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Pesticide Illness Part 2

Pesticide Illness Part 2. Insecticides. Prepared by: Rupali Das, MD, MPH, California Department of Health Services, Michael O’Malley, MD, MPH, University of California, Davis, Laura Styles, MPH, Public Health Institute.

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Pesticide Illness Part 2

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  1. Pesticide IllnessPart 2 Insecticides Prepared by: Rupali Das, MD, MPH, California Department of Health Services, Michael O’Malley, MD, MPH, University of California, Davis, Laura Styles, MPH, Public Health Institute

  2. Toxicology, Diagnosis & Management of Pesticide Illness by Functional Category • Insecticides • Fumigants • Fungicides • Herbicides • Disinfectants • Miscellaneous

  3. Insecticides • Cholinesterase Inhibitors • Carbamates • Organophosphates • Pyrethrins & Pyrethroids • Organochlorines

  4. InsecticidesCholinesterase Inhibitors • N-methyl Carbamates • aldicarb (Temik), carbofuran (Furadan), carbaryl (Sevin) • Organophosphates (OPs) • chlorpyrifos (Dursban, Lorsban), diazinon, malathion R O N C R X Generic structure for N—methyl carbamates RO O P OX RO Generic structure for organophosphates

  5. Cholinesterase Normal Function 1. Nerve signal releases ACh Acetyl CoA + Choline 5. Choline reuptake Acetylcholine (ACh) Choline + Acetyl Cholinergic Nerve Terminal Acetylcholinesterase 2. ACh binds to receptor 4. Choline regeneration by acetylcholinesterase 3. End organ activates in presence of acetylcholine

  6. Inhibition of Cholinesterase 1. Nerve signal releases ACh 4. OP binds to cholinesterase, preventing regeneration Acetylcholine R1 R2 O==P O Cholinergic Nerve Terminal 2. ACh binds to receptor 3. Activity of end organ does not cease

  7. Organophosphates & Carbamates Signs & Symptoms (I) System Receptor Organ Sign/symptom ParasympatheticMuscarinicEyeMiosis,Blurred vision Parasympathetic MuscarinicGlandsTearing, salivation,sweating, & Sympathetic pulmonaryedema Heart Bradycardia,arrhythmia Misc. Broncho-,smooth constriction,muscle vomiting, diarrhea, excess or involuntary urination

  8. Organophosphates & Carbamates Signs & Symptoms (II) System Receptor Organ Sign/symptom Neuro- NicotinicSkeletal Fasciculations, muscularmuscle cramps, twitching (Parasympathetic) muscle weakness, paralysis CNS Brain Headache,dizziness, malaise, confusion,bizarre behavior, loss of consciousness

  9. Salivation Lacrimation Urination Diarrhea Diarrhea Urination Miosis Bronchorrhea Emesis Lacrimation Salivation Commonly-used Acronyms for Cholinesterase Inhibition Syndromes

  10. Cholinesterase Inhibitors Clinical Presentations Vary • Some signs & symptoms may be absent • Bronchorrhea more likely with high-dose exposures (ingestion) • Common presentations • Nausea, vomiting • Miosis • Sweating, urinary frequency • Non-specific constitutional symptoms

  11. Case Farmworker with Multiple Symptoms • 66 year-old male with eye irritation, abdominal pain, nausea, vomiting, headache, dizziness, frequent urination, muscle shaking. Symptoms began after weeding a cotton field for 4 hours. • Occasional palpitations but no other symptoms over the past 6 months • 33 other crew members complain of similar symptoms

  12. Farmworker with Multiple SymptomsExposure History • 4:00 am: Aerial application of • Carbofuran (N-methyl carbamate) • Abamectin (macrolytic lactone) • Mepiquat chloride (growth regulator) • 6:00 am: Workers entered field • 10:00 am: Symptoms

  13. Farmworker with Multiple SymptomsPhysical Exam • Nausea & abdominal pain • Conjunctival injection • Irregularly irregular pulse; rate 106-155, • Lungs clear, no murmurs; neurological exam normal This warning sign was posted after the workers entered the field and became ill.

  14. Farmworker with Multiple SymptomsInitial Laboratory Results • EKG • TFTs, CPK

  15. Farmworker with Multiple Symptoms Initial Summary & Differential Diagnosis • Differential diagnoses • Myocardial infarction (ruled out with CPK) • Thyroid disease (ruled out with TFT) • Food-borne illness (ruled out: no common food source) • Atrial fibrillation unrelated to pesticides • Pesticide-related illness

  16. Farmworker with Multiple SymptomsToxicity of Pesticides Involved • Carbofuran: N-methyl carbamate • Abamectin: macrolytic lactone • Mepiquat chloride: growth regulator

  17. Cholinesterase-inhibitor Poisoning: Confirmatory Tests • Cholinesterase blood tests • Urine metabolites • Foliage and clothing pesticide residues • Diagnosis is primarily clinical

  18. Cholinesterase Blood Tests • Two cholinesterase enzymes • RBC • “true”/ acetylcholinesterase • Plasma • “pseudo”/ butyrylcholinesterase • Preferential inhibition possible • Dichlorvos: plasma > RBC cholinesterase

  19. Cholinesterase Blood Tests Interpretation • 20% variability in population “baseline” • Correlation with symptoms unpredictable • Enzyme activity reversible • Carbamates • Sample temperature • Storage time

  20. Cholinesterase Blood TestsUses Biologic monitoring of workers potentially exposed to cholinesterase inhibitors Retrospective diagnosis of acute poisoning with cholinesterase inhibitors RBC Plasma

  21. Urine Metabolites • Sensitive indicator of pesticide exposure • Results do not correlate with health effects • Requires specific pesticide information • Clinical labs may not perform tests

  22. Pesticide Residues on Foliage & Clothing • Provides evidence of pesticide exposure in environment • Does not prove internal exposure • Limited clinical availability

  23. Farmworker with Multiple SymptomsPesticide Lab Test Results • Cholinesterase • Plasma-- 4,142 u/L • (lab normal range 1,667-5,883) • RBC-- 4,167 u/L • (lab normal range 8,871-16,993) • Urine metabolites of carbofuran • Carbofuran 7-phenol • Carbofuran 3-keto-7-phenol • Carbofuran 3-hydroxy-7-phenol

  24. Foliage Carbofuran up to 0.77 g/cm2 Abamectin up to 0.009 g/cm2 Dicofol up to 0.58 g/cm2 Clothing (per item) Carbofuran up to 91 mg Abamectin up to 6000 g Farmworker with Multiple SymptomsPesticide Residue Analysis

  25. Farmworker with Multiple SymptomsAssessment & Case Classification Definite Pesticide-Related Illness1: • Evidence of pesticide exposure • Pesticide-related adverse health effects • Exposure—effect relationship 1NIOSH case definition (CDC 2000) http://www.cdc.gov/niosh/pestsurv/

  26. Specific Management for Cholinesterase Inhibitor Poisoning • Collect serum, urine, & clothing samples • Hospitalize for severe symptoms • Specific treatment • Atropine • Pralidoxime (2-PAM)--OPs only • Workplace restrictions

  27. Cholinesterase Inhibitors: TreatmentAtropine vs. 2-PAM

  28. Treatment: Atropine • Reverses SLUD, DUMBELS syndrome • Intravenous dose: • Diagnostic • 1 mg adult • 0.01 mg/kg pediatric • Therapeutic • 1 mg - 4 mg adult • 0.05 mg/kg pediatric • Repeat every 10-30 minutes

  29. Treatment: Pralidoxime (2-PAM) • Enzyme aging occurs if not treated • Treatment effective within 48 hours • 2-PAM reactivates cholinesterase • Cholinesterase levels rise Permanent bond No treatment Aging AChE OP AChE--OP 2-PAM AChE + OP 2-PAM Regenerated enzyme

  30. 2-PAM Treatment Regimen • IV infusion over 30 minutes or longer • > 12 years • 1.0-2.0 g at < 0.2 g/min in 100 mL saline • < 12 years • 20-50 mg/kg body weight in 100 mL saline • Repeat doses usually required • 1-2 hours, then 10-12 hour intervals • Treatment side effects • Arrhythmia • Hypertension

  31. Farmworker with Multiple SymptomsCase Management & Course • Decontamination • Intravenous hydration • Treatment of atrial fibrillation • Converted to sinus rhythm as outpatient • Grower fined

  32. Farmworker with Multiple SymptomsCarbamates and Persistent Effects • Health effects reported three months after exposure • Possible explanations: • Persistent effects of acute exposure • Continued exposure • Anecdotal reports but literature lacking

  33. Case Grape Harvester with Subacute Poisoning • 25 year-old grape harvester with dizziness, disorientation, and vomiting. • Vital signs normal; mild epigastric and suprapubic tenderness. CBC and chemistry normal. • Discharged after treatment with 2.5 liters of 5% dextrose/ 0.25 normal saline

  34. Grape Harvester with Subacute PoisoningPersistent Symptoms • 24 hours later: persistent weakness, dizziness, diarrhea, crampy abdominal pain, lacrimation, and salivation. • Examination: weak, pulse rate 48 beats/min; vital signs otherwise normal. Pupils 3 mm, lungs clear, abdomen nontender. • Labs: • Normal CBC, chemistry panel, UA. • Cholinesterase: Plasma 304 u/L (964 - 2,400) RBC 4,360 u/L (9,348 - 16,996 u/L)

  35. Grape Harvester with Subacute PoisoningExposure History • Phosalone emulsion applied to grapes • half-life up to 30 days • Worker entered field one week after restricted entry interval • Residues of phosalone on leaf samples

  36. Severe bradycardia while in hospital Heart rate responded to atropine IV Excess respiratory secretions absent Grape Harvester with Subacute PoisoningHospital Course

  37. Health effects among crew: Asymptomatic bradycardia Asymptomatic plasma, RBC cholinesterasedepression Grape Harvester with Subacute PoisoningIllness Among Coworkers

  38. Grape Harvester with Subacute PoisoningIncident Summary • Gradual-onset poisoning • Respiratory symptoms absent • Sentinel health event • Phosalone use restricted

  39. Acute Non-Cholinesterase Effects of Organophosphates • Odor health effects • Irritant effects • Organophosphate-induced delayed polyneuropathy (OPIDP)

  40. Insecticides • Cholinesterase Inhibitors • Carbamates • Organophosphates • Pyrethrins & Pyrethroids • Organochlorines

  41. InsecticidesPyrethrins & Pyrethroids • Pyrethrins • Natural insecticidal extract • Unstable • Pyrethroids • Synthetic derivatives • Used with piperonyl butoxide

  42. Pyrethrins: Health Effects • Low systemic toxicity • Respiratory sensitization • Asthma • Skin reactions • Paresthesia • Allergic dermatitis

  43. Pyrethroid Insecticides • Use increasing • Examples of use • Structural & agricultural • Pet flea control • Pediculicide • Vector control • West Nile virus • Aircraft “disinsection” Source: CDC

  44. Pyrethroids: Health Effects • Skin • Paresthesia, dermatitis • Respiratory • Rhinitis • Systemic • Dizziness, headache • Fasciculations, seizures, • Hormonal disruption in vitro

  45. Pyrethrins & PyrethroidsMechanism of Toxicity • Prolong inactivation of nerve membrane sodium channels • Pyrethroid structure • Type I (non-cyano) • Shorter inactivation • Type II (-cyano) • Longer inactivation Pyrethroid structure Compound R R’

  46. Pyrethrin & Pyrethroid Illness: Treatment • Decontamination • Vitamin E cream • Symptomatic therapy • Remove from further exposure if needed

  47. Case Woman Exposed to Flea Bomb • 35 year-old non-pregnant female with skin burning, itching and chest tightness after putting on clothes from closet. • Physical exam • Arms and face bright red • Vital signs normal • Lungs clear

  48. Woman Exposed to Flea BombIngredients • Label • 0.435% permethrin • 0.05% pyrethrins • 0.4% piperonyl butoxide • 99.115% inert ingredients • Recommended no entry for 4 hours after fogging

  49. Insecticides • Cholinesterase Inhibitors • Carbamates • Organophosphates • Pyrethrins & Pyrethroids • Organochlorines

  50. Insecticides: Organochlorines • DDT (prototype) • Chlordane • Lindane (Kwell, etc.) • Hexachlorobenzene • (Fungicide)

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