Biological monitoring of pesticide exposures in residents living near agricultural land.

STUDY PROTOCOL Open Access
Biological monitoring of pesticide exposures in
residents living near agricultural land
Karen S Galea1*, Laura MacCalman1, Kate Jones2, John Cocker2, Paul Teedon3, Anne J Sleeuwenhoek1,
John W Cherrie1 and Martie van Tongeren1
Abstract
Background: There is currently a lack of reliable information on the exposures of residents and bystanders to
pesticides in the UK. Previous research has shown that the methods currently used for assessing pesticide exposure
for regulatory purposes are appropriate for farm workers [1]. However, there were indications that the exposures of
bystanders may sometimes be underestimated. The previous study did not collect data for residents. Therefore, this
study aims to collect measurements to determine if the current methods and tools are appropriate for assessing
pesticide exposure for residents living near agricultural fields.
Methods/design: The study will recruit owners of farms and orchards (hereafter both will be referred to as farms)
that spray their agricultural crops with certain specified pesticides, and which have residential areas in close
proximity to these fields. Recruited farms will be asked to provide details of their pesticide usage throughout the
spray season. Informed consenting residents (adults (18 years and over) and children(aged 4-12 years)) will be
asked to provide urine samples and accompanying activity diaries during the spraying season and in additionfor a
limited number of weeks before/after the spray season to allow background pesticide metabolite levels to be
determined. Selected urine samples will be analysed for the pesticide metabolites of interest. Statistical analysis and
mathematical modelling will use the laboratory results, along with the additional data collected from the farmers
and residents, to determine systemic exposure levels amongst residents. Surveys will be carried out in selected
areas of the United Kingdom over two years (2011 and 2012), covering two spraying seasons and the time
between the spraying seasons.
Discussion: The described study protocol was implemented for the sample and data collection procedures carried
out in 2011. Based on experience to date, no major changes to the protocol are anticipated for the 2012 spray
season although the pesticides and regional areas for inclusion in 2012 are still to be confirmed.
Background
The use of pesticides and their possible health effects is
a subject that gives rise to much public concern and dis-
cussion, with some people living next to agricultural
land in the UK, rightly or wrongly, attributing health
problems to their exposure to pesticides sprayed on
these fields. The Royal Commission on Environmental
Pollution (RCEP) published a report on “Crop Spraying
and the Health of Residents and Bystanders” which gen-
erated considerable interest and comment [2]. RCEP
focussed on the possible risks for chronic fatigue syn-
drome and multiple chemical sensitivity from bystander
or residential exposure. They recognised that the epide-
miological literature showing associations between these
conditions and pesticide exposure was equivocal, but
concluded that the risk between pesticide exposure and
chronic health conditions was plausible. This report and
the responses to it [3-5] have ensured that the issue has
remained in the public eye.
In Great Britain the use of pesticides in agriculture,
horticulture, forestry, food storage and the home or gar-
den is regulated to protect human health and the envir-
onment. The regulatory system is administered for the
Department of Environment Food and Rural Affairs
(DEFRA) by the Chemical Regulation Directorate (CRD)
of the Health and Safety Executive. The scientific para-
digm underpinning the approval of pesticides involves
* Correspondence: karen.galea@iom-world.org
1Institute of Occupational Medicine, Riccarton, Edinburgh, UK
Full list of author information is available at the end of the article
Galea et al. BMC Public Health 2011, 11:856
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© 2011 Galea et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.

the comparison of estimated human exposure with some
limit or limits, below which there is considered to be
high confidence that there will be no adverse health
effects. The system is generally considered to be conser-
vative such that estimated exposures represent some
multiple of the likely exposure. The exposures are typi-
cally estimated for those who apply the pesticide, work-
ers who may be involved in post-application activities
such as harvesting, and bystanders or residents living
nearby. There are no mandated methods to estimate
exposure and applicants for pesticide approval may use
measurements made during application or other work
with the product, other analogous measurement data or
one of a number of exposure models, such as POEM
(Pesticide Operator Exposure Model).1 In addition the
development and validation of a Bystander and Residen-
tial Exposure Assessment Model (BREAM) being under-
taken by the Silsoe Spray Applications Unit is due for
final reporting end 2011 [6].
Biological monitoring of pesticide metabolites in the
urine of subjects has shown that the methods currently
used in the UK for assessing pesticide exposure for reg-
ulatory purposes were likely to be appropriate for farm
workers [1]. However, the methods in current use
appeared to underestimate the levels of exposure that
could occur in bystanders. This study did not collect
data for residents. There is currently a lack of reliable
exposure information for residents and bystanders in
the UK therefore there is a need to carry out further
measurements to determine if the current tools and
methods are appropriate for assessing exposure for resi-
dents living near agricultural fields.
The relatively short biological half-life of modern pes-
ticide compounds or their metabolites in the human
body presents a major challenge to linking biological
monitoring data to specific spray events. Studies must
ensure urine samples are collected within about 24
hours of spraying. Farming activities are inherently
unpredictable because of the changing weather and the
presence of insects or other potentially damaging infes-
tations. There is generally no communication between
farmers and residents about spraying activities and so an
individual may not realise that a neighbouring field has
been treated with pesticide.
Aims and objectives
This study aims to investigate pesticide exposure during
and outside the spraying season for residents (adults
and children) living next to agricultural fields. It also
aims to assess whether the exposure models used for
pesticide regulatory risk assessment in the UK produce
sufficiently conservative estimates to ensure that their
health is sufficiently protected. Exposure to pesticides
will be measured using urine samples, while a
pharmacokinetic model will be used to determine sys-
temic exposure levels amongst residents.
Methods
Summary of study design and sample size
Recruitment for the study will concentrate on two
groups of people; farmers and residents. Firstly, the
study will recruit owners of farms and orchards (here-
after both will be referred to as farms) that spray their
agricultural crops with specified pesticides of interest to
the study and which have residential areas in close
proximity to these fields.
Table 1 provides details of the pesticides being consid-
ered in this study. The inclusion of pesticides into the
study is restricted to those where validated analytical
methods are available to the project team to analyse for
the associated urinary metabolites. As further validated
methods become available during the study, the list of
pesticides for inclusion may be expanded.
Recruited farms will be asked to provide details of
their planned and actual pesticide usage throughout a
spray season.
Residents living within approximately 100 m of the
edge of a field belonging to a recruited farm, and that is
likely to be treated with pesticides, will be approached
to participate in the study. Informed consenting adults
(18 years and over) and children in their care (aged 4-12
years) will be asked to complete an initial background
questionnaire and then provide urine samples and
accompanying activity diaries during the spraying season
and also for a limited number of weeks before/after the
spraying season to allow background pesticide metabo-
lite levels to be determined.
Collected urine samples selected for laboratory analy-
sis will be analysed by the Health and Safety Laboratory
(HSL) for the pesticide metabolites of interest. Statistical
analysis and modelling will be undertaken to determine
systemic exposure levels amongst residents.
Surveys are planned to be carried out in three areas in
the UK (East Lothian, Kent and East Anglia) over two
years (2011 and 2012), covering two spraying seasons
and the intervals between the spraying seasons. East
Lothian and East Anglia are major arable crop growing
areas, while most of the orchards in the UK are located
in Kent. The method of spraying used for orchards is
likely to result in higher exposures and so it is likely
that these will represent the worst-case exposure sce-
nario. Sampling in these three areas should result in the
collection of exposure data for a variety of agricultural
pesticide usage situations.
During the first full survey, to be carried out in East
Lothian and Kent, the aim is to recruit 10 farms (6 in
East Lothian and 4 in Kent), each with at least 5 partici-
pating households with the aim of recruiting 50 adults
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and approximately 25 children. During the second sur-
vey the aim is to recruit 16 farms (6 in East Lothian, 4
in Kent and 6 in East Anglia), again each with 5 partici-
pating households, resulting in a study sample of
approximately 80 adults and 40 children.
We will compensate each individual participating in
the study for their time incurred in completing the
questionnaire and providing urine samples by offering
them a gift voucher of their choice. A voucher of similar
amount will be made available to the parents of the par-
ticipating children. The value of the voucher is based on
a rate of £5 for each questionnaire and urine sample
provided, which is a similar rate to that used in a pre-
vious study [7] where individuals completed a question-
naire and provided a urine sample. Farmers will be
compensated on a similar weekly rate for providing
information about spraying events. Participants will be
asked to sign a form acknowledging receipt of the
compensation.
Ethical considerations
Full ethical approval for the study has been obtained
from the South East Scotland Research Ethics Commit-
tee (SESREC) 3 (study number 10/S1103/63). An Advi-
sory Committee comprising of four independent experts
will monitor the study progress throughout the project.
Identification and recruitment of participants
Recruitment of and liaison with individuals participating
in the study will be carried out by community research-
ers. We will employ community researchers from the
areas in which the study will be undertaken, who are
familiar with the farming community and have detailed
knowledge of the local area. The community researchers
will assist with recruitment and will visit participants
regularly, not only to collect information, but to main-
tain good relationships and to provide regular feedback
on the progress of the study. It is hoped that such
engagement will help minimise attrition of study
participants. The following sections describe the general
approaches that will be used for the recruitment of
farmers and residents living near them into the study.
Local farms and orchards will be identified using pub-
lically available sources such as the Yellow Pages2 as
well as via the community researcher’s knowledge of the
local area. Farmers will be approached initially by a let-
ter, briefly explaining the study aims and followed up
via a telephone call. Telephone scripts and prompts will
be used to assist with the telephone recruitment, with
further details of the study aims and objectives, what
input would be required from the farmer as well as
questions to assess the farmers’ suitability for participa-
tion in the study being asked.
A Microsoft Excel spreadsheet will be used to track
recruitment. Each recruited farm will be assigned a
unique identifier.
Eligible farmers are those who are likely to spray their
crops with one or more of the pesticides under study
(Table 1) and have residential areas within 100 m of
these crops. Eligible farmers who have expressed an
interest will be visited in person by the community
researcher at a mutually convenient time to discuss the
study in more detail and to discuss the process of data
collection.
Once farmers are recruited, those households within
approximately 100 m from the edge of a crop that is
likely to be treated will be selected for recruitment.
Residents will be contacted firstly by letter which will
also contain copies of two participation information
leaflets, the first being for adults (defined as being 18
years and over) and the second for children aged 4-12
years. The participant information leaflet will be
included at this stage to give recipients adequate time to
consider whether they wish to participate. Leaflets for
children will be piloted in advance for intelligibility and
understanding amongst comparable non-sampled chil-
dren. We will attempt to obtain a response via several
methods. A reply form will be enclosed with the letter
Table 1 Pesticides of interest to the study
Active Substance Function Relevant crops approveda for use
Captan Fungicide Apple, pear
Chlormequat Growth regulator Cereals
Chlorpyrifos Insecticide Apple, cereals, veg incl. potato
Cypermethrin Insecticide Apple and various arable crops incl. potato
Deltamethrin Insecticide Apple and various arable crops (not potato)
Diquat Herbicide/desiccant Various arable crops incl. potato
Iprodione Fungicide Field beans, oil seed rape
Penconazole Fungicide Apple, blackcurrant, hops
Pririmicarb Insecticide Apple and various arable crops incl. potato
Thiophanate-methyl Fungicide Wheat, triticale, field beans, oil seed rape
aapproval in 2011
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through which individuals can register their interest or
otherwise in the project. In instances where we have a
contact telephone number for the home, an approach
will also be made via this communication route. How-
ever, in addition, as we anticipate difficulties in obtain-
ing residents’ phone numbers and that individuals may
simply forget to return the form or contact the
researcher, the letter will state that the community
researcher will be working in the area during the week
and that they will try to establish in-person contact.
As the success of this study will depend on enlisting
and retaining volunteer participants, we will use a vari-
ety of ways to engage with the local community. This
may include adverts in local newspapers and community
notice boards and presentations to key groups in the
community. In addition each individual participating in
the study will be compensated for the time spent in
completing questionnaires and providing urine samples.
Both adults and children in their care will be invited
to participate. Children will, however, only be recruited
alongside a consenting parent or guardian and consent
must be given by the parent or guardian.
In addition, farmers and their partners and children
(aged 4-12 years) will be given the opportunity to take
part in the study by providing urine samples throughout
the spraying season if they do not themselves spray or
come into contact with the spray equipment or enter
the crop following treatment with the pesticides. Where
the farmer is the operator or the farmer states that he
entered the field shortly after spraying, his results will
not be considered. Similarly, farm workers who are
actively involved in the application of pesticides will not
be eligible for inclusion in the study.
A Microsoft Excel spreadsheet will be used to track
residents’ recruitment. Each household will be assigned
a unique identifier. Once a household has agreed to par-
ticipate in the study, unique sample identification num-
bers, based on the household identifier, will be allocated
to each consenting participant.
Individuals who express an interest in participating in
the study and who satisfy the inclusion criteria will then
be visited in person by the community researcher at a
mutually convenient time to discuss the study in more
detail, explain the arrangements for data collection, and
obtain written consent.
No excessive attempts will be made to obtain a
response from residents or farmers. A response of ‘no’
to participation in the study will be accepted and no
further contact will be made.
Data collection
Farms
Participating farmers will be asked to sign a consent
form confirming that they are willing to provide the
study team with information concerning their pesticide
usage. Participating farmers will be asked to provide
information on planned pesticide usage for the forth-
coming year. Farmers will also be asked to indicate what
fields are theirs on a map of the area surrounding their
farm and which, typically, have pesticides applied. In
instances where farmers demonstrate that they already
maintain comprehensive records of their pesticide usage,
the researcher will ask whether copies of these can be
made at regular intervals throughout the spray season.
In any instances where detailed records are not already
maintained, participating farmers will then be asked to
record details of spraying events on a weekly basis
throughout the spraying season using an adaptation of
the form recommended in Annex F ‘Code of practice
for using plant protection products’.4
The community researcher will contact participating
farmers on a regular basis to ensure continued participa-
tion, collect pesticide usage records and obtain updated
information on their planned pesticide usage.
From the records of pesticide usage provided by the
farmers we will obtain details, for example, of the pesti-
cide used, date of application, method of spraying and
time taken to spray. Details of prevailing weather condi-
tions on the day of spraying and afterwards will be
obtained from the relevant weather station from the
Met Office. All of this information will then be entered
into a designated Microsoft Access database at IOM’s
Edinburgh office.
At the last visit to the farm during a spraying season,
the community researcher will recheck the farmers
spray records to ensure that details of all relevant spray
periods have been recorded. The participant will be
issued with the appropriate value of gift vouchers and
asked to complete and sign the compensation acknowl-
edgement form to confirm receipt. Participants of the
2011 spray season will be asked if they would be happy
for the community researcher to approach them for
their involvement in the 2012 spray season and their
response will be recorded and followed up as
appropriate.
Residents
Interested individuals will be visited and the study
explained to them and will be issued with further copies
of the participant information leaflets. Informed consent
will be obtained from those agreeing to take part and a
short background questionnaire will then be adminis-
tered. The questionnaire to be completed by adult parti-
cipants includes questions concerning their personal
details (e.g. age, gender, weight), lifestyle (e.g. leisure
activities), occupational and para-occupational exposure
to pesticides (exposure via, for example, family mem-
bers, who work with pesticides and live in the same
home) and pesticide usage within the home. The
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questionnaire to be completed by the adult on behalf of
a child (4-12 years) participating in the study is shorter
and includes questions concerning their personal details,
education/nursery location and leisure activities.
Participating residents will be asked to provide a first-
morning void urine sample (around 70 ml) on specified
days during the spraying season. In addition, we will
collect a limited number of urinary samples from parti-
cipants outside the spraying season to determine back-
ground excretion of the biomarkers of interest.
Two strategies will be employed to collect urine sam-
ples throughout the spray season:
i) In instances where the farmer has indicated that
that they are very likely to spray the pesticides of inter-
est (Table 1) during a given period of the spray season,
relevant participating households will be allocated one
day of the week on which they are to provide weekly
urine samples throughout the indicated period. Further,
if we are made aware that spraying has occurred in an
associated field involving one or more of the pesticides
listed in Table 1 all relevant participating residents will
be contacted and asked to provide an additional first-
morning void sample on the day following the spray
event.
ii) Where the farmer has indicated that it is more diffi-
cult to predict their usage of the pesticides listed in Table
1, and that such usage is unlikely, but good communica-
tion links have been established, participants will be
asked to provide a urine sample preferably the day after
each relevant spray event, although samples will be col-
lected 2 days after a relevant spray event if the first day
after is missed. For this strategy, the participants will be
contacted by the community researcher when they have
been made aware that the farmer intends to spray.
All participants will be supplied with sufficient sam-
pling materials and will receive simple instructions for
the collection of the urine samples. Along with each
urine sample provided, we will ask the participants to
complete a brief activity diary for the preceding two days.
The activity diary to be completed by adult partici-
pants requests information on time spent at home, time
spent at home outdoors (e.g. in the garden), use of pes-
ticides, and any potential occupational/para-occupational
exposure to pesticides. In addition, the participants will
be asked to provide information on consumption of any
home grown vegetables. The questionnaire to be com-
pleted by the adult on behalf of a child participating in
the study is shorter and includes questions concerning
the time spent by the child in both outdoor and indoor
environments.
Samples and diaries will be stored immediately after
collection/completion in a cool bag by the participant.
The community researcher will collect the cool bag
from the participant’s home on the designated day
(within a period of no greater than 12 hours from sam-
ple provision), checking that it contains the expected
number of completed study packs and that in each
study pack, the sample code on the diary matches that
on the urine sample receptacle. The community
researcher will check that the diaries have been fully
and correctly completed and that the date and time of
collection has been written on the urine sample recepta-
cle. In the event that any part of the questionnaire
needs clarification the community researcher will
approach the resident to rectify this.
All collected data will then be entered into a desig-
nated Microsoft Access database at IOM’s Edinburgh
office.
At the end of the data collection period participants
will be asked if they would be happy for the community
researcher to approach them for their involvement in
the 2012 data collection period and their response will
be recorded and followed up as appropriate.
Labelling and tracking samples
A robust sampling and tracking system will be imple-
mented to ensure that the contextual information from
the completed diaries remains linked to each collected
urine sample and that the location of each urine sample
is known. This will be achieved through the use of the
unique farm, resident and sample identifiers along with
the recording of all relevant information in Microsoft
Excel spreadsheets and Access databases.
All study packs will be identified by a unique sample
identification number which provide a permanent link
to the individual which is known only to the project
team. In instances where there is more than one partici-
pant within a household, a removable label will be
placed on the sample pack, indicating which individual
the pack relates to. Participants will be instructed to
remove this upon collection of the urine sample and
completion of the accompanying diary. This will ensure
that the packs are used by the correct participants and
also that their data are anonymised to those outside the
study team. Participants will however be requested to
record their date of birth on the urine samples recepta-
cle and completed diary in order for the study team to
verify that the correct study pack was used.
Urine sample storage and transportation
Upon collection by the community researchers the study
packs (diary and urine sample) will be placed in a small
table-top freezer. On a weekly to fortnightly basis
(depending on the number of samples collected) the
community researcher will courier the collected samples
to the IOM, Edinburgh using next day delivery, or deli-
ver them by hand (East Lothian only). The community
researcher will ensure the frozen study packs are
securely packed in the packaging material supplied by
IOM. Upon receipt at the IOM each diary and urine
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