Understanding and Managing Pesticide Illness

1. Pesticide Illness Part 3 Pesticide Illness Part 3 Fumigants, Fungicides, Herbicides, Disinfectants, Miscellaneous Pesticides 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

2. 2 Toxicology, Diagnosis & Management of Pesticide Illness by Functional Category Toxicology, Diagnosis & Management of Pesticide Illness by Functional Category I I n n s s e e c c t t i i c c i i d d e e s s F F u u m m i i g g a a n n t t s s F F u u n n g g i i c c i i d d e e s s H H e e r r b b i i c c i i d d e e s s D D i i s s i i n n f f e e c c t t a a n n t t s s M M i i s s c c e e l l l l a a n n e e o o u u s s

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

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

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

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

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

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

9. 9 Methyl Bromide Chronic Toxicity Serum Bromide Levels Methyl Bromide Chronic Toxicity Serum Bromide Levels Long serum half life Long serum half life 1115 days 1115 days Chronic exposure Chronic exposure Asymptomatic high levels possible Asymptomatic high levels possible

10. 10 Case Illness After House Fumigation Case Illness After House Fumigation

11. 11 Illness After House Fumigation Pesticide Application History 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

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

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

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

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

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

17. 17 Transportation Worker with Cough Exposure History Transportation Worker with Cough Exposure History Tank car derailment Tank car derailment >19,000 gallons metam sodium released >19,000 gallons metam sodium released Worker involved in response to accident Worker involved in response to accident Symptoms onset within 20 minutes Symptoms onset within 20 minutes Worked 6.5 hours alongside river Worked 6.5 hours alongside river

18. 18 Transportation Worker with Cough Physical Evaluation Transportation Worker with Cough Physical Evaluation Exam 6 months later Exam 6 months later Mild nasal inflammation, Mild nasal inflammation, Spirometry Spirometry FEV 1 : 87%, FVC: 101%, FEV 1 /FVC: 69%, FEF 25-75 : 26% FEV 1 : 87%, FVC: 101%, FEV 1 /FVC: 69%, FEF 25-75 : 26% Methacholine challenge test Methacholine challenge test PC 100 : 1.2 mg/ml (normal >4 mg/ml) PC 100 : 1.2 mg/ml (normal >4 mg/ml)

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

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

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

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

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

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

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

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

27. 27 Fungicides: Thiocarbamates Fungicides: Thiocarbamates Resemble rubber accelerator thiuram Resemble rubber accelerator thiuram Sensitization reported in exposed workers Sensitization reported in exposed workers S C H 3 N C S C H 3 S C N C H 3 C H 3 S T h i r a m C H 3 C H 3 N C S Z n S C N C H 3 C H 3 S S X > 1 X S N H C S C H 2 C H 2 C S M n N H S Z i r a m M a n e b

28. 28 Thiocarbamates Antabuse-like Reactions Thiocarbamates Antabuse-like Reactions

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

44. 44 Paraquat (PQ) PQ Alveolar cell membrane PQ 2+ O 2 O 2 - Lipid peroxidation Cell death Paraquat Toxicity: Ingestion Paraquat Toxicity: Ingestion 1 1 - - 4 4 d d a a y y s s G G I I t t r r a a c c t t e e d d e e m m a a , , u u l l c c e e r r s s 2 2 4 4 - - 7 7 2 2 h h o o u u r r s s H H e e p p a a t t o o c c e e l l l l u u l l a a r r i i n n j j u u r r y y A A c c u u t t e e t t u u b b u u l l a a r r n n e e c c r r o o s s i i s s 7 7 2 2 - - 9 9 6 6 h h o o u u r r s s P P u u l l m m o o n n a a r r y y f f i i b b r r o o s s i i s s NADPH NADP +

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

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

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

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

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

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

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

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

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

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

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

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

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

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