Monitoring Pesticide Exposed Workers

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Monitoring Pesticide Exposed Workers

• Matthew Keifer MD MPH
• Associate Professor Medicine and Environmental
  Health Sciences
• University of Washington
• Director, International Scholars in Occupational
  and Environmental Health

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Monitoring Pesticide Exposed Workers

• What is biological monitoring?
• What advantages are there to biological
  monitoring over exposure monitoring?
• What are the basic requirements for monitoring?
• Why do we monitor workers for overexposure?
• What pesticides are adaptable to monitoring?
• What tools are available?

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Monitoring Pesticide Exposed Workers

• Cholinesterase Inhibitors are Unique Pesticides
• ChE Monitoring
• Why?
• What is accomplished?
• What are the problems?
• How do we do it?
• What do we do with results?

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What Is Monitoring?

• A systematic or repetitive health-related
  activity designed to lead, if necessary to
  corrective action.
• EEC sponsored seminar on monitoring

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Advantages of Biological Monitoring

• Integrates all sources of exposure.
• In some cases integrates over time as well.
• May lead to the identification of unrecognized
  sources of exposure.
• May be used to validate exposure monitoring and
  return to non-invasive exposure monitoring
• May be used to connect dose to disease.

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The Decision Do Monitoring Should be Subject to
High StandardsEthical and Practical

• Worker monitoring is done to protect the worker
  from the consequences of further exposure.
• As opposed to studies using
• monitoring techniques.

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Presuppositions About Monitoring

• Detectable The chemical or metabolites or an
  associated effect are detectable in the body or
  available so as to be sampled.
• Valid Valid methods exist for measurement.
• Representative The measurements strategy is
  representative.
• Useful Information The results can be
  interpreted in a meaningful and practical way.
• Acceptable Sampling is acceptable to those being
  tested.

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Detectable and Valid

• The chemical or metabolites or an associated
  effect are detectable in the body or available so
  as to be sampled.
• Valid methods exist for measurement.
• This part of the equation is advancing rapidly.
• New methods and understanding of pesticide
  metabolite detection and quantification are being
  developed.

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Are Results Meaningful

• The measurement strategy is representative.
• The results can be interpreted in a meaningful
  and practical way.
• The results must reflect the status of the worker
  being monitored. (time is of the essence).
• The results lead to action that of benefit to the
  worker. (removal of the exposure, correction in
  safety practices, removal from exposure,
  assurance).

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Acceptable

• What is acceptable is a moving target.
• May be temporally and will be culturally
  dependent.
• Are the risks for all involved truly considered?
  (workers, testers).
• Do we have the right to monitor?

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Why Monitor for Pesticide Exposure?

• Yearly in the world
• 3,000,000 serious pesticide poisonings
• 200,000 deaths from pesticide poisonings
• 25,000,000 less severe poisonings
• gt90 occur in developing countries

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Why Monitor for Pesticide Exposure?

• In the US, 10,000-20,000 agricultural workers
  poisoned per year
• In Washington, 500 human pesticide overexposure
  reports per year. ½ are agricultural, ½ are Def,
  Prob, Poss.
• 50-70 applicators poisoned annually
• Mostly by cholinesterase inhibitors

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Why Are We Monitoring?

• It may help prevent poisonings.
• Removal of workers who are asymptomatic but
  running a high body burden of intoxicant may
  prevent intoxication.
• Identifying and acting on the condition of those
  workers may lead to a raising of consciousness in
  that worker.

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Why Are We Monitoring?

• It should identify unsafe work practices.
• The biological monitoring provides a window into
  where the safety system breaks down.
• It goes beyond exposure monitoring.
• Actually provide dose information.
• It is integrative in toxicants with long
  biological half lives.

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Why Are We Monitoring?

• Raise awareness among workers.
• The testing session provides a teachable moment.
• Not much data on this point.
• No reports have described the effect of ChE
  testing on teaching prevention.
• It likely makes clear the health significance of
  the pesticides involved.

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Why Are We Monitoring?

• Assist in medical decision making about return to
  work.
• If a latent condition of sub-clinical
  overexposure or increased body burden increases
  susceptibility to subsequent overexposure,
  monitoring will help us decide when a worker can
  return to exposure.

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Why Are We Monitoring?

• It may influence practice.
• The expense of a monitoring program may influence
  the employers choice of pesticides.
• IH principle remove the hazard.
• The expense may cause the employer to
  redistribute the exposure.
• IH principle administrative changes to control
  overexposure.

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What Pesticides Can We Monitor?

• Many
• But for which do we have a standard to compare?
• Arsenic, Coumarins, DNOC, Parathion,
  Pentachlorophenol, DDT, MCPA, 2,4-D.
• Organophosphates and Carbamates.

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Arsenic

• Chromated Copper Arsenate. A wood preservative.
• Arsenic in urine must be inorganic arsenic
  measured with HPLC.
• German standards exist (EKA) and the ACGIH has
  proposed a BEI of 50ug/g creatinine.

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Pentachlorophenol

• Uncouples Oxidative-phosphorylation.
• 7-20 day half-life.
• Measurable in Blood and Urine
• Tests are Straight-forward.
• Parameters for overexposure are not clear.

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Organochlorines

• DDT and family, Cyclodienes (Heptachlor et al),
  Benzenehexachloride isomers (Lindane et al.).
• Methods are available and some data available on
  population and exposed worker levels.
• Hepatic enzyme induction may constitute a
  meaningful threshold for these chemicals.

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Cholinesterase Inhibitors are Unique

• Organophosphates and Carbamates
• Widely used, Many poisonings
• Pre-clinical state which indicates susceptibility
  to future illness
• Easily available test of functional group
• Level of depression acceptable reflection of
  toxicity
• Response to low AChE is clear and effective

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The Target Cholinesterase

• Essential for nervous system function
• Important in voluntary muscles,
  
  autonomic central nervous system
• The target of a specific group of widely used
  pesticides
• Measurable in blood

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Two Kinds of Cholinesterase

• Plasma ChE (ChE, PChE, pseudo ChE)
  
  floats free in plasma
• made by liver
• no known function
• rapid recovery from depression
• sensitive to most ChE inhibitor exposures

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Two Kinds of Cholinesterase

• Red blood cell ChE (ache, true ChE)
• Bound to red blood cell surface
• Replaced with the RBCs
• No known function on the red cell
• Recovery from depression 0.8/day
• Slower to depress, slower to recover

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Testing ChE

• How is it done
• ChE can have very low test-retest variability in
  good hands
• Several very straight forward methods
• Intra-individual variation 15,
• Inter-individual variation is high
• Requires a baseline for above reasons

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When to Test

• Baseline obtained before exposure
• 30 days since last exposure
• Repeated every two years
• CA recommends duplicate baselines
• 3-15 days apart (greater than 15 discrepency,
  repeat
• Working baseline acceptable if in mid to high
  normal range for test.

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What to Do With Results

• Options Include
• Worker removal
• If PChE below 60 of baseline
• If AChE below 70 of baseline
• Equipment and behavior review and training
• If either 80 of activity (confirmed)
• Product substitution
• The best option

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How To Interpret Results

• What can cause false positives?
• Plasma ChE
• Liver disease
• Drugs (anticholinergics, hormones, INH,
  chloroquin, alcoholism, cocaine, CS2, organic
  mercury, BCPs, Metachlopromide)
• Xanthine containing foods
• Pregnancy
• RBC ChE
• Anemia, reticulocytosis
• Drugs (anticholinergics, quinine)

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How To Interpret Results

• What causes false negatives?
• Depressed baseline values
• Testing errors
• Certain anemias

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Does ChE monitoring prevent illness? A study103
worker/years monitoring experience

• 24 were removed (mean duration 3.5 weeks)
• 17 had toxic ChE depression (gt50 ChE)
• 5 had toxic symptoms (WHO symptom profile)
• Workers with ChE 60-80 of baseline had
• 9 fold risk of developing toxic symptoms
• 6 fold risk of below threshold ChE during the
  season
• A cholinesterase testing program for pesticide
  applicators. Filmore and Lessenger JOM 35(1) 1993

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What ChE Monitoring Accomplishes ?

• Prevents poisonings
• Identifies hazardous conditions/practices
• Increases worker/employer hazard awareness
• Assists in medical return to work
• May avoid problems from chronic exposure
• Influences economic decisions
• Increases costs of production
• May influence choice of pesticide

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Other Loose Ends

• Congenital plasma cholinesterase deficiency
• 3 of Anglos, 1 of Blacks carry the gene
• May effect susceptibility to ChE inhibitors
• Will have low baseline values for PChE
• Will have normal RBC ChE values
• Use the Same Laboratory
• Follow-up baselines can demonstrate previous
  depression in acute intoxications

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What Are the Potential Problems?

• Worker misunderstanding, worker suspicion
• Physician misunderstanding
• Laboratory Quality control
• Specimen collection methods
• Laboratory inconsistency
• Costs
• the test, the doc, the worker
• Blood exposure that wasnt there before

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Monitoring of Pesticide Exposed Workers

• We can measure lots of pesticides
• It is not practical to monitor for most
  pesticides
• Short response window
• Short susceptible period
• Cost
• No clear connection to illness
• Cholinesterase inhibitors are an exception

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The Need reliable, inexpensive ChE methods in
Washington State

• A class action suite about cholinesterase
• Rios Vs. Dept. Labor Industries
• Complaint
• Protection not afforded by voluntary ChE
  monitoring
• Remedy
• Required monitoring for workers exposed ChE
  inhibitors