pharmacology and toxicology slides .pptx

toxicology

1. Presentation on : Toxicity of pesticides and household products Prepared by: Mahderekal Welegewergis ID NO: CHS/PRB/001/16 7/14/2024 1

2. OUTLINES Introduction to pesticides Toxicity of Insecticides Toxicity of Herbicides Toxicity of Fungicides Toxicity of Rodenticides T oxicity of household products 7/14/2024 2

3. DEFINITION OF PESTIC I DES “ Any substance or mixture of substances intended for preventing, destroying, repelling, or mitigating any insects, rodents, nematodes, fungi, or weeds, or any other forms of life declared to be pests; any substance or mixture of substances intended for use as a plant regulator, defoliant, or desiccant.” --Federal Insecticide, Fungicide, and Rodenticide Act (US EPA) 7/14/2024 3

4. 1. INSECTICIDES ORGANOPHOSPHATES AND CARBAMATES Group of chemicals share a common mechanism of cholinesterase inhibition and hence can cause similar symptoms . The inhibition of acetyl cholinesterase is responsible for the acute symptomatology Unlike organophosphate poisoning, carbamate poisoning tend to be of shorter duration because the inhibition of nerve tissue AChE is reversible. 7/14/2024 4

5. Organophosphates Mechanism of toxic action irreversible inhibition of enzymes, particularly of acetylcholinesterase on nerve synapses (by phosphorylation of hydroxyl group of serine bound in the active centre of ACHE). 7/14/2024 5

6. Carbamate pesticides - insecticides - herbicides - fungicides Mechanism of the toxic action – reversible inhibition of acetylcholinesterase (by carboxylation of hydroxyl group of serine bound in the active centre of ACHE). Carbofuran is very up-to-date substance in toxicology. It is used to control vermin (foxes) and is used in baits. Birds are 10 times more sensitive to carbofuran than mammals (LD50 for mammals 3 – 19 mg/kg body weight). Frequent carbofuran poisoning cases among predatory birds. 7/14/2024 6

7. OP Carbamates Parathion Propoxur Azinphos-methyl Methomyl Diclorvos Carbofuran Naled Aldicarb Fenamiphos Carbaryl Methidathion Fenoxycarb Oxydemeton-methyl Thiodicarb malathion Oxamyl C ont ’ 7/14/2024 7

8. CLINICAL SIGNS Eye contact: - Irritation or pain, lacrymation, swelling, blurring of vision. Inhalation: - Cough, difficulty in breathing, bronchitis, pneumonia. Ingestion: - Nausea, vomiting, diarrhoea, sweating, salivation, small or pin point pupils, muscle twitching, fasciculation. 7/14/2024 8

9. Management of toxicity Antidotes: Atropine: Blocks muscarinic receptors, reversing the effects of acetylcholine buildup, but does not address nicotinic effects. Pralidoxime (2-PAM ): Reactivates acetylcholinesterase , allowing the breakdown of acetylcholine and reversing both muscarinic and nicotinic effects. Supportive Care : Airway management (intubation if necessary) Oxygen therapy Fluid resuscitation Decontamination (removing contaminated clothing, washing skin with soap and water) Monitor for complications: seizures, respiratory failure, and cardiac arrhythmias. 7/14/2024 9

10. ORGANOCHLORINES Very few organochlorines are used now as pesticides. Organochlorines are very toxic if ingested or inhaled. Some are readily absorbed through the intact skin. MECHANISM OF ACTION :- Organochlorines works by opening the sodium ion channels in the neurons or nerve cell thus prduces spasm and cotractions . 7/14/2024 10

11. CLINICAL SIGNS Skin contact: - Dermatitis Inhalation: - Inhalation can give rise to irritation of eyes, nose, throat and cough. Ingestion: - Nausea, vomiting, diarrhoea, abdominal pain, headache, dizziness, convulsions and coma. 7/14/2024 11

12. Management Antidote: No specific antidote available. Supportive Care : Seizure management: Benzodiazepines (e.g., diazepam) Hepatic support: Monitor liver function and provide supportive care. Decontamination (removing contaminated clothing, washing skin with soap and water) Monitor for complications: respiratory failure, and cardiac arrhythmias. 7/14/2024 12

13. Pyrethroids Mechanism of the toxic action - pyrethroids T (tremor) – contain no α- cyano group cause reversible block of sodium channels (e.g. permethrin ) pyrethroids CS ( choreoatetosis , salivation) – contain α- cyano group cause reversible block of sodium channels and inhibition of GABA (e.g. deltamethrin ) 7/14/2024 13

14. CLINICAL SIGNS Inhalation :- Allergic manifestations such as wheezing. Ingestion: After ingestion pyrethrums have low toxicity, vomiting, epigastric pain and diarrhoea are the common features. Eye contact: Lacrymation , oedema of the eyelids. Skin contact: Allergic dermatitis. 7/14/2024 14

15. Management of toxicity Antidote: No specific antidote available . Supportive Care : Seizure management: Benzodiazepines (e.g., diazepam) Respiratory support: Oxygen therapy and mechanical ventilation if necessary. Decontamination (removing contaminated clothing, washing skin with soap and water) Monitor for complications: respiratory failure, and cardiac arrhythmias . 7/14/2024 15

16. 2 . Herbicides Phenoxyacetic acid based herbicide (MCPA ) Mechanism of the toxic action – disruption of oxidation and phosphorylation processes (drop in the ATP production and disruption of energy metabolism). They are little toxic for mammals, fish, bees. Symptoms of poisoning: hypotermia , hypodynamia , paresis, paralysis, tympania in ruminants. But: In the production and use of those herbicides (2, 4-D; 2,4,5-T) dioxin was produced. 7/14/2024 16

17. Bipyridil – based herbicides They are very rapidly deactivated in soil, but leave residues in plants: diquat for 3 – 5 days, paraquat for 21 days. Diquat ( Reglone ) LD 50 for cattle 30 – 50 mg.kg -1 l.w . for rabbit 280 mg.kg -1 l.w . Symptoms of poisoning – pulmonary oedema, damage of liver and kidneys, arthritis, periarthritis 7/14/2024 17

18. Paraquat ( Gramoxone ) LD 50 for man 40 mg.kg -1 l.w . for cattle and pigs 30 – 70 mg.kg -1 l.w . for dogs and cats 25 – 50 mg.kg -1 l.w . Mechanism of toxic action – is mediated by - free oxygen radicals - proteolytic enzymes formed by active neutrophilic leucocytes Symptoms of poisoning – pulmonary oedema, fibrotic pneumonia fetotoxicity,retardation of ossification 7/14/2024 18

19. Diazine and triazine herb icides Diazine pesticides are less toxic than triazine ones Mechanism of the toxic action – triazines are antimetabolites of pirimidine bases - components of nucleic acids and folic acid atrazine damages the liver detoxication functions simazine , prometryne , terbutryne – inhibit haematopoiesis Toxicity: toxic for fish relatively harmless for bees LD 50 for mammals exceeds 1000 mg.kg -1 live weight 7/14/2024 19

20. Serious risk of triazine – based herbicides very low biodegradability (risk for drinking water) triazines are secondary amines (secondary amines + nitrosation agents nitrosamines) atrazine has xenoestrogenic effects (causes abnormal development of gonads, turns amphibians into hermaphrodites) 7/14/2024 20

21. Management of toxicity Decontamination: Remove contaminated clothing and wash skin with soap and water. Irrigate eyes with water for 15 minutes. Gastrointestinal Decontamination: Activated charcoal may be administered if ingested within 1 hour. * **Supportive Care:** Monitor for complications and provide treatment for any specific symptoms. 7/14/2024 21

22. 3. Fungicides Pentachlorophenol Pentachlorophenol is one of known fungicide It is also called penta , and used as a wood preservative for fungus decay or against termites, as well as a molluscicide Pentachlorophenol is absorbed via the skin, lung, and gastrointestinal tract In fatal cases of poisoning from pentachlorophenol, body temperatures increases as high as 41.8 °C (107.4 °F) 7/14/2024 22

23. Cont ’ Mechanism of action The biochemical mechanism of action is through an increase in oxidative metabolism from the uncoupling of oxidative phosphorylation  This increase in oxidative metabolism in poisonings can lead to an increase in body temperature 7/14/2024 23

24. Clinical signs Severe overexposure to pentachlorophenol can cause delirium, flushing, pyrexia, diaphoresis, tachypnea, abdominal pain, nausea, and tachycardia 7/14/2024 24

25. Dithiocarbamates / Thiocarbamates The dithiocarbamates and the thiocarbamates are used as fungicidal compounds and have little insecticidal toxicity, unlike the N -methyl carbamates , Thiocarbamate fungicides include: Thiram ( AAtack ), Metam -sodium ( Vapam ), Ziram ( Ziram 76), Ferbam , and Ethylene bis dithiocarbamate (EBDC) compounds 7/14/2024 25

26. Cont ’ Thiram dust may cause eye, skin, and mucous membrane irritation, with contact dermatitis and sensitization  Thiram , like disulfiram , is not a cholinesterase inhibitor, but does cause inhibition of the enzyme acetaldehyde dehydrogenase (responsible for the conversion of acetaldehyde to acetic acid)  Exposure to ziram , ferbam, and the EBDC compounds have been associated with skin, eye, and respiratory tract irritation in humans  Maneb and zineb have been associated with cases of chronic dermatological disease, possibly due to dermal sensitization to these compounds in workers 7/14/2024 26

27. Chlorothalonil Chlorothalonil (Bravo, Daconil ) (2,4,5,6-tetrachloro-1,3-benzenedicarbonitrile) has been reported to cause dermal and mucous membrane irritant effects Chlorothalonil appears to have low potential for toxicity in humans Copper Compounds Exposure to dust and powder formulations of copper-based fungicides has been reported to cause irritation of the skin, eyes, and respiratory tract Systemic intoxication in humans by copper fungicides has been rarely reported 7/14/2024 27

28. Management of toxicity Decontamination by inducing vomiting and gastric lavage. Specific antidote is superactivated charcoal and immunosuppressants . Supportive care for organ dysfunction. 7/14/2024 28

29. 4. Rodenticides The most efficient route of exposure of these compounds is via ingestion The rodenticides acts by depression of the vitamin K synthesis of the blood clotting factors II ( prothrombin ), VII, IX, and X This anti-coagulant property manifests as diffuse internal hemorrhaging occurring typically after several days of rodenticide bait ingestion Warfarin is a commonly used coumarin rodenticide 7/14/2024 29

30. Thallium Sulfate  Thallium sulfate is readily absorbed via ingestion and dermally, as well as via inhalation  The target organs of thallium sulfate are gastrointestinal tract (hemorrhagic gastroenteritis), heart and blood vessels, kidneys, liver, skin, and the hair  Symptoms such as headache, lethargy, muscle weakness, numbness, tremor, ataxia, myoclonia , convulsions, delirium, and coma  Death from thallium sulfate intoxication is due to respiratory paralysis or cardiovascular failure 7/14/2024 30

31. Sodium Fluoroacetate Sodium fluoroacetate is also known as 1080 (registered trademark) This compound is easily absorbed via ingestion as well as through inhalation and dermal routes Fluorocitrate adversely affects cellular respiration through disruption of the tricarboxylic acid cycle (inhibiting the enzyme cis-aconitase ) The accumulation of citrate in tissues also accounts for some of the acute toxicity associated with this compound 7/14/2024 31

32. Management of toxicity Serum, urine, and hair thallium levels can be used to assess exposure to this compound There is no specific treatment for thallium sulfate and Sodium fluoroacetate poisoning , and treatment is supportive Syrup of ipecac and activated charcoal can be used to decrease gastrointestinal absorption 7/14/2024 32

33. Household products Household products are a common source of poisoning, especially in children . C hildren are particularly vulnerable to household toxicity due to their smaller size and tendency to explore. O lder adults may also be susceptible to the effects of toxins due to accidental and intentional poisoning 7/14/2024 33

34. Cleaning Products Alkalis (Caustic): Lye, drain cleaners, oven cleaners, ammonia, bleach. Acids : Toilet bowl cleaners, rust removers. Solvents: Acetone, turpentine, paint thinners. Detergents : Dishwashing liquids, laundry detergents. 7/14/2024 34

35. Personal Care Products Cosmetics : Nail polish remover, hair dye, perfume. Medications : Over-the-counter pain relievers, cough syrups, vitamins, and prescription medications. 7/14/2024 35

36. Household Chemicals Glues and Adhesives: Super glue, epoxy resin. Paints and Stains: Paint thinners, varnishes. Batteries : Button batteries 7/14/2024 36

37. Others Plants : Certain houseplants can be toxic if ingested (e.g., lilies, dieffenbachia). Food : Spoiled food, improperly stored food. Metals : Lead-based paints, mercury thermometers . Pesticides 7/14/2024 37

38. Signs and Symptoms of Household Toxicity: Ingestion : Nausea, vomiting, abdominal pain, diarrhea, drooling, difficulty swallowing, burning sensation in the mouth and throat . Inhalation: Coughing, wheezing, shortness of breath, dizziness, headache, nausea. Dermal: Skin irritation, redness, rash, blistering, burns. Ocular: Eye irritation, redness, burning sensation, blurred vision. Neurological : Drowsiness, confusion, seizures, coma. Cardiovascular : Rapid or slow heart rate, irregular heartbeat, low blood pressure. 7/14/2024 38

39. Management of Household Toxicity 7/14/2024 39

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