INSTITUTE OF OCCUPATIONAL MEDICINE . Edinburgh . UK www.iom-world.org

Monitoring of pesticide exposure in residents – Approach adopted in recent UK study

KS Galea1, L MacCalman1, K Jones2, J Cocker2, P Teedon3,

JW Cherrie1 and M van Tongeren1

1. Centre for Human Exposure Science, IOM, Edinburgh

2. HSL, Buxton

3. School of Engineering and the Built Environment, Glasgow Caledonian University

Presentation overview

• Background & aims of DEFRA funded project

• Overview of study methodology

• Challenges

• Benefits of using community researchers

• Lessons learned from undertaking study

• Not discuss results

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Background

• Public concern about health effects from pesticides

• Use of pesticides well regulated in the UK

• Requires risk assessment comparing estimated exposure with Acceptable Operator Exposure Level (AOEL) or Acceptable daily intake (ADI)

• However, little empirical evidence on pesticide exposure in UK

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Background

• Lack of information on pesticide exposure for residents & bystanders in Britain (and elsewhere)

• Sleeuwenhoek et al (2007)

• regulatory methods appropriate for farm workers

• methods may underestimate bystander exposure

• Residents not assessed (recruitment issues)

• DEFRA funded study (Oct 2010 – Sept 2015) • Budget ~£720k

• Led by IOM, collaborated with HSL and Glasgow Caledonian University

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Project aims

1. Assess exposure to pesticides for residents living <100m from agricultural land and investigate if exposures are elevated following spray events

2. Assess whether exposure methods used in UK pesticides regulatory risk assessment (RRA) process are appropriate by comparing urinary metabolite concentrations with internal exposure estimates provided by RRA

ANSES workshop - Pesticide exposure in residents, Paris, 21 March 2016

Survey strategy

• 3 UK geographical regions

• Use of community researchers

• Farmers - info. on pesticide usage & spray events

• Residents (adults and children (4-12 years) living within 100m of fields

• First morning void urine sample & questionnaire • Weekly samples during & outwith spraying season

• Reactive samples - 1 & 2 days after spray event

• Urine sample analysis • 1 and 2 days after relevant spraying event

• Background within & outwith spray season (up to 3 each)

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Challenges…

• Anticipated reluctance of farmers to participate

• Farming activities inherently unpredictable

• Several locations, diverse communities

• Maintaining scientific rigour

• Linking biological monitoring data to specific spray events due to relatively short biological half-life of modern pesticides

• ‘Attrition’ & research fatigue

etc, etc….

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Why use community researchers?

• Can help minimise attrition, through their ability to build and maintain effective relationships with participants and their local knowledge.

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Community researchers

• Recruitment - rigorous interviewing

• In-depth training sessions

• Study protocol

• Assessment of suitability for inclusion

• Data & sample integrity

• Considerable support and liaison with CRs

• It is exceptionally effective but…

• not the cheap option

• requires the correct people (‘face’ of the project)

• time demanding

ANSES workshop - Pesticide exposure in residents, Paris, 21 March 2016

Pesticides of interest

• Selected on basis of availability of urinary biomarker and likelihood of application

Pesticide Class Function Relevant crops approveda

for use

Captan Phthalamide Fungicide Apple, pear

Chlormequat Chlorocholine Growth regulator Cereals

Chlorpyrifos Organophosphate Insecticide Apple, cereals, veg. incl. potato

Cypermethrin Pyrethroid Insecticide Apple, various arable crops

Penconazole Triazole Fungicide Apple, blackcurrant, hops

ANSES workshop - Pesticide exposure in residents, Paris, 21 March 2016

• Limited number in comparison to those actually applied over a spray season

Pesticides of interest

• Liaise with agronomists at an early stage to establish current practices

• Need for further biomarker analysis development (however time consuming and costly)

• Pesticides of interest one year may differ the next due to differences in weather, pests etc…

• Products rarely used in isolation – tank mixing

• May not be relevant to any health concerns

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Farmers data collection

• Details of anticipated pesticide usage /crops

• Regular contact to establish predicted use

• Records of actual usage inc.

• Start / finish times

• Weather conditions

• Product sprayed and quantities applied

• Spray method

• Records obtained at convenient time periods

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Farmers data collection

• Farmers will forget to inform about spray events / change plans

• need for effective communication

• Spray records may not always be complete

• Variability in weather data (own / formal)

• Obtained farmers records and also used http://www.wunderground.com/

• Understand ‘when’ to contact farmers

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Residents – why <100m from field?

• Balance between proximity to agricultural land and available participants

• modelling vapour dispersion reported conc. sig. ↓

after distance of 100m (dependent on field size)

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Household position

• Prevailing wind???

• Distance (m) between field and household; field to garden

• http://gridreferencefinder.com

• Assessment of how ‘surrounded’ household is by agricultural land

• Presence of trees, buildings etc between household and field

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Residents – children

• Why not < 4 years and 13-17 years?

• Likely difficulties with obtaining relevant urine samples from babies / toddlers

• Adolescents potentially less engaged with study

• Area for further work?

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Urine sample collection

• Urine samples • reactive (24- and 48-hr after spray event)

• weekly urine sample collections (within and outwith spray season

• First morning void

• Reasons for strategy • Ensure timing with relevant spray event

• Participant own ‘control’

• Prolonged sample collection

• Findings of modelling, other work (e.g. Kissel et al, 2005)

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Urine sample collection

• Careful consideration to relevant sample collection

• Use larger receptacles for ease of collection

• Mark maximum level and clearly state this

• Overfilling may lead to cracking of receptacles

• Robust sample numbering and tracking system

• Include assessment of storage stability

• Consider costs associated with freezers, cool bags, storage receptacles, labels etc…

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Contextual information with each sample

• Activities (and where)

• Use of pesticide – home/occupational/para-occ

• Consumption of home grown produce

• For 24-hr and 48-hr period before sample collection

• Limitations

• Restricted set of questions

• not possible to establish if and when exposure occurred / route of exposure

• dietary-related questions kept to a minimum, others may have helped inform results

• Participant recall

ANSES workshop - Pesticide exposure in residents, Paris, 21 March 2016

Methods: Data analysis

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• Samples creatinine conc. < 2 or >30 mmol/l excluded

• Analysis based on creatinine corrected measurements

• Random imputation procedure used to replace values < LOD. Results summarised by sample type

• In case of very high proportion < LOD - proportion of detects, 95th percentile and max. conc. presented

• For each participant, GM ratio obtained (spray event and for within and outwith spray season background)

• Generalised Linear Mixed Models used to examine factors that may explain concentration differences

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Methods: RRA comparisons

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• RRA approach applied • Spray drift adults, breathing zone 8 m

• Adults & children, 24hr vapour exposure

• Children dermal, hand to mouth, object to mouth, from average drift fallout in adjacent area

• Pathway providing highest predicted exposure used for comparison

• Kinetic model estimates amount excreted given internal dose

• Predicted urinary levels compared with sample results

Dose of AI of interest (ug/day)

Metabolite of Interest (ug/l)

Cb – Conc. in body (ug/l)

Urine (ug/l)

D

M

MV

RS

m

od

.

ke

ANSES workshop - Pesticide exposure in residents, Paris, 21 March 2016

Analysis considerations &

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• Dealing with high no. of results <LOD?

• PK model

• Previously used for some, not all, of the pesticides

• Other complex models available - necessary?

• Little information on input parameters - sensitivity analysis to evaluate impact on predictions

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And finally….

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• Strong multidisciplinary team

• Include an Advisory committee

• Clear aims and objectives

• Manage stakeholder expectations

• Keep them informed

• Plan, plan and plan again

• Appropriate dissemination plan

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Peer-reviewed publications

• Galea KS, et al (2011) Biological monitoring of pesticide exposures in residents living near agricultural land. BMC Public Health; 11:856.

• Teedon P, et al (2015) Engaging with community researchers for exposure science: lessons learned from a pesticide biomonitoring study. PLOS One; DOI: 10.1371/journal.pone.0136347.

• Galea KS, et al (2015) Urinary biomarker concentrations of captan, chlormequat, chlorpyrifos and cypermethrin in UK adults and children living near agricultural land. JESEE; doi:jes.2015.54.

• Galea KS, et al (2015) Comparison of residents’ pesticide exposure with predictions obtained using the UK regulatory exposure assessment approach. Reg Tox Pharm. DOI: 10.1016/j.yrtph.2015.09.012.

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Acknowledgements

• DEFRA for funding (PS2620)

• All participating farmers and householders

• Community researchers: S Attwood, J Cadzow, A Carr, D Dahrendorf, T Hogg, L Jewsbury & F MacIver.

• IOM: A Sleeuwenhoek, D Todd, S Rashid, P Ritchie, Y O’Neill, M Davis, J O’Neill, S Argoub and A Sanchez Jimenez.

• HSL: C Sams, L Kenny, S Iqbal and F Garner.

• Advisory Committee: Prof. D Coggon, P Hamey, Prof. L Levy and Dr. S Semple.

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Surveillance de l'exposition aux pesticides chez les riverains,

approche adoptée lors d’une récente étude britannique

Karen Galea

Institute of Occupational Medicine (IOM – Royaume-Uni)

Biographie

Karen Galea est directrice de la section scientifique sur les expositions de l’IOM (Institute of

Occupational Medicine) à Edimbourg. Elle dirige et participe à un grand nombre de projets de

recherche qui visent à évaluer l’exposition de l’homme à différentes substances pouvant être

dangereuses pour la santé. Ces projets concernent notamment des études sur l’exposition en milieu

professionnel, via l’air en zone urbaine, ainsi que sur l’exposition des consommateurs et des

riverains. Ella a dirigé le projet financé par le DEFRA (Department for Environment, Food and Rural

Affairs) dont il a été rendu compte l’an dernier, consacré à l’exposition des riverains aux pesticides au

Royaume-Uni.

Résumé de la présentation

En 2011, l’IOM a lancé un projet sur l’exposition aux pesticides des riverains au Royaume-Uni. Ce

projet a un double objectif : premièrement, il vise à évaluer l’exposition aux pesticides des riverains

vivant à moins de 100m des terres agricoles, et à étudier si les expositions augmentent suite aux

épisodes d’épandage. Le second objectif est d’évaluer si le protocole d’exposition utilisé dans

l’évaluation des risques réglementaires (ERR) liés aux pesticides au Royaume-Uni, est approprié en

comparant les concentrations des métabolites urinaires aux estimations de l’exposition interne

fournies par l’ERR. Aujourd’hui, Karen Galea présentera la méthodologie utilisée pour répondre aux

objectifs de l’étude, les motifs de sélection et les éventuelles limites de l’étude. En outre, elle

partagera les enseignements tirés par l’équipe d’étude lors de la réalisation du projet.

Résumé de l’étude

Contexte : Il convient de noter le manque actuel d’informations fiables sur l’exposition aux pesticides

des riverains et des passants au Royaume-Uni. Des études antérieures ont montré que les méthodes

couramment utilisées pour évaluer l’exposition aux pesticides à des fins réglementaires sont

appropriées pour les travailleurs agricoles. Toutefois, des données semblaient indiquer que les

expositions des passants pourraient être parfois sous-estimées. La précédente étude n’a pas collecté

de données portant sur les riverains.

Objectifs : Cette étude vise à recueillir des mesures en vue de déterminer si les méthodes et outils

actuels sont adéquats pour évaluer l’exposition aux pesticides des personnes vivant à proximité des

terres agricoles.

Protocole et méthodes : Cette étude a ciblé des exploitations agricoles, dont des verges, utilisant des

pesticides préalablement identifiés pour l’étude et dont les champs sont situés directement à

proximité de zones résidentielles. Il a été demandé aux propriétaires de ces exploitations de fournir

des renseignements détaillés sur leur utilisation des pesticides pendant toute la période d’épandage.

Les riverains vivant à moins de 100 m de ces exploitations et consentants (adultes de 18 ans et plus

et enfants entre 4 et 12 ans) ont fourni des échantillons d’urine et tenu un journal sur leurs activités

pendant la période d’épandage et pendant un nombre limité de semaines en amont et en aval de

cette période, afin d’établir des niveaux de référence pour les métabolites des pesticides. Les études

ont effectuées dans des régions choisies du Royaume-Uni, pendant deux ans (2011 et 2012),

couvrant deux périodes de pulvérisation, et l’intervalle entre ces périodes.

L’analyse des échantillons urinaires pour les métabolites des pesticides auxquels s’intéresse l’étude

ont été mis en relation avec les données collectées auprès des exploitants agricoles et des riverains,

afin de d’interpréter les niveaux d’exposition chez les riverains.