More Related Content
Similar to Pesticides
Similar to Pesticides (20)
Recently uploaded
Recently uploaded (20)
Pesticides
- 1. PESTICIDES
- 2. PESTICIDES • Single or mixture of substances • Used from ancient to modern times • Arsenic – herbicide, fumigant • Copper-fungicide, utensils • Nicotine – insecticide • Gerhard Schrader- Father of organophophorous insecticide • Toxicity – mostly non-target species • Dermal, inhalation and oral route
- 3. Regulatory • EPA • Federal Insecticide, Fungicide and Rodenticide Act – Pesticides for use • Federal Food, Drug and Cosmetic Act – allowable residues in human and animal food
- 4. Insecticides • All neurotoxicants • Nontarget species • Organophosphorous • Carbamates • Pyrethroids • Organochlorine • Other and Old New Insecticides • Rotenoids • Nicotine • Neonicotinoids • Formamidines • Avermectins • Phenylpyrozoles • Diamides • Bacillus Thuringiensis • Insect Repellents • DEET • Picaridin
- 5. Organophosphorous Compounds • Phosphorous double bonded to oxygen (P=S, phosphorothio) • Sensitive to hydrolysis • Target esterases & Glutathione S-transferases • A –esterases (paraoxanase) • B-esterases (butylcholine) • Acetyl choline esterase (Hallmark of OP toxicity) • Toxicity of ACE inhibition • Overstimulation of cholinergenic receptors (Symptoms, increased sweating, saliva, brochonconstriction, secretion, miosis, increased gastronintestional motility, diarrhea, tremors, muscular twitching, and various central nervous system) • Reactivation slow depends on dimethoxy>diethoxy>>diisopropoxy
- 6. Organophosphorous Toxicity • Treatment • Atropine – dosage important • Oxime (2-PAM) – none or harmful effect • Diazepam to reduce anxiety • Aging is a factor • Biochemical measurements • RBC AChE and Plasma BuChE • P-nitrophenol in urine for parathion or methyl parathion • 3,5,6 trichloropyridinol –chlorpyrifos or methyl chlorpyrifos • DMP, DEP, DMTP and DETP • Toxicity • Intermediate Syndrome – weakness in muscles • Organophosphate induced delayed polyneuropathy • Tingling of hands and feet, progressive muscle weekness, sensory loss, distal sensory motor axonopathy • Classic example – Ginger Jake Paralysis. Tri-ortho-cresyl phosphate (TOCP) • Caused by NEUROPATHY TARGET ESTERASE • Depending on Aging, treatment can promote or prevent the damage Long term – Developmental toxicity in Children
- 7. Carbamates • Derive from carbamic acid • Carbaryl – low tox and Aldicarb – high tox • Inhibit AceE and ButE, rapidly reversible • Symptoms, miosis, urination, diarrhea, salivation, muscle fasciculation • Direct inhibitors of AceE, do not require bioactivation • Atropine treatment • Oximes – aggravate the toxicity • Somecase peripheral neuropathy • Aging do not require • Before OP toxicity –carbamate protection • After OP toxicity - promotion
- 8. Pyrethroids • Extracts of chrisanthenum cinerariaefolium • Natural one decomposes under light • Acid moiety, ester bond and alcohol moiety • Modify voltage gated sodium channels • Exits in cis and trans form; cis more toxic than trans • Eg: LD50 trans-resmethirin 8000mg/kg cis 100 mg/kg • Type I and Type II ( Cyano group) • Biotransformation • Hydrolysis of ester – CarE (heptatic and plasma) • Oxidation of alcohol moiety – CytP450 • Type II less sensitive to hydrolysis because of cyano group • Type II- bioactivation by CyP450 • Piperonyl butoxide used as synergist; (inhibits CyP450)
- 9. Type II Pyrethroid • Behavioral arousal, aggressive sparing and tremor • T-Syndrome • Disruption of voltage gated sodium channel • Slow the activation( opening) • Stable hyperexcitable state Type I Pyrethroid • Clonic Seizures and choreoathetosis • CS- Syndrome • Presence of cyano group • Prolongs channel opening • Eventually depolarization • GABA gated chloride channels (ivermectin and phenobarbital prevents) • Calcium ATPase and Ca channels, stimulate PKC • Deltamethrin impregnated beds do not pose problems in children • Occupational paresthesia (tingling) • Topical Vit E • Toxic to fish but not birds
- 10. Organochlorine Compounds • DDT and analogs, cyclodienes and hexachlorocyclohexanes • World over, malaria control • Acute – neurotoxic (moderate than OP) • Chronic – Liver and reproductive system • Isomers (p,p’-DDT strongest) • Stored in adipose; slow biotransformation; excreted in bile, urine and milk • Acute effects - motor unrest, spontaneous muscle movement, abnormal susceptible to fear and other stimuli. fine and course tremors and tonic-clonic convulsions • Hyperesthesia and paresthesia • Mechanism: Sodium channel, Na+ K+ and Ca+ ATPase • Phenytoin and calcium gluconate – in animals • Diazepam and phenobarbital –in humans • Potent inducer of P450cyp2b and CYP3A. • Hepatocarcinogenic in mice and rats; lung tumors and adenoma • Possible human carcinogen • Current alternative dimethoxy pp DDT – Similar effects • Picrotoxin toxin binding site
- 11. Hexachlorocyclohexanes and Cyclodienes • Neurotoxic • Lindane –gamma isomer of BHC • Banned Agri but in shampoo • Convulsions • GABA chloride channel • Phenobarbital and diazepam Mirex and chlordecone • Fire ants and leaf eating insects • Hopewell, VA incident • Tremors • Inhibition of Na, K and Mg ATPases and catecholamine intake • Cholestryamine
- 12. Rotenoids • East Asian Derris Plant • High content rotenone • Toxic to fish; fish capture • Blocks NADH-ubiquinone reductase or complex 1 • Increase cardiac rates and respiration depression • Role in Parkinson Disease Models • Protein inclusions and lewy bodies – rotenone model of PD Nicotine • Alkaloid in tobacco plants • Activates NAChreceptors • Nausea, vomiting, muscle weakness and green tobacco sickness
- 13. Neonicotinoids • Nitromethylene, nitroimine and cyanoimine • Targeted towards insect NAChReceptors Formamidines • Structural similar to norepinephrine • Activates Octopamine dependent adenylate cyclase • (OctP receptors same as adrengenic receptors) • Probable human carcinogen • Bradycardia and hypotension • Yohimbine and adrenoceptor antagonists
- 14. Avermectins • Fungal product • Macrocyclic lactones • Veterinary (antihelminitic and antiparistic) • Humans (intestinal worms, river blindness and lymphatic filariasis) • Activate GABA chloride • Interact with -PGlycoprotein Phenylpyrazole • Block GABA-Cl • Glutamate-activated chloride
- 15. Diamides • Activation of Ryanodine receptors (Ca Receptors) • Muscle contraction Bacillus Thuringiensis • Soil microorganism – produce insecticidal protein • Bt spores contain crystals of Cry and Cyt proteins • Insect ingest, protein toxin in midgut and K+influx; high PH, osmotic lysis
- 16. Insect Repellants DEET • Biotransform CYP450 and excreted in urine/ No strong evidence • Lesions in male rats (alpha-2- globulin) • Similar to nikethamide (convulsant) • Inconclusive BBB transport • Recommended • Children: 10% Adults 30% Picaridin • Biotransform hydroxylation and glucuronidation, and excreted in urine • Olfactory receptors