1. 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

2. 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?

3. 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?

4. * EEC sponsored seminar on monitoring
What Is Monitoring?
“A systematic or repetitive health-related activity designed to lead, if necessary to corrective action.”*
* EEC sponsored seminar on monitoring

5. 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.

6. The Decision Do Monitoring Should be Subject to High Standards: Ethical and Practical
Worker monitoring is done to protect the worker from the consequences of further exposure.
As opposed to studies using
monitoring techniques.

7. 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.

8. 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.

9. 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).

10. 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?

11. 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
>90% occur in developing countries

12. 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

13. 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.

14. 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.

15. 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.

16. 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.

17. Why Are We Monitoring? It may influence practice.
The expense of a monitoring program may influence the employer’s 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.

18. 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.

19. 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.

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

21. 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.

22. 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

23. 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

24. 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

25. Two Kinds of Cholinesterase
Red blood cell ChE: (ache, true ChE)
Bound to red blood cell surface
Replaced with the RBC’s
No known function on the red cell
Recovery from depression 0.8%/day
Slower to depress, slower to recover

26. 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

27. 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.

28. 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

29. 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)

30. How To Interpret Results
What causes false negatives?
Depressed baseline values
Testing errors
Certain anemias

31. Does ChE monitoring prevent illness
Does ChE monitoring prevent illness? A study:103 worker/years monitoring experience
24% were removed (mean duration 3.5 weeks)
17% had “toxic” ChE depression (>50% 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

32. 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

33. 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

34. 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 wasn’t there before

35. 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

36. 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