Pesticide Illness Part 3 Fumigants Fungicides Herbicides Disinfectants

Pesticide Illness Part 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 u Insecticides u Fumigants u Fungicides u Herbicides u Disinfectants u Miscellaneous 2

Fumigants u Halogenated hydrocarbons – Methyl bromide – Ethylene dibromide, DBCP u Inorganic compounds u US DOT – Sulfuryl fluoride Pro-fumigants – Metam sodium u Metal phosphides – Aluminum, Zinc, Magnesium 3

Fumigants Methyl Bromide u High vapor pressure u Heavier than air u Odorless – Chloropicrin added u Toxic mechanism – Tissue methylation 4

Methyl Bromide Acute Toxicity u Vesicant – Blistering dermatitis u Lower respiratory toxicant – Delayed pulmonary edema u Central nervous system depressant – Usual cause of death 5

Methyl Bromide Acute Toxicity Differential Diagnosis u CNS depression – Other CNS depressants u Pulmonary edema – Hepatic & renal disease – Acute severe asthma 6

Methyl Bromide Acute Toxicity Management u Serum bromide levels – 3 -6 ppm: Possible exposure – >15 ppm: Acute poisoning – >50 ppm: Severe poisoning/ death u Treatment Bromide levels - Reporting units u ppm = mg/liter u mg/L=10 mg /deciliter (USA) u ppm = 80 milli-equivalents (meq)/liter (European) – Symptomatic 7

Methyl Bromide Chronic Toxicity u Central nervous system – Cognitive, behavioral effects – Polyneuropathy u Reproductive system – Teratogen – Genotoxic, mutagenic 8

Methyl Bromide Chronic Toxicity Serum Bromide Levels u Long serum half life – 11— 15 days u Chronic exposure – Asymptomatic high levels possible 9

Case Illness After House Fumigation 10

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 11

Illness After House Fumigation Health Effects u u u Tenant found convulsing on floor the following evening Serum bromide level 270 ppm Refractory seizures, intermittent fever, multi-organ failure 12

Methyl Bromide Phase-out u Ozone depletion – “ 100% reduction” in 2005 u Exemptions – Critical agricultural uses – Pre-shipment & quarantine – Emergency uses u No “ideal” substitute Source: US EPA “Frequently Asked Questions” 13 on methyl bromide phase-out

Fumigants Sulfuryl Fluoride u Pulmonary – Dyspnea, cough, delayed pulmonary edema, fatal hypoxia u Renal u CNS – Weakness, nausea, vomiting, restlessness, muscle twitching, seizures 14

Fumigants Metam Sodium u Hydrolyzes u Health to mixture of irritants effects – Irritant dermatitis – Reactive airways dysfunction syndrome/asthma 15

Case Transportation Worker with Cough u 40 year-old male transportation worker with metallic taste; burning eyes, chest, nose; nausea; dizziness. u Recurrent cough with wheezing, phlegm for 5 days. Chest tightness, dyspnea on exertion. 16

Transportation Worker with Cough Exposure History u Tank car derailment – >19, 000 gallons metam sodium released u Worker involved in response to accident – Symptoms onset within 20 minutes – Worked 6. 5 hours alongside river 17

Transportation Worker with Cough Physical Evaluation u Exam 6 months later – Mild nasal inflammation, – Spirometry u FEV 1: 87%, FVC: 101%, FEV 1/FVC: 69%, FEF 25 -75: 26% – Methacholine challenge test u PC 100: 1. 2 mg/ml (normal >4 mg/ml) 18

Fumigants Chronic Effects Neurologic Methyl bromide Sulfuryl fluoride Metam sodium Reproductive Cognitive, behavioral Olfactory, cognitive Other Animal studies RADS, asthma 19

Case Drift After Metam Application u u Metam sodium applied to carrot fields Illness reported among – School children – Workers California Department of Health Services, 2001 20

Drift After Metam Application Investigation Findings u MITC detected at school, beyond 500 foot buffer zone u Workers required to monitor field for odor 21

Fumigants Phosphide Compounds u Metal phosphides hydrolyze – Aluminum, zinc, magnesium u Phosphine – Colorless, fish/garlic odor – Highly explosive, corrosive – Rapidly oxidizes to phosphoric acid 22

Phosphine: Illness Syndromes u May resemble viral syndromes u Pulmonary u CNS toxicity u Multi-organ failure 23

Case Fatality After In-Transit Fumigation u Unemployed male in railcar fumigated with aluminum phosphide Source: BC Workers Comp u Badly decomposed body found on arrival at destination 24

Fungicides u Thiocarbamates – Zineb, maneb, ziram, thiram u Pthalimide derivatives – Captan, captafol, u Substituted aromatics – Chlorothalonil, hexachlorobenzene u Inorganic – Sulfur 25

Health Effects of Fungicides u Acute – Irritant & allergic dermatitis u Chronic – Chronic dermatitis – Possible carcinogens 26

Fungicides: Thiocarbamates CH 3 u Resemble rubber accelerator thiuram N C S S C N S S CH 3 Thiram CH 3 N C S CH 3 Zn CH 3 S C N S CH 3 S Ziram u Sensitization reported in exposed workers CH 3 S CH 2 NH C S Mn X X>1 S Maneb 27

Thiocarbamates Antabuse-like Reactions 28

Case Pear Pickers with Skin Rash 26 people picking pears complained of skin rashes u Physical exam: u – Contact dermatitis u Applied five days before: – NAA 800 – Ziram Granuflo USDA Graphics 29

Pear Pickers with Skin Rash Pesticide Application u Workers followed requirements for re -entry u Ziram applications – D'Anjou pears, Golden Delicious apples – Symptoms in Bosc pear pickers only u Postulated mechanism of dermatitis – Sharp latent bud on Bosc pears – Increased susceptibility to dermal irritation 30

Pear Pickers with Skin Rash Regulatory Action u Re-entry interval of 14 days established formulations of ziram on Bosc pears 31

Fungicides: Captan u Dermatitis u 5% of volunteers sensitized 32

Case Nursery Worker with Urticaria Itching and hives in redwood nursery worker u Chlorothalonil patch test: u – Local Type I hypersensitivity u 1% chlorothalonil open test – Systemic Type I reaction 33

Chlorothalonil: Pigmentary Changes Blue-gray pigmentation in antecubital area u Positive skin reaction to chlorothalonil u Diagnosis: Ashy dermatitis u 34

Ashy Dermatitis: Mechanism u u Disruption of basal membrane of epidermis Melanin deposits in dermis 35 Panagos et al. 1996

Fungicides: Elemental Sulfur u Potent irritant skin – Animal experiments equivocal u Airway irritant 36

Case Applicator With Skin Irritation u Pesticide applicator applied sulfur dust to roses u Contact dermatitis – Burning pain – Maculopapular rash . 37

Sulfur: Allergic Skin Reactions u u Positive patch test reactions to sulfur in nursery workers applying sulfur Case reports support sulfurinduced allergy 38

Postulated Mechanism of Sulfur Irritation and Allergy u Allergic reactions – Oxidation/reduction products u Type IV delayed hypersensitivity 39

Herbicides u Dipyridyl compounds – Paraquat – Diquat u Glyphosate u Phenoxy compounds – 2, 4, 5 -trichlorophenoxyacetic acid (2, 4, 5 -T) – 2, 4 dichlorophenoxyacetic acid (2, 4 -D) 40

u Paraquat u Diquat Source: Finnish Platform of the EU-NGDO Liaison Committee Herbicides: Dipyridyl Compounds 41

Dipyridyl Compounds: Paraquat u Extremely ingestion toxic via – LD 50 3 -5 mg/kg u Toxicity – Skin, pulmonary – Parkinson Disease? 42

Hoffer and Teitelman, 1989 Botella et al, 1985 Paraquat Toxicity 43

Paraquat Toxicity: Ingestion u 1 -4 days – GI tract edema, ulcers u 24 -72 hours – Hepatocellular injury – Acute tubular necrosis u 72 -96 hours – Pulmonary fibrosis Paraquat (PQ) rane ell memb c Alveolar NADPH NADP+ PQ 2+ PQ O 2 - Lipid peroxidation Cell death 44

Paraquat Levels Predict Outcome Urine level, 24 hours (mg/m. L)1 Survival <1 likely Pulmonary 1 -1000 fibrosis Death within 24 hours Plasma level (mg/kg)2 < 20 20 -40 10 -10, 000 > 40 mg 45

Paraquat Toxicity: Treatment u Skin, Eye Decontamination u GI decontamination u Fluids u Hemoperfusion u Oxygen contraindicated u Severe cases – High dose steroids and cyclophosphamide 46

Case Farmer Attempts Suicide u 46 year-old male farmer intentionally ingested a greenish liquid. u Complains of dysphagia, sore throat. Previous history of depression. u Profuse, u Plasma prolonged vomiting paraquat at 4 hours – 3 mg/m. L 47

Farmer Attempts Suicide Hospital Course u Day 2: Severe dysphagia u Day 3: SOB u Day 4 -9: p. O 2 33. u Day 12: Pt died due to respiratory failure. 48

Herbicides: Glyphosate u Health effects – Case reports of eye, skin irritation – Death due to ingestion of large amounts – Experimental studies fail to show skin irritation u Mechanism unknown of human toxicity – Surfactant preservative? 49

Chlorophenoxy Herbicides u 2, 4, 5 -trichlorophenoxyacetic (2, 4, 5 -T) acid – Derived from tetrachlorobenzene – Dioxin byproducts u 2, 4 -dichlorophenoxyacetic (2, 4 -D) acid – Derived from phenol – Dioxin contaminants not present 50

Chlorophenoxy Herbicides u Acute – CNS depression – Skin, GI, mucous membrane irritation – Renal failure, myopathy u Chronic – Anemia, hepatic, renal effects – Tumor formation(? ) 51

Antimicrobials & Disinfectants u Sodium hypochlorite u Isopropyl alcohol u Gluteraldehyde, formaldehyde u Mixtures – Na. OCl + H+ => Cl 2 – Na. OCl + NH 3=> NHCl 2, NH 2 Cl 52

Chlorine Disinfectant Mixtures Toxicity u Acute – Asthma exacerbation, bronchitis u Chronic: – RADS u Treatment – Oxygen, bronchodilators 53

Case Custodian with Shortness of Breath u 29 year-old custodian with cough, sore throat, shortness of breath after mixing bleach and ammonia u Exam: – Cough, dyspnea, RR=36; – Lungs: rales & wheezes; – O 2 saturation 94% on room air – PEFR 80% 54

Miscellaneous Pesticides u Propargite (Omite) u Diethyltoluamide (DEET) 55

Acaricide Propargite Contact Dermatitis u Sustained-release propargite u Severe dermatitis with scarring 56

Insect Repellant DEET Acute Toxicity u Skin – Irritation – Contact urticaria u CNS – Seizures, encephalopathy u Children < 5 years u High dose/concentrations 57

Acute Toxicity Summary u Organs most often affected – Skin – Lungs – CNS u Severity greatest in developing nations u Exposures occur at work, home, etc. u Prevention: regulation, substitution 58