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Pesticide Illness Pesticide Illness. 2 PesticidesPesticides  Farmers, pesticide applicators, crop duster pilots, and manufacturers with high exposures.

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Presentation on theme: "Pesticide Illness Pesticide Illness. 2 PesticidesPesticides  Farmers, pesticide applicators, crop duster pilots, and manufacturers with high exposures."— Presentation transcript:

1 Pesticide Illness Pesticide Illness

2 2 PesticidesPesticides  Farmers, pesticide applicators, crop duster pilots, and manufacturers with high exposures to pesticides, have high rates of blood and lymphatic system cancers, cancers of the lip, stomach, lung, brain, and prostate, as well as melanoma and other skin cancers.

3 3 Toxicology, Diagnosis & Management of Pesticide Illness by Functional Category IIIInsecticides FFFFumigants FFFFungicides HHHHerbicides DDDDisinfectants MMMMiscellaneous

4 4 Insecticides CCCCholinesterase Inhibitors –C–C–C–Carbamates –O–O–O–Organophosphates PPPPyrethrins & Pyrethroids OOOOrganochlorines

5 5 Insecticides Cholinesterase Inhibitors  N-methyl Carbamates –aldicarb (Temik), carbofuran (Furadan), carbaryl (Sevin)  Organophosphates (OPs) –chlorpyrifos (Dursban, Lorsban), diazinon, malathion RO O P OX RO N C RX Generic structure for N— methyl carbamates Generic structure for organophosphates

6 6 Cholinesterase Normal Function Acetylcholine (ACh) 3. End organ activates in presence of acetylcholine Acetylcholinesterase Choline + Acetyl 5. Choline reuptake Acetyl CoA + Choline Cholinergic Nerve Terminal 2. ACh binds to receptor 1. Nerve signal releases ACh 4. Choline regeneration by acetylcholinesterase

7 7 Inhibition of Cholinesterase Acetylcholine R 1 R 2 O==P O Cholinergic Nerve Terminal 3. Activity of end organ does not cease 1. Nerve signal releases ACh 2. ACh binds to receptor 4. OP binds to cholinesterase, preventing regeneration

8 8 Organophosphates & Carbamates Signs & Symptoms (I) SystemReceptorOrganSign/symptom ParasympatheticMuscarinicEye Miosis, Blurred vision Parasympathetic Muscarinic Glands Tearing, salivation, sweating, & Sympathetic pulmonary edema Heart Bradycardia, arrhythmia Misc. Broncho-, smooth constriction, muscle vomiting, diarrhea, excess or involuntary urination

9 9 SystemReceptorOrgan Sign/symptom Neuro-NicotinicSkeletal Fasciculations, muscular muscle cramps, twitching (Parasympathetic)muscle weakness, paralysis CNSBrainHeadache, dizziness, malaise, confusion, bizarre behavior, loss of consciousness Organophosphates & Carbamates Signs & Symptoms (II)

10 10 Commonly-used Acronyms for Cholinesterase Inhibition Syndromes  Salivation  Lacrimation  Urination  Diarrhea  Urination  Miosis  Bronchorrhea  Emesis  Lacrimation  Salivation

11 11 Cholinesterase Inhibitors Clinical Presentations Vary  Some signs & symptoms may be absent –Bronchorrhea more likely with high- dose exposures (ingestion)  Common presentations –Nausea, vomiting –Miosis –Sweating, urinary frequency –Non-specific constitutional symptoms

12 12  66 year-old male with eye irritation, abdominal pain, nausea, vomiting, headache, dizziness, frequent urination, muscle shaking. Symptoms began after weeding a cotton field for 4 hours.  Occasional palpitations but no other symptoms over the past 6 months  33 other crew members complain of similar symptoms Case Farmworker with Multiple Symptoms

13 13 Farmworker with Multiple Symptoms Exposure History  4:00 am: Aerial application of –Carbofuran (N-methyl carbamate) –Abamectin (macrolytic lactone) –Mepiquat chloride (growth regulator)  6:00 am: Workers entered field  10:00 am: Symptoms

14 14 Farmworker with Multiple Symptoms Physical Exam  Nausea & abdominal pain  Conjunctival injection  Irregularly irregular pulse; rate ,  Lungs clear, no murmurs; neurological exam normal This warning sign was posted after the workers entered the field and became ill.

15 15 Farmworker with Multiple Symptoms Initial Laboratory Results  EKG  TFTs, CPK

16 16 Farmworker with Multiple Symptoms Initial Summary & Differential Diagnosis  Differential diagnoses –Myocardial infarction (ruled out with CPK) –Thyroid disease (ruled out with TFT) – Food-borne illness (ruled out: no common food source) –Atrial fibrillation unrelated to pesticides –Pesticide-related illness

17 17 Farmworker with Multiple Symptoms Toxicity of Pesticides Involved  Carbofuran: N-methyl carbamate  Abamectin: macrolytic lactone  Mepiquat chloride: growth regulator

18 18 Cholinesterase-inhibitor Poisoning: Confirmatory Tests  Cholinesterase blood tests  Urine metabolites  Foliage and clothing pesticide residues  Diagnosis is primarily clinical

19 19 Cholinesterase Blood Tests  Two cholinesterase enzymes –RBC  “true”/ acetylcholinesterase –Plasma  “pseudo”/ butyrylcholinesterase  Preferential inhibition possible –Dichlorvos: plasma > RBC cholinesterase

20 20 Cholinesterase Blood Tests Interpretation  20% variability in population “baseline”  Correlation with symptoms unpredictable  Enzyme activity reversible –Carbamates –Sample temperature –Storage time

21 21 Cholinesterase Blood Tests Uses Biologic monitoring of workers potentially exposed to cholinesterase inhibitors Retrospective diagnosis of acute poisoning with cholinesterase inhibitors RBC Plasma

22 22 Urine Metabolites  Sensitive indicator of pesticide exposure  Results do not correlate with health effects  Requires specific pesticide information  Clinical labs may not perform tests

23 23 Pesticide Residues on Foliage & Clothing  Provides evidence of pesticide exposure in environment  Does not prove internal exposure  Limited clinical availability

24 24 Farmworker with Multiple Symptoms Pesticide Lab Test Results  Cholinesterase –Plasma-- 4,142 u/L  (lab normal range 1,667-5,883) –RBC-- 4,167 u/L  (lab normal range 8,871-16,993)  Urine metabolites of carbofuran –Carbofuran 7-phenol –Carbofuran 3-keto-7-phenol –Carbofuran 3-hydroxy-7-phenol

25 25 Farmworker with Multiple Symptoms Pesticide Residue Analysis Foliage –Carbofuran up to 0.77 g/cm 2 –Abamectin up to g/cm 2 –Dicofol up to 0.58 g/cm 2 Clothing (per item) –Carbofuran up to 91 mg –Abamectin up to 6000 g

26 26 Farmworker with Multiple Symptoms Assessment & Case Classification Definite Pesticide-Related Illness 1 : 1.Evidence of pesticide exposure 2.Pesticide-related adverse health effects 3.Exposure—effect relationship 1 NIOSH case definition (CDC 2000)

27 27 Specific Management for Cholinesterase Inhibitor Poisoning  Collect serum, urine, & clothing samples  Hospitalize for severe symptoms  Specific treatment –Atropine –Pralidoxime (2-PAM)--OPs only  Workplace restrictions

28 28 Cholinesterase Inhibitors: Treatment Atropine vs. 2-PAM

29 29 Treatment: Atropine  Reverses SLUD, DUMBELS syndrome  Intravenous dose: –Diagnostic  1 mg adult  0.01 mg/kg pediatric –Therapeutic  1 mg - 4 mg adult  0.05 mg/kg pediatric  Repeat every minutes

30 30 Treatment: Pralidoxime (2-PAM) AChE--OP OP 2-PAM AChE OP Aging Regenerated enzyme Permanent bond No treatment 2-PAM AChE +  Enzyme aging occurs if not treated  Treatment effective within 48 hours  2-PAM reactivates cholinesterase  Cholinesterase levels rise

31 31 2-PAM Treatment Regimen  IV infusion over 30 minutes or longer –> 12 years  g at < 0.2 g/min in 100 mL saline –< 12 years  mg/kg body weight in 100 mL saline  Repeat doses usually required –1-2 hours, then hour intervals  Treatment side effects –Arrhythmia –Hypertension

32 32 Farmworker with Multiple Symptoms Case Management & Course  Decontamination  Intravenous hydration  Treatment of atrial fibrillation  Converted to sinus rhythm as outpatient  Grower fined

33 33 Farmworker with Multiple Symptoms Carbamates and Persistent Effects  Health effects reported three months after exposure  Possible explanations: –Persistent effects of acute exposure –Continued exposure  Anecdotal reports but literature lacking

34 34 Case Grape Harvester with Subacute Poisoning  25 year-old grape harvester with dizziness, disorientation, and vomiting.  Vital signs normal; mild epigastric and suprapubic tenderness. CBC and chemistry normal.  Discharged after treatment with 2.5 liters of 5% dextrose/ 0.25 normal saline

35 35 Grape Harvester with Subacute Poisoning Persistent Symptoms  24 hours later: persistent weakness, dizziness, diarrhea, crampy abdominal pain, lacrimation, and salivation.  Examination: weak, pulse rate 48 beats/min; vital signs otherwise normal. Pupils 3 mm, lungs clear, abdomen nontender.  Labs: –Normal CBC, chemistry panel, UA. –Cholinesterase: Plasma 304 u/L ( ,400) RBC 4,360 u/L (9, ,996 u/L)

36 36 Grape Harvester with Subacute Poisoning Exposure History  Phosalone emulsion applied to grapes –half-life up to 30 days  Worker entered field one week after restricted entry interval  Residues of phosalone on leaf samples

37 37 Grape Harvester with Subacute Poisoning Hospital Course  Severe bradycardia while in hospital  Heart rate responded to atropine IV  Excess respiratory secretions absent

38 38 Grape Harvester with Subacute Poisoning Illness Among Coworkers  Health effects among crew: –Asymptomatic bradycardia –Asymptomatic plasma, RBC cholinesterase depression

39 39 Grape Harvester with Subacute Poisoning Incident Summary  Gradual-onset poisoning  Respiratory symptoms absent  Sentinel health event  Phosalone use restricted

40 40 Acute Non-Cholinesterase Effects of Organophosphates  Odor health effects  Irritant effects  Organophosphate- induced delayed polyneuropathy (OPIDP)

41 41 Insecticides CCCCholinesterase Inhibitors –C–C–C–Carbamates –O–O–O–Organophosphates PPPPyrethrins & Pyrethroids OOOOrganochlorines

42 42 Insecticides Pyrethrins & Pyrethroids  Pyrethrins –Natural insecticidal extract –Unstable  Pyrethroids –Synthetic derivatives –Used with piperonyl butoxide

43 43 Pyrethrins: Health Effects  Low systemic toxicity  Respiratory sensitization –Asthma  Skin reactions –Paresthesia –Allergic dermatitis

44 44 Pyrethroid Insecticides  Use increasing  Examples of use –Structural & agricultural –Pet flea control –Pediculicide  Vector control –West Nile virus –Aircraft “disinsection ” Source: CDC

45 45 Pyrethroids: Health Effects  Skin  Paresthesia, dermatitis  Respiratory  Rhinitis  Systemic  Dizziness, headache  Fasciculations, seizures,  Hormonal disruption in vitro

46 46 Pyrethrins & Pyrethroids Mechanism of Toxicity  Prolong inactivation of nerve membrane sodium channels  Pyrethroid structure  Type I (non-cyano)  Shorter inactivation Type II (-cyano)  Longer inactivation Pyrethroid structure R’RCompound

47 47 Pyrethrin & Pyrethroid Illness: Treatment  Decontamination  Vitamin E cream  Symptomatic therapy  Remove from further exposure if needed

48 48 Case Woman Exposed to Flea Bomb  35 year-old non-pregnant female with skin burning, itching and chest tightness after putting on clothes from closet.  Physical exam –Arms and face bright red –Vital signs normal –Lungs clear

49 49 Woman Exposed to Flea Bomb Ingredients  Label –0.435% permethrin –0.05% pyrethrins –0.4% piperonyl butoxide –99.115% inert ingredients  Recommended no entry for 4 hours after fogging

50 50 Insecticides CCCCholinesterase Inhibitors –C–C–C–Carbamates –O–O–O–Organophosphates PPPPyrethrins & Pyrethroids OOOOrganochlorines

51 51 Insecticides: Organochlorines  DDT (prototype)  Chlordane  Lindane (Kwell, etc.)  Hexachlorobenzene –(Fungicide)

52 52 Organochlorine Toxicity  CNS toxicity –Headache, dizziness, irritability, incoordination, tremor, seizures, paresthesia (DDT),  Carcinogenicity –Hepatic tumors in rodents –Breast cancer (?)  Endocrine disruption

53 53 Skin Effects of Organochlorines  DDT –Chloracne  Lindane –Irritant reactions –Negative in patch test series

54 54 Skin Effects of Organochlorines Dienochlor Patch test develops hyperpigmentation in % of subjects tested with dienochlor - resembles reaction to Balsam of Peru

55 55 Case Child With Seizures  9 year-old child with myoclonic seizures witnessed by parents. No history of seizures, head trauma, etc.  In ER, child sleepy, oriented; complaining of abdominal cramping, throat burning. Exam normal. Photo courtesy of California Poison Control System

56 56 Insecticide Illness: Summary  Occupational and environmental exposure  Toxicity varies by chemical class  Specific therapy limited  Prevent illness by reducing use Source: USDA


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