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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 O’Malley, MD, MPH, University of California, Davis, Laura Styles, MPH, Public Health Institute
Toxicology, Diagnosis & Management of Pesticide Illness by Functional Category • Insecticides • Fumigants • Fungicides • Herbicides • Disinfectants • Miscellaneous
Fumigants • Halogenated hydrocarbons • Methyl bromide • Ethylene dibromide, DBCP • Inorganic compounds • Sulfuryl fluoride • Pro-fumigants • Metam sodium • Metal phosphides • Aluminum, Zinc, Magnesium US DOT
Fumigants Methyl Bromide • High vapor pressure • Heavier than air • Odorless • Chloropicrin added • Toxic mechanism • Tissue methylation
Methyl Bromide Acute Toxicity • Vesicant • Blistering dermatitis • Lower respiratory toxicant • Delayed pulmonary edema • Central nervous system depressant • Usual cause of death
Methyl Bromide Acute ToxicityDifferential Diagnosis • CNS depression • Other CNS depressants • Pulmonary edema • Hepatic & renal disease • Acute severe asthma
Serum bromide levels 3-6 ppm: Possible exposure >15 ppm: Acute poisoning >50 ppm: Severe poisoning/ death Treatment Symptomatic Bromide levels - Reporting units ppm = mg/liter mg/L=10 mg /deciliter (USA) ppm = 80 milli-equivalents (meq)/liter (European) Methyl Bromide Acute Toxicity Management
Methyl Bromide Chronic Toxicity • Central nervous system • Cognitive, behavioral effects • Polyneuropathy • Reproductive system • Teratogen • Genotoxic, mutagenic
Methyl Bromide Chronic ToxicitySerum Bromide Levels • Long serum half life • 11—15 days • Chronic exposure • Asymptomatic high levels possible
Illness AfterHouse FumigationPesticide Application History Methyl bromide fumigation Uncovered electrical conduit: one pipe had a 2” diameter and the others a 1” diameter
Illness AfterHouse FumigationHealth Effects • Tenant found convulsing on floor the following evening • Serum bromide level 270 ppm • Refractory seizures, intermittent fever, multi-organ failure
Ozone depletion “100% reduction” in 2005 Exemptions Critical agricultural uses Pre-shipment & quarantine Emergency uses No “ideal” substitute Methyl Bromide Phase-out Source: US EPA “Frequently Asked Questions” on methyl bromide phase-out
FumigantsSulfuryl Fluoride • Pulmonary • Dyspnea, cough, delayed pulmonary edema, fatal hypoxia • Renal • CNS • Weakness, nausea, vomiting, restlessness, muscle twitching, seizures
FumigantsMetam Sodium • Hydrolyzes to mixture of irritants • Health effects • Irritant dermatitis • Reactive airways dysfunction syndrome/asthma
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.
Transportation Worker with CoughExposure History • Tank car derailment • >19,000 gallons metam sodium released • Worker involved in response to accident • Symptoms onset within 20 minutes • Worked 6.5 hours alongside river
Transportation Worker with CoughPhysical 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 >4 mg/ml)
CaseDrift After Metam Application • Metam sodium applied to carrot fields • Illness reported among • School children • Workers California Department of Health Services, 2001
Drift After Metam ApplicationInvestigation Findings • MITC detected at school, beyond 500 foot buffer zone • Workers required to monitor field for odor
FumigantsPhosphide Compounds • Metal phosphides hydrolyze • Aluminum, zinc, magnesium • Phosphine • Colorless, fish/garlic odor • Highly explosive, corrosive • Rapidly oxidizes to phosphoric acid
Phosphine: Illness Syndromes • May resemble viral syndromes • Pulmonary toxicity • CNS toxicity • Multi-organ failure
CaseFatality After In-Transit Fumigation • Unemployed male in railcar fumigated with aluminum phosphide • Badly decomposed body found on arrival at destination Source: BC Workers Comp
Fungicides • Thiocarbamates • Zineb, maneb, ziram, thiram • Pthalimide derivatives • Captan, captafol, • Substituted aromatics • Chlorothalonil, hexachlorobenzene • Inorganic • Sulfur
Health Effects of Fungicides • Acute • Irritant & allergic dermatitis • Chronic • Chronic dermatitis • Possible carcinogens
Fungicides: Thiocarbamates C H C H 3 3 • Resemble rubber accelerator thiuram • Sensitization reported in exposed workers N C S S C N 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 N H C S M n X 2 X > 1 S M a n e b
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
Pear Pickers with Skin RashPesticide 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
Pear Pickers with Skin RashRegulatory Action • Re-entry interval of 14 days established for formulations of ziram on Bosc pears
Fungicides: Captan • Dermatitis • 5% of volunteers sensitized
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
Chlorothalonil: Pigmentary Changes • Blue-gray pigmentation in antecubital area • Positive skin reaction to chlorothalonil • Diagnosis: Ashy dermatitis
Ashy Dermatitis: Mechanism • Disruption of basal membrane of epidermis • Melanin deposits in dermis Panagos et al. 1996
Fungicides: Elemental Sulfur • Potent skin irritant • Animal experiments equivocal • Airway irritant
CaseApplicator With Skin Irritation • Pesticide applicator applied sulfur dust to roses • Contact dermatitis • Burning pain • Maculopapular rash .
Sulfur: Allergic Skin Reactions • Positive patch test reactions to sulfur in nursery workers applying sulfur • Case reports support sulfur-induced allergy
Postulated Mechanism ofSulfur Irritation and Allergy • Allergic reactions • Oxidation/reduction products • Type IV delayed hypersensitivity
Herbicides • Dipyridyl compounds • Paraquat • Diquat • Glyphosate • Phenoxy compounds • 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) • 2,4 dichlorophenoxyacetic acid (2,4-D)
Herbicides: Dipyridyl Compounds • Paraquat • Diquat Source: Finnish Platform of the EU-NGDO Liaison Committee
Dipyridyl Compounds: Paraquat • Extremely toxic via ingestion • LD50 3-5 mg/kg • Toxicity • Skin, pulmonary • Parkinson Disease?
Paraquat Toxicity Botella et al, 1985 Hoffer and Teitelman, 1989
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
Paraquat Toxicity: Treatment • Skin, Eye Decontamination • GI decontamination • Fluids • Hemoperfusion • Oxygen contraindicated • Severe cases • High dose steroids and cyclophosphamide
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
Farmer Attempts SuicideHospital Course • Day 2: Severe dysphagia • Day 3: SOB • Day 4-9: pO2 33. • Day 12: Pt died due to respiratory failure.
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?
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