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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

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

toxicology diagnosis management of pesticide illness by functional category
Toxicology, Diagnosis & Management of Pesticide Illness by Functional Category
  • Insecticides
  • Fumigants
  • Fungicides
  • Herbicides
  • Disinfectants
  • Miscellaneous
insecticides
Insecticides
  • Cholinesterase Inhibitors
    • Carbamates
    • Organophosphates
  • Pyrethrins & Pyrethroids
  • Organochlorines
insecticides cholinesterase inhibitors
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

cholinesterase normal function
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

inhibition of cholinesterase
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

organophosphates carbamates signs symptoms i
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

organophosphates carbamates signs symptoms ii
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

commonly used acronyms for cholinesterase inhibition syndromes
Salivation

Lacrimation

Urination

Diarrhea

Diarrhea

Urination

Miosis

Bronchorrhea

Emesis

Lacrimation

Salivation

Commonly-used Acronyms for Cholinesterase Inhibition Syndromes
cholinesterase inhibitors clinical presentations vary
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
case farmworker with multiple symptoms
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
farmworker with multiple symptoms exposure history
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
farmworker with multiple symptoms physical exam
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.

farmworker with multiple symptoms initial summary differential diagnosis
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
farmworker with multiple symptoms toxicity of pesticides involved
Farmworker with Multiple SymptomsToxicity of Pesticides Involved
  • Carbofuran: N-methyl carbamate
  • Abamectin: macrolytic lactone
  • Mepiquat chloride: growth regulator
cholinesterase inhibitor poisoning confirmatory tests
Cholinesterase-inhibitor Poisoning: Confirmatory Tests
  • Cholinesterase blood tests
  • Urine metabolites
  • Foliage and clothing pesticide residues
  • Diagnosis is primarily clinical
cholinesterase blood tests
Cholinesterase Blood Tests
  • Two cholinesterase enzymes
    • RBC
      • “true”/ acetylcholinesterase
    • Plasma
      • “pseudo”/ butyrylcholinesterase
  • Preferential inhibition possible
    • Dichlorvos: plasma > RBC cholinesterase
cholinesterase blood tests interpretation
Cholinesterase Blood Tests Interpretation
  • 20% variability in population “baseline”
  • Correlation with symptoms unpredictable
  • Enzyme activity reversible
    • Carbamates
    • Sample temperature
    • Storage time
cholinesterase blood tests uses
Cholinesterase Blood TestsUses

Biologic monitoring of workers potentially exposed to cholinesterase inhibitors

Retrospective diagnosis of acute poisoning with cholinesterase inhibitors

RBC

Plasma

urine metabolites
Urine Metabolites
  • Sensitive indicator of pesticide exposure
  • Results do not correlate with health effects
  • Requires specific pesticide information
  • Clinical labs may not perform tests
pesticide residues on foliage clothing
Pesticide Residues on Foliage & Clothing
  • Provides evidence of pesticide exposure in environment
  • Does not prove internal exposure
  • Limited clinical availability
farmworker with multiple symptoms pesticide lab test results
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
farmworker with multiple symptoms pesticide residue analysis
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
farmworker with multiple symptoms assessment case classification
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/

specific management for cholinesterase inhibitor poisoning
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
treatment atropine
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
treatment pralidoxime 2 pam
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

2 pam treatment regimen
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
farmworker with multiple symptoms case management course
Farmworker with Multiple SymptomsCase Management & Course
  • Decontamination
  • Intravenous hydration
  • Treatment of atrial fibrillation
  • Converted to sinus rhythm as outpatient
  • Grower fined
farmworker with multiple symptoms carbamates and persistent effects
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
case grape harvester with subacute poisoning
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
grape harvester with subacute poisoning persistent symptoms
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)
grape harvester with subacute poisoning exposure history
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
grape harvester with subacute poisoning hospital course
Severe bradycardia while in hospital

Heart rate responded to atropine IV

Excess respiratory secretions absent

Grape Harvester with Subacute PoisoningHospital Course
grape harvester with subacute poisoning illness among coworkers
Health effects among crew:

Asymptomatic bradycardia

Asymptomatic plasma, RBC cholinesterasedepression

Grape Harvester with Subacute PoisoningIllness Among Coworkers
grape harvester with subacute poisoning incident summary
Grape Harvester with Subacute PoisoningIncident Summary
  • Gradual-onset poisoning
  • Respiratory symptoms absent
  • Sentinel health event
  • Phosalone use restricted
acute non cholinesterase effects of organophosphates
Acute Non-Cholinesterase Effects of Organophosphates
  • Odor health effects
  • Irritant effects
  • Organophosphate-induced delayed polyneuropathy (OPIDP)
insecticides40
Insecticides
  • Cholinesterase Inhibitors
    • Carbamates
    • Organophosphates
  • Pyrethrins & Pyrethroids
  • Organochlorines
insecticides pyrethrins pyrethroids
InsecticidesPyrethrins & Pyrethroids
  • Pyrethrins
    • Natural insecticidal extract
    • Unstable
  • Pyrethroids
    • Synthetic derivatives
    • Used with piperonyl butoxide
pyrethrins health effects
Pyrethrins: Health Effects
  • Low systemic toxicity
  • Respiratory sensitization
    • Asthma
  • Skin reactions
    • Paresthesia
    • Allergic dermatitis
pyrethroid insecticides
Pyrethroid Insecticides
  • Use increasing
  • Examples of use
    • Structural & agricultural
    • Pet flea control
    • Pediculicide
  • Vector control
    • West Nile virus
    • Aircraft “disinsection”

Source: CDC

pyrethroids health effects
Pyrethroids: Health Effects
  • Skin
    • Paresthesia, dermatitis
  • Respiratory
    • Rhinitis
  • Systemic
    • Dizziness, headache
    • Fasciculations, seizures,
    • Hormonal disruption in vitro
pyrethrins pyrethroids mechanism of toxicity
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’

pyrethrin pyrethroid illness treatment
Pyrethrin & Pyrethroid Illness: Treatment
  • Decontamination
  • Vitamin E cream
  • Symptomatic therapy
  • Remove from further exposure if needed
case woman exposed to flea bomb
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
woman exposed to flea bomb ingredients
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
insecticides49
Insecticides
  • Cholinesterase Inhibitors
    • Carbamates
    • Organophosphates
  • Pyrethrins & Pyrethroids
  • Organochlorines
insecticides organochlorines
Insecticides: Organochlorines
  • DDT (prototype)
  • Chlordane
  • Lindane (Kwell, etc.)
  • Hexachlorobenzene
    • (Fungicide)
organochlorine toxicity
Organochlorine Toxicity
  • CNS toxicity
    • Headache, dizziness, irritability, incoordination, tremor, seizures, paresthesia (DDT),
  • Carcinogenicity
    • Hepatic tumors in rodents
    • Breast cancer (?)
  • Endocrine disruption
skin effects of organochlorines
Skin Effects of Organochlorines
  • DDT
    • Chloracne
  • Lindane
    • Irritant reactions
    • Negative in patch test series
skin effects of organochlorines dienochlor
Skin Effects of Organochlorines Dienochlor

Patch test develops hyperpigmentation in 15-20% of subjects tested with dienochlor - resembles reaction to Balsam of Peru

case child with seizures
Case Child With Seizures
  • 9 year-old child with myoclonic seizures witnessed by parents. No history of seizures, head trauma, etc.
  • In ER, child sleepy, oriented; complaining of abdominal cramping, throat burning. Exam normal.

Photo courtesy of California Poison Control System

insecticide illness summary
Insecticide Illness: Summary
  • Occupational and environmental exposure
  • Toxicity varies by chemical class
  • Specific therapy limited
  • Prevent illness by reducing use

Source: USDA