Dislodgeable Foliar Residue Measurements and Assessment of Dermal Exposure to Captan for Workers in Apple Orchards.

Captan dislodgeable foliar residues (DFRs) were determined by following the applications of this fungicide in an apple orchard. The study comprised an investigation of the variability of captan DFR values and 14 days of DFR monitoring to assess kinetic modeling. A method combining solid-phase microextraction (SPME) gas chromatography and high-resolution mass spectrometry (GC-QTOF-MS) was developed for the quantification of captan residues from DFR aqueous extracts. The results evidenced that (1) sampling parameters such as the position of the tree in a row and the height of foliar significantly influenced captan DFR levels (247-1450 ng·cm-2), highlighting the need to implement a comprehensive sampling strategy; (2) the DFR captan dissipation kinetic model best matched with a biphasic one, with half-lives of DFRcaptan of 3.4 and 12.8 days, respectively, for the initial rapid phase 1 decline (day 0-5) and the slower phase 2 decline phase (day 6-14). Furthermore, through DFR measurements, the potential dermal exposure (PDE) of workers was assessed using transfer coefficients (TCs) from the literature. Compared to the acceptable operator exposure levels (AOELs), the results showed that the re-entry interval for captan may not sufficiently protect workers whose arms, hands, and legs are not covered.

Pesticide Residues in Organic and Conventional Agricultural Soils across Europe: Measured and Predicted Concentrations.

During the growing season of 2021, 201 soil samples from conventionally and organically managed fields from 10 European countries and 8 cropping systems were taken, and 192 residues of synthetic pesticides were analyzed. Pesticide residues were found in 97% of the samples, and 88% of the samples contained mixtures of at least 2 substances. A maximum of 21 substances were found in conventionally managed fields, and a maximum of 12 were found in organically managed fields. The number and concentration of pesticide residues varied significantly between conventional and organic fields in 70 and 50% of the case study sites, respectively. Application records were available for a selected number of fields (n = 82), and these records were compared to the detected substances. Residues from 52% of the applied pesticides were detected in the soils. Only 21% of the pesticide residues detected in the soil samples were applied during the 2021 growing season. From the application data, predicted environmental concentrations of residues in soil were calculated and compared to the measured concentrations. These estimates turned out not to be accurate. The results of this study show that most European agricultural soils contain mixtures of pesticide residues and that current calculation methods may not reliably estimate their presence.

Pesticide residues in European sediments: A significant concern for the aquatic systems?

The presence of pesticide residues in waterbed sediments poses a significant concern for aquatic ecosystems' health. This study examined pesticide contamination in sediments of 38 water bodies, embedded in agricultural-dominated regions, across eight European countries. Three indicators were targeted: occurrence, type, and concentrations of multiple pesticide residues in sediments. 196 pesticide residues (including degradation products) were tested in the sediment samples. The analytical results showed that only one sample was 'pesticide-free', three samples contained a single pesticide residue, and the remaining 34 samples contained mixtures of residues. Overall, 99 different residues were found in the sediments, with a maximum of 48 in a single sample. Twenty-seven out of the 99 detected residues were not approved for agricultural use at the time of sampling. The numbers of detected residues and pesticide levels varied among countries. AMPA, glyphosate and DDTs were the most common residues in sediment samples with frequencies of 76, 61, and 52%, respectively. The sediments from the Czech Republic had the highest pesticide concentrations, with total pesticide concentrations ranging between 600 and 1200 µg kg-1. The lowest total pesticide concentrations were found in Slovenia, Switzerland, Croatia, and Denmark, ranging between 80 and 120 µg kg-1. Sediments presented a mix of non-persistent and persistent compounds. Twelve of the detected pesticides are very persistent/stable in sediments, raising concerns about the long-term impacts of pesticides. Our study on the distribution of pesticide residues in European sediments provides valuable insights into the extent of pesticide contamination and possible risks of pesticides to water bodies' health. It also underlines the need for monitoring, research, and policy efforts to mitigate the impacts of pesticides, and to evaluate potential risks of re-use of dredged sediments.

FOLFIRI plus BEvacizumab or aFLIbercept after FOLFOX-bevacizumab failure for COlorectal cancer (BEFLICO): An AGEO multicenter study.

After failure of first line FOLFOX-bevacizumab for metastatic colorectal cancer (mCRC), adding either bevacizumab or aflibercept to second-line FOLFIRI increases survival compared to FOLFIRI alone. In this French retrospective multicentre cohort, we included patients with a mCRC treated with either FOLFIRI-aflibercept or FOLFIRI-bevacizumab. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival (PFS), disease control rate (DCR: CR + PR + SD) and safety. We included 681 patients from 36 centers, 326 and 355 in the aflibercept and bevacizumab groups, respectively. Median age was 64.2 years and 45.2% of patients were men. Most patients had RAS-mutated tumors (80.8%) and synchronous metastases (85.7%). After a median follow up of 31.2 months, median OS was 13.0 months (95% CI: 11.3-14.7) and 10.4 months (95% CI: 8.8-11.4) in the bevacizumab and aflibercept groups, respectively (P < .0001). Median PFS was 6.0 months (95% CI: 5.4-6.5) and 5.1 months (95% CI: 4.3-5.6) (P < .0001). After adjustment on age, PS, PFS of first line, primary tumor resection, metastasis location and RAS/BRAF status, bevacizumab was still associated with better OS (HR: 0.71, 95% CI: 0.59-0.86, P = .0003). FOLFIRI-bevacizumab combination was associated with longer OS and PFS, and a better tolerability, as compared to FOLFIRI-aflibercept after progression on FOLFOX-bevacizumab.

Baseline tumour size is an independent prognostic factor for overall survival in PD-L1 ≥ 50% non-small cell lung cancer patients treated with first-line pembrolizumab.

BACKGROUND: Advanced non-small cell lung cancer (NSCLC) with a PD-L1 tumour proportion score ≥ 50% can be treated with pembrolizumab alone. Our aim was to assess the impact of baseline tumour size (BTS) on overall survival (OS) in NSCLC patients treated with pembrolizumab versus chemotherapy. METHODS: This retrospective, multicentre study included all patients with untreated advanced NSCLC receiving either pembrolizumab (PD-L1 ≥ 50%) or platinum-based chemotherapy (any PD-L1). The primary endpoint was the impact of BTS (defined as the sum of the dimensions of baseline target lesions according to RECIST v1.1 criteria) on OS. RESULTS: Between 09-2016 and 06-2020, 188 patients were included, 96 in the pembrolizumab (P-group) and 92 in the chemotherapy group (CT-group). The median follow-up was 26.9 months (range 0.13-37.91) and 44.4 months (range 0.23-48.62), respectively, while the median BTS was similar, 85.5 mm (IQR 57.2-113.2) and 86.0 mm (IQR 53.0-108.5), respectively (p = 0.42). The median P-group OS was 18.2 months [95% CI 12.2-not reached (NR)] for BTS > 86 mm versus NR (95% CI 27.2-NR) for BTS ≤ 86 mm (p = 0.0026). A high BTS was associated with a shorter OS in univariate analyses (p = 0.009) as well as after adjustment on confounding factors (HR 2.16, [95% CI 1.01-4.65], p = 0.048). The CT-group OS was not statistically different between low and high BTS patients, in univariate and multivariate analyses (p = 0.411). CONCLUSIONS: After adjustment on major baseline clinical prognostic factors, BTS was an independent prognostic factor for OS in PD-L1 ≥ 50% advanced NSCLC patients treated first-line with pembrolizumab.

Pesticide exposure of workers in apple growing in France.

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.

Identifying pesticides of high concern for ecosystem, plant, animal, and human health: A comprehensive field study across Europe and Argentina.

The widespread and excessive use of pesticides in modern agricultural practices has caused pesticide contamination of the environment, animals, and humans, with confirmed serious health consequences. This study aimed to identify the 20 most critical substances based on an analysis of detection frequency (DF) and median concentrations (MC) across environmental and biological matrices. A sampling campaign was conducted across 10 case study sites in Europe and 1 in Argentina, each encompassing conventional and organic farming systems. We analysed 209 active substances in a total of 4609 samples. All substances ranked among the 20 most critical were detected in silicon wristbands worn by humans and animals and indoor dust from both farming systems. Five of them were detected in all environmental matrices. Overall, higher values of DF and MC, including in the blood plasma of animals and humans, were recorded in samples of conventional compared to organic farms. The differences between farming systems were greater in the environmental samples and less in animal and human samples. Ten substances were detected in animal blood plasma from conventional farms and eight in animal blood plasma from organic farms. Two of those, detected in both farming systems, are classified as hazardous for mammals (acute). Five substances detected in animal blood plasma from organic farms and seven detected in animal blood plasma from conventional farms are classified as hazardous for mammals (dietary). Three substances detected in human blood plasma are classified as carcinogens. Seven of the substances detected in human blood plasma are classified as endocrine disruptors. Six substances, of which five were detected in human blood plasma, are hazardous for reproduction/development. Efforts are needed to elucidate the unknown effects of mixtures, and it is crucial that such research also considers biocides and banned substances, which constitute a baseline of contamination that adds to the effect of substances used in agriculture.

Assessing pesticide residues occurrence and risks in water systems: A Pan-European and Argentina perspective.

Freshwater ecosystems face a particularly high risk of biodiversity loss compared to marine and terrestrial systems. The use of pesticides in agricultural fields is recognized as a relevant stressor for freshwater environments, exerting a negative impact worldwide on the overall status and health of the freshwater communities. In the present work, part of the Horizon 2020 funded SPRINT project, the occurrence of 193 pesticide residues was investigated in 64 small water bodies of distinct typology (creeks, streams, channels, ditches, rivers, lakes, ponds and reservoirs), located in regions with high agricultural activity in 10 European countries and in Argentina. Mixtures of pesticide residues were detected in all water bodies (20, median; 8-40 min-max). Total pesticide levels found ranged between 6.89 and 5860 ng/L, highlighting herbicides as the dominant type of pesticides. Glyphosate was the compound with the highest median concentration followed by 2,4-D and MCPA, and in a lower degree by dimethomorph, fluopicolide, prothioconazole and metolachlor(-S). Argentina was the site with the highest total pesticide concentration in water bodies followed by The Netherlands, Portugal and France. One or more pesticides exceeded the threshold values established in the European Water Framework Directive for surface water in 9 out of 11 case study sites (CSS), and the total pesticide concentration surpassed the reference value of 500 ng/L in 8 CSS. Although only 5 % (bifenthrin, dieldrin, fipronil sulfone, permethrin, and terbutryn) of the individual pesticides denoted high risk (RQ > 1), the ratios estimated for pesticide mixtures suggested potential environmental risk in the aquatic compartment studied.

Herbicide exposure during occupational knapsack spraying in French gardeners and municipal workers.

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.

Occurrence of pesticide residues in indoor dust of farmworker households across Europe and Argentina.

Pesticides are widely used as plant protection products (PPPs) in farming systems to preserve crops against pests, weeds, and fungal diseases. Indoor dust can act as a chemical repository revealing occurrence of pesticides in the indoor environment at the time of sampling and the (recent) past. This in turn provides information on the exposure of humans to pesticides in their homes. In the present study, part of the Horizon 2020 funded SPRINT project, the presence of 198 pesticide residues was assessed in 128 indoor dust samples from both conventional and organic farmworker households across Europe, and in Argentina. Mixtures of pesticide residues were found in all dust samples (25-121, min-max; 75, median). Concentrations varied in a wide range (<0.01 ng/g-206 µg/g), with glyphosate and its degradation product AMPA, permethrin, cypermethrin and piperonyl butoxide found in highest levels. Regarding the type of pesticides, insecticides showed significantly higher levels than herbicides and fungicides. Indoor dust samples related to organic farms showed a significantly lower number of residues, total and individual concentrations than those related to conventional farms. Some pesticides found in indoor dust were no longer approved ones (29 %), with acute/chronic hazards to human health (32 %) and with environmental toxicity (21 %).

Pesticide residues with hazard classifications relevant to non-target species including humans are omnipresent in the environment and farmer residences.

Intensive and widespread use of pesticides raises serious environmental and human health concerns. The presence and levels of 209 pesticide residues (active substances and transformation products) in 625 environmental samples (201 soil, 193 crop, 20 outdoor air, 115 indoor dust, 58 surface water, and 38 sediment samples) have been studied. The samples were collected during the 2021 growing season, across 10 study sites, covering the main European crops, and conventional and organic farming systems. We profiled the pesticide residues found in the different matrices using existing hazard classifications towards non-target organisms and humans. Combining monitoring data and hazard information, we developed an indicator for the prioritization of pesticides, which can support policy decisions and sustainable pesticide use transitions. Eighty-six percent of the samples had at least one residue above the respective limit of detection. One hundred residues were found in soil, 112 in water, 99 in sediments, 78 in crops, 76 in outdoor air, and 197 in indoor dust. The number, levels, and profile of residues varied between farming systems. Our results show that non-approved compounds still represent a significant part of environmental cocktails and should be accounted for in monitoring programs and risk assessments. The hazard profiles analysis confirms the dominance of compounds of low-moderate hazard and underscores the high hazard of some approved compounds and recurring "no data available" situations. Overall, our results support the idea that risk should be assessed in a mixture context, taking environmentally relevant mixtures into consideration. We have uncovered uncertainties and data gaps that should be addressed, as well as the policy implications at the EU approval status level. Our newly introduced indicator can help identify research priority areas, and act as a reference for targeted scenarios set forth in the Farm to Fork pesticide reduction goals.

Pesticide Exposure in Fruit-Growers: Comparing Levels and Determinants Assessed under Usual Conditions of Work (CANEPA Study) with Those Predicted by Registration Process (Agricultural Operator Exposure Model).

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.

Increased risk of central nervous system tumours with carbamate insecticide use in the prospective cohort AGRICAN.

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.

Agricultural exposures to carbamate herbicides and fungicides and central nervous system tumour incidence in the cohort AGRICAN.

BACKGROUND: Pesticides exposures could be implicated in the excess of Central Nervous System (CNS) tumors observed in farmers, but evidence concerning individual pesticides remains limited. Carbamate derivative pesticides, including herbicides and fungicides (i.e. (thio/dithio)-carbamates), have shown evidence of carcinogenicity in experimental studies in animals. In the French AGRICAN cohort, we assessed the associations between potential exposures to carbamate herbicides and fungicides and the incidence of CNS tumors, overall and by histological subtype. METHODS: AGRICAN enrolled 181,842 participants involved in agriculture. Incident CNS tumors were identified by linkage with cancer registries from enrollment (2005-2007) until 2013. Individual exposures were assessed by combining information on lifetime periods of pesticide use on crops and the French crop-exposure matrix PESTIMAT, for each of the 14 carbamate and thiocarbamate herbicides and the 16 carbamate and dithiocarbamate fungicides registered in France since 1950. Associations were estimated using proportional hazard models with age as the underlying timescale, adjusting for gender, educational level and smoking. RESULTS: During an average follow-up of 6.9 years, 381 incident cases of CNS tumors occurred, including 164 gliomas and 134 meningiomas. Analyses showed increased risks of CNS tumors with overall exposure to carbamate fungicides (Hazard Ratio, HR = 1.88; 95% CI: 1.27-2.79) and, to a lesser extent, to carbamate herbicides (HR = 1.44; 95% CI: 0.94-2.22). Positive associations were observed with specific carbamates, including some fungicides (mancozeb, maneb, metiram) and herbicides (chlorpropham, propham, diallate) already suspected of being carcinogens in humans. CONCLUSIONS: Although some associations need to be corroborate in further studies and should be interpreted cautiously, these findings provide additional carcinogenicity evidence for several carbamate fungicides and herbicides.