The Challenges of

Operator Exposure Studies

Sven Buckingham
Buckingham QA Consultancy Ltd
The Guidelines
OECD Guidance Document #9 (1997)
Conduct of Studies of Occupational Exposure
to Pesticides During Agricultural Application

Focus is on mixer/loader/applicator exposure
during agricultural use of pesticides

The study should be conducted to GLP
Guidelines (cont)
EMA Guideline for user safety for
pharmaceutical veterinary products (2010)

Looks at pre-application, application and post-
application phases

Considers the user, route of exposure, type and
level of exposure
Types of study - examples
Seed treatment
Spraying - by hand or using tractor
Worker re-entry (+ dislodgeable foliar residues
(DFR))
Orchard
Glasshouse
Potato storage

Veterinary products e.g. drenches, dips
Basic premise
Operators wear dosimeters, e.g.
Inner and outer clothing
Air filters
Face wipes and hand wash
May take urine and blood samples
Work to normal practices for a normal day
Take dosimeters for analysis
Assess potential and actual exposure
Study plan and planning
Single sponsor or Task Force
May need permits for use of test item
Number of sites and operators
Allow for loss of operators
Location
Duration of normal day
Number of operators at any one time

Use of non-GLP compliant facility
The GLPMA routinely do not need to be
notified when using farms for Operator
Exposure studies
See FAQ #16

But, if in doubt ask!!
Planning
Prepare labels, bags in advance
Have sufficient spares (pots, bags, labels)
Prepare hand wash solution
Pre-wash clothing dosimeters
Size of clothing, including belts
Spare equipment
Labels to include operator ID (number)
Accessibility of sites
Often remote
Usually budget airline locations
Hotels
Timing of working day
Availability of contamination free working
areas
Training
Must train those staff who perform monitoring
May be from collaborator companies (GLP)
Need training records training in test facility
SOPs
Operators will need instruction too
Language
Informed consents verify translation
Briefing of operators
Potential difficulty during monitoring
Facilitators/translators essential
Avoid any potential misunderstanding
Test item
Storage conditions
Need to know what chemicals are also in the
mix
Samples of test item?
Accuracy of amount used, including vehicle
Safety precautions
Previous use (bio-monitoring)
Monitoring
Dressing of operator
Synchronise watches
Handwriting
Record what is important (study objectives)
Checks that air pump is working
Potential contamination noted
Workers follow their normal procedures
Each operator needs a monitor (usually)
Interim dosimeter sampling
Hand wash
Face wipes
For breaks (tea/coffee and lunch)
Toilet
Extra coveralls for lunch?
Labelling of interim samples
Fresh or frozen?
Pooling of face wipes and hand wash
Final dosimeter samples
Area well away from contamination
Good control of operator
Lots of gloves
Consider contamination from hair
Cloths line - separation of operators
Proper sectioning and bagging
Dont rush!
DFR Sampling
Control matrix for spikes
Control equipment
Consistent disc size (and number)
Sampling scheme number of trees, sub-plots
Speed of extraction

Ensure operators do not enter the sub plots!
Photos
Of operator at start with ID
Of test item label?
During activities
Of working environment
Activities that pose high risk of contamination
Of operator at the end
Sample storage
Often freezer truck
Power supply?
Temperature monitoring
Portable freezers?
Separation of samples from each operator
Chain of custody to analytical laboratory
Field spikes
Why?
Avoid contamination
Adequate labelling
Storage of spiking solutions
Occlusion of matrices
Air pump duration mimics working day
Urine samples
Adequate containers provided to operator
Variable volumes
Storage by operator (Fridge?)
Sub-sampling
Contamination
Consider additional operators
Blood samples
Who will take the samples?
Timing intervals and acceptable +/-
Processing required?
Duplicate samples
Storage

Data
Original entries by GLP personnel
Records from farmers
Copies of records from farmers
Records from computer systems
Transcribed data
Integrity of key data
QA of in-life phases
Key aspects:
Monitoring exposure
Sampling of dosimeters
Urine sub-sampling
Field spikes
Repeat inspections?
Data QC and QA
QC is essential
Field data
Chemistry data
Transcription checked
Spreadsheets audited before report is written
100% or sample?
Rounding consistency between tables
Final report non-compliances
SD compliance statement must be accurate
Will be exceptions given, e.g.:
Amount of test item used
Treated areas/amount
Information supplied by the farmer
Digital photographs

SOPs
Adequate SOPs
Cover basic procedures
Availability at each site
Retraining/familiarity before each study
Translations?
Covered in QA SOPs too
And finally
Studies are expensive and time consuming
Much time spent in planning
Expect the unexpected
Involve the Sponsor
Consider the end result - is all about operator
safety