Pesticide Illness Part 3

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Pesticide IllnessPart 3

• Fumigants, Fungicides, Herbicides, Disinfectants,
  Miscellaneous Pesticides

Prepared by Rupali Das, MD, MPH, California
Department of Health Services, Michael OMalley,
MD, MPH, University of California, Davis,
Laura Styles, MPH, Public Health Institute
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Toxicology, Diagnosis Management of Pesticide
Illness by Functional Category

• Insecticides
• Fumigants
• Fungicides
• Herbicides
• Disinfectants
• Miscellaneous

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Fumigants

• Halogenated hydrocarbons
• Methyl bromide
• Ethylene dibromide, DBCP
• Inorganic compounds
• Sulfuryl fluoride
• Pro-fumigants
• Metam sodium
• Metal phosphides
• Aluminum, Zinc, Magnesium

US DOT
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Fumigants Methyl Bromide

• High vapor pressure
• Heavier than air
• Odorless
• Chloropicrin added
• Toxic mechanism
• Tissue methylation

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Methyl Bromide Acute Toxicity

• Vesicant
• Blistering dermatitis
• Lower respiratory toxicant
• Delayed pulmonary edema
• Central nervous system depressant
• Usual cause of death

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Methyl Bromide Acute ToxicityDifferential
Diagnosis

• CNS depression
• Other CNS depressants
• Pulmonary edema
• Hepatic renal disease
• Acute severe asthma

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Methyl Bromide Acute Toxicity Management

• Serum bromide levels
• 3-6 ppm Possible exposure
• gt15 ppm Acute poisoning
• gt50 ppm Severe poisoning/ death
• Treatment
• Symptomatic

• Bromide levels - Reporting units
• ppm mg/liter
• mg/L10 mg /deciliter (USA)
• ppm 80 milli-equivalents (meq)/liter (European)

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Methyl Bromide Chronic Toxicity

• Central nervous system
• Cognitive, behavioral effects
• Polyneuropathy
• Reproductive system
• Teratogen
• Genotoxic, mutagenic

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Methyl Bromide Chronic ToxicitySerum Bromide
Levels

• Long serum half life
• 1115 days
• Chronic exposure
• Asymptomatic high levels possible

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Case Illness After House Fumigation
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Illness After House Fumigation Pesticide
Application History
Methyl bromide fumigation
Uncovered electrical conduit one pipe had a 2
diameter and the others a 1 diameter
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Illness After House Fumigation Health Effects

• Tenant found convulsing on floor the following
  evening
• Serum bromide level 270 ppm
• Refractory seizures, intermittent fever,
  multi-organ failure

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Methyl Bromide Phase-out

• Ozone depletion
• 100 reduction in 2005
• Exemptions
• Critical agricultural uses
• Pre-shipment quarantine
• Emergency uses
• No ideal substitute

Source US EPA Frequently Asked Questions on
methyl bromide phase-out
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FumigantsSulfuryl Fluoride

• Pulmonary
• Dyspnea, cough, delayed pulmonary edema, fatal
  hypoxia
• Renal
• CNS
• Weakness, nausea, vomiting, restlessness, muscle
  twitching, seizures

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FumigantsMetam Sodium

• Hydrolyzes to mixture of irritants
• Health effects
• Irritant dermatitis
• Reactive airways dysfunction syndrome/asthma

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Case Transportation Worker with Cough

• 40 year-old male transportation worker with
  metallic taste burning eyes, chest, nose
  nausea dizziness.
• Recurrent cough with wheezing, phlegm for 5 days.
  Chest tightness, dyspnea on exertion.

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Transportation Worker with Cough Exposure History

• Tank car derailment
• gt19,000 gallons metam sodium released
• Worker involved in response to accident
• Symptoms onset within 20 minutes
• Worked 6.5 hours alongside river

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Transportation Worker with Cough Physical
Evaluation

• Exam 6 months later
• Mild nasal inflammation,
• Spirometry
• FEV1 87, FVC 101, FEV1/FVC 69, FEF25-75
  26
• Methacholine challenge test
• PC100 1.2 mg/ml (normal gt4 mg/ml)

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FumigantsChronic Effects
Neurologic Reproductive Other
Methyl bromide Cognitive, behavioral Animal studies
Sulfuryl fluoride Olfactory, cognitive
Metam sodium Animal studies RADS, asthma
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CaseDrift After Metam Application

• Metam sodium applied to carrot fields
• Illness reported among
• School children
• Workers

California Department of Health Services, 2001
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Drift After Metam Application Investigation
Findings

• MITC detected at school, beyond 500 foot buffer
  zone
• Workers required to monitor field for odor

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FumigantsPhosphide Compounds

• Metal phosphides hydrolyze
• Aluminum, zinc, magnesium
• Phosphine
• Colorless, fish/garlic odor
• Highly explosive, corrosive
• Rapidly oxidizes to phosphoric acid

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Phosphine Illness Syndromes

• May resemble viral syndromes
• Pulmonary toxicity
• CNS toxicity
• Multi-organ failure

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Case Fatality After In-Transit Fumigation

• Unemployed male in railcar fumigated with
  aluminum phosphide
• Badly decomposed body found on arrival at
  destination

Source BC Workers Comp
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Fungicides

• Thiocarbamates
• Zineb, maneb, ziram, thiram
• Pthalimide derivatives
• Captan, captafol,
• Substituted aromatics
• Chlorothalonil, hexachlorobenzene
• Inorganic
• Sulfur

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Health Effects of Fungicides

• Acute
• Irritant allergic dermatitis
• Chronic
• Chronic dermatitis
• Possible carcinogens

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Fungicides Thiocarbamates
C
H
C
H
3
3
N
C
S
S
C
N

• Resemble rubber accelerator thiuram
• Sensitization reported in exposed workers

C
H
C
H
3
3
S
S
T
h
i
r
a
m
C
H
3
C
H
3
N
C
S
Z
n
S
C
N
C
H
C
H
S
S
3
3
Z
i
r
a
m
S
N
H
C
S
C
H
2
C
H
C
S
M
n
N
H
X
2
X
gt
1
S
M
a
n
e
b
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Thiocarbamates Antabuse-like Reactions
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CasePear Pickers with Skin Rash

• 26 people picking pears complained of skin rashes
  
• Physical exam
• Contact dermatitis
• Applied five days before
• NAA 800
• Ziram Granuflo

USDA Graphics
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Pear Pickers with Skin Rash Pesticide Application

• Workers followed requirements for re-entry
• Ziram applications
• D'Anjou pears, Golden Delicious apples
• Symptoms in Bosc pear pickers only
• Postulated mechanism of dermatitis
• Sharp latent bud on Bosc pears
• Increased susceptibility to dermal irritation

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Pear Pickers with Skin Rash Regulatory Action

• Re-entry interval of 14 days established for
  formulations of ziram on Bosc pears

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Fungicides Captan

• Dermatitis
• 5 of volunteers sensitized

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Case Nursery Worker with Urticaria

• Itching and hives in redwood nursery worker
• Chlorothalonil patch test
• Local Type I hypersensitivity
• 1 chlorothalonil open test
• Systemic Type I reaction

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Chlorothalonil Pigmentary Changes

• Blue-gray pigmentation in antecubital area
• Positive skin reaction to chlorothalonil
• Diagnosis Ashy dermatitis

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Ashy Dermatitis Mechanism

• Disruption of basal membrane of epidermis
• Melanin deposits in dermis

Panagos et al. 1996
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Fungicides Elemental Sulfur

• Potent skin irritant
• Animal experiments equivocal
• Airway irritant

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CaseApplicator With Skin Irritation

• Pesticide applicator applied sulfur dust to roses
• Contact dermatitis
• Burning pain
• Maculopapular rash

.
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Sulfur Allergic Skin Reactions

• Positive patch test reactions to sulfur in
  nursery workers applying sulfur
• Case reports support sulfur-induced allergy

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Postulated Mechanism ofSulfur Irritation and
Allergy

• Allergic reactions
• Oxidation/reduction products
• Type IV delayed hypersensitivity

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Herbicides

• Dipyridyl compounds
• Paraquat
• Diquat
• Glyphosate
• Phenoxy compounds
• 2,4,5-trichlorophenoxyacetic acid (2,4,5-T)
• 2,4 dichlorophenoxyacetic acid (2,4-D)

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Herbicides Dipyridyl Compounds

• Paraquat
• Diquat

Source Finnish Platform of the EU-NGDO Liaison
Committee
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Dipyridyl Compounds Paraquat

• Extremely toxic via ingestion
• LD50 3-5 mg/kg
• Toxicity
• Skin, pulmonary
• Parkinson Disease?

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Paraquat Toxicity
Botella et al, 1985
Hoffer and Teitelman, 1989
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Paraquat Toxicity Ingestion

• 1-4 days
• GI tract edema, ulcers
• 24-72 hours
• Hepatocellular injury
• Acute tubular necrosis
• 72-96 hours
• Pulmonary fibrosis

Paraquat (PQ)
Alveolar cell membrane
NADPH
NADP
PQ
PQ2
O2
O2-
Lipid peroxidation
Cell death
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Paraquat Levels Predict Outcome
Outcome Urine level, 24 hours (mg/mL)1 Plasma level (mg/kg)2
Survival likely lt1 lt 20
Pulmonary fibrosis 1-1000 20-40
Death within 24 hours 10-10,000 gt 40mg
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Paraquat Toxicity Treatment

• Skin, Eye Decontamination
• GI decontamination
• Fluids
• Hemoperfusion
• Oxygen contraindicated
• Severe cases
• High dose steroids and cyclophosphamide

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Case Farmer Attempts Suicide

• 46 year-old male farmer intentionally ingested a
  greenish liquid.
• Complains of dysphagia, sore throat. Previous
  history of depression.
• Profuse, prolonged vomiting
• Plasma paraquat at 4 hours
• 3 mg/mL

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Farmer Attempts Suicide Hospital Course

• Day 2 Severe dysphagia
• Day 3 SOB
• Day 4-9 pO2 33.
• Day 12 Pt died due to respiratory failure.

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Herbicides Glyphosate

• Health effects
• Case reports of eye, skin irritation
• Death due to ingestion of large amounts
• Experimental studies fail to show skin irritation
• Mechanism of human toxicity unknown
• Surfactant preservative?

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Chlorophenoxy Herbicides

• 2,4,5-trichlorophenoxyacetic acid (2,4,5-T)
• Derived from tetrachlorobenzene
• Dioxin byproducts
• 2,4-dichlorophenoxyacetic acid (2,4-D)
• Derived from phenol
• Dioxin contaminants not present

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Chlorophenoxy Herbicides

• Acute
• CNS depression
• Skin, GI, mucous membrane irritation
• Renal failure, myopathy
• Chronic
• Anemia, hepatic, renal effects
• Tumor formation(?)

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Antimicrobials Disinfectants

• Sodium hypochlorite
• Isopropyl alcohol
• Gluteraldehyde, formaldehyde
• Mixtures
• NaOCl H gt Cl2
• NaOCl NH3gt NHCl2, NH2Cl

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Chlorine Disinfectant Mixtures Toxicity

• Acute
• Asthma exacerbation, bronchitis
• Chronic
• RADS
• Treatment
• Oxygen, bronchodilators

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CaseCustodian with Shortness of Breath

• 29 year-old custodian with cough, sore throat,
  shortness of breath after mixing bleach and
  ammonia
• Exam
• Cough, dyspnea, RR36
• Lungs rales wheezes
• O2 saturation 94 on room air
• PEFR 80

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Miscellaneous Pesticides

• Propargite (Omite)
• Diethyltoluamide (DEET)

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AcaricidePropargite Contact Dermatitis

• Sustained-release propargite
• Severe dermatitis with scarring

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Insect Repellant DEET Acute Toxicity

• Skin
• Irritation
• Contact urticaria
• CNS
• Seizures, encephalopathy
• Children lt 5 years
• High dose/concentrations

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Acute Toxicity Summary

• Organs most often affected
• Skin
• Lungs
• CNS
• Severity greatest in developing nations
• Exposures occur at work, home, etc.
• Prevention regulation, substitution