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

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?

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?

* 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

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.

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.

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.

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.

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).

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?

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

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

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.

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.

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.

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.

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.

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.

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.

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

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.

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

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

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

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

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

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.

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

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)

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

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

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

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

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

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

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