Cholinesterase Basics 1 & 2

Pesticide Issues Conference
  • Boiko, Patricia

Information about Cholinesterase Monitoring can be found at the Washington State Department of Labor and Industries website: http://www.lni.wa.gov/Safety/Topics/AtoZ/Cholinesterase/

Contents

Cholinesterase Basics 1

Patricia Boiko

Goal: To provide information and resources to growers and managers.

Schedule Growers/Manager Breakout

1:30- 2:00 Cholinesterase basics Patricia Boiko

2:00- 2:30 Cholinesterase monitoring rules John Furman

2:30- 3:00 Cholinesterase testing and informed consent/dissent John Furman

3:00- 3:15 Break- Handlers interact with growers and health care providers

3:15- 3:35 Practicalities of the rule Dr. Todd Denny

3:35- 4:00 Grower experiences a monitoring programs

The Rule

Employers must provide cholinesterase monitoring

  • Baseline plasma and rbc cholinesterase
  • Follow-up plasma and rbc level
  • To OP and Carbamate pesticide handlers
    • Who handle for 50 hours or more in a thirty day period for 2004, 30 hours in 2005

Medical Providers Role

According to WAC 296-307-148 Licensed Health Care Providers must:

  • Discuss the risks and benefits of handler participation in cholinesterase monitoring
  • Obtain a signed declination if the handler chooses not to participate
  • Provide and interpret baseline and periodic testing of blood cholinesterase levels
  • Provide other written occupational health recommendations as indicated.

Cholinesterase Basics: >20% Depression From Baseline

Understand

  • Basic science of cholinesterase and cholinesterase inhibiting pesticides
  • Everything about monitoring
    • Testing methods
    • Responses to a positive test: Cholinesterase depression false positives
  • Quality assurance evaluation

The Rule

  • Listen for
    • Which pesticides
      • OP, carbamates
    • Which workers
      • handlers
    • What is the responsibility of growers/managers

Handler Consent

  • Rule says the handler must sign a written declination statement of which a copy goes to the grower
  • WHAT DOES THIS MEAN FOR YOU??

Reporting Requirements and Poisoning

  • Pesticide-related illness
    • Reportable condition to the Washington State Department of Health (WAC 246-10)
    • All types pesticide-related cases must be reported
      • Including skin, eye injuries, systemic poisonings, suicides, homicides,
      • Home and occupational exposures.

Why is ChE Testing Useful?

  • ChE reflects the substance on its target
  • Integrates exposure over time
  • The test is available
  • Blood tests are available

    BUT!

    • Baseline is needed
    • Good lab methods needed
    • Interpretation and timing important
    • Sample handling important

Objective

To understand the basic biology of cholinesterase and cholinesterase inhibiting pesticides.

Biology of Cholinesterase

  • Present from paramecia to sapiens
  • Very Fast enzyme Ubiquitous in the human body
  • Critical for many nervous system functions

Cholinesterase Enzyme

  • Produced in tissues and blood
  • Hydrolyzes acetylcholine: A key neurotransmitter
  • Present in the autonomic, central and peripheral nervous systems

Image of the enzyme

Two Different Kinds of ChE enzymes

-Some behaviors in common

  • Plasma Cholinesterase
    • Butyrylcholinesterase, pseudocholinesterase, PChE, or just cholinesterase and ChE
  • RBC Cholinesterase
    • True cholinesterase, acetylcholinesterase, or AChE

Plasma ChE

  • Floats freely in plasma
  • Made by liver
  • Rapid recovery from depression
  • Rapid replacement by new synthesis
  • Liver disease may affect levels
  • Sensitive to most ChE inhibitor pesticide exposures

Red Blood Cell Cholinesterase

  • Bound to red blood cells
  • Made at the same time as the Rbc's
  • Recovery from depression 0.8%/day
  • Slower to depress, slower to recover
  • Low RBC count may cause lower levels
  • Identical to neuronal ChE

What Cholinesterase Does: Physiologically

  • Autonomic Nervous System
    • Parasympathetic
    • Presynaptic Sympathetic l
    • The Autonomic Nervous System
      The autonomic Nervous System with pictures and labels of the cranial and senses and organs

      PNS

      • Skeletal muscle

      CNS

      • Memory & others

      Cholinesterase

      • Found at the synapse
      • It turns off the chemical messenger
      • When inhibited the messenger builds
      • Over stimulation results

      Pesticides That Inhibit Cholinesterase

      • Organophosphates
        • Inhibit irreversibly "aging of complex"
        • ChE must be replaced by the body
      • Carbamates
        • Inhibit temporarily
        • No "aging"
        • Reversal is rapid and level related
        • ChE reactivates and is ready to go

      Toxicity of ChE Inhibitors

      • 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/

       

      CHOLINESTERASE BASICS 2

      Author: Carol Ramsay

      Insecticides

      • Most insecticides affect the nervous system of animals (insects and humans)
      • DOSE is the primary factor as to why insects are most susceptible, but with increased doses (exposure) humans are susceptible

      Nervous System Review

      Peripheral Nervous System (input/output)

      • Nerve to nerve transmission
      • Nerve to muscle transmission
      • Nerve to organ transmission

      Nerve Cells (neurons)

      nerve cells
      • Cell body
      • Dendrite - receives the message
      • Axon - sends the message
      • Synapse - chemical transmitter released, cleansing enzyme shuts off transmission

      • Sensory stimulation evokes a motor

      Neural Transmission

      • Axon to dendrite
      • Axon to muscle
      • Synapse
        • chemical transmitter = acetylcholine
        • cleansing enzyme = cholinesterase
        Cholinesterase stops the continual transmission. Nerves then are back to normal resting state, awaiting next stimulation

      Monitoring Cholinesterase

      • Baseline in off season (30-day exposure free)
      • Red blood cell
        • drop 30% or more from baseline
      • Plasma
        • drop 40% or more from baseline
      • You can return to handling when levels return to within 20% of baseline

      Exposure to Organophosphate and Carbamate Insecticides

      • These two classes of insecticides actually TRAP the cholinesterase (cholinesterase inhibition)
      • Once inhibited, there is NO free cholinesterase enzyme to cleanse the synapse
      • Thus, acetylcholine (transmitter) continually stimulates the nerves, muscles, glands
      • Muscles and glands remain overexcited (this is poisoning).
      • Poisoning can be mild, moderate, severe, or deadly.

      Symptoms from Over-Stimulation (insecticide poisoning)

      • Too much neural transmitter
      • Not enough cholinesterase (50% decreased)
      • Headache, dizzy, nauseous, diarrhea
      • Muscle aches, clumsy, cramps, out of breath breath
      • Pin point pupils, blurred vision
      • Convulsions, coma
      • Death

      Function of Cholinesterase

      • An enzyme that is critical for “cleaning out” the synapse and stopping the ongoing transmission of neural messages to muscles and glands.
      • Cholinesterase is found in the blood system and nervous system (“equally ”), so measuring levels in the blood is a great indicator of the bodies’ supply of cholinesterase in nerves.

      Examples of Exposure

      k

      Body Builds Cholinesterase

      • Your body continually makes more cholinesterase enzyme (Liver and bone marrow)
      • Keep exposure low so that you do not deplete your body’s reserves of cholinesterase to a harmful level, especially organophosphates
      • The body does not recognize the depletion, and only builds so much a day (1% per day for red blood cells)
      • It may take a month or two for your body to build back to a safe level

      HAZARD

      • Amount of exposure needed to cause harm
      • Levels are predetermined
      • Risk of pesticide use and symptoms vary
        • Frequency of exposure – Concentration of the pesticide
      • Toxicity can be cumulative
        • Rate of depletion, rate of generation

      Factors that may produce a low baseline

      • Genetic Trait
      • Liver disease
      • Certain medications

      Preventive measures

      • Become familiar with pesticides used
      • Save labels!
      • Wear appropriate equipment
      • Clothing should provide an effective barrier to pesticide sprays and dusts!
      • Respirators should be chemical specific

      Hand protection

      • Use unlined rubber or plastic gloves
      • Never wear leather!
      • Not too tight
      • Not too big
      • Wear on the outside of the sleeve
      • Wash gloves after use
      • Dispose of old gloves

      Foot protection

      • Wear Neoprene or nitrile boots
      • Do not wear leather
      • Wear pant legs outside of boots

      Closed Systems

      Used closed systems. When using closed systems, you do not add those hours handling to the total exposure period prior to testing.


      Disclaimer and Reproduction Information: Information in NASD does not represent NIOSH policy. Information included in NASD appears by permission of the author and/or copyright holder. More

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