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Cholinesterase (ChE) Monitoring in Washington State

Cholinesterase (ChE) Monitoring in Washington State. John Furman, Ph.D., MSN, COHN-S Thank you to Dr. Matthew Keifer. Biology of Cholinesterase. An enzyme Produced in tissues and blood Hydrolyses acetylcholine

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Cholinesterase (ChE) Monitoring in Washington State

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  1. Cholinesterase (ChE) Monitoring inWashington State John Furman, Ph.D., MSN, COHN-S Thank you to Dr. Matthew Keifer

  2. Biology of Cholinesterase • An enzyme • Produced in tissues and blood • Hydrolyses acetylcholine • Present in the autonomic, central and peripheral nervous systems • Excellent web page on the enzyme http://www.weizmann.ac.il/Structural_Biology/Pages/Sussman/webpage2/kurt/che.html

  3. Two Kinds of ChE in the Body • Different enzymes with some behaviors in common • Plasma Cholinesterase • Butyrylcholinesterase, pseudocholinesterase, PChE, or just cholinesterase and ChE • RBC Cholinesterase • True cholinesterase, acetylcholinesterase, or AChE

  4. Pesticides That Inhibit Cholinesterase • Organophosphates • Inhibit irreversibly • “aging of complex” • ChE must be replaced by the body • N-methyl-Carbamates • Inhibit temporarily • No “aging” • Reversal is rapid and level related • ChE reactivates and is ready to go

  5. Mild cases: tiredness, weakness, dizziness, nausea and blurred vision Moderate cases: headache, sweating, tearing, drooling, vomiting, tunnel vision, and twitching Severe cases: abdominal cramps, urinating, diarrhea, muscular tremors, staggering gait, pinpoint pupils, hypotension (abnormally low blood pressure), slow heartbeat, breathing difficulty, and possibly death Extoxnet http://ace.ace.orst.edu/info/extoxnet/ Toxicity of ChE Inhibitors

  6. Why is ChE Testing Useful? • ChE reflects the toxicant on its target • Integrates exposure over time • The test is widely available • A blood sample all that is needed • BUT! • Baseline is needed • Good lab methods needed • Interpretation and timing important • Sample handling important

  7. What ChE monitoring accomplishes ? • Identifies hazardous conditions/practices • Increases worker/employer hazard awareness • Assists in medical return to work • Avoids problems from chronic exposure • Influences economic decisions: • - Increases costs of production • - May influence choice of pesticide

  8. Regulatory Background • 1993 - ChE monitoring recommendation • 1995 - Tag report • 2002 - Rios decision • 2003 - Rule adoption, chapter 296-307-148 WAC

  9. When to Test? Class I and II Carbamates & Organophosphates “DANGER” or “WARNING” LD 50 of < 50 mg oral or 100 dermal LD 50 of >50 <500 oral or <1000 dermal Threshold: 50 hrs in 30 days

  10. Baselines • Obtain before exposure • 30 days since last handling • Maintain records for future comparison • If its abnormally low • Recheck, average or discard • More tests are better than less

  11. How Often to Test? • Retest with the same laboratory, same methods • Department of Health (DOH) laboratory doing all testing through 2005 • Ellman method • Retesting every 30 days of reaching exposure threshold

  12. How to Interpret Results Large difference between upper and lower range of normal 20% depression- Significant 30% AChE- Removal* 50% AChE- Poisoning 40% PChE- Removal* 60% PChE- Poisoning *California, WHO and ACGIH recommendations on removal thresholds

  13. What Response to Depressed Results • Act promptly • You’re already late • Evaluate for false positives • Communicate with worker and with employer • Assure removal if meets threshold • Be sure the workplace is evaluated

  14. False Positives Plasma Cholinesterase Drugs: therapeutic and recreational BCPs, metaclopramide, cocaine? INH Liver Disease-alcoholism Congenital Deficiency (3%) Pregnancy Nephrotic syndrome Carbon disulfide, organic mercury RBC Cholinesterase Drugs and Reticulocytosis

  15. Medical Removal • Remove from all exposure to class I & II OPS and CBs • Medical removal protection benefits • Up to 3 months for each occurrence • Return to handling when ChE levels return to within 20% of baseline

  16. Industrial Insurance • No effect on industrial insurance system • Associated symptomology must be present • Pesticide illness reporting

  17. Surveillance • DOH conducting all testing • Cholinesterase Monitoring data System (CMDS) • Data Sharing agreement with L&I

  18. Program Status as of 5/3/04 • Employers • Employees 2600+ • Periodic tests 345 • Significant depressions • Employees 82 • Employers 27 • Work removal 20

  19. Rule Evaluation • Stakeholder committee • Scientific team • Legislative requirements • Annual reports • Correlation of handling hours with test results • Reimbursement of clinical costs • Data gathering

  20. Challenges • Medical provider resources • Consistent laboratory methodology • Test validity • Greater than expected affected population • Timely reporting • Surveillance • False positives

  21. Questions ? John Furman Department of Labor & Industries WISHA Services 360-902-5666 furk235@lni.wa.gov

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