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Results from the Agricultural Health Study Pesticide Exposure Study. Linda Sheldon a , Kent Thomas a , Guadalupe Chapa a , Sydney Gordon b Martin Jones c , James Raymer d , Dale Sandler e , Jane Hoppin e Mustafa Dosemeci f , Aaron Blair f , and Michael Alavanja f
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Results from the Agricultural Health StudyPesticide Exposure Study Linda Sheldona, Kent Thomasa, Guadalupe Chapaa, Sydney Gordonb Martin Jonesc, James Raymerd, Dale Sandlere, Jane Hoppine Mustafa Dosemecif, Aaron Blairf, and Michael Alavanjaf aNational Exposure Research Laboratory, U.S. Environmental Protection Agency bBattelle Memorial Institute, cUniversity of Iowa, dRTI International; eNational Institute of Environmental Health Sciences, fNational Cancer Institute
PRESENTATIONOVERVIEW • Background of the Agricultural Health Study • Purpose of the Pesticide Exposure Study • Exposure Study Procedures • Applicator Exposure Measurement Results • Spouse and Child Measurement Results
AGRICULTURAL HEALTH STUDY RESEARCHERS • NCI and NIEHS are leading the epidemiological study and investigations of cancer and non-cancer health outcomes • University of Iowa Department of Epidemiology operates the Iowa AHS Field Station • Battelle Center for Public Health Research and Evaluation operates the North Carolina AHS Field Station • Westat operates the AHS Coordinating Center • EPA and NIOSH are leading AHS exposure sub-studies • Battelle, University of Iowa, and RTI International conducted the AHS Pesticide Exposure Study
AHS BACKGROUND • The epidemiological study is designed to: • Measure cancer and non-cancer health risks in the agricultural community • Examine associations between use of agricultural chemicals, other exposures, and disease • Determine factors that promote good health
AHS PHASE I (1993 – 1997) • Prospective cohort enrolled in Iowa and North Carolina: • 52,395 private licensed pesticide applicators • 32,347 spouses of private pesticide applicators • 4,916 commercial applicators (IA only) • Questionnaires collected information about pesticide use, work practices, other exposures, lifestyle factors, and health.
AHS PHASE II (1998 – 2004) Follow-up through cancer registries and vital records linkage 5-year follow-up questionnaire via computer assisted telephone interview (CATI) Update health status, exposures, and lifestyle Buccal Cell Collection and Dietary Health Questionnaire Nested studies of exposure and specific health outcomes AHS PHASE III (2005 - 2008) Continued cancer and mortality follow-up Follow-up telephone interview Cross sectional and panel studies, nested case-control studies
AHS RESULTS DISSEMINATION • AHS Web Site • www.aghealth.org • Direct communication to study participants • Fact sheets and other information distributed to and through Iowa and North Carolina Cooperative Extension Services • Scientific and Informational Presentations • Journal Publications
AHS PESTICIDE EXPOSURE CLASSIFICATION The AHS is examining possible links between pesticide use and health risks Information on use of up to 50 common insecticides, herbicides, fungicides, and fumigants obtained from AHS enrollment and take-home questionnaires – current and historical uses Information on work practices collected from questionnaires
AHS EXPOSURE CLASSIFICATION 1) Ever/Never Use of a Pesticide 2) Cumulative Exposure Years Used x Days/Year 3) Adjusted Cumulative Exposure Years Used x Days/Year x Intensity Score
AHS EXPOSURE INTENSITY ALGORITHM Intensity Score = (Mix + Appl + Repair) * PPE where, Mix : Mixing Frequency of Pesticides (0, 3, 9) Appl : Application Method (0 - 9) Repair : Repair of Application Equipment (0, 2) PPE : Personal Protective Equipment (0.1 - 1.0) Dosemeci et al., Ann Occ Hyg, 46:2, 2002
AHS PESTICIDE EXPOSURE STUDY • Overall Goal • Measure exposure to applied pesticides for a subset of AHS applicators to evaluate and improve the AHS exposure algorithm • Specific Objectives • Measure exposure to target applied pesticides • Compare measurements to algorithm exposure intensity scores • Identify key exposure factors • Assess potential spouse/child exposure to farm- applied pesticides
STUDY DESIGN OVERVIEW • Target pesticides 2,4-D and Chlorpyrifos • Eight exposure strata based on application method and PPE • Applicators monitored on one day while using their normal procedures • Observation of activities • Dermal, personal air, urine samples • Questionnaires after use • Spouse and child biomarker measurement
PARTICIPANT SELECTION AND RECRUITMENT • Sample Frame • AHS cohort members; completed AHS Phase I & II • Reside in one of 22 Iowa or 22 NC counties • Previous use of a target chemical • Eligibility Screening • Telephone screening • Eligible with planned use of a target chemical • Recruitment • In-home visit to discuss study • Applicator, spouse, child consent/assent • Schedule monitoring visits
OVERALL MONITORING TOTALS IA NC Total Pesticide Applicators 84a 24 108 Spouses (urine) 38b 11 49 Children (urine) 9 3 12 a Includes 24 repeat monitoring visits for applicators b Includes 8 repeat monitoring visits for spouses
NUMBER OF OBSERVATIONS IN EXPOSURE STRATA Broadcast Spray – Liquid 2,4-D or Chlorpyrifos No gloves, no enclosed cab 9 No gloves, enclosed cab 9 Gloves, no enclosed cab 14 Gloves, enclosed cab 21 In-Furrow – Granular Chlorpyrifos No enclosed cab 7 Enclosed cab 6 Hand Spray – Liquid 2,4-D No gloves 22 Gloves 20
MONITORING SCHEDULE Visit 1 • Provide urine sample containers; discuss scheduling Visit 2 • Sample collection (dermal, air, urine) • Observe activities • Application questionnaire Visit 3 • Sample collection (urine pick-up) • Activity questionnaire
MEASUREMENTS • Dermal Patches • 10 Patches, sized proportionally to body area, under • PPE and over clothing, combined for analysis • Hand Wipe • Combined wipes from 12 small areas on each hand • Personal Air • Personal monitor (pump and filter) • Applicator Urine • Pre-Application morning void • Post-Application Composite (start of pesticide use • through the following morning) • Spouse and Child Urine • Pre-Application morning void • Post-Application morning void (2 days later)
APPLICATOR MEASUREMENT RESULTS Comparison of exposure measurements across eight exposure strata Assessment of the relative contribution of hand loading, body loading, and air exposures to urinary biomarker levels Bivariate analyses for >80 pesticide use, work, and hygiene factor variables – selected results shown here
Applicator Chlorpyrifos Levels (Geometric Means) By Physical State (as applied) a Measured as 3,5,6-trichloro-2-pyridinol (TCP) metabolite b Near average pre-application background levels of 9.8 g/L Preliminary Results
Exposure Pathway Model Results Preliminary Results
Hand Loading vs. Post-Application Urine Concentration (For liquid products only) Preliminary Results
Applicator 2,4-D Levels (Geometric Means) By Application Method * 0.05 > p > 0.001 or **p ≤ 0.001 for significance of difference Preliminary Results
Applicator Post-Application 2,4-D Urine Levels Regression with Selected Variables * 0.1 > p > 0.05 ** 0.05 > p > 0.001 *** p ≤ 0.001 Preliminary Results
Applicator Post-Application 2,4-D Urine Levels (Geometric Mean ug/L) for Selected Variablesa a Minimum number in any cell = 5 **p ≤ 0.01 for significance of difference Preliminary Results
Applicator Post-Application 2,4-D Urine Levels (Geometric Mean ug/L) for Selected Variablesa a Minimum number in any cell = 5 * 0.05 > p > 0.01 or **p ≤ 0.01 for significance of difference Preliminary Results
Hand-Spray Applicator 2,4-D Levels (Geometric Means) by Footwear Type Preliminary Results
Broadcast Spray Applicator 2,4-D Levels (Geometric Means) by Tractor Cab Type a Measurement result divided by kg of pesticide active ingredient used Preliminary Results
Broadcast Spray Applicator 2,4-D Levels (Geometric Means) by Enclosed Cab Variable Preliminary Results
FAMILY MEASUREMENT RESULTS Measurement of urinary biomarkers for participating applicator family members Relationships between spouse and applicator urinary biomarkers Relationship between spouse 2,4-D urine levels and applicator work practices or household factors
1000 Spearman Correlation is 0.64, p < 0.0001 100 10 Spouse Urine (ug/L) 1 0.1 0.1 1 10 100 1000 Applicator Urine (ug/L) SPOUSE AND APPLICATOR POST-APPLICATION URINE 2,4-D CONCENTRATIONS Preliminary Results
Spouse’s Post-Application 2,4-D Levels based on Selected Applicator’s Work Practices aMann-Whitney U Non parametric comparison test Preliminary Results
Spouse’s Post-Application 2,4-D Levels Based on Selected Household Activities aMann-Whitney U Non parametric comparison test Preliminary Results
Spouse’s Post-Application 2,4-D Levels Based on Home’s Distance from Pesticide Use aMann-Whitney U Non parametric comparison test Preliminary Results
APPLICATOR MEASUREMENTS PRELIMINARY FINDINGS Large range in exposures for spray 2,4-D applicators in this study Lower exposures and range of exposures for chlorpyrifos applicators in this study Chlorpyrifos exposures for users of liquid products were much higher than those for users of granular products Significant differences in exposure were found between many exposure strata
APPLICATOR MEASUREMENTS PRELIMINARY FINDINGS Differences in exposure for different application methods (hand spray > broadcast > in-furrow) Glove use was an important factor – wearing protective gloves reduced urine levels ~70% Role of enclosed tractor cabs in reducing exposures is less clear for mixer/loader/applicators Significant associations between urine and dermal or air measures – strongest for hand loading Several other factors appear to be important in increasing or decreasing exposures to 2,4-D
SPOUSE AND CHILD PRELIMINARY FINDINGS Urinary 2,4-D levels were low but measurable for a majority of the spouses and children of 2,4-D applicators (geometric means 2 ug/L) One spouse reported directly handling a product containing 2,4-D and had the highest urine level (59 ug/L) Urinary TCP levels were measurable for the spouses and children of chlorpyrifos applicators – but these levels were similar to those found in non-farm populations
SPOUSE AND CHILD PRELIMINARY FINDINGS Spouse and applicator post-application urine 2,4-D levels were significantly associated Some pesticide applicator work practices were significantly associated with spouse urine 2,4-D levels Some hygiene and household (laundering work clothing, removal of work boots, distance to fields) were not associated with significantly higher exposures to family members in this study Further study is needed with more people and for different chemicals
COMMUNICATION OF RESULTS • Journal articles in preparation • Plan for development of AHS/PES outreach materials (brochure and slide sets) • Audience • AHS participants • Pesticide safety educators • Cooperative Extension Services • Pesticide users
ACKNOWLEDGEMENTS Researchers at several organizations provided key contributions to the AHS Pesticide Exposure Study design and implementation: EPA: Ruth Allen (OPP), Carry Croghan, Paul Jones AHS Federal Investigators: Cynthia Hines (NIOSH) NC AHS Field Station: Charles Knott and Joy Pierce (Battelle CPHRE) IA AHS Field Station: Charles Lynch and Ellen Heywood (University of Iowa) Field Study: Steven Reynolds (Colorado St. University), Gerald Akland (RTI International), Craig Hayes (North Carolina Department of Agriculture and Statistical Services) Sample Analysis: Marcia Nishioka (Battelle Columbus), Robin Helburn (RTI International), and David Camann (Southwest Research Institute) DISCLAIMER Although this work was reviewed by EPA and approved for publication, it may not necessarily reflect official Agency policy.