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Since 2014, the Agricultural Operator Exposure Model (AOEM) has been the harmonised European model used for estimating non-dietary operator exposure to pesticide. It is based on studies conducted by the pesticide companies and it features 13 different crops including non-agricultural areas such as amenity grasslands. The objective of this study was to compare the dermal exposure measured during a field study conducted in a non-agricultural area with the corresponding values estimated by the model AOEM. The non-controlled field study was conducted in France in 2011 and included 24 private and public gardeners who apply glyphosate with knapsack sprayers. Dermal exposure was measured using the whole-body method and cotton gloves. Each measured value had an estimated value given by AOEM and we tested their correlation using linear regression. The model overestimated body exposure for all observations and there was no correlation between values. However, it underestimated hand exposure by 42 times and it systematically underestimated the exposure when the operators were wearing gloves, especially during the application. The model failed at being conservative regarding hand exposure and highly overestimated the protection afforded by the gloves. At a time of glyphosate renewed approval in Europe, non-controlled field studies conducted by academics are needed to improve AOEM model, especially in the non-agricultural sector. Indeed, among the 34 studies included in the model, none were conducted on a non-agricultural area and only four assessed the exposure when using a knapsack sprayer. Moreover, knapsack sprayers being the main equipment used worldwide in both agricultural and non-agricultural settings, it is also crucial to integrate new data specific to this equipment in the model. Operator exposure should be estimated with accuracy in the registration process of pesticides to ensure proper safety as well as in epidemiological studies to improve exposure assessment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Context: There is a lack of data on pesticide exposure levels during spraying with a knapsack, while it could have important implications for their users' health., Methods: We assessed levels and determinants of exposure in 24 male private landscapers/gardeners and municipal workers in France in 2011. Actual dermal exposure to glyphosate was assessed with cotton undergarments and gloves, and a cotton coverall changed between mixing and spraying to assess the contribution of each phase and body area to overall contamination. A field monitor observed the whole workshift and filled in a standardized observation grid., Results: The median actual contamination was 5,256 µg for the body, and 4,620 µg for hands. Spraying was more exposing than mixing/loading for all body parts except hands, which contributed to nearly 90% of body exposure during mixing/loading, and 30% during spraying, followed by back (14%). In the most exposed quartile, levels were close to some observations in agriculture., Conclusion: Our study provides new data on pesticide exposure levels of knapsack sprayer users; it should lead to a reinforced prevention, in order to make exposures as low as possible and lessen the risk of chronic diseases., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.)

Objective: Although apple trees are heavily sprayed, few studies have assessed the pesticide exposure of operators and workers in apple orchards. However, these data are crucial for assessing the health impact of such exposures. The aim of this study was to measure pesticide exposure in apple growing according to tasks and body parts., Methods: A non-controlled field study was conducted in apple orchards in 4 regions of France during the 2016 and 2017 treatment seasons. Workers' external contamination and their determinants were assessed over 156 working days corresponding to 30 treatment days, 68 re-entry days and 58 harvesting days. We measured pesticide dermal contamination during each task and made detailed observations of work characteristics throughout the day. Captan and dithianon were used as markers of exposure., Results: The median dermal contamination per day was 5.50 mg of captan and 3.33 mg of dithianon for operators, 24.39 mg of captan and 1.84 mg of dithianon for re-entry workers, and 5.82 mg of captan and 0.74 mg of dithianon for harvesters. Thus, workers performing re-entry tasks, especially thinning and anti-hail net opening, presented higher contamination, either equal to or higher than in operators. For these last ones, mixing/loading and equipment cleaning were the most contaminating tasks. Most of the contamination was observed on workers' hands in all tasks, except for net-opening in which their heads accounted for the most daily contamination., Conclusions: This study highlights the importance of taking indirect exposures into account during re-entry work in apple growing., (© 2021. The Author(s).)

Knowledge of pesticide exposure levels in farmers is necessary for epidemiological studies and regulatory purposes. In the European pesticide registration process, operators' exposure is predicted using the Agricultural Operator Exposure Model (AOEM), created in 2014 by the European Food Safety Authority based on studies conducted by the pesticide industry. We compared operators' exposures during treatment days in the apple-growing industry under non-controlled working conditions and AOEM-predicted values. The dermal exposure of thirty French apple-growers from the CANEPA study when applying two fungicides was measured using body patches and cotton gloves. For each observation, the corresponding exposure was calculated by means of the AOEM, using data recorded about the operator, spraying equipment and personal protective equipment (PPE) used. A significant linear correlation was observed between calculated and measured daily exposures. The model overestimated the daily exposure approximately 4-fold and the exposure during application 10-fold. However, exposure was underestimated during mixing/loading for 70% of the observations when the operator wore PPE. The AOEM did not overestimate exposures in all circumstances, especially during mixing/loading, when operators handle concentrated products. The protection provided by PPE appeared to be overestimated. This could be due to the optimal working conditions under which the "industrial" studies are conducted, which may not be representative of real working conditions of operators in fruit-growing.

Background: Pesticide exposures are suspected to be implicated in the excess of central nervous system (CNS) tumours observed in farmers, but evidence concerning individual pesticides remains limited. Carbamate insecticides, used on a wide range of crops, have shown evidence of carcinogenicity in some experimental studies. In the cohort AGRICAN (AGRIculture & CANcer), we assessed the associations between potential exposures to carbamate insecticides and the incidence of CNS tumours, overall and by histological subtype., Methods: AGRICAN enrolled 181 842 participants involved in agriculture. Incident CNS tumours were identified by linkage with cancer registries from enrolment (2005-07) until 2013. Carbamate exposure was assessed by combining information on lifetime periods of pesticide use on crop or livestock and the French crop-exposure matrix PESTIMAT, individually for each of the 19 carbamate insecticides registered in France since 1950. Associations were estimated using proportional hazards models with age as the underlying time scale, adjusting for gender, educational level and smoking., Results: During a 6.9-year average follow-up, 381 incident cases of CNS tumours occurred, including 164 gliomas and 134 meningiomas. Analyses showed increased risks of CNS tumours with overall exposure to carbamate insecticides and linear trends with duration of use of each carbamate. Considering tumour subtypes, hazard ratios for gliomas ranged from 1.18 for thiofanox to 4.60 for formetanate, and for meningiomas from 1.51 for carbaryl to 3.67 for thiofanox., Conclusions: Findings reinforce carcinogenicity evidence for already suspected active ingredients and draw attention to additional active ingredients, notably used on fruit trees, vineyards, potatoes and beets., (© The Author(s) 2018; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Purpose: The effect of one pesticide spraying season on DNA damage was measured on B and T lymphocytes among open-field farmers and controls., Methods: At least two peripheral blood samples were collected from each individual: one in a period without any pesticide application, several weeks after the last use (January, at period P0), and another in the intensive pesticide spraying period (May or June, at period P4). DNA damage was studied by alkaline comet assay on isolated B or T lymphocytes., Results: Longitudinal comparison of DNA damage observed at both P0 and P4 periods revealed a statistically significant genotoxic effect of the pesticide spraying season in both B (P = 0.02) and T lymphocytes (P = 0.02) in exposed farmers. In contrast, non-farmers did not show any significant modifications. DNA damage levels in B and T lymphocytes were significantly higher in farmers than in non-farmers during the P4 period (P = 0.003 and P = 0.001 for B and T lymphocytes, respectively) but not during the P0 period. The seasonal effect observed among farmers was not correlated with either total farm area, farm area devoted to crops or recent solar exposure. On average, farmers used pesticides for 21 days between P0 and P4. Between the two time points studied, there was a tendency for a potential effect of the number of days of fungicide treatments (r (2) = 0.43; P = 0.11) on T lymphocyte DNA damage., Conclusions: A genotoxic effect was found in lymphocytes of farmers exposed to pesticides, suggesting in particular the possible implication of fungicides.

The t(14;18) translocation constitutes the initiating event of a causative cascade leading to follicular lymphoma (FL). t(14;18) translocations are present in blood from healthy individuals, but there is a trend of increased prevalence in farmers exposed to pesticides, a group recently associated with higher risk of t(14;18)(+) non-Hodgkin's lymphoma development. A direct connection between agricultural pesticide use, t(14;18) in blood, and malignant progression, however, has not yet been demonstrated. We followed t(14;18) clonal evolution over 9 yr in a cohort of farmers exposed to pesticides. We show that exposed individuals bear particularly high t(14;18) frequencies in blood because of a dramatic clonal expansion of activated t(14;18)(+) B cells. We further demonstrate that such t(14;18)(+) clones recapitulate the hallmark features of developmentally blocked FL cells, with some displaying aberrant activation-induced cytidine deaminase activity linked to malignant progression. Collectively, our data establish that expanded t(14;18)(+) clones constitute bona fide precursors at various stages of FL development, and provide a molecular connection between agricultural pesticide exposure, t(14;18) frequency in blood, and clonal progression.

Objectives: Identification of parameters associated with measured pesticide exposure of farmers in open-field farming in France., Methods: Open-field volunteer farmers were monitored during 1 day use of the herbicide isoproturon on wheat and/or barley during the winters 2001 (n = 9) or 2002 (n = 38) under usual conditions of work. The whole-body method was used to assess potential dermal exposure using coveralls and cotton gloves. Mixing-loading and application tasks were assessed separately with 12 different body areas (hands, arms, forearms, legs, chest, back and thighs) measured for each task (mixing-loading and application separately)., Results: Daily potential dermal exposure to isoproturon ranged from 2.0 to 567.8 mg (median = 57.8 mg) in 47 farmers. Exposure during mixing-loading tasks accounted for 13.9-98.1% of the total exposure (median = 74.8%). For mixing-loading, hands and forearms were the most contaminated body areas accounting for an average of 64 and 14%, respectively. For application, hands were also the most contaminated part of the body, accounting for an average of 57%, and thighs, forearms and chest or back were in the same range as one another, 3-10%. No correlations were observed between potential dermal exposure and area sprayed, duration of spraying or size of the farm. However, a significant relationship was observed between exposure and the type of spraying equipment, with a rear-mounted sprayer leading to a higher exposure level than trailer sprayers. Technical problems, particularly the unplugging of nozzles, and the numbers mixing-loading or application tasks performed were also significantly related with higher levels of exposure., Conclusions: The main results obtained in this study on a large number of observation days are as follows: (i) the mixing-loading step was the most contaminated task in open field accounting for two-thirds of the total daily exposure, (ii) no positive correlation was noted with classically used pesticide-related parameters: farm area, area sprayed and duration of application and (iii) relevant parameters were the type of spraying equipment, the type and number of tasks and technical problems or cases of overflowing.

The aetiology of brain tumours remains unclear. Occupational exposures to pesticides and organic solvents are suspected risk factors. The case-control study CEREPHY (221 cases, 442 controls) carried in the Departement de la Gironde in France revealed a significantly increased risk of brain tumours for subjects most exposed to pesticides. In some cancers, TP53 mutations could reflect exposure to specific carcinogens. These mutations are present in approximately 30% of astrocytic brain tumours. In a pilot study, we explored the hypothesis that pesticide or solvent exposure could raise the frequency of TP53 mutations in brain tumour cells. We investigated TP53 mutations in exons 2-11 by denaturing high performance liquid chromatography (DHPLC) and sequencing, and p53 accumulation by immunohistochemistry in brain tumour of the 30 patients from CEREPHY study with a history of occupational exposure to pesticides (n = 21) and/or organic solvents (n = 14) for whom tumoral tissue was available. Included cases concerned 27% of CEREPHY cases exposed to pesticides and, based on the cumulative index of occupational exposure, they were more exposed to pesticides. There were 12 gliomas, 6 meningiomas, 7 neurinomas, 2 central nervous system lymphomas and 3 tumours of other histological types. We detected TP53 mutations in three tumours, which is similar to the expected number (3.3) calculated from 46 published studies referenced in the IARC TP53 mutations database, taking into account histological types. Considering TP53 mutations previously detected in the laboratory by DHPLC and the frequency of TP53 polymorphisms detected in this sample (similar to published data), the TP53 mutations rate is probably not underestimated. These preliminary results, even if it was on a limited number of tumours, are not in favour of the role of pesticide or organic solvent exposure in the occurrence of TP53 mutations in brain tumours.

Increasing incidence of non-Hodgkin's lymphoma have been associated repeatedly with farming occupation and particular attention focused on the role of pesticide exposure to potentially explain part of this trend. A genetic hallmark of non-Hodgkin's lymphoma is the presence of recurrent chromosomal translocations involving the immunoglobulin heavy chain gene. Of these, the t(14;18), which deregulates BCL2 expression and inhibits apoptosis, is the most frequent in follicular lymphoma and has been detected consistently in peripheral blood lymphocytes of healthy individuals. As BCL2-IGH translocation represents an early step of the malignant process, we evaluated the occurrence and molecular characteristics of BCL2-IGH translocation in 56 individuals occupationally exposed to pesticides in open field farming They were selected from a representative cohort of farmers with a well-defined assessment of pesticide exposure taking into account potential confounding factors, smoking, sunlight, and age. Our results suggest that occupational exposure to pesticides would increase BCL2-IGH prevalence together with the frequency of BCL2-IGH-bearing cells especially during the high pesticide use period. Distribution of BCL2 or IGH breakpoint positions seemed to be independent of pesticide exposure and was similar to those found in other healthy populations or lymphoma patients. Finally, these results provide additional evidence that BCL2-IGH translocation measurements could be a measure of acquired genetic instability in relation to genotoxic exposure in a gene directly relevant in term of lymphomagenesis.