- channel

Cl- influx into neurons

Partial Repolarization

Uncontrolled ExcitationCyclodiene Inhibition of Some ion transporters like Na+/K+-ATPase, Ca2+-ATPase, Ca-Mg ATPase. Inhibition of Calmodulin- Ca2+ binding.centration It produce changes in concentration of various biogenic amines- Serotonin ,nor adrenaline - Hyperthermia Ach-tremors & ConvulsionsSmall concentrations - depress mitochondrial respiration.Large concentration of OC cause lysis of mitochodrial membrane,uncoupling phosphorylation & blockade of ETS/ETC.(Neurotoxicity)They have endocrine disrupting properties perhaps act either as endogenous harmone mimetics or harmone blockersDDT- Estrogen agonistDDE- Estrogen Partial agonist & antagonistAnti-androgen by bind to androgen receptor(disrupt Reproductive development)

DDT - potent inducers of mixed function oxidaseDDT retained on pasture grass10percentVan Nostrand Enc. of Science and Technology (1995), p1725DDT ingested by cow and excreted in cow's milk25percentModern Toxicology (1997), p114Milk per cow per year2,769kgEncyclopedia Britannica (1906)Pasture required for one cow3.5acresEncyclopedia Britannica (1906)DDT, Pasture Grass, and Milk Per Cow

Lethal dose-50 (mg/kg)

Clinical SignsAccute toxicity: ( Within 24 hr )Fever(108 F)NauseaVomitingDiarrhoea , Urination, Salivation Bradycardia or TachycardiaRestlessness, staggers , TremorIntermittent clonic seizures- convulsionAbnormal postures, Head pressingOpisthotonus , Mydriasis Paddling, Clamping of jaws.Intoxicated bird-Sudden deathRespiratory FailureComa , Death

Resting on sternum

Emaciated

DDT toxicity

Chronic Toxicity:Sometimes deathAcute nervous signs- sed milk, egg, appetite, weightInterupted oestrous cycle, Reproductive problemsBirds Thinning of egg shells, sed HatchabilityTeratogenicity- endocrine disruptionCarcinogenicity

Endosulfan toxicity

What effects does DDT have on wildlife?

DDT is slightly to moderately toxic to birds when eaten DDE decreases the reproductive rate of birds by causing eggshell thinning and embryo deaths

DDT is highly toxic to aquatic animals (15)-affects the heart and brain

DDT is highly toxic to fish .Fish have a poor ability to detect DDT in water .

DDT moderately toxic to amphibians like frogs, toads, and salamanders. Immature amphibians are more sensitive to the effects of DDT than adults (15).

Post mortem findingsNonspecific & unreliableCarcass- bruised, Lacerated, & dirty due to convulsionsRigor is prominentPale musculature after seizures, HyperthermiaCongestion & odema of different organsDiffused endocardial haemorrhage, exceesive pericardial fluid, Congestion of lungsPetechiae on heart, Intestine, lungsOdema of brain & spinal cordDog liver centrilobular necrosis & Adrenal gland haemorrhageDiagnosisHistoryClinical signs & Clinical lesionsChemical analysis-Milk, Blood, Liver, KidneySamples- suspected sources, stomach contents, vomitus, milk fat and adipose tissues

Differential diagnosisNaCl Poisoning -no increase in temperature

Lead poisoning Not cause abnormal posture Convulsions are less

Urea poisoning- no abnormal posture ,no colic

Strychnine poisoning- convulsions -not tonic

Fluroacetate poisoning- no convulsion

Anticholinesterase poisoning OPC & Carbamate poisoning responds to it but not OCC

Comparison between organophosphates, organochlorines, and pyrethroids

TreatmentCNS Depressants : Sedatives- 24-48 hrBenzodiapines- Diazepam (0.1-0.5 mg/kg), (0.3-1.0 mg/kg) Barbiturates- Phenobarbitone Cattle & Horses 3-6 g I/V Sheep /Goat,Pig 1-2 g I/V Dog cat 2 mg/kg PO bid or tid

DogCat Xylazine Dog cat- 1 mg/kg I/V or 1-3 mg/kg I/M Cattle 0.05-0.3 mg/kg I/M Horses 0.6- 1 mg/kg I/V or 2.2-3 mg/kg I/M Sheep goat 0.05-0.1 mg/kg I/V or 0.1-0.2 mg/kg I/M Chloral hydrate Horses, Cattle 40-60 g PO or 30-40g I/V Sheep goat 2-4 gI/V

Note : IF Animal is already depressed, CNS depressants contraindicated

Calcium borogluconate (LA-200-400 ml)-prevent liver damage &neutralise preconvulsive hyperkalemia

Activated charcoal-GI contamination

Cholestyramine high lipophillic agents

Saline purgatives or Gastric lavage- oil purgatives contraindicated

If dermal route exposed-scribble gently with soapAnmal placed in warm & comfortable placePrognosisGuarded or good

Public health and ControlAccumulation of OCC in edible tissues of food animalsConsumption/ immediate sale of such toxic animals is avoidedExcessive contamination of ecosystem should be prohibited/restrictedLess usage of insecticides

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