Will Mueller ISEE 2022 19 September Athens Greece Background 4M tonnes of active ingredients applied globally each year 1 Occupational exposure to pesticides linked to poorer health cancers ID: 1043154
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1. Pesticide exposure assessment in farmers from Malaysia, Uganda, and the United Kingdom: an analysis of urinary biomarker concentrationsWill MuellerISEE 202219 SeptemberAthens, Greece
2. Background4M tonnes of active ingredients applied globally each year1Occupational exposure to pesticides linked to poorer health: cancers2, neurological effects3, acute poisoning45x more studies use indirect (e.g. self-reported) vs direct (e.g. biomarkers) exposure assessment methods5 Both may lead to misclassification/bias in epi studiesAim: To evaluate associations between different exposure-modifying factors and urine metabolite measurements across multiple cohorts ISEE 20221FAOSTAT 2020; 2Alavanja & Bonner 2012; 3Fuhrimann et al 2021; 4Solomon et al 2007; 5Ohlander et al 2020
3. IMPRESS study: CohortsImproving Exposure Assessment Methodologies for Epidemiological Studies on Pesticides (IMPRESS) project1 (www.impress-project.org)Prospective Investigation of Pesticide Applicators' Health (PIPAH) study Prospective cohort (>5700 users) of pesticide users in professional registers in the UKAim: monitor long-term healthPesticide Use in Tropical Settings Project (PESTROP) Smallholder farmers (< 2 ha) in rural areas of Wakiso District, UgandaAim: investigate environmental, health and regulatory dimensions of pesticide use in conventional and organic agriculture in LMICsMalaysian farm workersMale farmers from 3 districts in Sabah registered on the Sabah Agricultural databaseAim: assess organophosphate exposure and semen quality, acute ill-health1Jones et al 2020ISEE 2022
4. IMPRESS study: Data collection & biomarkersPre- and post-activity (handling, spraying, re-entry) urine samples Diaries capturing duration, application methods, active ingredients (AIs) used, hygiene behaviours, and use of personal protective equipment (PPE)Selection of urinary biomarkers based on number of AI users and existence of validated methodsISEE 2022Biomarker Active ingredient TypeHalf-life range (hours)Limit of Quant. (µg/L) 3PBAPyrethroids Insecticide5.7-8.70.5DCVACypermethrin, cyfluthrin, permethrin Insecticide6.4-38.50.5 CFVALambda-cyhalothrin, bifenthrin Insecticide4.2-11.20.6 DBVADeltamethrin Insecticide3.60.7 ETUMancozeb Fungicide20-1000.5 Glyphosate Glyphosate Herbicide5.5-9.00.5 TCPyrChlorpyrifos Insecticide6-501.0
5. Statistical analysisISEE 2022Models (separately by cohort and AI): Multi-level censored (Tobit) regression, random intercept for participant (and visit)Dependent variableLog of pre- and post-activity concentrationExposure Modifying Factors: Use of AI that day Total duration of specific AI use (mixing & spraying)PPE for mixing/spraying (low/med/high based on protection of body parts)Any hygiene behaviours (e.g., change gloves, wash hands)Type of application (boom/manual)Activity (spraying, re-entry, mixing)Also adjusted for:Sampling time, Age, Sex, Education/Literacy, Creatinine concentrationsSensitivity analyses (e.g., prior AI use, specific product, time since AI use)
6. ResultsISEE 2022StudyStudy participants (n)Urine samples (n)Age (years)Mean (SD)Sex (male)(%)UK10621257 (8.1)100Uganda8538446 (11.6)76Malaysia8116246 (15.6)100Study3PBADCVACFVADBVAETUGlyphosateTCPyrUK64646464021264Uganda216216216216384384216Malaysia1471471471476440147
7. ResultsISEE 2022UKMalaysiaUgandaBiomarkerActive ingredients% use% detected % use% detected % use% detected 3PBAPyrethroids 164547933160DCVACypermethrin, cyfluthrin, permethrin 41935773168CFVALambda-cyhalothrin, bifenthrin 8253745DBVADeltamethrin 51471403ETUMancozeb 2012113384GlyphosateGlyphosate 88580271842TCPyrChlorpyrifos 16730100287Selected 3PBA and glyphosate for analysis: % AI use and biomarker detection across cohorts
8. Results – Pyrethroid & Glyphosate Users 3PBA (Pyrethroids)Higher post-activity urinary biomarker concentrations with glyphosateGlyphosateUgandaUKMalaysiaNo users2.22.20.90.80.87.60.50.50.51.7
9. Fold-change in 3PBA (Pyrethroids) concentrationsISEE 2022UgandaUKMalaysiaLower PPE & longer activity duration were associated with higher concentrationsAdditional analysis:UK - Lower concentrations with changing glovesMalaysia - Higher concentrations with cypermethrin use
10. Fold-change in Glyphosate concentrationsISEE 2022UgandaUKLower PPE, education and longer activity duration were associated with higher concentrationsAdditional analysis:UK - Lower concentrations with changing maskUganda – High concentrations with Glyphosate use in previous week (not year)
11. InterpretationUrinary biomarker concentrations are higher in applicators in Malaysia and Uganda than UKGreater increases in urinary biomarkers for glyphosate vs pyrethroid useMay be due to exposure routes (e.g. delayed dermal uptake), metabolismDuration of activity was found to be important across cohort and AI (i.e. not just AI use)Lower education/illiteracy was associated with higher concentrations for glyphosateIndication of lower exposure with PPE, but only in the UKLower levels of PPE worn in tropical, LMIC settingsNo exposure factor was identified consistently across all analysesBiomarkers can objectively indicate exposure, but may be complicated by (other) exposure routes & metabolism ISEE 2022
12. AcknowledgementsISEE 2022Co-authors: Kate Jones, Anne-Helen Harding, Andy Povey, Martie van Tongeren, Ioannis Basinas, Hans Kromhout, Samuel Fuhrimann, Zulkhairul Naim Bin Sidek Ahmad, Aggrey Atuhaire, Karen GaleaThanks to our Scientific Advisory Board (SAB): Mark Montforts (Chair), RIVM (The Netherlands)Len Levy, Cranfield University (UK)Silvia Fustinoni, University of Milan (Italy)Aaron Blair, National Cancer Institute (USA) (now retired from SAB)To all our study participantsProject funded by CropLife EuropeThank you for listening!will.mueller@iom-world.orgwww.impress-project.org