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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