pesticide illness part 3 fumigants, fungicides, herbicides, disinfectants, miscellaneous pesticides...

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Pesticide Illness Part 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 Slide 2 2 Toxicology, Diagnosis & Management of Pesticide Illness by Functional Category IIIInsecticides FFFFumigants FFFFungicides HHHHerbicides DDDDisinfectants MMMMiscellaneous Slide 3 3 Fumigants Halogenated hydrocarbons Methyl bromide Ethylene dibromide, DBCP Inorganic compounds Sulfuryl fluoride Pro-fumigants Metam sodium Metal phosphides Aluminum, Zinc, Magnesium US DOT Slide 4 4 Fumigants Methyl Bromide High vapor pressure Heavier than air Odorless Chloropicrin added Toxic mechanism Tissue methylation Slide 5 5 Methyl Bromide Acute Toxicity Vesicant Blistering dermatitis Lower respiratory toxicant Delayed pulmonary edema Central nervous system depressant Usual cause of death Slide 6 6 Methyl Bromide Acute Toxicity Differential Diagnosis CNS depression Other CNS depressants Pulmonary edema Hepatic & renal disease Acute severe asthma Slide 7 7 Methyl Bromide Acute Toxicity Management 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) Slide 8 8 Methyl Bromide Chronic Toxicity Central nervous system Cognitive, behavioral effects Polyneuropathy Reproductive system Teratogen Genotoxic, mutagenic Slide 9 9 Methyl Bromide Chronic Toxicity Serum Bromide Levels Long serum half life 1115 days Chronic exposure Asymptomatic high levels possible Slide 10 10 Case Illness After House Fumigation Slide 11 11 Illness After House Fumigation Pesticide Application History Uncovered electrical conduit: one pipe had a 2 diameter and the others a 1 diameter Methyl bromide fumigation Slide 12 12 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 Slide 13 13 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 Slide 14 14 Fumigants Sulfuryl Fluoride Pulmonary Dyspnea, cough, delayed pulmonary edema, fatal hypoxia Renal CNS Weakness, nausea, vomiting, restlessness, muscle twitching, seizures Slide 15 15 Fumigants Metam Sodium Hydrolyzes to mixture of irritants Health effects Irritant dermatitis Reactive airways dysfunction syndrome/asthma Slide 16 16 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. Slide 17 17 Transportation Worker with Cough Exposure 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 Slide 18 18 Transportation Worker with Cough Physical Evaluation Exam 6 months later Mild nasal inflammation, Spirometry FEV 1 : 87%, FVC: 101%, FEV 1 /FVC: 69%, FEF 25-75 : 26% Methacholine challenge test PC 100 : 1.2 mg/ml (normal >4 mg/ml) Slide 19 19 Fumigants Chronic Effects NeurologicReproductiveOther Methyl bromide Cognitive, behavioral Animal studies Sulfuryl fluoride Olfactory, cognitive Metam sodium Animal studies RADS, asthma Slide 20 20 Case Drift After Metam Application Metam sodium applied to carrot fields Illness reported among School children Workers California Department of Health Services, 2001 Slide 21 21 Drift After Metam Application Investigation Findings MITC detected at school, beyond 500 foot buffer zone Workers required to monitor field for odor Slide 22 22 Fumigants Phosphide Compounds Metal phosphides hydrolyze Aluminum, zinc, magnesium Phosphine Colorless, fish/garlic odor Highly explosive, corrosive Rapidly oxidizes to phosphoric acid Slide 23 23 Phosphine: Illness Syndromes May resemble viral syndromes Pulmonary toxicity CNS toxicity Multi-organ failure Slide 24 24 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 Slide 25 25Fungicides Thiocarbamates Zineb, maneb, ziram, thiram Pthalimide derivatives Captan, captafol, Substituted aromatics Chlorothalonil, hexachlorobenzene Inorganic Sulfur Slide 26 26 Health Effects of Fungicides Acute Irritant & allergic dermatitis Chronic Chronic dermatitis Possible carcinogens Slide 27 27 Fungicides: Thiocarbamates Resemble rubber accelerator thiuram Sensitization reported in exposed workers S CH 3 NCS CH 3 SCN CH 3 CH 3 S Thiram CH 3 CH 3 NCSZnSCN CH 3 CH 3 SS X>1 X S NHCS CH 2 CH 2 CSMnNH S Ziram Maneb Slide 28 28 Thiocarbamates Antabuse-like Reactions Slide 29 29 Case Pear 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 Slide 30 30 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 Slide 31 31 Pear Pickers with Skin Rash Regulatory Action Re-entry interval of 14 days established for formulations of ziram on Bosc pears Slide 32 32 Fungicides: Captan Dermatitis 5% of volunteers sensitized Slide 33 33 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 Slide 34 34 Chlorothalonil: Pigmentary Changes Blue-gray pigmentation in antecubital area Positive skin reaction to chlorothalonil Diagnosis: Ashy dermatitis Slide 35 35 Ashy Dermatitis: Mechanism Disruption of basal membrane of epidermis Melanin deposits in dermis Panagos et al. 1996 Slide 36 36 Fungicides: Elemental Sulfur Potent skin irritant Animal experiments equivocal Airway irritant Slide 37 37 Case Applicator With Skin Irritation Pesticide applicator applied sulfur dust to roses Contact dermatitis Burning pain Maculopapular rash. Slide 38 38 Sulfur: Allergic Skin Reactions Positive patch test reactions to sulfur in nursery workers applying sulfur Case reports support sulfur- induced allergy Slide 39 39 Postulated Mechanism of Sulfur Irritation and Allergy Allergic reactions Oxidation/reduction products Type IV delayed hypersensitivity Slide 40 40 Herbicides Dipyridyl compounds Paraquat Diquat Glyphosate Phenoxy compounds 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) 2,4 dichlorophenoxyacetic acid (2,4-D) Slide 41 41 Herbicides: Dipyridyl Compounds Paraquat Diquat Source: Finnish Platform of the EU-NGDO Liaison Committee Slide 42 42 Dipyridyl Compounds: Paraquat Extremely toxic via ingestion LD 50 3-5 mg/kg Toxicity Skin, pulmonary Parkinson Disease? Slide 43 43 Paraquat Toxicity Botella et al, 1985 Hoffer and Teitelman, 1989 Slide 44 44 Paraquat (PQ) PQ Alveolar cell membrane PQ 2+ O2O2 O2-O2- Lipid peroxidation Cell death Paraquat Toxicity: Ingestion 1111-4 days GGGGI tract edema, ulcers 22224-72 hours HHHHepatocellular injury AAAAcute tubular necrosis 77772-96 hours PPPPulmonary fibrosis NADPHNADP + Slide 45 45 Outcome Urine level, 24 hours (mg/mL) 1 Plasma level (mg/kg) 2 Survival likely40mg Paraquat Levels Predict Outcome Slide 46 46 Paraquat Toxicity: Treatment Skin, Eye Decontamination GI decontamination Fluids Hemoperfusion Oxygen contraindicated Severe cases High dose steroids and cyclophosphamide Slide 47 47 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 Slide 48 48 Farmer Attempts Suicide Hospital Course Day 2: Severe dysphagia Day 3: SOB Day 4-9: pO 2 33. Day 12: Pt died due to respiratory failure. Slide 49 49 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? Slide 50 50 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 Slide 51 51 Chlorophenoxy Herbicides Acute CNS depression Skin, GI, mucous membrane irritation Renal failure, myopathy Chronic Anemia, hepatic, renal effects Tumor formation(?) Slide 52 52 Antimicrobials & Disinfectants Sodium hypochlorite Isopropyl alcohol Gluteraldehyde, formaldehyde Mixtures NaOCl + H + => Cl 2 NaOCl + NH 3 => NHCl 2, NH 2 Cl Slide 53 53 Chlorine Disinfectant Mixtures Toxicity Acute Asthma exacerbation, bronchitis Chronic: RADS Treatment Oxygen, bronchodilators Slide 54 54 Case Custodian with Shortness of Breath 29 year-old custodian with cough, sore throat, shortness of breath after mixing bleach and ammonia Exam: Cough, dyspnea, RR=36; Lungs: rales & wheezes; O 2 saturation 94% on room air PEFR 80% Slide 55 55 Miscellaneous Pesticides Propargite (Omite) Diethyltoluamide (DEET) Slide 56 56 Acaricide Propargite Contact Dermatitis Sustained-release propargite Severe dermatitis with scarring Slide 57 57