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Urinary biomarker concentrations of captan, chlormequat, chlorpyrifos and cypermethrin in UK adults and children living near agricultural land

Urinary biomarker concentrations of captan, chlormequat, chlorpyrifos and cypermethrin in UK... Journal of Exposure Science and Environmental Epidemiology (2015) 25, 623–631 OPEN © 2015 Nature America, Inc. All rights reserved 1559-0631/15 www.nature.com/jes ORIGINAL ARTICLE Urinary biomarker concentrations of captan, chlormequat, chlorpyrifos and cypermethrin in UK adults and children living near agricultural land 1 1 2 2 3 1,4 1 Karen S. Galea , Laura MacCalman , Kate Jones , John Cocker , Paul Teedon , John W. Cherrie and Martie van Tongeren There is limited information on the exposure to pesticides experienced by UK residents living near agricultural land. This study aimed to investigate their pesticide exposure in relation to spray events. Farmers treating crops with captan, chlormequat, chlorpyrifos or cypermethrin provided spray event information. Adults and children residing ≤ 100 m from sprayed fields provided first-morning void urine samples during and outwith the spray season. Selected samples (1–2 days after a spray event and at other times (background samples)) were analysed and creatinine adjusted. Generalised Linear Mixed Models were used to investigate if urinary biomarkers of these pesticides were elevated after spray events. The final data set for statistical analysis contained 1518 urine samples from 140 participants, consisting of 523 spray event and 995 background samples which were analysed for pesticide urinary biomarkers. For captan and cypermethrin, the proportion of values below the limit of detection was greater than 80%, with no difference between spray event and background samples. For chlormequat and chlorpyrifos, the geometric mean urinary biomarker concentrations following spray events were 15.4 μg/g creatinine and 2.5 μg/g creatinine, respectively, compared with 16.5 μg/g creatinine and 3.0 μg/g creatinine for background samples within the spraying season. Outwith the spraying season, concentrations for chlorpyrifos were the same as those within spraying season backgrounds, but for chlormequat, lower concentrations were observed outwith the spraying season (12.3 μg/g creatinine). Overall, we observed no evidence indicative of additional urinary pesticide biomarker excretion as a result of spray events, suggesting that sources other than local spraying are responsible for the relatively low urinary pesticide biomarkers detected in the study population. Journal of Exposure Science and Environmental Epidemiology (2015) 25, 623–631; doi:10.1038/jes.2015.54; published online 16 September 2015 Keywords: exposure; pesticides; residents INTRODUCTION involves the comparison of estimated potential human exposures with toxicological reference values levels, for example, acceptable The use of pesticides can give rise to public concern. The Royal operator exposure level and acceptable daily intake (ADI), at and Commission on Environmental Pollution (RCEP) published a report below which there is considered to be high confidence that there on bystander and resident exposure to pesticides and recognised will be no adverse health effects. The RRA is therefore generally that the epidemiological literature showing associations between considered to be a conservative estimate of exposure. chronic fatigue syndrome and multiple chemical sensitivity and There are no specific studies on the exposures of people living pesticide exposure was plausible but equivocal. The RCEP report near agricultural land to pesticides in the UK. There are a number and the responses to it have ensured that the issue has remained 2–4 of reported studies from elsewhere in the world which have in the public eye. explored residents’ exposures. For example, Koureas et al. found In the UK, Government Ministers must approve all pesticides no difference in urinary dialkylphosphates (generic biomarkers of before they can be marketed or used, including those used in organophosphate pesticides) between urban and rural residents agriculture, horticulture, forestry, food storage and the home or in Thessaly, Greece, whilst pesticide sprayers had significantly garden, to ensure that they do not present health risks to the increased levels. A Canadian study showed a significant general public, consumers, people who apply them or work in or difference in urban and rural residents for exposure to pyrethroids, near areas that have been treated with pesticides, the environ- ment and animals. The Chemicals Regulation Directorate of the UK whereas in Japan no differences were seen between rural and Health and Safety Executive acts as the Regulator for pesticide suburban residents. Rural residents in Nicaragua showed sig- products and authorises their sale, supply, use and storage in the nificantly lower acetylcholinesterase activity which were asso- ciated with aerial pesticide spraying from planes. Crop maps were UK and represents the UK in the European Union process for the used by Ward et al. to predict that increasing acreage of corn and registration of new active substances and for the renewal (review) of active substances already approved. The health regulatory risk soybean fields within 750 m of homes in Iowa, USA, was assessment (RRA) underpinning the approval of pesticides associated with significantly elevated odds of detecting 1 2 3 Centre for Human Exposure Science, Institute of Occupational Medicine (IOM), Edinburgh, UK; Health and Safety Laboratory, Buxton, UK; School of Engineering and the Built Environment, Glasgow Caledonian University, Glasgow, UK and School of Life Sciences, Heriot Watt University, Edinburgh, UK. Correspondence: Dr. K Galea, Centre for Human Exposure Science, Institute of Occupational Medicine (IOM), Research Avenue North, Riccarton, Edinburgh EH14 4AP, UK. Tel.: +44(0)131 449 8034. Fax: +44(0)131 449 8084. E-mail: [email protected] Received 1 March 2015; revised 19 June 2015; accepted 29 July 2015; published online 16 September 2015 Pesticide exposure in residents near farm land Galea et al Table 1. Pesticides of interest. Pesticide Class Function Relevant crops approved for use Captan Phthalimide Fungicide Apple, pear Chlormequat Chlorocholine Growth regulator Cereals Chlorpyrifos Organophosphate Insecticide Apple, cereals, vegetables including potato Cypermethrin Pyrethroid Insecticide Apple, various arable crops including potato Penconazole Triazole Fungicide Apple, blackcurrent, hops a b Approval in 2011. Results pertaining to penconazole are presented elsewhere. agricultural herbicides inside homes compared with homes with Residents (adults aged 18 years and over and children in their care aged 4–12 years) living within 100 m of the edge of a field belonging to a no crops within 750 m. These studies present an unclear picture of recruited farm were approached to participate in the study. Farmers and pesticide exposure in rural residents and are difficult to translate their family members residing within 100 m of the fields were also invited to the UK situation. to participate providing they were not directly involved in pesticide spray This manuscript reports on a study (‘Biological monitoring of or crop re-entry activities and they fulfilled the other eligibility criterion. pesticide exposure in residents’) funded by the UK Government Informed consenting participants completed a background question- Department of Environment, Food and Rural Affairs (DEFRA), naire. This included questions concerning their age, sex, weight, typical which aimed to assess exposure to pesticides for adults and consumption of organic food and home-grown produce, occupation/ children living within 100 m from the edge of agricultural land and education, occupational and para-occupational exposure to pesticides and typical pesticide usage around the home or garden. The children’s to investigate whether exposures were elevated following spray questionnaire was shorter and was completed by the consenting adult. events. Urine Sample Collection and Accompanying Activity METHODS Questionnaire The study received ethical approval from the South East Scotland Research Following due consideration of preliminary modelling (not presented), the Ethics Committee 3 (study number 10/S1103/63). Our study protocol 13 peer-reviewed literature and the need to obtain samples over a provides details of the methodology employed and is briefly summarised sustained period of time, first-morning void samples were chosen as the below. To obtain an estimate of the number of subjects required for the most appropriate urine sample to request from participants. First-morning study, a range of conservative power calculations were carried out a priori void urine samples and accompanying sample-related questionnaires were for a number of pesticides identified as being most likely to be applied collected using two strategies. during the spray seasons in the target areas. 1. Residents were asked to provide first-morning void urine samples and complete accompanying questionnaire once a week on a designated Recruitment of Study Participants day during the spraying season and also for 3 weeks after the spraying Sample and data collection took place in three locations in the UK: East season. Lothian, Kent and Norfolk. Data in East Lothian and Kent were collected in 2. In instances when a community researcher was advised of a relevant 2011 and 2012, while in Norfolk data collection took place in 2012 only. spray event occurring on a given field, participants living within 100 m East Lothian and Norfolk are major arable crop growing areas, while most of the field were contacted and asked to collect additional first-morning of the orchards in the UK are located in Kent. Recruitment of, and liaison void urine samples one and two days following the day of the spray with, farmers and residents participating in the study were carried out by event as well as complete a sample-related questionnaires on community researchers who had local knowledge of the study areas and both days. communities. Farmers were identified through publicly available resources and Each sample-related questionnaire completed by adult participants contacted via letter explaining the aims and objectives of the study. This requested information on their time spent indoors and outdoors at home was then followed by telephone contact. The pesticides of interest, the and other locations, domestic use and para-occupational exposure to crops on which they were likely to be applied were discussed during this pesticides, as well as their dietary consumption of home-grown produce contact as was the proximity of residential areas to these fields. If the within the previous 48-hour period. The sample-related questionnaire farmer was willing to participate and considered a suitable candidate for completed by the adult on behalf of a child participant was shorter and inclusion in the study, an in-person meeting was arranged at the farm. The included questions concerning the time spent by the child in both outdoor community researchers recruited owners/managers of farms and orchards and indoor environments. (hereafter both referred to as farms) that reported when they were likely to The spraying season was considered to be between the months of spray their agricultural crops with certain specified pesticides and which March–August, coinciding with the main crop growing season, and had residential areas within 100 m of these fields. Informed consenting stopping before harvest. First-morning void samples were requested and farmers were asked to provide details of their pesticide usage throughout the time the urine sample collection was recorded by the participant. the spray season. The spray information included information on the start Urine samples (~70 ml) were collected in polypropylene containers and finish times of spraying, product and active ingredients used, spray (Starplex Scientific, Canada) along with the completed sample-related method and weather conditions. In instances where farmers demonstrated questionnaire were collected at agreed times by the community researcher that they already maintained comprehensive records of their pesticide on the day of sample provision. The urine samples were stored in a cool usage, the researcher requested copies of these to be made available. bag before collection by the community researcher. The samples were Where detailed records were not already maintained, participating farmers frozen as soon as possible (o6 h after collection) and couriered to the were asked to record the relevant information using an adaptation of the laboratory, being stored at a temperature ranging from − 15 to − 20 °C spray record form recommended by the Department of Environment, Food before analysis. The community researchers checked the completeness of and Rural Affairs. the sample-related questionnaires. Farmers’ spray records were reviewed Table 1 provides details of the pesticides considered in the study and alongside the dates that participants’ urine samples were provided. reported in this manuscript. Inclusion was restricted to those approved pesticides where analytical methods for the associated urinary biomarkers Urine Sample Analysis were available to the project team. No validated method was available for determining penconazole or its metabolites in urine, and so a novel Urine samples were selected for analysis as follows, with a relevant spray method was developed during this project, details of which, as well as the event referring to those involving the application of pesticides including penaconazole results from this study are reported elsewhere. the active ingredients captan, chlormequat, chlorpyrifos and cypermethrin: Journal of Exposure Science and Environmental Epidemiology (2015), 623 – 631 © 2015 Nature America, Inc. Pesticide exposure in residents near farm land Galea et al captan was based on that reported by Berthet et al. measuring cis- Table 2. Description of the participants (background questionnaire 1,2,3,6-tetrahydrophthalimide (THPI). The analytical method for chlorpyr- responses). 16 ifos was based on that reported by Sams et al. measuring 3,5,6- trichlorpyridinol (TCP). The analytical method for cypermethrin measured Descriptor N % cis- and trans- 2,2-dichlorovinyl-3,3-dimethylcyclopropane-1-carboxylic acid (DCVA). Adult 118 84 Further analytical methodology details are provided as Supplementary Child 22 16 Information. Sex Male 54 39 Female 86 61 Data Analysis Urine samples with a creatinine concentration below 2 or 430 mmol/l Location 18,19 (0.23 g/l and 3.39 g/l, respectively) were excluded from the analyses. East Lothian 29 21 Next, participants for which either no spray event-related samples or no Kent 45 32 background (either within or outwith) samples were available were Norfolk 66 47 excluded. The descriptive characteristics of the participants were summarised, Employment (adults) along with summaries of their responses to the background questionnaire, Full time employment 29 25 in terms of percentage in each category or mean and range for continuous Part time employment 37 32 variables (Table 2). Full time education 1 1 Urinary measurements were corrected for creatinine by dividing the Part time education 39 34 urinary biomarker concentration by the creatinine concentration and are Retired 8 7 reported as μg biomarker per g creatinine. A very high proportion of Non-paid employment 1 1 samples were below the analytical limit of detection (LOD) for captan Missing or no answer 29 25 (89%) (LOD = 0.1 μg/l) and cypermethrin (93%) (LOD = 1.0 μg/l) and for these two pesticides only the proportion of detects, 95th percentile and Education (children) the maximum levels are reported. Secondary 2 9 For chlormequat and chlorpyrifos a random imputation procedure was Primary 18 82 used to replace the values below the LOD (0.6 μg/l and 0.8 μg/l, Full time nursery 0 0 respectively). The geometric mean (GM) and geometric standard deviation Part time nursery 2 9 (GSD) of concentrations above the LOD were determined, assuming a log- normal distribution. Each of the values below LOD was then replaced by a Smoke 5 4 value between 0 and the LOD which was randomly generated from this Own a pet 85 61 distribution. As is typical of data of this nature, concentrations were not Job involves travelling around the local area 22 16 normally distributed. Transforming by taking the natural logarithm Use pesticides at work 6 4 improves the normality of the data significantly and therefore the sample Family use pesticides at work 7 5 Use pesticides in the home at least once a year 112 80 results are summarised in terms of GM and GSD. For each individual the GM of their samples was determined separately Mean Range for samples provided after a spray event and for within and outwith spray Age (adult) 55 (18–83) season backgrounds. The GM ratio of the spray event sample to the Age (child) 8 (4–12) backgrounds was then calculated by taking the log of each individual ratio, averaging and exponentiating. Results are reported as GM and associated 95% confidence interval. A confidence interval containing the value 1 means that the ratio is not significantly different from 1, that is, spray event 1. Urine samples collected within 2 days of relevant pesticide spray events samples are not significantly higher or lower than backgrounds. taking place in fields within 100 m of the participant’s residence (spray The data were further examined to investigate factors from either the event-related samples). background questionnaire (person-specific) or the sample-related ques- 2. For each participant providing at least one relevant pesticide spray tionnaires (sample-specific) that might explain any differences between event sample, up to three randomly selected background samples the biomarker concentrations. General linear mixed models were used obtained within the spraying season which did not coincide with a with the log of the biomarker level as the response. The participant was relevant spray event (within spray season background samples). treated as a random variable, to account for repeated measures from the 3. For each participant providing at least one relevant spray event sample, same individuals. Sample type was treated as a fixed effect of a priori up to three randomly selected background samples collected outwith interest, where the levels of sample type were defined as; outwith and the spraying season (during November–December) (outwith spray within spray season backgrounds, samples provided the day after spraying season background samples). (24 h), samples provided the second day after a spray event (48 h) or sample was provided after 2 consecutive days of spraying (24 and 48 h). In Urine samples collected within 2 days of a relevant spraying event were a step-wise manner variables were considered for inclusion in the model analysed only for the relevant pesticide(s) sprayed during the event. where they significantly improved the fit of the model, based on the Background samples, both within and outwith the spray season, were likelihood ratio test or affected the coefficients of terms already in the analysed for all the relevant pesticides of interest to the study. model (by 410%). Samples were analysed according to established methods by the Health Imputation was carried out using R v3.1.0, while all statistical analyses and Safety Laboratory (HSL), which participates in external quality were carried out using Genstat v16 (ref. 22) and plots were prepared using assurance schemes for chlorpyrifos and cypermethrin (G-EQUAS, www.g- Sigmaplot v10). equas.de). The analysts were blind to whether the urine samples were related to spray events or were background samples. Detection limits were comparable to previous reported studies looking at general population RESULTS levels. All analytes were quantified using multi-point matrix-matched calibration curves and quality control samples were run every five samples. A total of 13 participating farms during 2011 and 17 farms during Samples were analysed in duplicate and the mean value reported. Aliquots 2012 reported sprayed events using at least one of the relevant of positive samples were reanalysed throughout the project to evaluate pesticides. The breakdown by region is provided in Table 3, along sample stability. There was no evidence of sample degradation for any with details of the number of relevant spray events after which biomarker studied throughout the assessment period (see Supplementary urine samples were collected. All participating Kent farms were Information). orchards while the farms in East Lothian and Norfolk were The analytical method for chlormequat was based on that reported by Lindh et al. measuring chlormequat itself. The analytical method for arable farms. © 2015 Nature America, Inc. Journal of Exposure Science and Environmental Epidemiology (2015), 623 – 631 Pesticide exposure in residents near farm land Galea et al Table 3. Participating farms and relevant spray events by pesticide and geographical area. Area No. farms Pesticide No. spray events East Lothian 7 Chlormequat 57 Cypermethrin 2 Kent 9 Captan 214 Chlorpyrifos 51 Norfolk 4 Chlormequat 15 Cypermethrin 3 Spray event numbers derived by multiplying the number of farms applying the pesticide by the number of relevant fields on which the pesticide was applied. For example if farm A sprayed captan in six fields on four occasions, the number of spray events for this farm would be 24. Table 4. Urinary biomarker concentrations (μg/g creatinine). Pesticide N NoLOD %oLOD Max GM GSD 95th % ile Figure 1. Participant numbers by area, sex. Captan aa Outwith 440 387 88 3.5 0.4 aa Within 553 489 88 3.9 0.5 Table 4 summarises the urine sample results for spray events aa Spray 255 232 91 1.2 0.2 and backgrounds (within and outwith spray season). For captan and cypermethrin, the proportion of spray event values below the Cypermethrin LOD was 91 and 98%, respectively, whereas the proportion of aa b Outwith 344 329 96 15.4 aa background results below the LOD was 88% for captan and in Within 349 312 89 10.8 5.1 aa b excess of 90% for cypermethrin. The captan biomarker concentra- Spray 46 45 98 7.0 tions ranged from below the LOD to almost 4 μg/g creatinine. Chlormequat There is a slightly higher proportion of non-detects in the spray Outwith 440 17 4 281.6 12.3 3.1 65.6 event-related samples with the largest individual result being Within 555 4 1 388.2 16.5 2.7 89.7 associated with a background sample collected within the spray Spray 197 3 2 248.1 15.4 2.7 72.4 season. The cypermethrin biomarker concentrations follow a similar pattern, with the maximum concentration (15.4 μg/g Chlorpyrifos creatinine) found to be in a background sample obtained outwith Outwith 440 54 12 22.7 3.0 2.2 9.6 the spray season. Within 554 69 12 76.4 3.0 2.4 10.8 Figure 2 shows boxplots of the creatinine adjusted urinary Spray 63 7 11 14.8 2.5 2.1 7.9 biomarker concentrations (μg/g) for chlorpyrifos and chlormequat Abbreviations: GM, geometric mean; GSD, geometric standard deviation; for the spray event-related samples as well as the within and LOD, limit of detection; Max, maximum; N, number; 95% ile, 95th outwith spray season background samples. Both figures show that percentile. GM and GSD were not calculated due to the high proportion b spray event-related samples did not appear to contain elevated of values below LOD. 95th percentile not calculated as over 95% of the concentrations of urinary biomarkers compared with the back- samples were below LOD. ground levels. Spray event sample concentrations for chlormequat are statistically significantly higher than outwith spray season back- A total of 296 participants were recruited to the study (238 ground, with the GM of the individual ratios being 1.22 (95% CI: adults, 58 children), providing 3275 urine samples. One hundred 1.09, 1.38) but there is no significant difference between spray forty-one people provided at least one sample that was related to event-related sample concentrations and within spray season backgrounds (GM ratio 0.96 (95% CI: 0.87, 1.06)) (Table 5). a relevant spray event involving captan, chlormequat, chlorprifos Interestingly, the average spray event-related chlorpyrifos urinary or cypermethrin and had at least one background, resulting in biomarker concentrations are lower than both the outwith and 1565 samples results. Altogether, 73% of participants had the full within spray season background sample results (GM ratio: 0.80, complement of outwith spray season backgrounds and 76% had 95% CI: 0.74, 0.87 and 1.01; 95% CI: 0.92, 1.11, respectively). the full complement of within spray season backgrounds. There were minor differences in chlormequat biomarker Application of the creatinine exclusion criterion resulted in 40 concentrations measured for males and females, with males samples being excluded from the analysis (12 sprays and 28 having slightly higher urinary biomarker levels than females backgrounds). Following the application of this exclusion criterion, (Table 6). This difference was not significant for outwith season one further person was removed due to no spray event-related backgrounds and spray event-related samples but was significant samples remaining and as such were no longer eligible to be for within spray season backgrounds (P = 0.036). There were no included in the data analysis (six backgrounds). statistically significant differences in the chlorpyrifos concentra- The final data set for statistical analysis contained 1518 sample tions measured in samples provided by males and females results for 140 people, consisting of 995 background samples (Table 6). The levels of chlormequat and chlorpyrifos were higher (440 outwith and 555 within season) (Figure 1) and 523 spray in samples provided by children than adults, although not event-related samples. The spray samples included 255 captan, 63 significantly so; the variation in the children’s sample results also chlorpyrifos, 46 cypermethrin and 197 chlormequat spray event tended to be greater. To ensure these patterns were not the result results, respectively (some spray events involved multiple relevant of variation in creatinine levels, which tend to be higher in males pesticides). than females and in adults than children, the uncorrected Journal of Exposure Science and Environmental Epidemiology (2015), 623 – 631 © 2015 Nature America, Inc. Pesticide exposure in residents near farm land Galea et al Table 6. Urinary biomarker concentrations (μg/g creatinine) for males and females and for adults and children for chlormequat and chlorpyrifos. Pesticide Female Male NNoLOD GM GSD N NoLOD GM GSD Chlormequat Outwith 262 11 11.8 3.2 178 6 13.0 2.9 Within 335 4 15.4 2.8 220 0 18.3 2.7 Spray 120 1 14.4 2.6 77 2 17.1 2.7 Chlorpyrifos Outwith 262 32 3.3 2.1 178 22 2.7 2.3 Within 334 42 3.0 2.4 220 27 2.8 2.4 Spray 41 7 2.5 2.2 22 0 2.5 1.9 Child Adult NNoLOD GM GSD N NoLOD GM GSD Chlormequat Outwith 59 3 11.4 4.2 381 14 12.4 3.0 Within 79 3 19.3 3.4 476 1 16.1 2.7 Spray 40 0 17.7 2.8 157 3 14.9 2.6 Chlorpyrifos Outwith 59 4 3.7 2.2 381 50 2.9 2.2 Within 79 4 3.8 2.5 475 65 2.8 2.4 Spray 8 1 2.2 2.3 55 6 2.6 2.0 Abbreviations: GM, geometric mean; GSD, geometric standard deviation; LOD, limit of detection; N, number. the sample was collected. For chlormequat, after including sample Figure 2. Creatinine adjusted urinary biomarker levels for spray type (i.e., spray event or background) in the model, the only event and within and outwith spray season background samples for (a) chlorpyrifos and (b) chlormequat. significant factor, based on Wald test for addition to the model, was the level of organic food consumption reported, where higher levels of organic food consumption were associated with higher levels of chlormequat (where organic food consumption was recorded by participants as; none, little, some and most). However Table 5. GM ratio of creatinine corrected concentrations following this factor did not significantly improve the fit of the model. As spray events to the GM of backgrounds. shown before, the statistically significant differences in the urinary Outwith spray season Within spray season biomarker levels between sample type is driven by the fact that outwith season background levels are lower than spray event- Pesticide GM ratio 95% CI GM ratio 95% CI related sample levels and within season backgrounds. The results of the modelling are very similar for chlorpyrifos. Although some Chlormequat 1.22 1.09 1.38 0.96 0.87 1.06 of the factors were significant (including age, sex and time spent Chlorpyrifos 0.80 0.74 0.87 1.01 0.92 1.11 outdoors), according to the Wald test, they did not significantly Abbreviations: CI, confidence Interval; GM, geometric mean. improve the fit of the model and therefore were not included in the final model. The significance of the sample type variable in the model for chlorpyrifos is likely being driven by the levels in the creatinine urinary biomarker concentrations were analysed and spray event-related samples being lower than background levels, similar patterns were observed. both outwith and within. There were no statistically significant differences in chlorme- quat or chlorpyrifos concentration for the samples collected at 1 and 2 days after the spray events (Table 7). In addition, we DISCUSSION investigated if there is any relationship between biomarker We report on a study that aimed to assess exposure to pesticides concentrations and timing of spray event and no significant for UK adults and children living within 100 m from the edge of relationship was found. agricultural land, and identify whether or not exposures We investigated whether other factors such as age, sex, were elevated following spray events. A distance of 100 m was location, smoking status, typical consumption of organic food selected as a balance between proximity to agricultural land and and typical use of pesticides (as answered in background available potential study participants. In addition, researchers questionnaire), whether the subject had used pesticides in the modelling vapour dispersion reported that vapour concentration previous 48 h, time spent indoors and outdoors in the previous is significantly reduced after a distance of 100 m (dependent on 48 h (based on the sample-related questionnaires) might explain any differences in the biomarker concentrations between when field size). © 2015 Nature America, Inc. Journal of Exposure Science and Environmental Epidemiology (2015), 623 – 631 Pesticide exposure in residents near farm land Galea et al Table 7. Description of spray sample results by whether the sample was the day after a spray event (24 h) or 2 days after (48 h). 24 h Spray samples 48 h Spray samples NNoLOD GM GSD 95th % N NoLOD GM GSD 95th % Chlormequat 100 1 15.9 2.7 72.8 97 2 15.0 2.6 63.2 Chlorpyrifos 27 4 2.4 2.2 8.1 33 2 2.7 2.0 8.0 Abbreviations: GM, geometric mean; GSD, geometric standard deviation; LOD, limit of detection; N, number; 95%, 95th percentile. Level of Urinary Biomarker Levels the adult residents, as indicated by urinary 3,5,6-TCP biomonitor- ing, did not increase as a result of the application. Another study The urinary biomarker levels for captan and cypermethrin were reported urinary TCP concentrations of 0.1–7.8 μg/g creatinine in very low in this population with ~ 90% of samples having 41 residents from houses where chlorpyrifos had been detected in undetectable concentrations. For chlormequat and chlorpyrifos, 34 35 collected indoor air samples. Alexander et al. reported a study the GM urinary biomarker concentrations following spray events of farm family members (spouses, and children aged 4–17 years) were 15.4 μg/g creatinine and 2.5 μg/g creatinine, respectively, from Minnesota and South Carolina. Five consecutive 24-h urine compared with 16.5 μg/g creatinine and 3.0 μg/g creatinine for samples were obtained from 34 families of licensed pesticide within season background. applicators from one day before to three days after a chlorpyrifos For chlormequat, we have only been able to identify one other, application. The spouses’ GM exposure was reported as being relevant, study. Lindh et al. reported a general population study 3.6 μg/g creatinine pre-application, 3.8 μg/g creatinine on the day in southern Sweden where the chlormequat concentrations of application and then 4.2 μg/g μg/g creatinine on days 1 and 2 ranged from 0.4–30.2 μg/g creatinine (median 2.9, 95th percentile post application. The reported children’s exposure was 5.1 μg/g o17.3 μg/g creatinine, N = 100). These values are somewhat lower μg/g creatinine pre-application, 6.0 μg/g creatinine on day of than our reported concentrations for all the chlormequat spray application and 5.0 and 5.9 μg/g creatinine for days 1 and 2 post event and background samples combined (median 15.1, 95th application. These are all higher than the GMs that we observed. percentile 79.8 μg/g creatinine). Despite these higher concentra- A number of general population studies have been reported for tions, UK exposures are two orders of magnitude below the values cypermethrin exposure. The US CDC NHANES study reports 95th obtained from an oral dose at half the ADI (Lindh et al.). The only percentiles for adults as 0.9 μg/g creatinine (N = 1128) and 2.5 μg/g other report of measuring chlormequat in human urine was in an creatinine (N = 1123) for cis-DCVA and trans-DCVA respectively in accidental poisoning case, but levels were not quantified. 2001/02. Detection rates were reported as less than 50% for cis- Excluding the different time periods of sample collection in our DCVA and o25% for trans-DCVA. A study of 1149 pregnant and Lindh et al.’s study, it is possible that we observed higher women in China found median levels of 0.7 μg/g creatinine for cis- chlormequat urinary concentrations due to different farming DCVA and 1.9 μg/g creatinine for trans-DCVA. In the UK the 95th practices for cereal crops and consumption of foods and percentiles for adults (on the voting register) in the general beverages derived from cereal crops for which this growth population were reported as 0.7 μg/g creatinine (N = 405) and regulator was applied. For example, the mean daily per capita 1.8 μg/g creatinine (N = 404) for cis-DCVA and trans-DCVA, consumption for bread and rolls, bakery products, cereal and respectively and 2.3 μg/g creatinine combined as total-DCVA. products in the UK was reported as 103, 44 and 36 g, respectively, 26 In comparison, the 95th percentile was 5.8 μg/g creatinine for the compared with 96, 21 and 25 g for Sweden. spray event samples and 5.2 μg/g creatinine for our within spray Approximately 90% of the captan urinary biomarker concentra- season samples (which includes both adults and children). tions in this study were below the LOD, with the maximum value Although the 95th percentile results for our data are greater than of 3.9 μg/g creatinine detected in a background sample. There are reported by Bevan et al., the number of samples above the LOD very few data available on environmental exposures to captan. 27 was far lower despite the same detection limit. These differences Berthet et al. reported mean “pre-season” urine biomarker may reflect regional differences in exposure (our study was concentrations of 0.2 μg/l (~0.15 μg/g creatinine) but this was 28 conducted in three regions compared with across the whole of based on only four samples. Verberk et al. reported results below the UK for Bevan et al. ) or temporal differences in pesticide use the LOD (8, ~ 5.9 μg/g creatinine) for six unexposed controls. and food residues of pyrethroids (our samples were collected in Recent occupational studies have determined post-exposure THPI 27 2011 and 2012 whereas those of Bevan et al. were collected in levels of o5 μg/l (~3.1 creatinine). No other published general 2005/06). population studies could be found. There is an extensive literature on the use of urinary trichloro-2- Do Spray Events Result in Elevated Exposures to Residents Living pyridinol (TCP) as a biomarker of chlorpyrifos exposure. The US Near Agricultural Land? CDC NHANES study reports 95th percentiles for adults as 6.4 μg/g creatinine, N = 832 and 7.4 μg/g creatinine, N = 1,113 for 1999- The results presented in this paper provide no evidence that, in /2000 and 2001/2002, respectively. A study of 100 pregnant this study population, the spray events resulted in elevated women in the Netherlands found a 95th percentile of 6.4 μg/l exposures compared with background samples taken within the (~4.7 μg/g creatinine) with a maximum of 158 μg/l (~116 μg/g season. For chlormequat, the biomarker levels (both spray event 30 31 32 creatinine). Studies in Germany and Italy showed similar and background) were higher within the spray season compared values. For Germany, the 95th percentile was 11.3 μg/l (~8.3 μg/g with outwith the season. Chlormequat is a plant growth regulator, creatinine, N = 50) and for Italy, the estimated 95th percentile was which acts by inhibiting cell elongation hence shortening and 6.5 μg/g creatinine (N = 42). Our data for all the spray and strengthening the stem producing a sturdier plant. It also background samples combined (95th percentile 10.1 μg/g creati- influences the developmental cycle, leading to increased flower- nine) are comparable with these data from other general ing and harvest. Growth regulating products containing population studies, despite the varied geographical sources of chlormequat are widely used by the UK. The Pesticide Usage the data sets. A study of residents’ exposure to chlorpyrifos after Survey Teams of the Food & Environment Research Agency (FERA) treatment inside the home showed that potential exposures to conducted surveys of pesticide usage in arable crops in 2011/12 Journal of Exposure Science and Environmental Epidemiology (2015), 623 – 631 © 2015 Nature America, Inc. Pesticide exposure in residents near farm land Galea et al by visiting holdings throughout the UK. In this survey they start and finish times were obtained and residents were asked to reported that chlormequat, applied alone or in mixtures, provide details of their activities in the 48 h period before accounted for 59% of the area of arable crops treated with provision of each urine sample. However, it was not possible to specific growth regulators: in addition there was a 13% increase in establish from this when, where or how the residents’ potential area treated using chlormequat since the previous survey exposure to the assessed pesticides may have occurred. Following conducted in 2010. due consideration of preliminary modelling and the peer- Although not the primary aim of the study and reporting on reviewed literature, first-morning void samples were requested different pesticides, Jones et al. reported a statistically significant from participants. There is the possibility that the urine void with difference for dialkylphosphate levels (organophosphate) in the highest biomarker concentration was missed however no young children (o5 years) during different seasons, with autumn significant relationship between biomarker concentrations and resulting in the highest levels. No seasonal effect was however timing of spray event was found for any of the pesticides. Weather observed for pirimicarb or carbaryl. Our chlormequat findings information, whilst obtained by both the farmer and the research could be due to other sources of exposure. The most recent team, was typically reported from weather stations located in publication presenting results of pesticide residues in food some instances several miles away from where the spray took commodities (including both raw and processed) sampled during place. It is possible that the available wind speed and direction the calendar year 2010 in the 27 European Union Member States information may not reflect what actually occurred during the and two European Free Trade Association countries (Iceland and given spray event and so was not considered further. Good spray Norway) reported chlormequat/oats to be the pesticide/crop event information was obtained from the farmers participating in combination for which residue concentrations were most the study. However it is not possible to establish whether frequently above the reporting level (64.6% of the samples). In residents were potentially exposed to any additional relevant addition, the highest percentage of maximum residue limit (MRL) spray applied by non-participating farmers in the locality. Given exceedances in foods was found for chlormequat in oats (8.1% of the scope of the study, the number of dietary-related questions all samples). In rye, the most frequently found pesticide residue was kept to a minimum, restricted to the consumption of food was also chlormequat (35.9%). Of the 178 pesticides included in from the residents’ garden and organic food (as reported in the the 2010 EU-coordinated programme, the most frequent MRL background questionnaire). In retrospect, the inclusion of addi- exceedances were detected for chlormequat (3.6% of the tional food-related questions may have been useful in explaining samples). Chlormequat was also detected in a small number of some of the results observed. Residents (adults aged 18 years and organic food samples analysed (13 out of the 3571 samples), with over and children in their care aged 4–12 years) were recruited, measured residue levels ranging from 0.127–0.0011 mg/kg. with infants (o4 years old) and adolescents (13–17 years) being Whilst in most instances these data relate to unprocessed food excluded from the study. This pragmatic decision was taken due commodities and residue levels may decrease during food to likely difficulties being encountered with obtaining relevant production, it is considered that diet is the primary source of urine samples from babies and toddlers and adolescents exposure. For chlorpyrifos, the biomarker levels were very similar potentially being less engaged with the study and so the for the various sample types. Finally, for captan and cypermethrin exposures of these sub groups was not determined. a very large proportion of the measurements were below the LOD, All laboratory methods for the urine samples showed good day- whether or not these samples were collected following spray to-day repeatability and were based, where possible, on validated events. methods (see Supplementary Information) with comparable LODs The relatively short biological half-life of pesticide compounds to those already reported and used in environmental exposure and their biomarkers in the human body presents a major studies. Where known, the primary or most abundant biomarker challenge to linking biological monitoring data to specific spray was measured; measuring multiple biomarkers for the same events and so urine samples have to be collected ideally within pesticide would not have increased the sensitivity of measure- 24 h, and no later than 48 h following the spray events (depending ment unless all metabolites are converted to a single biomarker. All chlorpyrifos and chlormequat samples were analysed within on the urinary biomarker half-life). Farming activities, and in particular spaying with pesticides, are inherently unpredictable the timeframe of the stability trials. The length of each analyte because of the changing weather and the presence of insects or stability trial was determined by available samples within the data other potentially damaging infestations which influence pesticide set. Some samples for captan and cypermethrin were analysed selection and application. Along with the planned weekly urine outside of the evaluated stability time frame. These samples have sample collections, there was a need for effective engagement not necessarily degraded but extended sample stability was not with farmers to elicit this spray information at short notice and evaluated due to insufficient sample volume. It is considered that with residents to obtain the required spray event samples the biomarkers and methodology used were demonstrably fit for reactively. Through the use of community researchers, located in purpose. and knowledgeable of the geographical areas and familiar with When considering the generalisablity of the study results to local farming practices, effective engagement was achieved and other pesticides, consideration should be given to the spray over 3000 urine samples were collected. techniques used and their potential to distribute the pesticide The methodology applied in this study is robust but is not beyond the target area and the propensity for the pesticide to without some limitations. The participating farmers may not be redistribute post application. The spray equipment and techni- representative of all farmers within the study areas although there ques used by the participating farmers were not atypical and were is no reason to suggest that their spraying practices are any reportedly used when applying other pesticide products to the different to those of the wider farming communities. In the UK, given crops throughout the spray season. The range of vapour Government Ministers must approve all pesticides before they can pressures for the relevant products considered in this study be marketed or used and everyone who uses pesticides must have ranged from 0.0023 to 1.43 mPa at 25 °C, of which the highest was adequate guidance, instruction or training for their correct use for chlorpyrifos. Monitoring in the USA suggests that chlorpyrifos and must ensure that all reasonable precautions are taken to is the worst known case for vapour concentrations and so we prevent spray drift. It was clear from the farmers’ spray records consider that our study covers both the likely spectrum and worst that a number of pesticide products were applied throughout the case vapour pressures used in modern day pesticides in the UK spraying season (dependent on crops, infestation, weather (and perhaps more widely). Orchard spray techniques are usually conditions and other factors) and so the number of relevant considered as potentially giving rise to higher levels of pesticide spray events observed may differ from year to year. Spray event drift (and therefore potential exposure) in comparison to field crop © 2015 Nature America, Inc. Journal of Exposure Science and Environmental Epidemiology (2015), 623 – 631 Pesticide exposure in residents near farm land Galea et al spraying practices. For example, measurements of bystander REFERENCES exposure during UK field crop spraying and orchard spraying 1 RCEP. Crop Spraying and The Health of Residents and Bystanders. Royal Commission 43,44 on Environmental Pollution: London, UK, 2005. applications have been reported. For boom sprayers the 2 ACP. Crop Spraying and the Health of Residents and Bystanders. A Commentary average potential dermal exposure (PDE) for a bystander, on the Report Published by the Royal Commission on Environmental Pollution in positioned 8 m downwind from the sprayer and the average September 2005. Advisory Committee on Pesticides: York, UK, 2005. amount of spray potentially inhaled in the breathing zone were 3 Committees on toxicity and carcinogenicity of chemicals in food, 0.1 ml spray/person and 0.006 ml spray/person, respectively. For consumer products and the environment. Statement on Royal Commission on orchard sprayer applications the equivalent PDE and inhalation Environmental Pollution: Crop spraying and the health of residents and bystan- ders. Available at: http://cot.food.gov.uk/sites/default/files/cot/cotsection06.pdf values were 3.7 ml spray/person and 0.002 ml spray/person. Given (accessed on 1 September 2015). that we collected in excess of 300 orchard spray event samples, 4 DEFRA. The Royal Commission on Environmental Pollution report on Crop Spraying which also included those related to chlorpyrifos, we consider that and the Health of Residents and Bystanders–Government Response. Department for our study adequately considers potentially higher risk spray Environment, Food and Rural Affairs: UK, 2006a. techniques, of which the majority of the urinary biomarker results 5 Koureas M, Tsakalof A, Tzatzarakis M, Vakonaki E, Tsatsakis A, Hadjichristodoulou C were observed to be less than the analytical LOD. et al. Biomonitoring of organophosphate exposure of pesticide sprayers and comparison of exposure levels with other population groups in Thessaly (Greece). Occup Environ Med 2013; 71:126–133. CONCLUSION 6 Couture C, Fortin MC, Carrier G, Dumas P, Tremblay C, Bouchard M. Assessment of exposure to pyrethroids and pyrethrins in a rural population of the Montérégie This study reports urinary biomarker concentrations for a number area, Quebec, Canada. J Occup Envrion Hyg 2009; 6: 341–352. of active ingredients both for spray event and background 7 Kimata A, Kondo T, Ueyama J, Yamamoto K, Yoshitake J, Takagi K et al. samples amongst people living within 100 m of agricultural land, Comparison of urinary concentrations of 3-phenoxybenzoic acid among general which has not previously been undertaken and reported on such a residents in rural and suburban areas and employees of pest control firms. Int scale for a UK population. It has also, as far as we are aware, not Arch Occup Environ Health 2009; 82: 1173–1178. 8 Keifer M, Rivas F, Dong Moon J, Checkoway H. Symptoms and cholinesterase been studied as systematically anywhere else. Our study did not activity among rural residents living near cotton fields in Nicaragua. Occup Environ set out to determine whether rural residents have greater Med 1996; 53:726–729. exposure to pesticides than non-rural residents and so is not 9 Ward MH, Lubin J, Giglierano J, Colt JS, Wolter C, Bekiroglu N. Proximity to crops directly comparable to other studies that may have sought to and residential exposure to agricultural herbicides in Iowa. Environ Health Perspect do this. 2006; 114:893–897. The primary conclusion of the study is that there is no evidence 10 Galea KS, MacCalman L, Jones K, Cocker J, Teedon P, Sleeuwenhoek AJ et al. Biological monitoring of pesticide exposures in residents living near of increased pesticide biomarker excretion in rural residents agricultural land. BMC Public Health 2011; 11:856. following a spray event within 100 m of their home, when 11 Teedon P, Galea KS, MacCalman L, Jones K, Cocker J, Cherrie JW et al. Engaging compared with the urinary biomarker levels obtained when communities for exposure science–lessons learned from a pesticide biomonitor- relevant spray events did not take place. The levels of urinary ing study. PLOS One 2015 (doi:10.1371/journal.pone.0136347). biomarkers detected in our population were generally comparable 12 DEFRA. Pesticides Code of Practice for Using Plant Protection Products. DEFRA: to other studies of exposure in the general population, where such London, UK, 2006. 13 Kissel JC, Curl CL, Kedan G, Lu C, Griffith W, Barr DB et al. Comparison of orga- data are available, and this supports the view that general nophosphorus pesticide metabolite levels in single and multiple daily urine population exposures to pesticides are primarily from non-spray samples collected from preschool children in Washington State. J Expo Anal event sources such as diet. It appears that the population Epidemiol 2005; 15: 164–171. recruited to this study exhibits greater exposure to chlormequat 14 Lindh CH, Littorin M, Johannesson G, Jonsson BAG. Analysis of chlormequat in than detected in a Swedish population sub-set. Whether this is a human urine as a biomarker of exposure using liquid chromatography triple characteristic of our particular rural residents or is more widely quadrupole mass spectrometry. J Chromatogr B Anal Technol Biomed Life Sci 2011; 879:1551–1556. applicable to the entire UK general population is not known and 15 Berthet A, Bouchard M, Schüpfer P, Vernez D, Danuser B, Huynh CK. Liquid may be an area of further work. Exposure levels for cypermethrin chromatography-tandem mass spectrometry (LC/APCI-MS/MS) methods for the and captan were very low. quantification of captan and folpet phthalimide metabolites in human plasma and urine. Anal Bioanal Chem 2011; 399: 2243–2255. 16 Sams C, Jones K. Human volunteer studies investigating the potential for CONFLICT OF INTEREST toxicokinetic interactions between the pesticides deltamethrin; pirimicarb and Dr. Galea is a member of the UK Government Pesticide Incidents Appraisal Panel and chlorpyrifos-methyl following oral exposure at the acceptable daily intake. Toxicol Dr. Cocker was a member of the UK Government Advisory Committee on Pesticides Lett 2011; 200:41–45. (January 2009-December 2014). The authors declare no conflict of interest. 17 Jones K, Sams C, Patel K, Johnson P. Development of cost-effective biomarkers for herbicides and fungicides. Available at: http://www.foodbase.org.uk/results.php? f_report_id = 407 (accessed on 11 June 2014). ACKNOWLEDGEMENTS 18 Cocker J, Mason HJ, Warren ND, Cotton RJ. Creatinine adjustment of biological monitoring results. Occup Med Oxf 2011; 61:349–353. This project was funded by the UK Government Department for Environment Food 19 EWDTS. European Laboratory Guidelines for Legally Defensible Workplace Drug and Rural Affairs (DEFRA), project code PS2620. We thank the following individuals Testing. 2002. Available at: www.ewdts.org (accessed on 1 September 2015) (in alphabetical order) for their work as community researchers in this project: 20 Helsel DR. Nondetects and Data Analysis: Statistics for Censored Environmental S Attwood, J Cadzow, A Carr, D Dahrendorf, T Hogg, L Jewsbury and F MacIver. Their Data. John Wiley and Sons: New York, USA, 2005. hard work was crucial to the success of the recruitment and data collection in this 21 R Core Team. R: A Language and Environment for Statistical Computing. R Foun- project. Thanks also to the independent project Advisory Committee (Prof. David dation for Statistical Computing: Vienna, Austria, 2014. Coggon, Paul Hamey, Prof. Len Levy and Dr. Sean Semple) for their helpful comments 22 Payne RW, Harding SA, Murray DA, Soutar DM, Baird DB, Glaser AI et al. The Guide to throughout the project and on earlier manuscript drafts; Dr. Anne Sleeuwenhoek and GenStat Release 14, Part 2: Statistics. VSN International: Hemel Hempstead, UK, 2011. David Todd (IOM) for their assistance with the storage of the urine samples and 23 Systat Software SigmaPlot version 10. Systat Software, Inc., San Jose California related administration tasks; IOM personnel (Anne Sleeuwenhoek, Shahzad Rashid, USA. www.sigmaplot.com. Peter Ritchie, Yvonne O’Neill, Marlyn Davis, Julie O’Neill, Selima Argoub and Araceli 24 The Arable Group. PS2005. The Development and Validation of a Bystander and Sanchez Jimenez) for assistance with data storage, data input and other Resident Exposure Assessment Model (BREAM) Research Project Final Report. DEFRA: administrative tasks; and HSL personnel (Drs Craig Sams, Laura Kenny, Shahwaiz York, UK, 2010. Iqbal and Fiona Garner) for the urine sample analysis. We express our sincere 25 Winek CL, Wahba WW, Edelstein JM. Sudden-death following accidental ingestion gratitude to all the farmers and householders who participated in the study. of chlormequat. J Anal Toxicol 1990; 14: 257–258. Journal of Exposure Science and Environmental Epidemiology (2015), 623 – 631 © 2015 Nature America, Inc. Pesticide exposure in residents near farm land Galea et al 26 DAFNE. The Pan-European food bank based on household budget 36 Qi X, Zheng M, Wu C, Wang G, Feng C, Zhou Z. Urinary pyrethroid metabolites surveysNational and Kapodistrian University of Athens: Athens, 2006, http://www. among pregnant women in an agricultural area of the Province of Jiangsu, China. nut.uoa.gr/dafnesoftweb/. Int J Hyg Environ Health 2012; 215: 487–495. 27 Berthet A, Heredia-Ortiz R, Vernez D, Danuser B, Bouchard M. A detailed urinary 37 Bevan R, Jones K, Cocker J, Assem FL, Levy LS. Reference ranges for key bio- markers of chemical exposure within the UK population. Int J Hyg Environ Health excretion time course study of captan and folpet biomarkers in workers for the 2013; 216: 170–174. estimation of dose, main route-of-entry and most appropriate sampling and 38 Tomlin C (ed). The Pesticide Manual: A World Compendium. 15th edn. British Crop analysis strategies. Ann Occup Hyg 2012; 56:815–828. Protection Council, 2009. 28 Verberk MM, Brouwer DH, Brouwer EJ, Bruyzeel DP, Emmen HH, Van Hemmen JJ 39 Garthwaite DG, Hudson S, Barker I, Parrish G, Smith L, Pietravalle S. Pesticide et al. Health effects of pesticides in the flower-bulb culture in Holland. Med Lav Usage Survey Reports 250. Arable Crops in the United Kingdom 2012 (Including 1990; 81: 530–541. Aerial Applications 2012) DEFRA: York, UK, 2014. 29 CDC. Third National Report on Human Exposure to Environmental Chemicals. NCEH 40 Jones K, Everard M, Harding AH. Investigation of gastrointestinal effects of Pub. No. 05-0570, Atlanta, Georgia, USA, 2005. organophosphate and carbamate pesticide residues on young children. Int J Hyg 30 Ye X, Pierik FH, Hauser R, Duty S, Angerer J, Park MM et al. Urinary metabolite Environ Health 2014; 217:392–398. concentrations of organophosphorous pesticides, bisphenol A, and phthalates 41 EFSA. Scientific report of EFSA. The 2010 European Union Report on among pregnant women in Rotterdam, the Netherlands: The Generation R study. Pesticide Residues in Food. European Food Safety Authority (EFSA). EFSA J 2013; Environ Res 2008; 108: 260–267. 11: 3130. 31 Koch HM, Hardt J, Angerer J. Biological monitoring of exposure of the general 42 California Environmental Protection Agency. Report for the Application and population to the organophosphorus pesticides chlorpyrifos and chlorpyrifos- Ambient Air Monitoring for Chlorpyrifos (and the Oxon Analogue) in Tulare County methyl by determination of their specific metabolite 3,5,6-trichloro-2-pyridinol. Int During Spring/Summer 1996. Air Resources Board, California Environmental Pro- J Hyg Environ Health 2001; 204: 175–180. tection Agency, USA, 1998. 32 Aprea C, Betta A, Catenacci G, Lotti A, Magnaghi S, Barisano A et al. Reference 43 Lloyd GA, Bell GJ. Hydraulic Nozzles: Comparative Spray Drift Study. MAFF/ADASUK, values of urinary 3,5,6-trichloro-2-pyridinol in the Italian population—validation of analytical method and preliminary results (Multicentric study). J AOAC Int 1999; 44 Lloyd GA, Bell GJ, Samuels SW, Cross JV, Berrie AM. Orchard Sprayers: Comparative 82: 305–312. Operator Exposure and Spray Drift Study. MAFF Report, UK Pesticide Registration 33 Byrne SL, Shurdut BA, Saunders DG. Potential chlorpyrifos exposure to residents and Surveillance Department, UK, 1987. following standard crack and crevice treatment. Environ Health Perspect 1998; 106: 725–731. 34 Dai H, Asakawa F, Suna S, Hirao T, Karita T, Fukunaga I et al. Investigation of indoor This work is licensed under a Creative Commons Attribution- air pollution by chlorpyrifos: determination of chlorpyrifos in indoor air and 3,5,6- NonCommercial-NoDerivs 4.0 International License. The images or trichloro-2-pyridinol in residents' urine as an exposure index. Environ Health Prev other third party material in this article are included in the article’s Creative Commons Med 2003; 8:139–145. license, unless indicated otherwise in the credit line; if the material is not included under 35 Alexander BH, Burns CJ, Bartels MJ, Acquavella JF, Mandel JS, Gustin C et al. the Creative Commons license, users will need to obtain permission from the license Chlorpyrifos exposure in farm families: results from the farm family holder to reproduce the material. To view a copy of this license, visit http:// exposure study. J Expo Sci Environ Epidemiol 2006; 16:447–456. creativecommons.org/licenses/by-nc-nd/4.0/ Supplementary Information accompanies the paper on the Journal of Exposure Science and Environmental Epidemiology website (http:// www.nature.com/jes) © 2015 Nature America, Inc. Journal of Exposure Science and Environmental Epidemiology (2015), 623 – 631 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Exposure Science & Environmental Epidemiology Springer Journals

Urinary biomarker concentrations of captan, chlormequat, chlorpyrifos and cypermethrin in UK adults and children living near agricultural land

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Springer Journals
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Medicine & Public Health; Medicine/Public Health, general; Epidemiology
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Journal of Exposure Science and Environmental Epidemiology (2015) 25, 623–631 OPEN © 2015 Nature America, Inc. All rights reserved 1559-0631/15 www.nature.com/jes ORIGINAL ARTICLE Urinary biomarker concentrations of captan, chlormequat, chlorpyrifos and cypermethrin in UK adults and children living near agricultural land 1 1 2 2 3 1,4 1 Karen S. Galea , Laura MacCalman , Kate Jones , John Cocker , Paul Teedon , John W. Cherrie and Martie van Tongeren There is limited information on the exposure to pesticides experienced by UK residents living near agricultural land. This study aimed to investigate their pesticide exposure in relation to spray events. Farmers treating crops with captan, chlormequat, chlorpyrifos or cypermethrin provided spray event information. Adults and children residing ≤ 100 m from sprayed fields provided first-morning void urine samples during and outwith the spray season. Selected samples (1–2 days after a spray event and at other times (background samples)) were analysed and creatinine adjusted. Generalised Linear Mixed Models were used to investigate if urinary biomarkers of these pesticides were elevated after spray events. The final data set for statistical analysis contained 1518 urine samples from 140 participants, consisting of 523 spray event and 995 background samples which were analysed for pesticide urinary biomarkers. For captan and cypermethrin, the proportion of values below the limit of detection was greater than 80%, with no difference between spray event and background samples. For chlormequat and chlorpyrifos, the geometric mean urinary biomarker concentrations following spray events were 15.4 μg/g creatinine and 2.5 μg/g creatinine, respectively, compared with 16.5 μg/g creatinine and 3.0 μg/g creatinine for background samples within the spraying season. Outwith the spraying season, concentrations for chlorpyrifos were the same as those within spraying season backgrounds, but for chlormequat, lower concentrations were observed outwith the spraying season (12.3 μg/g creatinine). Overall, we observed no evidence indicative of additional urinary pesticide biomarker excretion as a result of spray events, suggesting that sources other than local spraying are responsible for the relatively low urinary pesticide biomarkers detected in the study population. Journal of Exposure Science and Environmental Epidemiology (2015) 25, 623–631; doi:10.1038/jes.2015.54; published online 16 September 2015 Keywords: exposure; pesticides; residents INTRODUCTION involves the comparison of estimated potential human exposures with toxicological reference values levels, for example, acceptable The use of pesticides can give rise to public concern. The Royal operator exposure level and acceptable daily intake (ADI), at and Commission on Environmental Pollution (RCEP) published a report below which there is considered to be high confidence that there on bystander and resident exposure to pesticides and recognised will be no adverse health effects. The RRA is therefore generally that the epidemiological literature showing associations between considered to be a conservative estimate of exposure. chronic fatigue syndrome and multiple chemical sensitivity and There are no specific studies on the exposures of people living pesticide exposure was plausible but equivocal. The RCEP report near agricultural land to pesticides in the UK. There are a number and the responses to it have ensured that the issue has remained 2–4 of reported studies from elsewhere in the world which have in the public eye. explored residents’ exposures. For example, Koureas et al. found In the UK, Government Ministers must approve all pesticides no difference in urinary dialkylphosphates (generic biomarkers of before they can be marketed or used, including those used in organophosphate pesticides) between urban and rural residents agriculture, horticulture, forestry, food storage and the home or in Thessaly, Greece, whilst pesticide sprayers had significantly garden, to ensure that they do not present health risks to the increased levels. A Canadian study showed a significant general public, consumers, people who apply them or work in or difference in urban and rural residents for exposure to pyrethroids, near areas that have been treated with pesticides, the environ- ment and animals. The Chemicals Regulation Directorate of the UK whereas in Japan no differences were seen between rural and Health and Safety Executive acts as the Regulator for pesticide suburban residents. Rural residents in Nicaragua showed sig- products and authorises their sale, supply, use and storage in the nificantly lower acetylcholinesterase activity which were asso- ciated with aerial pesticide spraying from planes. Crop maps were UK and represents the UK in the European Union process for the used by Ward et al. to predict that increasing acreage of corn and registration of new active substances and for the renewal (review) of active substances already approved. The health regulatory risk soybean fields within 750 m of homes in Iowa, USA, was assessment (RRA) underpinning the approval of pesticides associated with significantly elevated odds of detecting 1 2 3 Centre for Human Exposure Science, Institute of Occupational Medicine (IOM), Edinburgh, UK; Health and Safety Laboratory, Buxton, UK; School of Engineering and the Built Environment, Glasgow Caledonian University, Glasgow, UK and School of Life Sciences, Heriot Watt University, Edinburgh, UK. Correspondence: Dr. K Galea, Centre for Human Exposure Science, Institute of Occupational Medicine (IOM), Research Avenue North, Riccarton, Edinburgh EH14 4AP, UK. Tel.: +44(0)131 449 8034. Fax: +44(0)131 449 8084. E-mail: [email protected] Received 1 March 2015; revised 19 June 2015; accepted 29 July 2015; published online 16 September 2015 Pesticide exposure in residents near farm land Galea et al Table 1. Pesticides of interest. Pesticide Class Function Relevant crops approved for use Captan Phthalimide Fungicide Apple, pear Chlormequat Chlorocholine Growth regulator Cereals Chlorpyrifos Organophosphate Insecticide Apple, cereals, vegetables including potato Cypermethrin Pyrethroid Insecticide Apple, various arable crops including potato Penconazole Triazole Fungicide Apple, blackcurrent, hops a b Approval in 2011. Results pertaining to penconazole are presented elsewhere. agricultural herbicides inside homes compared with homes with Residents (adults aged 18 years and over and children in their care aged 4–12 years) living within 100 m of the edge of a field belonging to a no crops within 750 m. These studies present an unclear picture of recruited farm were approached to participate in the study. Farmers and pesticide exposure in rural residents and are difficult to translate their family members residing within 100 m of the fields were also invited to the UK situation. to participate providing they were not directly involved in pesticide spray This manuscript reports on a study (‘Biological monitoring of or crop re-entry activities and they fulfilled the other eligibility criterion. pesticide exposure in residents’) funded by the UK Government Informed consenting participants completed a background question- Department of Environment, Food and Rural Affairs (DEFRA), naire. This included questions concerning their age, sex, weight, typical which aimed to assess exposure to pesticides for adults and consumption of organic food and home-grown produce, occupation/ children living within 100 m from the edge of agricultural land and education, occupational and para-occupational exposure to pesticides and typical pesticide usage around the home or garden. The children’s to investigate whether exposures were elevated following spray questionnaire was shorter and was completed by the consenting adult. events. Urine Sample Collection and Accompanying Activity METHODS Questionnaire The study received ethical approval from the South East Scotland Research Following due consideration of preliminary modelling (not presented), the Ethics Committee 3 (study number 10/S1103/63). Our study protocol 13 peer-reviewed literature and the need to obtain samples over a provides details of the methodology employed and is briefly summarised sustained period of time, first-morning void samples were chosen as the below. To obtain an estimate of the number of subjects required for the most appropriate urine sample to request from participants. First-morning study, a range of conservative power calculations were carried out a priori void urine samples and accompanying sample-related questionnaires were for a number of pesticides identified as being most likely to be applied collected using two strategies. during the spray seasons in the target areas. 1. Residents were asked to provide first-morning void urine samples and complete accompanying questionnaire once a week on a designated Recruitment of Study Participants day during the spraying season and also for 3 weeks after the spraying Sample and data collection took place in three locations in the UK: East season. Lothian, Kent and Norfolk. Data in East Lothian and Kent were collected in 2. In instances when a community researcher was advised of a relevant 2011 and 2012, while in Norfolk data collection took place in 2012 only. spray event occurring on a given field, participants living within 100 m East Lothian and Norfolk are major arable crop growing areas, while most of the field were contacted and asked to collect additional first-morning of the orchards in the UK are located in Kent. Recruitment of, and liaison void urine samples one and two days following the day of the spray with, farmers and residents participating in the study were carried out by event as well as complete a sample-related questionnaires on community researchers who had local knowledge of the study areas and both days. communities. Farmers were identified through publicly available resources and Each sample-related questionnaire completed by adult participants contacted via letter explaining the aims and objectives of the study. This requested information on their time spent indoors and outdoors at home was then followed by telephone contact. The pesticides of interest, the and other locations, domestic use and para-occupational exposure to crops on which they were likely to be applied were discussed during this pesticides, as well as their dietary consumption of home-grown produce contact as was the proximity of residential areas to these fields. If the within the previous 48-hour period. The sample-related questionnaire farmer was willing to participate and considered a suitable candidate for completed by the adult on behalf of a child participant was shorter and inclusion in the study, an in-person meeting was arranged at the farm. The included questions concerning the time spent by the child in both outdoor community researchers recruited owners/managers of farms and orchards and indoor environments. (hereafter both referred to as farms) that reported when they were likely to The spraying season was considered to be between the months of spray their agricultural crops with certain specified pesticides and which March–August, coinciding with the main crop growing season, and had residential areas within 100 m of these fields. Informed consenting stopping before harvest. First-morning void samples were requested and farmers were asked to provide details of their pesticide usage throughout the time the urine sample collection was recorded by the participant. the spray season. The spray information included information on the start Urine samples (~70 ml) were collected in polypropylene containers and finish times of spraying, product and active ingredients used, spray (Starplex Scientific, Canada) along with the completed sample-related method and weather conditions. In instances where farmers demonstrated questionnaire were collected at agreed times by the community researcher that they already maintained comprehensive records of their pesticide on the day of sample provision. The urine samples were stored in a cool usage, the researcher requested copies of these to be made available. bag before collection by the community researcher. The samples were Where detailed records were not already maintained, participating farmers frozen as soon as possible (o6 h after collection) and couriered to the were asked to record the relevant information using an adaptation of the laboratory, being stored at a temperature ranging from − 15 to − 20 °C spray record form recommended by the Department of Environment, Food before analysis. The community researchers checked the completeness of and Rural Affairs. the sample-related questionnaires. Farmers’ spray records were reviewed Table 1 provides details of the pesticides considered in the study and alongside the dates that participants’ urine samples were provided. reported in this manuscript. Inclusion was restricted to those approved pesticides where analytical methods for the associated urinary biomarkers Urine Sample Analysis were available to the project team. No validated method was available for determining penconazole or its metabolites in urine, and so a novel Urine samples were selected for analysis as follows, with a relevant spray method was developed during this project, details of which, as well as the event referring to those involving the application of pesticides including penaconazole results from this study are reported elsewhere. the active ingredients captan, chlormequat, chlorpyrifos and cypermethrin: Journal of Exposure Science and Environmental Epidemiology (2015), 623 – 631 © 2015 Nature America, Inc. Pesticide exposure in residents near farm land Galea et al captan was based on that reported by Berthet et al. measuring cis- Table 2. Description of the participants (background questionnaire 1,2,3,6-tetrahydrophthalimide (THPI). The analytical method for chlorpyr- responses). 16 ifos was based on that reported by Sams et al. measuring 3,5,6- trichlorpyridinol (TCP). The analytical method for cypermethrin measured Descriptor N % cis- and trans- 2,2-dichlorovinyl-3,3-dimethylcyclopropane-1-carboxylic acid (DCVA). Adult 118 84 Further analytical methodology details are provided as Supplementary Child 22 16 Information. Sex Male 54 39 Female 86 61 Data Analysis Urine samples with a creatinine concentration below 2 or 430 mmol/l Location 18,19 (0.23 g/l and 3.39 g/l, respectively) were excluded from the analyses. East Lothian 29 21 Next, participants for which either no spray event-related samples or no Kent 45 32 background (either within or outwith) samples were available were Norfolk 66 47 excluded. The descriptive characteristics of the participants were summarised, Employment (adults) along with summaries of their responses to the background questionnaire, Full time employment 29 25 in terms of percentage in each category or mean and range for continuous Part time employment 37 32 variables (Table 2). Full time education 1 1 Urinary measurements were corrected for creatinine by dividing the Part time education 39 34 urinary biomarker concentration by the creatinine concentration and are Retired 8 7 reported as μg biomarker per g creatinine. A very high proportion of Non-paid employment 1 1 samples were below the analytical limit of detection (LOD) for captan Missing or no answer 29 25 (89%) (LOD = 0.1 μg/l) and cypermethrin (93%) (LOD = 1.0 μg/l) and for these two pesticides only the proportion of detects, 95th percentile and Education (children) the maximum levels are reported. Secondary 2 9 For chlormequat and chlorpyrifos a random imputation procedure was Primary 18 82 used to replace the values below the LOD (0.6 μg/l and 0.8 μg/l, Full time nursery 0 0 respectively). The geometric mean (GM) and geometric standard deviation Part time nursery 2 9 (GSD) of concentrations above the LOD were determined, assuming a log- normal distribution. Each of the values below LOD was then replaced by a Smoke 5 4 value between 0 and the LOD which was randomly generated from this Own a pet 85 61 distribution. As is typical of data of this nature, concentrations were not Job involves travelling around the local area 22 16 normally distributed. Transforming by taking the natural logarithm Use pesticides at work 6 4 improves the normality of the data significantly and therefore the sample Family use pesticides at work 7 5 Use pesticides in the home at least once a year 112 80 results are summarised in terms of GM and GSD. For each individual the GM of their samples was determined separately Mean Range for samples provided after a spray event and for within and outwith spray Age (adult) 55 (18–83) season backgrounds. The GM ratio of the spray event sample to the Age (child) 8 (4–12) backgrounds was then calculated by taking the log of each individual ratio, averaging and exponentiating. Results are reported as GM and associated 95% confidence interval. A confidence interval containing the value 1 means that the ratio is not significantly different from 1, that is, spray event 1. Urine samples collected within 2 days of relevant pesticide spray events samples are not significantly higher or lower than backgrounds. taking place in fields within 100 m of the participant’s residence (spray The data were further examined to investigate factors from either the event-related samples). background questionnaire (person-specific) or the sample-related ques- 2. For each participant providing at least one relevant pesticide spray tionnaires (sample-specific) that might explain any differences between event sample, up to three randomly selected background samples the biomarker concentrations. General linear mixed models were used obtained within the spraying season which did not coincide with a with the log of the biomarker level as the response. The participant was relevant spray event (within spray season background samples). treated as a random variable, to account for repeated measures from the 3. For each participant providing at least one relevant spray event sample, same individuals. Sample type was treated as a fixed effect of a priori up to three randomly selected background samples collected outwith interest, where the levels of sample type were defined as; outwith and the spraying season (during November–December) (outwith spray within spray season backgrounds, samples provided the day after spraying season background samples). (24 h), samples provided the second day after a spray event (48 h) or sample was provided after 2 consecutive days of spraying (24 and 48 h). In Urine samples collected within 2 days of a relevant spraying event were a step-wise manner variables were considered for inclusion in the model analysed only for the relevant pesticide(s) sprayed during the event. where they significantly improved the fit of the model, based on the Background samples, both within and outwith the spray season, were likelihood ratio test or affected the coefficients of terms already in the analysed for all the relevant pesticides of interest to the study. model (by 410%). Samples were analysed according to established methods by the Health Imputation was carried out using R v3.1.0, while all statistical analyses and Safety Laboratory (HSL), which participates in external quality were carried out using Genstat v16 (ref. 22) and plots were prepared using assurance schemes for chlorpyrifos and cypermethrin (G-EQUAS, www.g- Sigmaplot v10). equas.de). The analysts were blind to whether the urine samples were related to spray events or were background samples. Detection limits were comparable to previous reported studies looking at general population RESULTS levels. All analytes were quantified using multi-point matrix-matched calibration curves and quality control samples were run every five samples. A total of 13 participating farms during 2011 and 17 farms during Samples were analysed in duplicate and the mean value reported. Aliquots 2012 reported sprayed events using at least one of the relevant of positive samples were reanalysed throughout the project to evaluate pesticides. The breakdown by region is provided in Table 3, along sample stability. There was no evidence of sample degradation for any with details of the number of relevant spray events after which biomarker studied throughout the assessment period (see Supplementary urine samples were collected. All participating Kent farms were Information). orchards while the farms in East Lothian and Norfolk were The analytical method for chlormequat was based on that reported by Lindh et al. measuring chlormequat itself. The analytical method for arable farms. © 2015 Nature America, Inc. Journal of Exposure Science and Environmental Epidemiology (2015), 623 – 631 Pesticide exposure in residents near farm land Galea et al Table 3. Participating farms and relevant spray events by pesticide and geographical area. Area No. farms Pesticide No. spray events East Lothian 7 Chlormequat 57 Cypermethrin 2 Kent 9 Captan 214 Chlorpyrifos 51 Norfolk 4 Chlormequat 15 Cypermethrin 3 Spray event numbers derived by multiplying the number of farms applying the pesticide by the number of relevant fields on which the pesticide was applied. For example if farm A sprayed captan in six fields on four occasions, the number of spray events for this farm would be 24. Table 4. Urinary biomarker concentrations (μg/g creatinine). Pesticide N NoLOD %oLOD Max GM GSD 95th % ile Figure 1. Participant numbers by area, sex. Captan aa Outwith 440 387 88 3.5 0.4 aa Within 553 489 88 3.9 0.5 Table 4 summarises the urine sample results for spray events aa Spray 255 232 91 1.2 0.2 and backgrounds (within and outwith spray season). For captan and cypermethrin, the proportion of spray event values below the Cypermethrin LOD was 91 and 98%, respectively, whereas the proportion of aa b Outwith 344 329 96 15.4 aa background results below the LOD was 88% for captan and in Within 349 312 89 10.8 5.1 aa b excess of 90% for cypermethrin. The captan biomarker concentra- Spray 46 45 98 7.0 tions ranged from below the LOD to almost 4 μg/g creatinine. Chlormequat There is a slightly higher proportion of non-detects in the spray Outwith 440 17 4 281.6 12.3 3.1 65.6 event-related samples with the largest individual result being Within 555 4 1 388.2 16.5 2.7 89.7 associated with a background sample collected within the spray Spray 197 3 2 248.1 15.4 2.7 72.4 season. The cypermethrin biomarker concentrations follow a similar pattern, with the maximum concentration (15.4 μg/g Chlorpyrifos creatinine) found to be in a background sample obtained outwith Outwith 440 54 12 22.7 3.0 2.2 9.6 the spray season. Within 554 69 12 76.4 3.0 2.4 10.8 Figure 2 shows boxplots of the creatinine adjusted urinary Spray 63 7 11 14.8 2.5 2.1 7.9 biomarker concentrations (μg/g) for chlorpyrifos and chlormequat Abbreviations: GM, geometric mean; GSD, geometric standard deviation; for the spray event-related samples as well as the within and LOD, limit of detection; Max, maximum; N, number; 95% ile, 95th outwith spray season background samples. Both figures show that percentile. GM and GSD were not calculated due to the high proportion b spray event-related samples did not appear to contain elevated of values below LOD. 95th percentile not calculated as over 95% of the concentrations of urinary biomarkers compared with the back- samples were below LOD. ground levels. Spray event sample concentrations for chlormequat are statistically significantly higher than outwith spray season back- A total of 296 participants were recruited to the study (238 ground, with the GM of the individual ratios being 1.22 (95% CI: adults, 58 children), providing 3275 urine samples. One hundred 1.09, 1.38) but there is no significant difference between spray forty-one people provided at least one sample that was related to event-related sample concentrations and within spray season backgrounds (GM ratio 0.96 (95% CI: 0.87, 1.06)) (Table 5). a relevant spray event involving captan, chlormequat, chlorprifos Interestingly, the average spray event-related chlorpyrifos urinary or cypermethrin and had at least one background, resulting in biomarker concentrations are lower than both the outwith and 1565 samples results. Altogether, 73% of participants had the full within spray season background sample results (GM ratio: 0.80, complement of outwith spray season backgrounds and 76% had 95% CI: 0.74, 0.87 and 1.01; 95% CI: 0.92, 1.11, respectively). the full complement of within spray season backgrounds. There were minor differences in chlormequat biomarker Application of the creatinine exclusion criterion resulted in 40 concentrations measured for males and females, with males samples being excluded from the analysis (12 sprays and 28 having slightly higher urinary biomarker levels than females backgrounds). Following the application of this exclusion criterion, (Table 6). This difference was not significant for outwith season one further person was removed due to no spray event-related backgrounds and spray event-related samples but was significant samples remaining and as such were no longer eligible to be for within spray season backgrounds (P = 0.036). There were no included in the data analysis (six backgrounds). statistically significant differences in the chlorpyrifos concentra- The final data set for statistical analysis contained 1518 sample tions measured in samples provided by males and females results for 140 people, consisting of 995 background samples (Table 6). The levels of chlormequat and chlorpyrifos were higher (440 outwith and 555 within season) (Figure 1) and 523 spray in samples provided by children than adults, although not event-related samples. The spray samples included 255 captan, 63 significantly so; the variation in the children’s sample results also chlorpyrifos, 46 cypermethrin and 197 chlormequat spray event tended to be greater. To ensure these patterns were not the result results, respectively (some spray events involved multiple relevant of variation in creatinine levels, which tend to be higher in males pesticides). than females and in adults than children, the uncorrected Journal of Exposure Science and Environmental Epidemiology (2015), 623 – 631 © 2015 Nature America, Inc. Pesticide exposure in residents near farm land Galea et al Table 6. Urinary biomarker concentrations (μg/g creatinine) for males and females and for adults and children for chlormequat and chlorpyrifos. Pesticide Female Male NNoLOD GM GSD N NoLOD GM GSD Chlormequat Outwith 262 11 11.8 3.2 178 6 13.0 2.9 Within 335 4 15.4 2.8 220 0 18.3 2.7 Spray 120 1 14.4 2.6 77 2 17.1 2.7 Chlorpyrifos Outwith 262 32 3.3 2.1 178 22 2.7 2.3 Within 334 42 3.0 2.4 220 27 2.8 2.4 Spray 41 7 2.5 2.2 22 0 2.5 1.9 Child Adult NNoLOD GM GSD N NoLOD GM GSD Chlormequat Outwith 59 3 11.4 4.2 381 14 12.4 3.0 Within 79 3 19.3 3.4 476 1 16.1 2.7 Spray 40 0 17.7 2.8 157 3 14.9 2.6 Chlorpyrifos Outwith 59 4 3.7 2.2 381 50 2.9 2.2 Within 79 4 3.8 2.5 475 65 2.8 2.4 Spray 8 1 2.2 2.3 55 6 2.6 2.0 Abbreviations: GM, geometric mean; GSD, geometric standard deviation; LOD, limit of detection; N, number. the sample was collected. For chlormequat, after including sample Figure 2. Creatinine adjusted urinary biomarker levels for spray type (i.e., spray event or background) in the model, the only event and within and outwith spray season background samples for (a) chlorpyrifos and (b) chlormequat. significant factor, based on Wald test for addition to the model, was the level of organic food consumption reported, where higher levels of organic food consumption were associated with higher levels of chlormequat (where organic food consumption was recorded by participants as; none, little, some and most). However Table 5. GM ratio of creatinine corrected concentrations following this factor did not significantly improve the fit of the model. As spray events to the GM of backgrounds. shown before, the statistically significant differences in the urinary Outwith spray season Within spray season biomarker levels between sample type is driven by the fact that outwith season background levels are lower than spray event- Pesticide GM ratio 95% CI GM ratio 95% CI related sample levels and within season backgrounds. The results of the modelling are very similar for chlorpyrifos. Although some Chlormequat 1.22 1.09 1.38 0.96 0.87 1.06 of the factors were significant (including age, sex and time spent Chlorpyrifos 0.80 0.74 0.87 1.01 0.92 1.11 outdoors), according to the Wald test, they did not significantly Abbreviations: CI, confidence Interval; GM, geometric mean. improve the fit of the model and therefore were not included in the final model. The significance of the sample type variable in the model for chlorpyrifos is likely being driven by the levels in the creatinine urinary biomarker concentrations were analysed and spray event-related samples being lower than background levels, similar patterns were observed. both outwith and within. There were no statistically significant differences in chlorme- quat or chlorpyrifos concentration for the samples collected at 1 and 2 days after the spray events (Table 7). In addition, we DISCUSSION investigated if there is any relationship between biomarker We report on a study that aimed to assess exposure to pesticides concentrations and timing of spray event and no significant for UK adults and children living within 100 m from the edge of relationship was found. agricultural land, and identify whether or not exposures We investigated whether other factors such as age, sex, were elevated following spray events. A distance of 100 m was location, smoking status, typical consumption of organic food selected as a balance between proximity to agricultural land and and typical use of pesticides (as answered in background available potential study participants. In addition, researchers questionnaire), whether the subject had used pesticides in the modelling vapour dispersion reported that vapour concentration previous 48 h, time spent indoors and outdoors in the previous is significantly reduced after a distance of 100 m (dependent on 48 h (based on the sample-related questionnaires) might explain any differences in the biomarker concentrations between when field size). © 2015 Nature America, Inc. Journal of Exposure Science and Environmental Epidemiology (2015), 623 – 631 Pesticide exposure in residents near farm land Galea et al Table 7. Description of spray sample results by whether the sample was the day after a spray event (24 h) or 2 days after (48 h). 24 h Spray samples 48 h Spray samples NNoLOD GM GSD 95th % N NoLOD GM GSD 95th % Chlormequat 100 1 15.9 2.7 72.8 97 2 15.0 2.6 63.2 Chlorpyrifos 27 4 2.4 2.2 8.1 33 2 2.7 2.0 8.0 Abbreviations: GM, geometric mean; GSD, geometric standard deviation; LOD, limit of detection; N, number; 95%, 95th percentile. Level of Urinary Biomarker Levels the adult residents, as indicated by urinary 3,5,6-TCP biomonitor- ing, did not increase as a result of the application. Another study The urinary biomarker levels for captan and cypermethrin were reported urinary TCP concentrations of 0.1–7.8 μg/g creatinine in very low in this population with ~ 90% of samples having 41 residents from houses where chlorpyrifos had been detected in undetectable concentrations. For chlormequat and chlorpyrifos, 34 35 collected indoor air samples. Alexander et al. reported a study the GM urinary biomarker concentrations following spray events of farm family members (spouses, and children aged 4–17 years) were 15.4 μg/g creatinine and 2.5 μg/g creatinine, respectively, from Minnesota and South Carolina. Five consecutive 24-h urine compared with 16.5 μg/g creatinine and 3.0 μg/g creatinine for samples were obtained from 34 families of licensed pesticide within season background. applicators from one day before to three days after a chlorpyrifos For chlormequat, we have only been able to identify one other, application. The spouses’ GM exposure was reported as being relevant, study. Lindh et al. reported a general population study 3.6 μg/g creatinine pre-application, 3.8 μg/g creatinine on the day in southern Sweden where the chlormequat concentrations of application and then 4.2 μg/g μg/g creatinine on days 1 and 2 ranged from 0.4–30.2 μg/g creatinine (median 2.9, 95th percentile post application. The reported children’s exposure was 5.1 μg/g o17.3 μg/g creatinine, N = 100). These values are somewhat lower μg/g creatinine pre-application, 6.0 μg/g creatinine on day of than our reported concentrations for all the chlormequat spray application and 5.0 and 5.9 μg/g creatinine for days 1 and 2 post event and background samples combined (median 15.1, 95th application. These are all higher than the GMs that we observed. percentile 79.8 μg/g creatinine). Despite these higher concentra- A number of general population studies have been reported for tions, UK exposures are two orders of magnitude below the values cypermethrin exposure. The US CDC NHANES study reports 95th obtained from an oral dose at half the ADI (Lindh et al.). The only percentiles for adults as 0.9 μg/g creatinine (N = 1128) and 2.5 μg/g other report of measuring chlormequat in human urine was in an creatinine (N = 1123) for cis-DCVA and trans-DCVA respectively in accidental poisoning case, but levels were not quantified. 2001/02. Detection rates were reported as less than 50% for cis- Excluding the different time periods of sample collection in our DCVA and o25% for trans-DCVA. A study of 1149 pregnant and Lindh et al.’s study, it is possible that we observed higher women in China found median levels of 0.7 μg/g creatinine for cis- chlormequat urinary concentrations due to different farming DCVA and 1.9 μg/g creatinine for trans-DCVA. In the UK the 95th practices for cereal crops and consumption of foods and percentiles for adults (on the voting register) in the general beverages derived from cereal crops for which this growth population were reported as 0.7 μg/g creatinine (N = 405) and regulator was applied. For example, the mean daily per capita 1.8 μg/g creatinine (N = 404) for cis-DCVA and trans-DCVA, consumption for bread and rolls, bakery products, cereal and respectively and 2.3 μg/g creatinine combined as total-DCVA. products in the UK was reported as 103, 44 and 36 g, respectively, 26 In comparison, the 95th percentile was 5.8 μg/g creatinine for the compared with 96, 21 and 25 g for Sweden. spray event samples and 5.2 μg/g creatinine for our within spray Approximately 90% of the captan urinary biomarker concentra- season samples (which includes both adults and children). tions in this study were below the LOD, with the maximum value Although the 95th percentile results for our data are greater than of 3.9 μg/g creatinine detected in a background sample. There are reported by Bevan et al., the number of samples above the LOD very few data available on environmental exposures to captan. 27 was far lower despite the same detection limit. These differences Berthet et al. reported mean “pre-season” urine biomarker may reflect regional differences in exposure (our study was concentrations of 0.2 μg/l (~0.15 μg/g creatinine) but this was 28 conducted in three regions compared with across the whole of based on only four samples. Verberk et al. reported results below the UK for Bevan et al. ) or temporal differences in pesticide use the LOD (8, ~ 5.9 μg/g creatinine) for six unexposed controls. and food residues of pyrethroids (our samples were collected in Recent occupational studies have determined post-exposure THPI 27 2011 and 2012 whereas those of Bevan et al. were collected in levels of o5 μg/l (~3.1 creatinine). No other published general 2005/06). population studies could be found. There is an extensive literature on the use of urinary trichloro-2- Do Spray Events Result in Elevated Exposures to Residents Living pyridinol (TCP) as a biomarker of chlorpyrifos exposure. The US Near Agricultural Land? CDC NHANES study reports 95th percentiles for adults as 6.4 μg/g creatinine, N = 832 and 7.4 μg/g creatinine, N = 1,113 for 1999- The results presented in this paper provide no evidence that, in /2000 and 2001/2002, respectively. A study of 100 pregnant this study population, the spray events resulted in elevated women in the Netherlands found a 95th percentile of 6.4 μg/l exposures compared with background samples taken within the (~4.7 μg/g creatinine) with a maximum of 158 μg/l (~116 μg/g season. For chlormequat, the biomarker levels (both spray event 30 31 32 creatinine). Studies in Germany and Italy showed similar and background) were higher within the spray season compared values. For Germany, the 95th percentile was 11.3 μg/l (~8.3 μg/g with outwith the season. Chlormequat is a plant growth regulator, creatinine, N = 50) and for Italy, the estimated 95th percentile was which acts by inhibiting cell elongation hence shortening and 6.5 μg/g creatinine (N = 42). Our data for all the spray and strengthening the stem producing a sturdier plant. It also background samples combined (95th percentile 10.1 μg/g creati- influences the developmental cycle, leading to increased flower- nine) are comparable with these data from other general ing and harvest. Growth regulating products containing population studies, despite the varied geographical sources of chlormequat are widely used by the UK. The Pesticide Usage the data sets. A study of residents’ exposure to chlorpyrifos after Survey Teams of the Food & Environment Research Agency (FERA) treatment inside the home showed that potential exposures to conducted surveys of pesticide usage in arable crops in 2011/12 Journal of Exposure Science and Environmental Epidemiology (2015), 623 – 631 © 2015 Nature America, Inc. Pesticide exposure in residents near farm land Galea et al by visiting holdings throughout the UK. In this survey they start and finish times were obtained and residents were asked to reported that chlormequat, applied alone or in mixtures, provide details of their activities in the 48 h period before accounted for 59% of the area of arable crops treated with provision of each urine sample. However, it was not possible to specific growth regulators: in addition there was a 13% increase in establish from this when, where or how the residents’ potential area treated using chlormequat since the previous survey exposure to the assessed pesticides may have occurred. Following conducted in 2010. due consideration of preliminary modelling and the peer- Although not the primary aim of the study and reporting on reviewed literature, first-morning void samples were requested different pesticides, Jones et al. reported a statistically significant from participants. There is the possibility that the urine void with difference for dialkylphosphate levels (organophosphate) in the highest biomarker concentration was missed however no young children (o5 years) during different seasons, with autumn significant relationship between biomarker concentrations and resulting in the highest levels. No seasonal effect was however timing of spray event was found for any of the pesticides. Weather observed for pirimicarb or carbaryl. Our chlormequat findings information, whilst obtained by both the farmer and the research could be due to other sources of exposure. The most recent team, was typically reported from weather stations located in publication presenting results of pesticide residues in food some instances several miles away from where the spray took commodities (including both raw and processed) sampled during place. It is possible that the available wind speed and direction the calendar year 2010 in the 27 European Union Member States information may not reflect what actually occurred during the and two European Free Trade Association countries (Iceland and given spray event and so was not considered further. Good spray Norway) reported chlormequat/oats to be the pesticide/crop event information was obtained from the farmers participating in combination for which residue concentrations were most the study. However it is not possible to establish whether frequently above the reporting level (64.6% of the samples). In residents were potentially exposed to any additional relevant addition, the highest percentage of maximum residue limit (MRL) spray applied by non-participating farmers in the locality. Given exceedances in foods was found for chlormequat in oats (8.1% of the scope of the study, the number of dietary-related questions all samples). In rye, the most frequently found pesticide residue was kept to a minimum, restricted to the consumption of food was also chlormequat (35.9%). Of the 178 pesticides included in from the residents’ garden and organic food (as reported in the the 2010 EU-coordinated programme, the most frequent MRL background questionnaire). In retrospect, the inclusion of addi- exceedances were detected for chlormequat (3.6% of the tional food-related questions may have been useful in explaining samples). Chlormequat was also detected in a small number of some of the results observed. Residents (adults aged 18 years and organic food samples analysed (13 out of the 3571 samples), with over and children in their care aged 4–12 years) were recruited, measured residue levels ranging from 0.127–0.0011 mg/kg. with infants (o4 years old) and adolescents (13–17 years) being Whilst in most instances these data relate to unprocessed food excluded from the study. This pragmatic decision was taken due commodities and residue levels may decrease during food to likely difficulties being encountered with obtaining relevant production, it is considered that diet is the primary source of urine samples from babies and toddlers and adolescents exposure. For chlorpyrifos, the biomarker levels were very similar potentially being less engaged with the study and so the for the various sample types. Finally, for captan and cypermethrin exposures of these sub groups was not determined. a very large proportion of the measurements were below the LOD, All laboratory methods for the urine samples showed good day- whether or not these samples were collected following spray to-day repeatability and were based, where possible, on validated events. methods (see Supplementary Information) with comparable LODs The relatively short biological half-life of pesticide compounds to those already reported and used in environmental exposure and their biomarkers in the human body presents a major studies. Where known, the primary or most abundant biomarker challenge to linking biological monitoring data to specific spray was measured; measuring multiple biomarkers for the same events and so urine samples have to be collected ideally within pesticide would not have increased the sensitivity of measure- 24 h, and no later than 48 h following the spray events (depending ment unless all metabolites are converted to a single biomarker. All chlorpyrifos and chlormequat samples were analysed within on the urinary biomarker half-life). Farming activities, and in particular spaying with pesticides, are inherently unpredictable the timeframe of the stability trials. The length of each analyte because of the changing weather and the presence of insects or stability trial was determined by available samples within the data other potentially damaging infestations which influence pesticide set. Some samples for captan and cypermethrin were analysed selection and application. Along with the planned weekly urine outside of the evaluated stability time frame. These samples have sample collections, there was a need for effective engagement not necessarily degraded but extended sample stability was not with farmers to elicit this spray information at short notice and evaluated due to insufficient sample volume. It is considered that with residents to obtain the required spray event samples the biomarkers and methodology used were demonstrably fit for reactively. Through the use of community researchers, located in purpose. and knowledgeable of the geographical areas and familiar with When considering the generalisablity of the study results to local farming practices, effective engagement was achieved and other pesticides, consideration should be given to the spray over 3000 urine samples were collected. techniques used and their potential to distribute the pesticide The methodology applied in this study is robust but is not beyond the target area and the propensity for the pesticide to without some limitations. The participating farmers may not be redistribute post application. The spray equipment and techni- representative of all farmers within the study areas although there ques used by the participating farmers were not atypical and were is no reason to suggest that their spraying practices are any reportedly used when applying other pesticide products to the different to those of the wider farming communities. In the UK, given crops throughout the spray season. The range of vapour Government Ministers must approve all pesticides before they can pressures for the relevant products considered in this study be marketed or used and everyone who uses pesticides must have ranged from 0.0023 to 1.43 mPa at 25 °C, of which the highest was adequate guidance, instruction or training for their correct use for chlorpyrifos. Monitoring in the USA suggests that chlorpyrifos and must ensure that all reasonable precautions are taken to is the worst known case for vapour concentrations and so we prevent spray drift. It was clear from the farmers’ spray records consider that our study covers both the likely spectrum and worst that a number of pesticide products were applied throughout the case vapour pressures used in modern day pesticides in the UK spraying season (dependent on crops, infestation, weather (and perhaps more widely). Orchard spray techniques are usually conditions and other factors) and so the number of relevant considered as potentially giving rise to higher levels of pesticide spray events observed may differ from year to year. Spray event drift (and therefore potential exposure) in comparison to field crop © 2015 Nature America, Inc. Journal of Exposure Science and Environmental Epidemiology (2015), 623 – 631 Pesticide exposure in residents near farm land Galea et al spraying practices. For example, measurements of bystander REFERENCES exposure during UK field crop spraying and orchard spraying 1 RCEP. Crop Spraying and The Health of Residents and Bystanders. Royal Commission 43,44 on Environmental Pollution: London, UK, 2005. applications have been reported. For boom sprayers the 2 ACP. Crop Spraying and the Health of Residents and Bystanders. A Commentary average potential dermal exposure (PDE) for a bystander, on the Report Published by the Royal Commission on Environmental Pollution in positioned 8 m downwind from the sprayer and the average September 2005. Advisory Committee on Pesticides: York, UK, 2005. amount of spray potentially inhaled in the breathing zone were 3 Committees on toxicity and carcinogenicity of chemicals in food, 0.1 ml spray/person and 0.006 ml spray/person, respectively. For consumer products and the environment. Statement on Royal Commission on orchard sprayer applications the equivalent PDE and inhalation Environmental Pollution: Crop spraying and the health of residents and bystan- ders. Available at: http://cot.food.gov.uk/sites/default/files/cot/cotsection06.pdf values were 3.7 ml spray/person and 0.002 ml spray/person. Given (accessed on 1 September 2015). that we collected in excess of 300 orchard spray event samples, 4 DEFRA. The Royal Commission on Environmental Pollution report on Crop Spraying which also included those related to chlorpyrifos, we consider that and the Health of Residents and Bystanders–Government Response. Department for our study adequately considers potentially higher risk spray Environment, Food and Rural Affairs: UK, 2006a. techniques, of which the majority of the urinary biomarker results 5 Koureas M, Tsakalof A, Tzatzarakis M, Vakonaki E, Tsatsakis A, Hadjichristodoulou C were observed to be less than the analytical LOD. et al. Biomonitoring of organophosphate exposure of pesticide sprayers and comparison of exposure levels with other population groups in Thessaly (Greece). Occup Environ Med 2013; 71:126–133. CONCLUSION 6 Couture C, Fortin MC, Carrier G, Dumas P, Tremblay C, Bouchard M. Assessment of exposure to pyrethroids and pyrethrins in a rural population of the Montérégie This study reports urinary biomarker concentrations for a number area, Quebec, Canada. J Occup Envrion Hyg 2009; 6: 341–352. of active ingredients both for spray event and background 7 Kimata A, Kondo T, Ueyama J, Yamamoto K, Yoshitake J, Takagi K et al. samples amongst people living within 100 m of agricultural land, Comparison of urinary concentrations of 3-phenoxybenzoic acid among general which has not previously been undertaken and reported on such a residents in rural and suburban areas and employees of pest control firms. Int scale for a UK population. It has also, as far as we are aware, not Arch Occup Environ Health 2009; 82: 1173–1178. 8 Keifer M, Rivas F, Dong Moon J, Checkoway H. Symptoms and cholinesterase been studied as systematically anywhere else. Our study did not activity among rural residents living near cotton fields in Nicaragua. Occup Environ set out to determine whether rural residents have greater Med 1996; 53:726–729. exposure to pesticides than non-rural residents and so is not 9 Ward MH, Lubin J, Giglierano J, Colt JS, Wolter C, Bekiroglu N. Proximity to crops directly comparable to other studies that may have sought to and residential exposure to agricultural herbicides in Iowa. Environ Health Perspect do this. 2006; 114:893–897. The primary conclusion of the study is that there is no evidence 10 Galea KS, MacCalman L, Jones K, Cocker J, Teedon P, Sleeuwenhoek AJ et al. Biological monitoring of pesticide exposures in residents living near of increased pesticide biomarker excretion in rural residents agricultural land. BMC Public Health 2011; 11:856. following a spray event within 100 m of their home, when 11 Teedon P, Galea KS, MacCalman L, Jones K, Cocker J, Cherrie JW et al. Engaging compared with the urinary biomarker levels obtained when communities for exposure science–lessons learned from a pesticide biomonitor- relevant spray events did not take place. The levels of urinary ing study. PLOS One 2015 (doi:10.1371/journal.pone.0136347). biomarkers detected in our population were generally comparable 12 DEFRA. Pesticides Code of Practice for Using Plant Protection Products. DEFRA: to other studies of exposure in the general population, where such London, UK, 2006. 13 Kissel JC, Curl CL, Kedan G, Lu C, Griffith W, Barr DB et al. Comparison of orga- data are available, and this supports the view that general nophosphorus pesticide metabolite levels in single and multiple daily urine population exposures to pesticides are primarily from non-spray samples collected from preschool children in Washington State. J Expo Anal event sources such as diet. It appears that the population Epidemiol 2005; 15: 164–171. recruited to this study exhibits greater exposure to chlormequat 14 Lindh CH, Littorin M, Johannesson G, Jonsson BAG. Analysis of chlormequat in than detected in a Swedish population sub-set. Whether this is a human urine as a biomarker of exposure using liquid chromatography triple characteristic of our particular rural residents or is more widely quadrupole mass spectrometry. J Chromatogr B Anal Technol Biomed Life Sci 2011; 879:1551–1556. applicable to the entire UK general population is not known and 15 Berthet A, Bouchard M, Schüpfer P, Vernez D, Danuser B, Huynh CK. Liquid may be an area of further work. Exposure levels for cypermethrin chromatography-tandem mass spectrometry (LC/APCI-MS/MS) methods for the and captan were very low. quantification of captan and folpet phthalimide metabolites in human plasma and urine. Anal Bioanal Chem 2011; 399: 2243–2255. 16 Sams C, Jones K. Human volunteer studies investigating the potential for CONFLICT OF INTEREST toxicokinetic interactions between the pesticides deltamethrin; pirimicarb and Dr. Galea is a member of the UK Government Pesticide Incidents Appraisal Panel and chlorpyrifos-methyl following oral exposure at the acceptable daily intake. Toxicol Dr. Cocker was a member of the UK Government Advisory Committee on Pesticides Lett 2011; 200:41–45. (January 2009-December 2014). The authors declare no conflict of interest. 17 Jones K, Sams C, Patel K, Johnson P. Development of cost-effective biomarkers for herbicides and fungicides. Available at: http://www.foodbase.org.uk/results.php? f_report_id = 407 (accessed on 11 June 2014). ACKNOWLEDGEMENTS 18 Cocker J, Mason HJ, Warren ND, Cotton RJ. Creatinine adjustment of biological monitoring results. Occup Med Oxf 2011; 61:349–353. This project was funded by the UK Government Department for Environment Food 19 EWDTS. European Laboratory Guidelines for Legally Defensible Workplace Drug and Rural Affairs (DEFRA), project code PS2620. We thank the following individuals Testing. 2002. Available at: www.ewdts.org (accessed on 1 September 2015) (in alphabetical order) for their work as community researchers in this project: 20 Helsel DR. Nondetects and Data Analysis: Statistics for Censored Environmental S Attwood, J Cadzow, A Carr, D Dahrendorf, T Hogg, L Jewsbury and F MacIver. Their Data. John Wiley and Sons: New York, USA, 2005. hard work was crucial to the success of the recruitment and data collection in this 21 R Core Team. R: A Language and Environment for Statistical Computing. R Foun- project. Thanks also to the independent project Advisory Committee (Prof. David dation for Statistical Computing: Vienna, Austria, 2014. Coggon, Paul Hamey, Prof. Len Levy and Dr. Sean Semple) for their helpful comments 22 Payne RW, Harding SA, Murray DA, Soutar DM, Baird DB, Glaser AI et al. The Guide to throughout the project and on earlier manuscript drafts; Dr. Anne Sleeuwenhoek and GenStat Release 14, Part 2: Statistics. VSN International: Hemel Hempstead, UK, 2011. David Todd (IOM) for their assistance with the storage of the urine samples and 23 Systat Software SigmaPlot version 10. Systat Software, Inc., San Jose California related administration tasks; IOM personnel (Anne Sleeuwenhoek, Shahzad Rashid, USA. www.sigmaplot.com. Peter Ritchie, Yvonne O’Neill, Marlyn Davis, Julie O’Neill, Selima Argoub and Araceli 24 The Arable Group. PS2005. The Development and Validation of a Bystander and Sanchez Jimenez) for assistance with data storage, data input and other Resident Exposure Assessment Model (BREAM) Research Project Final Report. DEFRA: administrative tasks; and HSL personnel (Drs Craig Sams, Laura Kenny, Shahwaiz York, UK, 2010. Iqbal and Fiona Garner) for the urine sample analysis. We express our sincere 25 Winek CL, Wahba WW, Edelstein JM. Sudden-death following accidental ingestion gratitude to all the farmers and householders who participated in the study. of chlormequat. J Anal Toxicol 1990; 14: 257–258. Journal of Exposure Science and Environmental Epidemiology (2015), 623 – 631 © 2015 Nature America, Inc. Pesticide exposure in residents near farm land Galea et al 26 DAFNE. The Pan-European food bank based on household budget 36 Qi X, Zheng M, Wu C, Wang G, Feng C, Zhou Z. Urinary pyrethroid metabolites surveysNational and Kapodistrian University of Athens: Athens, 2006, http://www. among pregnant women in an agricultural area of the Province of Jiangsu, China. nut.uoa.gr/dafnesoftweb/. Int J Hyg Environ Health 2012; 215: 487–495. 27 Berthet A, Heredia-Ortiz R, Vernez D, Danuser B, Bouchard M. A detailed urinary 37 Bevan R, Jones K, Cocker J, Assem FL, Levy LS. Reference ranges for key bio- markers of chemical exposure within the UK population. Int J Hyg Environ Health excretion time course study of captan and folpet biomarkers in workers for the 2013; 216: 170–174. estimation of dose, main route-of-entry and most appropriate sampling and 38 Tomlin C (ed). The Pesticide Manual: A World Compendium. 15th edn. British Crop analysis strategies. Ann Occup Hyg 2012; 56:815–828. Protection Council, 2009. 28 Verberk MM, Brouwer DH, Brouwer EJ, Bruyzeel DP, Emmen HH, Van Hemmen JJ 39 Garthwaite DG, Hudson S, Barker I, Parrish G, Smith L, Pietravalle S. Pesticide et al. Health effects of pesticides in the flower-bulb culture in Holland. Med Lav Usage Survey Reports 250. Arable Crops in the United Kingdom 2012 (Including 1990; 81: 530–541. Aerial Applications 2012) DEFRA: York, UK, 2014. 29 CDC. Third National Report on Human Exposure to Environmental Chemicals. NCEH 40 Jones K, Everard M, Harding AH. Investigation of gastrointestinal effects of Pub. No. 05-0570, Atlanta, Georgia, USA, 2005. organophosphate and carbamate pesticide residues on young children. Int J Hyg 30 Ye X, Pierik FH, Hauser R, Duty S, Angerer J, Park MM et al. Urinary metabolite Environ Health 2014; 217:392–398. concentrations of organophosphorous pesticides, bisphenol A, and phthalates 41 EFSA. Scientific report of EFSA. The 2010 European Union Report on among pregnant women in Rotterdam, the Netherlands: The Generation R study. Pesticide Residues in Food. European Food Safety Authority (EFSA). EFSA J 2013; Environ Res 2008; 108: 260–267. 11: 3130. 31 Koch HM, Hardt J, Angerer J. Biological monitoring of exposure of the general 42 California Environmental Protection Agency. Report for the Application and population to the organophosphorus pesticides chlorpyrifos and chlorpyrifos- Ambient Air Monitoring for Chlorpyrifos (and the Oxon Analogue) in Tulare County methyl by determination of their specific metabolite 3,5,6-trichloro-2-pyridinol. Int During Spring/Summer 1996. Air Resources Board, California Environmental Pro- J Hyg Environ Health 2001; 204: 175–180. tection Agency, USA, 1998. 32 Aprea C, Betta A, Catenacci G, Lotti A, Magnaghi S, Barisano A et al. Reference 43 Lloyd GA, Bell GJ. Hydraulic Nozzles: Comparative Spray Drift Study. MAFF/ADASUK, values of urinary 3,5,6-trichloro-2-pyridinol in the Italian population—validation of analytical method and preliminary results (Multicentric study). J AOAC Int 1999; 44 Lloyd GA, Bell GJ, Samuels SW, Cross JV, Berrie AM. Orchard Sprayers: Comparative 82: 305–312. Operator Exposure and Spray Drift Study. MAFF Report, UK Pesticide Registration 33 Byrne SL, Shurdut BA, Saunders DG. Potential chlorpyrifos exposure to residents and Surveillance Department, UK, 1987. following standard crack and crevice treatment. Environ Health Perspect 1998; 106: 725–731. 34 Dai H, Asakawa F, Suna S, Hirao T, Karita T, Fukunaga I et al. Investigation of indoor This work is licensed under a Creative Commons Attribution- air pollution by chlorpyrifos: determination of chlorpyrifos in indoor air and 3,5,6- NonCommercial-NoDerivs 4.0 International License. The images or trichloro-2-pyridinol in residents' urine as an exposure index. Environ Health Prev other third party material in this article are included in the article’s Creative Commons Med 2003; 8:139–145. license, unless indicated otherwise in the credit line; if the material is not included under 35 Alexander BH, Burns CJ, Bartels MJ, Acquavella JF, Mandel JS, Gustin C et al. the Creative Commons license, users will need to obtain permission from the license Chlorpyrifos exposure in farm families: results from the farm family holder to reproduce the material. To view a copy of this license, visit http:// exposure study. J Expo Sci Environ Epidemiol 2006; 16:447–456. creativecommons.org/licenses/by-nc-nd/4.0/ Supplementary Information accompanies the paper on the Journal of Exposure Science and Environmental Epidemiology website (http:// www.nature.com/jes) © 2015 Nature America, Inc. Journal of Exposure Science and Environmental Epidemiology (2015), 623 – 631

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