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The isotopic composition of dioxygen in the atmosphere is a global tracer which depends on the biosphere flux of dioxygen toward and from the atmosphere (photosynthesis and respiration) as well as exchanges with the stratosphere. When measured in fossil air trapped in ice cores, the relative concentration of 16O, 17O, and 18O of O2 can be used for several applications such as ice core dating and past global productivity reconstruction. However, there are still uncertainties about the accuracy of these tracers as they depend on the integrated isotopic discrimination of different biological processes of dioxygen production and uptake, for which we currently have very few independent estimates. Here we determined the respiration and photosynthesis fractionation factors for atmospheric dioxygen from experiments carried out in a replicated vegetation–soil–atmosphere analogue of the terrestrial biosphere in closed chambers with growing Festuca arundinacea. The values for 18O discrimination during soil respiration and dark respiration in leaves are equal to -12.3±1.7 ‰ and -19.1±2.4 ‰, respectively. In these closed biological chambers, we also found a value attributed to terrestrial photosynthetic isotopic discrimination equal to +3.7±1.3 ‰. This last estimate suggests that the contribution of terrestrial productivity in the Dole effect may have been underestimated in previous studies.

The triple oxygen isotope composition of phytoliths (17O-excessphyto) can provide key information on past atmospheric relative humidity (RH) over land. Here, we examined how leaf-to-air temperature gradients and changes in the silica polymerization rate in response to stomatal conductance influence the interpretation of 17O-excessphyto in terms of RH. Further, we assessed the reliability of a theoretical isotope model of leaf water evaporation to predict the triple oxygen isotope composition of leaf water on diurnal and seasonal scale. For this purpose, we monitored a grass plot within a natural Mediterranean woodland for one year. We measured in particular the isotope composition of atmospheric water vapor and plot-scale grass leaf temperatures – two variables that are often only estimated. Grass leaf blades were collected in different seasons and over a 24-hour period for leaf water and phytolith isotope analysis. We found that the steady state model reliably predicts the triple oxygen isotope composition of leaf water during daytime but remains sensitive to uncertainties on the leaf-to-air temperature difference. Deviations from isotope steady state at night are well represented by the non-steady state model. In our study, the 17O-excessphyto best reflects average daytime RH over the growth period, rather than daily RH. Average daytime leaf-to-air temperature gradients of less than 2 °C introduce an insignificant bias to the RH estimate. The results also confirm the established triple oxygen isotope fractionation factors between phytoliths and leaf water. The findings of this study help to better understand how to interpret 17O-excessphyto of fossil phytolith assemblages in terms of past RH.

Ecosystems integrity and services are threatened by anthropogenic global changes. Mitigating and adapting to these changes require knowledge of ecosystem functioning in the expected novel environments, informed in large part through experimentation and modelling. This paper describes 13 advanced controlled environment facilities for experimental ecosystem studies, herein termed ecotrons, open to the international community. Ecotrons enable simulation of a wide range of natural environmental conditions in replicated and independent experimental units while measuring various ecosystem processes. This capacity to realistically control ecosystem environments is used to emulate a variety of climatic scenarios and soil conditions, in natural sunlight or through broad‐spectrum lighting. The use of large ecosystem samples, intact or reconstructed, minimizes border effects and increases biological and physical complexity. Measurements of concentrations of greenhouse trace gases as well as their net exchange between the ecosystem and the atmosphere are performed in most ecotrons, often quasi continuously. The flow of matter is often tracked with the use of stable isotope tracers of carbon and other elements. Equipment is available for measurements of soil water status as well as root and canopy growth. The experiments ran so far emphasize the diversity of the hosted research. Half of them concern global changes, often with a manipulation of more than one driver. About a quarter deal with the impact of biodiversity loss on ecosystem functioning and one quarter with ecosystem or plant physiology. We discuss how the methodology for environmental simulation and process measurements, especially in soil, can be improved and stress the need to establish stronger links with modelling in future projects. These developments will enable further improvements in mechanistic understanding and predictive capacity of ecotron research which will play, in complementarity with field experimentation and monitoring, a crucial role in exploring the ecosystem consequences of environmental changes., Experimentation and modelling are necessary to predict ecosystem functioning under future environments and to develop mitigating and adapting strategies. This paper describes 13 advanced controlled environment facilities, called ecotrons, open to the international community. An ecotron comprises a set of replicated enclosures designed to host ecosystems samples and enable realistic simulations of above‐ and belowground environmental conditions, while simultaneously and automatically measuring ecosystem processes. The characteristics of these infrastructures are given as well as examples of collaborative projects hosted so far.

RATIONALE Producing robust high frequency time series of raw atmospheric water vapor isotope data by laser spectrometry requires accurate calibration. Especially, the chemical composition of the analyzed sample gas can cause isotope bias. This study assesses the matrix effect on calibrated δ17 O, δ18 O, δ2 H, 17 O-excess, and d-excess values of atmospheric water vapor. METHODS A Picarro L2140-i cavity ring-down spectrometer combined with an autosampler and a vaporizer is used to analyze δ17 O, δ18 O, δ2 H, 17 O-excess and d-excess of two water standards. Isotope data obtained using synthetic air and dry ambient air as carrier gas at water mixing ratios ranging from 2000 to 30000 ppmv are compared. Based on the results, atmospheric water vapor measurements are calibrated. The expected precision is estimated by Monte Carlo simulation. RESULTS The dry air source strongly impacts raw isotope values of the two water standards, but has no effect on the mixing ratio dependency functions. When using synthetic air, δ17 O, δ18 O and 17 O-excess of calibrated atmospheric water vapor are overestimated by 0.6 ‰, 0.7 ‰, and 217 per meg, respectively, while δ2 H and d-excess are underestimated by 1.5 ‰ and 7.3 ‰. Optimum precisions for the calibrated δ17 O, δ18 O, δ2 H, 17 O-excess and d-excess values and 12-min integration time are 0.02 ‰, 0.03 ‰, 0.4 ‰, 14 per meg and 0.4 ‰, respectively. CONCLUSIONS In light of the obtained results, recommendations for the calibration of atmospheric water vapor isotope measurements are presented. The necessity to use dry ambient air as dry air source when running the standards for calibration is pointed out as a pre-requisite for accurate atmospheric water vapor 17 O-excess and d-excess measurements.

Sarcomas are a heterogeneous group of tumors whose incidence is nearly 5 per 100 000 inhabitants in Europe. Their causes are poorly understood, although occupational exposures (especially farming and pesticides) are suspected. The AGRICAN cohort is a prospective study of 181 842 individuals enrolled in 2005 to 2007 who completed an enrolment questionnaire with data on lifelong agricultural exposure. Associations between agricultural exposure and sarcoma overall, gastrointestinal stromal tumors (GIST) and myomatous and fibrous sarcoma together, were analyzed with a Cox model. Until 2015, 188 incident cases of sarcoma were identified. Increased risks were observed (a) among cattle farmers working10 years (HR

International audience

High precision measurements of triple isotopic composition of oxygen in the air trapped in ice cores is a useful tool to infer the global gross biosphere productivity in the past. The isotopic composition of oxygen is influenced by many physical, chemical and biological processes during consumption and production of oxygen by the oceanic and terrestrial biosphere. For an accurate quantification of the past biosphere productivity, it is thus important to determine the different fractionation processes occurring in the biosphere during respiration and photosynthesis processes.We present here quantification of fractionation coefficients associated with δ180 and the D170 of 02 during respiration and photosynthesis within the terrestrial biosphere. The experimental set-up relies on closed biological chambers in which all the environmental parameters are controlled and measured. Triple isotopic composition of oxygen is regularly measured through sampling of small aliquots at a low frequency (4 h to 4 days). Seven 2-month long experiments were performed in order to check the reproducibility of our set-up and quantify uncertainty on the determination of the fractionation coefficients.In order to improve our set-up for future experiments using different plants, we also present perspectives for a continuous measurement of the isotopic composition of oxygen using optical spectroscopy (Optical Feedback Cavity Enhanced Absorption Spectroscopy (OF-CEAS) technique). This instrument is currently being characterized and we will present its current performances.Triple isotopic composition of oxygen in the atmospheric dioxygen to reconstruct the dynamic of global biosphere productivity in the past from measurements in biological chambers.

High precision measurements of triple isotopic composition of oxygen in water is a useful tool to infer the dynamic of past hydrological cycle when measured in ice core together with δ18O and δD. In particular, the triple isotopic composition of oxygen in water provides information on the climatic conditions of the evaporative sources. In parallel, it has been shown that the triple isotopic composition of oxygen in the atmospheric dioxygen can be a useful tracer of the global biosphere productivity and hence reconstruct the dynamic of the global biosphere productivity in the past from measurements performed in the air bubbles. Measuring triple isotopic composition of oxygen both in the water and in the atmospheric dioxygen trapped in bubbles in ice cores is thus a strong added value to study the past variability of water cycle and biosphere productivity in parallel to climate change.Here, we first present new laboratory experiments performed in closed biological chambers to show how the triple isotopic composition of oxygen in atmospheric dioxygen can be used for quantification of the biosphere productivity with determination of fractionation coefficients. Then, we present new records of triple isotopic composition of oxygen in water and O2 trapped in bubbles from the EPICA Dome C ice core over the deglaciations of the last 800 ka.

The oxygen isotope signature of leaf water is used to trace several processes at the soil-plant-atmosphere interface. During photosynthesis, it is transferred to the oxygen isotope signature of atmospheric CO2 and O2, which can be used for reconstructing past changes in gross primary production. The oxygen isotope signature of leaf water additionally imprints leaf organic and mineral compounds, such as phytoliths, used as paleoclimate and paleovegetation proxies when extracted from sedimentary materials.Numerous experimental and modelling studies were dedicated to constrain the main parameters responsible for changes in the δ18O of leaf water. Although these models usually correctly depict the main trends of 18O-enrichment of the leaf water when relative humidity decreases, the calculated absolute values often depart from the observed ones by several ‰. Moreover, the δ18O of leaf water absorbed by plants is dependent on the δ18O value of meteoric and soil waters that can vary by several ‰ at different space and time scales. These added uncertainties make our knowledge of the parameters responsible for changes in the δ18O of leaf water and phytoliths flawed.Changes in the triple oxygen isotope composition of leaf water, expressed by the 17O-excess, are controlled by fewer variables than changes in δ18O. In meteoric water the 17O-excess varies slightly as it is weakly affected by temperature or phase changes during air mass transport. This makes the soil water fed by meteoric water and the atmospheric vapour in equilibrium with meteoric water changing little from a place to another. Hence the 17O-excess of leaf water is essentially controlled by the evaporative fractionation. The latest depends on the ratio of vapor pressure in the air to vapor pressure in the stomata intercellular space, close to relative humidity. Leaf water evaporative fractionation can lead to 17O-excess negative values that can exceed most of surficial water ones.Here we present the outcomes of several recent growth chamber and field studies, for the purpose of i) refining the grass leaf water and phytoliths δ18O and 17O-excess modelling, ii) assessing whether the δ18O and 17O-excess of grass leaf water can be reconstructed from phytoliths, and iii) examining the precision of the 17O-excess of phytoliths as a new proxy for past changes in continental atmospheric relative humidity. Atmospheric continental relative humidity is an important climate parameter poorly constrained in global climate models. A model-data comparison approach, applicable beyond the instrumental period, is essential to progress on this issue. However, there is currently a lack of proxies allowing quantitative reconstruction of past continental relative humidity. The 17O-excess signature of phytoliths could fill this gap.

BackgroundData on the effects of extremely low frequency electromagnetic fields (ELF-EMF) on pregnancy outcomes are inconclusive.ObjectiveTo study the relation between maternal cumulative exposure to ELF-EMF during pregnancy and the risk of prematurity or small for gestational age (SGA) in a pooled analysis of two French birth cohorts.MethodsElfe and Epipage2 are both population-based birth cohorts initiated in 2011 and included 18 329 and 8400 births, respectively. Health data and household, mother and child characteristics were obtained from medical records and questionnaires at maternity and during follow-up. A job exposure matrix was used to assess cumulative exposure to ELF-EMF during three periods: (1) until 15 weeks of gestation, (2) until 28 weeks of gestation and (3) until 32 weeks of gestation. Analyses were restricted to single live births in mainland France and to mothers with documented jobs (N=19 894). Adjusted logistic regression models were used.ResultsAccording to the period studied, 3.2%–4% of mothers were classified as highly exposed. Results were heterogeneous. Increased risks of prematurity were found among low exposed mothers for the three periods, and no association was observed among the most exposed (OR1=0.92 (95% CI 0.74 to 1.15); OR2=0.98 (95% CI 0.80 to 1.21); OR3=1.14 (95% CI 0.92 to 1.41)). For SGA, no association was observed with the exception of increased risk among the low exposed mothers in period 2 and the most exposed in period 3 (OR=1.25 (95% CI 1.02 to 1.53)).ConclusionSome heterogeneous associations between ELF-EMF exposure and prematurity and SGA were observed. However, due to heterogeneity (ie, their independence regarding the level of exposure), associations cannot be definitely explained by ELF-EMF exposure.

Continental relative humidity (RH) is a key climate parameter, but there is a lack of quantitative RH proxies suitable for climate model–data comparisons. Recently, a combination of climate chamber and natural transect calibrations have laid the groundwork for examining the robustness of the triple oxygen isotope composition (δ′18O and 17O-excess) of phytoliths, that can preserve in sediments, as a new proxy for past changes in RH. However, it was recommended that besides RH, additional factors that may impact δ′18O and 17O-excess of plant water and phytoliths be examined. Here, the effects of grass leaf length, leaf development stage and day–night alternations are addressed from growth chamber experiments. The triple oxygen isotope compositions of leaf water and phytoliths of the grass species F. arundinacea are analysed. Evolution of the leaf water δ′18O and 17O-excess along the leaf length can be modelled using a string-of-lakes approach to which an unevaporated–evaporated mixing equation must be added. We show that for phytoliths to record this evolution, a kinetic fractionation between leaf water and silica, increasing from the base to the apex, must be assumed. Despite the isotope heterogeneity of leaf water along the leaf length, the bulk leaf phytolith δ′18O and 17O-excess values can be estimated from the Craig and Gordon model and a mean leaf water–phytolith fractionation exponent (λPhyto-LW) of 0.521. In addition to not being leaf length dependent, δ′18O and 17O-excess of grass phytoliths are expected to be impacted only very slightly by the stem vs. leaf biomass ratio. Our experiment additionally shows that because a lot of silica polymerises in grasses when the leaf reaches senescence (58 % of leaf phytoliths in mass), RH prevailing during the start of senescence should be considered in addition to RH prevailing during leaf growth when interpreting the 17O-excess of grass bulk phytoliths. Although under the study conditions 17O-excessPhyto do not vary significantly from constant day to day–night conditions, additional monitoring at low RH conditions should be done before drawing any generalisable conclusions. Overall, this study strengthens the reliability of the 17O-excess of phytoliths to be used as a proxy of RH. If future studies show that the mean value of 0.521 used for the grass leaf water–phytolith fractionation exponent λPhyto-LW is not climate dependent, then grassland leaf water 17O-excess obtained from grassland phytolith 17O-excess would inform on isotope signals of several soil–plant-atmosphere processes.

International audience; 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 effect of ELF-MF on human health is still controversial, particularly as regards long-term health effects like cancer. The literature does suggest, however, that they could be involved in the occurrence of brain tumors, although results concerning residential exposure are scarce. Our objective was to investigate the association between residential proximity to power lines and brain tumors among adults in France by using a geographical information system.CERENAT is a population-based case-control study carried out in France in 2004-2006. We used geographical data sources on power line location to create exposure scores based on distance between residence and power lines, and on the number of lines near residences. Conditional logistic regression for matched sets was used to estimate Odds Ratios (ORs) and 95% confidence intervals (95%CI).We found significant associations between cumulated duration living at50 m to high voltage lines and: i) all brain tumors (OR 2.94; 95%CI 1.28-6.75); ii) glioma (OR 4.96; 95%CI 1.56-15.77). Further investigations are needed, particularly to improve the quality and availability of geographical and technical data on power lines.

International audience; PURPOSE:Epidemiological studies have found an increased risk of multiple myeloma (MM) in farmers. Few studies have investigated the detailed circumstances of occupational pesticide exposure which could explain these increased risks (pesticide use on crops, seeds or on animals, contact with treated crops) and the role of other exposures. In the Agriculture and Cancer cohort (AGRICAN), we assessed the associations between MM and crop- or animal-related activities, with specific attention to pesticide exposure via use on animals and crops or contact with treated crops and to disinfectant exposure.METHODS:Analyses concerned 155,192 participants, including 269 incident MM identified by cancer registries from enrolment (2005-2007) to 2013. Cox models using attained age as time scale were run to calculate hazard ratios (HR) and 95% confidence intervals (CI).RESULTS:MM risk was increased in farmers (i) who started using pesticides on crops in the 1960s, especially among those applying pesticides on corn (≥ 20 years: HR 1.73, 95% CI 1.08, 2.78, p for trend

International audience; Occupational exposure to pesticides concerns a wide population of workers not only in agriculture. The reliability of self-reported information on pesticide use is questionable because of the diversity of use. The PESTIPOP job-exposure matrix has been designed to assess pesticide occupational exposure in the general population. The matrix is composed of two axes: the first axis corresponding to jobs (combinations of occupations and industries) and the second one to pesticide exposure. The estimated exposure metric is the probability of exposure coupled with a reliability assessment (low, medium or high). These metrics were defined by combining different sources: (1) an a priori expert assessment (Agricultural industry experts); (2) data from a multicenter case-control study on brain tumors in the general population (occupational history, specific questionnaires); and (3) an a posteriori expert assessment based on the data of a case-control study. So far, 2559 jobs have been identified and 209 (8%) were found to be exposed to pesticides. Jobs with agricultural exposure had a higher exposure probability than jobs with non-agricultural exposure (wood preservation, park maintenance, pest control). Indirect exposure was more frequent than direct exposure. The PESTIPOP matrix will be transcoded into international classifications for use in epidemiological studies.

Studies in farmers suggest a possible role of pesticides in the occurrence of Central Nervous System (CNS) tumors but scientific evidence is still insufficient. Using data from the French prospective agricultural cohort AGRICAN (Agriculture & Cancer), we investigated the associations between exposure of farmers and pesticide users to various kinds of crops and animal farming and the incidence of CNS tumors, overall and by subtypes. Over the 2005-2007, 181,842 participants completed the enrollment questionnaire that collected a complete job calendar with lifetime history of farming types. Associations were estimated using proportional hazards models with age as underlying timescale. During a 5.2 years average follow-up, 273 incident cases of CNS tumors occurred, including 126 gliomas and 87 meningiomas. Analyses showed several increased risks of CNS tumors in farmers, especially in pesticide users (hazard ratio = 1.96; 95% confidence interval: 1.11-3.47). Associations varied with tumor subtypes and kinds of crop and animal farming. The main increases in risk were observed for meningiomas in pig farmers and in farmers growing sunflowers, beets and potatoes and for gliomas in farmers growing grasslands. In most cases, more pronounced risk excesses were observed among pesticide applicators. Even if we cannot completely rule out the contribution of other factors, pesticide exposures could be of primary concern to explain these findings.

The potential of the vegetation to sequester C is determined by the balance between assimilation and respiration. Respiration is under environmental and substrate-driven control, but the circadian clock might also contribute. To assess circadian control on night-time dark respiration (RD) and on light enhanced dark respiration (LEDR) - the latter providing information on the metabolic reorganization in the leaf during light-dark transitions - we performed experiments in macrocosms hosting canopies of bean and cotton. Under constant darkness (plus constant air temperature and air humidity), we tested whether circadian regulation of RD scaled from leaf to canopy respiration. Under constant light (plus constant air temperature and air humidity), we assessed the potential for leaf-level circadian regulation of LEDR. There was a clear circadian oscillation of leaf-level RD in both species and circadian patterns scaled to the canopy. LEDR was under circadian control in cotton, but not in bean indicating species-specific controls. The circadian rhythm of LEDR in cotton might indicate variable suppression of the normal cyclic function of the tricarboxylic-acid-cycle in the light. Since circadian regulation is assumed to act as an adaptive memory to adjust plant metabolism based on environmental conditions from previous days, circadian control of RD may help to explain temporal variability of ecosystem respiration. This study benefited from the CNRS human and technical resources allocated to the ECOTRONS Research Infrastructures as well as from the state allocation ‘Investissement d'Avenir’ AnaEE-France ANR-11-INBS-0001, ExpeER Transnational Access program, Ramón y Cajal fellowships (RYC-2012-10970 to VRD and RYC-2008-02050 to JPF), the Erasmus Mundus Master Course MEDfOR, internal grants from UWS-HIE to VRD and ZALF to AG and Juan de la Cierva-fellowships (IJCI-2014-21393 to JGA). We remain indebted to E. Gerardeau, D. Dessauw, J. Jean, P. Prudent (Aïda CIRAD), J.-J. Drevon, C. Pernot (Eco&Sol INRA), B. Buatois, A. Rocheteau (CEFE CNRS), A. Pra, A. Mokhtar and the full Ecotron team, in particular C. Escape, for outstanding technical assistance.

Continental relative humidity (RH) is a key-climate parameter. However, there is a lack of quantitative RH proxies suitable for climate model-data comparisons. Recently, a combination of climate chamber and natural transect calibrations laid the groundwork for examining the robustness of the triple oxygen isotope composition (δ18O, δ17O) of phytoliths as a new proxy for past changes in RH. However, it was recommended that besides RH, additional factors that may impact δ18O and δ17O of plant water and phytoliths be examined. Here, the effects of leaf anatomy, leaf development stage and day/night alternations are addressed from the growth of the grass species F. arundinacea in climate chambers. Plant water and phytoliths are analyzed in δ18O and δ17O. Silicification patterns are examined using light and scanning electron observation of phytoliths. The isotope data show the increasing contribution of evaporated epidermal water to the bulk leaf water, from sheath to proximal and apical leaf blade. However, despite this isotope heterogeneity, δ18O and δ17O of the bulk leaf water can be predicted by the Craig and Gordon model, in the given experimental conditions (high RH). Regarding phytoliths, their forming water (mainly epidermal) is, as expected, more impacted by evaporation than the bulk leaf water. This discrepancy increases from sheath to proximal and apical blade and can be explained by the steepening of the radial concentration gradient of evaporated water along the leaf. However, we show that because most of silica polymerizes in epidermal long cells of the apical blade of the leaves, the δ18O and δ17O of bulk grass phytoliths should not be impacted by the diversity in grass anatomy. The data additionally show that most of silica polymerizes at the end of the leaf elongation stage and at the transition towards leaf senescence. Thus, climate conditions at that time should be considered when interpreting δ18O and δ17O of phytoliths from the natural environment. At least, no light/dark effect was detected on the δ18O and δ17O signature of plant water and phytoliths of F. arundinacea. However, when day/night alternations are characterized by significant changes in RH, the lowest RH conditions favoring evaporation and silica polymerization should be considered when calibrating the phytolith proxy. This study contributes to the identification of the parameters driving the δ18O and δ17O of bulk grass phytoliths. It additionally brings elements to further understand and model the δ18O and δ17O of grass leaf water, which influences the isotope signal of several processes at the soil/plant/atmosphere interface.

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.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.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.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.

International audience; Extreme climatic events (ECEs) such as droughts and heat waves are predicted to increase in intensity and frequency and impact the terrestrial carbon balance. However, we lack direct experimental evidence of how the net carbon uptake of ecosystems is affected by ECEs under future elevated atmospheric CO2 concentrations (eCO2). Taking advantage of an advanced controlled environment facility for ecosystem research (Ecotron), we simulated eCO2 and extreme cooccurring heat and drought events as projected for the 2050s and analyzed their effects on the ecosystem-level carbon and water fluxes in a C3 grassland. Our results indicate that eCO2 not only slows down the decline of ecosystem carbon uptake during the ECE but also enhances its recovery after the ECE, as mediated by increases of root growth and plant nitrogen uptake induced by the ECE. These findings indicate that, in the predicted near future climate, eCO2 could mitigate the effects of extreme droughts and heat waves on ecosystem net carbon uptake.

Plant diversity positively impacts ecosystem services such as biomass production and soil organic matter (SOM) storage. Both processes counteract increasing atmospheric CO 2 concentration and global warming and consequently need better understanding. In general it is assumed that complementary resource use is driving the positive biomass effect and that the rhizospheric microbial community provides the necessary nutrients mineralizing SOM. So far however, it remains unclear how this link between the above and the belowground system is functioning; in detail it remains unclear if a more efficient CO 2 uptake at higher diversity levels leads to higher root exudation that stimulate the microbial mineralization. Contrastingly we show here for the first time that more diverse grassland communities provide a better access to root exudates for the rhizospheric community. We applied a continuous 13 CO 2 label in a controlled environment (The Montpellier European Ecotron) to ecosystem monoliths from the long-term The Jena Experiment and showed analyzing the δ 13 C content of phospholipid fatty acids and neutral lipid fatty acid that plant diversity increased the plant-derived C uptake of Gram negative bacteria and arbuscular mycorrhizal fungi (AMF). Root biomass but not the amount and δ 13 C content of root sugars positively influenced the plant diversity effect observed on Gram negative bacteria whereas the specific interaction between plant and AMF was independent from any plant trait. Our results demonstrate that plant diversity facilitated the accessibility of plant derived C but not the above-belowground transfer rates. This facilitating effect enabled more diverse plant communities to use complementary C and most likely nutrient resources both from soil organic matter mineralization for better growth. We anticipate from our results that plant diversity effects are less driven by the performance of individuals in mixtures (trait plasticity) but by the combination of individuals that interact independently (trait complementarity).

Introduction Les sarcomes sont un groupe de tumeurs tres heterogene et complexe, leur taux d’incidence en Europe est d’environ 5 pour 100 000 habitants et leur etiologie est encore inconnue et peu etudiee. Quelques facteurs de risques professionnels sont suspectes de jouer un role dans leur developpement, en particulier les pesticides. Notre objectif est d’etudier les associations entre activites et tâches professionnelles agricoles et la survenue de sarcomes. Materiel et methodes Nos analyses s’appuient sur les donnees de la cohorte prospective AGRICAN. Entre 2005 et 2007, 181 842 individus ont ete inclus, et ont rempli un questionnaire d’inclusion retracant leur histoire professionnelle et leurs expositions agricoles. Entre l’inclusion et 2013 nous avons identifie 156 cas de sarcomes incidents, dont 33 cas de GIST (tumeurs stromales gastro-intestinales) et 38 cas de myosarcomes ou fibrosarcomes. Les associations ont ete etudiees grâce a un modele de Cox avec l’âge comme echelle de temps. Resultats Plus de la moitie de notre population d’etude etait composee d’hommes (55,87 %). L’âge median a l’inclusion etait de 67 ans. Les analyses ont montre plusieurs augmentations de risque pour le sarcome. Pour les personnes faisant de l’elevage bovin pendant moins de dix ans (HR = 2,43 [1,25–4,75]), et en particulier ceux avec plus de 50 bovins (HR = 3,85 [1,40–10,61]). Mais egalement des elevations de risque non significatives, pour les eleveurs de plus de 45 volailles (HR = 1,70 [0,91–3,15]) et pour ceux utilisant des insecticides sur les volailles (HR = 1,54 [0,85–2,80]). Pour les cultures, une augmentation de risque a ete trouvee pour la culture legumiere en plein champ (HR = 1,62 [1,01–2,60]) et la culture sous serres (HR = 2,23 [1,22–4,07]). Pour les analyses par sous type, aucune association n’a pu etre mise en evidence avec les GIST. Neanmoins, malgre des effectifs faibles, des associations positives ont ete trouvees entre les myosarcomes et fibrosarcomes et certaines activites, telle que la culture legumiere en plein champ (HR = 8,75 [1,95–39,3]). Conclusions Diverses associations ont ete mises en evidence entre certains elevages (bovins, volaille) et cultures (culture legumiere, culture sous serres) et la survenue de sarcomes. Mais egalement pour les sous-types histologiques des myosarcomes et fibrosarcomes (culture legumiere), malgre de tres faibles effectifs. Enfin, notre etude apporte de nouvelles connaissances sur l’exposition professionnelle agricole et le risque de sarcome dans un contexte tres peu documente dans la litterature.

ObjectivesFarmers are considered at lower risk of lung cancer. However, specific tasks can expose them to hazardous air contaminants such as pesticides, diesel exhaust and mineral dust. This study aimed to assess the associations between various crops and related tasks and the risk of lung cancer, overall and by histological subtypes.MethodsAGRIculture and CANcer is a prospective French cohort of individuals affiliated to the agricultural health insurance scheme. Incident lung cancers (n=897) were identified by cancer registries from enrolment (2005–2007) to 2013. Data on crop and livestock exposure during lifetime were obtained from the enrolment questionnaire. We used a Cox model with attained age as timescale, adjusted for gender, smoking history and exposure to cattle and horses. Effects of duration and surface were assessed and analyses stratified on gender and smoking status were performed.ResultsWinegrowers were at higher risk of adenocarcinoma (HR=1.27 (95% CI 0.94 to 1.72)). We also found an association between pea growing and small cell lung cancer: significant effect of duration (ptrend=0.04) and the suggestion of a surface–effect relationship (ptrend=0.06); increased risk (HR=2.38 (95% CI 1.07 to 5.28)) for pesticide users; and significant effect of duration (ptrend=0.01) for harvesters. The risk of squamous cell carcinoma was increased for sunflower growing (HR=1.59 (95% CI 0.97 to 2.62), fruit-tree pruning (HR=1.44 (95% CI 0.92 to 2.27)) and pesticide use on beets (HR=1.47 (95% CI 0.92 to 2.34)). Corn and/or wheat/barley growers were at lower risk of lung cancer.ConclusionsOur results suggest associations between lung cancer and several crop-related tasks, even if we cannot rule out some chance findings due to multiple comparisons.

International audience; Inverse association between allergic conditions and glioma risk has been consistently reported in epidemiological studies with little attention paid to potential environmental confounders; the association with meningioma risk is less consistent. We examined the association between allergy history and risk of glioma and meningioma in adults using data from the CERENAT (CEREbral tumors: a NATional study) multicenter case-control study carried out in 4 areas in France in 2004-2010. Participants' histories of doctor-diagnosed allergic asthma, eczema, rhinitis/hay fever and other allergic conditions were collected at onset through a detailed questionnaire delivered in a face-to-face interview. Conditional logistic regression for matched sets was adjusted for participants' educational level and mobile phone use. A total of 273 glioma cases, 218 meningioma cases and 982 matched controls selected from the local electoral rolls were analyzed. A significant inverse association was found between glioma and a history of any allergy (OR 0.52, 95% CI 0.36-0.75), with a dose-effect relationship with the number of allergic conditions reported (p-trend = 0.001) and a particularly strong association with hay fever/allergic rhinitis (OR 0.46, 95% CI 0.30-0.72). Interestingly, associations with glioma risk were more pronounced in women. For meningioma, no association was observed with overall or specific allergic conditions. Our findings confirmed the inverse association between allergic conditions and glioma risk but questioned the role of allergy in meningioma risk. Future research is needed to clarify the biological mechanism of overall allergy and allergic rhinitis on glioma and to confirm the different effect by gender.

Objectives: To study the relations between maternal cumulative exposure to extremely low frequency electromagnetic fields (ELF EMF) and the risk of moderate prematurity and small for gestational age within the Elfe cohort. Methods: The Elfe study included 18,329 infants born at 33weeks of gestation or more in France in 2011 and was designed to follow the children until 20years of age. Gestational age and anthropometric data at birth were collected in medical records and small for gestational age was defined according to a French customized growth standard. During interviews, mothers were asked to report their job status during pregnancy. If employed, their occupation was coded according to the International Standard Classification of Occupations 1988 and the date on which they stopped their work was recorded. Cumulative exposure to ELF EMF during pregnancy was assessed, for both mothers who worked and those who did not during pregnancy, using a recently-updated job-exposure matrix (JEM). Cumulative exposure was considered as a categorical variable (

Objectives To study the relations between maternal cumulative exposure to extremely low frequency electromagnetic fields (ELF MF) and the risk of moderate prematurity and small for gestational age within the birth cohort Elfe. Methods The Elfe study included 18,329 infants born at 33 weeks of amenorrhea or more in France in 2011 and was designed to follow children until 20 years of age. Gestational age and anthropometric data at birth was collected in medical records and small for gestational age was defined according to a French customised growth standard. During interviews, mothers were asked to report their job status during pregnancy. If employed, their occupation was coded according to the ISCO-88 classification and the date on which they stopped their work was recorded. Cumulative exposure to ELF MF during pregnancy was assessed, for both mothers who worked and those who didn’t work during pregnancy, using a recently updated job-exposure matrix (JEM). Cumulative exposure was considered as a categorical variable ( Results Cumulative exposure was obtained for 96.0% of the mothers. Among them, 37.5% were classified in the 23.8–36.2 µT-days category, but high exposures were rare: 1.3% in the ≥61.6 µT-days category and 5.5% in the ≥44.1 µT-days category. No significant association was observed between maternal cumulative exposure and moderate prematurity and small for gestational age. Conclusion This large population-based study does not suggest that maternal exposure to ELF MF during pregnancy is highly associated with risk of moderate prematurity or small for gestational age.

Background Studies in farmers suggest a possible role of pesticides in the occurrence of Central Nervous System (CNS) tumours. However, scientific evidences are still insufficient because of methodological limits such as study designs, sample sizes or exposure assessments. We aimed to study the associations between occupational exposures to a range of farming activities and the incidence of primary CNS tumours, globally and by subtiles. Methods In the French prospective agricultural cohort AGRICAN, 181,842 participants completed the enrollment questionnaire over the period 2005–2011. Associations between exposures to 13 crops and 5 livestock and the risks of CNS tumours (identified through linkage to cancer registries) were estimated using Cox models with age as underlying timescale, adjusted on gender, professional status and educational level. Effects of specific tasks, duration and periods of exposure were also assessed. Results During a follow-up of 5.2 years in average, 273 incident cases of CNS tumours occurred, including 126 gliomas and 87 meningiomas. Analyses showed increased risks of CNS tumours that ranged from 10% to 85% with 11 of the 13 crops, significant in farmers growing peas and beets. Concerning gliomas, increases in risk were seen for all agricultural activities. A significant risk excess was observed in pesticide users (HR = 1.73; 95% CI: 1.05–2.84), especially in vine-growers performing treatments (HR = 1.86; 95% CI: 1.06–3.26). For meningiomas, significant positive associations were observed in sunflower growers, beet growers and hog raisers. A three-fold increased risk was seen in farmers using pesticides on potatoes (HR = 2.93; 95% CI: 1.15–7.47). Conclusion In the largest prospective agricultural cohort, we observed increased risks of CNS tumours among farmers. Even if we cannot completely rule out the contribution of other agricultural factors, pesticide exposures are our main hypothesis to explain these findings. Further analyses will explore the effects of some specific pesticides using the crop-exposure matrix PESTIMAT.

Objectifs Etudier les relations entre l’exposition cumulee aux champs electromagnetiques d’extremement basses frequences (EBFs) au cours de la grossesse et le risque de prematurite moderee et d’hypotrophie au sein de la cohorte de naissances Elfe. Methodes En 2011, 18 329 enfants nes en France metropolitaine a 33 semaines d’amenorrhee ou plus ont ete inclus dans l’etude Elfe afin de les suivre jusqu’a leurs 20 ans . L’âge gestationnel et les donnees anthropometriques a la naissance ont ete recueillis dans les dossiers medicaux et l’hypotrophie a ete calculee a partir de courbes de croissances francaises personnalisees. Lors des entretiens, les meres ont rapporte leur situation professionnelle au cours de leur grossesse. Les emplois declares ont ete codes selon la Classification Internationale Type des Professions 1988 et la date de cessation de l’activite professionnelle a ete recueillie. L’exposition cumulee aux EBFs au cours de la grossesse a ete estimee, pour l’ensemble des meres quel que soit leur situation professionnelle, grâce a une matrice emploi-exposition recemment mise a jour dans le cadre de l’etude cas-temoins internationale INTEROCC. L’exposition cumulee a ete consideree de facon categorielle ( Resultats L’exposition cumulee a ete obtenue pour 96 % des meres. Parmi elles, 38 % ont ete classees dans la categorie 23,8–36,2 μT-jours. Les hautes expositions cumulees etaient rares : 1,3 % dans la categorie ≥ 61,6 μT-jours concernant 16 professions dont les officiers mecaniciens de navire, les monteurs en appareillages electriques et les controleurs des transports publics qui avaient les plus hautes expositions journalieres. Aucune association significative n’a ete observee entre les niveaux d’exposition cumulee et la prematurite moderee ou l’hypotrophie. Conclusions Cette large etude suggere que des niveaux d’exposition maternelle aux EBFs de l’ordre de ceux rencontres en population generale ne sont pas associes au risque de prematurite moderee ou d’hypotrophie.

Continental atmospheric relative humidity (RH) is a key climate parameter. Combined with atmospheric temperature, it allows us to estimate the concentration of atmospheric water vapor, which is one of the main components of the global water cycle and the most important gas contributing to the natural greenhouse effect. However, there is a lack of proxies suitable for reconstructing, in a quantitative way, past changes of continental atmospheric humidity. This reduces the possibility of making model–data comparisons necessary for the implementation of climate models. Over the past 10 years, analytical developments have enabled a few laboratories to reach sufficient precision for measuring the triple oxygen isotopes, expressed by the 17O-excess (17O-excess = ln (δ17O + 1) – 0.528 × ln (δ18O + 1)), in water, water vapor and minerals. The 17O-excess represents an alternative to deuterium-excess for investigating relative humidity conditions that prevail during water evaporation. Phytoliths are micrometric amorphous silica particles that form continuously in living plants. Phytolith morphological assemblages from soils and sediments are commonly used as past vegetation and hydrous stress indicators. In the present study, we examine whether changes in atmospheric RH imprint the 17O-excess of phytoliths in a measurable way and whether this imprint offers a potential for reconstructing past RH. For that purpose, we first monitored the 17O-excess evolution of soil water, grass leaf water and grass phytoliths in response to changes in RH (from 40 to 100 %) in a growth chamber experiment where transpiration reached a steady state. Decreasing RH from 80 to 40 % decreases the 17O-excess of phytoliths by 4.1 per meg/% as a result of kinetic fractionation of the leaf water subject to evaporation. In order to model with accuracy the triple oxygen isotope fractionation in play in plant water and in phytoliths we recommend direct and continuous measurements of the triple isotope composition of water vapor. Then, we measured the 17O-excess of 57 phytolith assemblages collected from top soils along a RH and vegetation transect in inter-tropical West and Central Africa. Although scattered, the 17O-excess of phytoliths decreases with RH by 3.4 per meg/%. The similarity of the trends observed in the growth chamber and nature supports that RH is an important control of 17O-excess of phytoliths in the natural environment. However, other parameters such as changes in the triple isotope composition of the soil water or phytolith origin in the plant may come into play. Assessment of these parameters through additional growth chambers experiments and field campaigns will bring us closer to an accurate proxy of changes in relative humidity.

Background and Aim Epidemiological studies have reported an increased risk of Parkinson's disease (PD) in farmers exposed to pesticides, but no clear conclusion can be drawn on the type of pesticide and duration of use associated with an effect. In the French agricultural cohort AGRICAN, we assessed associations between PD and pesticide use according to the types of livestock and crops grown, including exposure to some active ingredients with duration of use. Methods Self-reported PD and history of lifetime exposure to 13 crops and 5 types of animals and pesticide use were collected at enrolment (2005-07) among 181 842 participants. Exposure to selected active ingredients and duration of use lifelong were assessed with the crop-exposure matrix PESTIMAT. Associations between pesticide use and PD were estimated by logistic regression according to crops and livestock, adjusted for sex, age, educational level, smoking status and alcohol consumption. Results PD was reported by 1732 subjects (1.2%) at enrolment in the cohort. Pesticide use lifelong was associated with an increased risk of PD in all types of activities [odds ratio (OR) = 1.31 (cattle) to 1.79 (peas), P

SummaryOptimal stomatal theory is an evolutionary model proposing that leaves trade-off Carbon (C) for water to maximise C assimilation (A) and minimise transpiration (E), thereby generating a marginal water cost of carbon gain (λ) that remains constant over short temporal scales. The circadian clock is a molecular timer of metabolism that controls A and stomatal conductance (gs), amongst other processes, in a broad array of plant species. Here, we test whether circadian regulation contributes towards achieving optimal stomatal behaviour. We subjected bean (Phaseolus vulgaris) and cotton (Gossypium hirsutum) canopies to fixed, continuous environmental conditions of photosynthetically active radiation, temperature and vapour pressure deficit over 48 hours. We observed a significant and self-sustained circadian oscillation in A and in stomatal conductance (gs) which also led to a circadian oscillation in λ. The lack of constant marginal water cost indicates that circadian regulation does not directly lead to optimal stomatal behaviour. However, the temporal pattern in gas exchange, indicative of either maximizing A or of minimizing E, depending upon time of day, indicates that circadian regulation could contribute towards optimizing stomatal responses. More broadly, our results add to the emerging field of plant circadian ecology and show that molecular controls may partially explain leaf-level patterns observed in the field.

Studies in farmers suggest a possible role of pesticides in the occurrence of Central Nervous System (CNS) tumors but scientific evidence is still insufficient. Using data from the French prospective agricultural cohort AGRICAN (AgricultureCancer), we investigated the associations between exposure of farmers and pesticide users to various kinds of crops and animal farming and the incidence of CNS tumors, overall and by subtypes. Over the 2005-2007, 181,842 participants completed the enrollment questionnaire that collected a complete job calendar with lifetime history of farming types. Associations were estimated using proportional hazards models with age as underlying timescale. During a 5.2 years average follow-up, 273 incident cases of CNS tumors occurred, including 126 gliomas and 87 meningiomas. Analyses showed several increased risks of CNS tumors in farmers, especially in pesticide users (hazard ratio = 1.96; 95% confidence interval: 1.11-3.47). Associations varied with tumor subtypes and kinds of crop and animal farming. The main increases in risk were observed for meningiomas in pig farmers and in farmers growing sunflowers, beets and potatoes and for gliomas in farmers growing grasslands. In most cases, more pronounced risk excesses were observed among pesticide applicators. Even if we cannot completely rule out the contribution of other factors, pesticide exposures could be of primary concern to explain these findings.

Studies on the dependence of the rates of ecosystem gas exchange on environmental parameters often rely on the up-scaling of leaf-level response curves ('bottom-up' approach), and/or the down-scaling of ecosystem fluxes ('top-down' approach), where one takes advantage of the natural diurnal covariation between the parameter of interest and photosynthesis rates. Partly independent from environmental variation, molecular circadian clocks drive ∼24 h oscillations in leaf-level photosynthesis, stomatal conductance and other physiological processes in plants under controlled laboratory conditions. If present and of sufficient magnitude at ecosystem scales, circadian regulation could lead to different results when using the bottom-up approach (where circadian regulation exerts a negligible influence over fluxes because the environment is modified rapidly) relative to the top-down approach (where circadian regulation could affect fluxes as it requires the passage of a few hours). Here we dissected the drivers of diurnal net CO2 exchange in canopies of an annual herb (bean) and of a perennial shrub (cotton) through a set of experimental manipulations to test for the importance of circadian regulation of net canopy CO2 exchange, relative to that of temperature and vapor pressure deficit, and to understand whether circadian regulation could affect the derivation of environmental flux dependencies. Contrary to conventional wisdom, we observed how circadian regulation exerted controls over net CO2 exchange that were of similar magnitude to the controls exerted by direct physiological responses to temperature and vapor pressure deficit. Diurnal patterns of net CO2 exchange could only be explained by considering effects of environmental responses combined with circadian effects. Consequently, we observed significantly different results when inferring the dependence of photosynthesis over temperature and vapor pressure deficit when using the top-down and the bottom up approaches. We remain indebted to E. Gerardeau, D. Dessauw, J. Jean, P. Prudent (Aïda CIRAD), J.-J. Drevon, C. Pernot (Eco&Sol INRA), B. Buatois, A. Rocheteau (CEFE CNRS), A. Pra, A. Mokhtar and the full Ecotron team, in particular C. Escape, for outstanding technical assistance during experiment set-up, plant cultivation and measurements. Earlier versions of the manuscript benefitted from comments by M. Dietze, B. Medlyn, R. Duursma and Y.-S. Lin. This study benefited from the CNRS human and technical resources allocated to the ECOTRONS Research Infrastructures as well as from the state allocation ‘Investissement d'Avenir’ ANR-11-INBS-0001, ExpeER Transnational Access program, Ramón y Cajal fellowships (RYC-2012-10970 to VRD and RYC-2008-02050 to JPF), the Erasmus Mundus Master Course Mediterranean Forestry and Natural Resources Management (MEDfOR) and internal grants from UWS-HIE to VRD and ZALF to AG. We thank the Associate Editor T. Vesala and two anonymous reviewers for their help to improve this manuscript.

Background Molecular clocks drive oscillations in leaf photosynthesis, stomatal conductance, and other cell and leaf-level processes over ~24 h under controlled laboratory conditions. The influence of such circadian regulation over whole-canopy fluxes remains uncertain; diurnal CO2 and H2O vapor flux dynamics in the field are currently interpreted as resulting almost exclusively from direct physiological responses to variations in light, temperature and other environmental factors. We tested whether circadian regulation would affect plant and canopy gas exchange at the Montpellier European Ecotron. Canopy and leaf-level fluxes were constantly monitored under field-like environmental conditions, and under constant environmental conditions (no variation in temperature, radiation, or other environmental cues). Results We show direct experimental evidence at canopy scales of the circadian regulation of daytime gas exchange: 20–79 % of the daily variation range in CO2 and H2O fluxes occurred under circadian entrainment in canopies of an annual herb (bean) and of a perennial shrub (cotton). We also observed that considering circadian regulation improved performance by 8–17 % in commonly used stomatal conductance models. Conclusions Our results show that circadian controls affect diurnal CO2 and H2O flux patterns in entire canopies in field-like conditions, and its consideration significantly improves model performance. Circadian controls act as a ‘memory’ of the past conditions experienced by the plant, which synchronizes metabolism across entire plant canopies. Electronic supplementary material The online version of this article (doi:10.1186/s13742-016-0149-y) contains supplementary material, which is available to authorized users.

Les tumeurs primitives du systeme nerveux central (SNC) regroupent plus d’une centaine de types histologiques, malins et benins. Une augmentation de l’incidence de ces tumeurs a ete observee, qui ne peut s’expliquer entierement par les progres des moyens diagnostics. Seules les radiations ionisantes et certains syndromes genetiques ont ete associes avec certitude a leur survenue. De nombreuses hypotheses etiologiques ont ete formulees, incluant des facteurs environnementaux et professionnels (pesticides, champs electromagnetiques, composes nitroses, metaux lourds, solvants…). L’analyse menee au sein du RNV3P a porte sur les codes CIM C70, C71, D43, C72, D32, D33, D35.3, D42, D44.4. Il s’agissait de decrire les expositions professionnelles principales de ces patients, avec une attention specifique pour les cas avec une imputabilite aux expositions professionnelles jugee moyenne ou forte. Entre 2001 et 2016, 376 patients atteints de tumeur du SNC ont ete enregistres dans le RNV3P. Pres des 3/4 etaient des hommes (70,5 %), d’âge median 46 ans. Parmi eux, 60 (16,0 %) etaient atteints d’une tumeur benigne, 293 (77,9 %) une tumeur maligne et 23 une tumeur d’evolution imprevisible ou incertaine. Le nombre de cas annuels enregistres dans le reseau etait inferieur a 10 avant 2005, de l’ordre d’une dizaine jusqu’en 2008 et entre 20 a 30 apres 2009. Pour 99 patients (26,3 %), la conclusion de la consultation etait celle d’une pathologie professionnelle. Pour la plupart des patients (77,2 %) une seule nuisance etait rapportee, avec un niveau d’imputation faible. Les 45 patients pour lesquels au moins une nuisance a ete associee a la tumeur avec une imputabilite moyenne (n = 40) ou forte (n = 5) etaient presque exclusivement des hommes (93,5 %), âges en moyenne de 56 ans, tous atteints d’une tumeur du SNC maligne, et d’apres les informations disponibles, de type neuro-epithelial. Concernant les expositions professionnelles, les nuisances les plus frequemment imputees a ces tumeurs etaient les pesticides (n = 15), les rayonnements ionisants (n = 5), les champs electromagnetiques (n = 6), les solvants et diluants (n = 6) et les hydrocarbures et derives (n = 4). Pour les autres patients, la nature des expositions imputees etait diverse. A noter qu’un patient atteint d’une tumeur maligne de l’encephale avait ete expose a des N-methyl-N-nitrosourees, avec un niveau d’imputation forte, et avait beneficie d’une declaration en maladie professionnelle, dans le seul tableau concernant a ce jour les tumeurs du SNC (Tableau RG 85 : glioblastomes dans le cadre des expositions a certains derives nitroses (N-methyl N’nitro N-nitrosoguanidine ; N-ethyl N’nitro N-nitrosoguanidine ; N-methyl N-nitrosouree ; N-ethyl N-nitrosouree).

Objectifs Des etudes epidemiologiques menees en population agricole evoquent le role possible des pesticides dans la survenue des tumeurs du Systeme nerveux central (SNC). En utilisant les donnees de la cohorte prospective francaise AGRICAN, nous avons etudie les associations entre l’exposition des agriculteurs et des utilisateurs de pesticides a differents types de cultures et d’elevages et l’incidence des tumeurs du SNC, globalement et par sous-types. Methodes Au cours de la periode 2005–2007, 181 842 participants ont complete le questionnaire d’inclusion qui comprenait une partie sur l’histoire professionnelle vie entiere et l’historique des activites agricoles. Les associations ont ete estimees en utilisant des modeles a risques proportionnels avec l’âge comme echelle de temps. Les analyses etaient ajustees sur le genre, le niveau d’education, le tabagisme et la consommation d’alcool. Resultats Pendant un suivi moyen de 5,2 annees, 273 cas incident de tumeurs du SNC sont survenus, dont 126 gliomes et 87 meningiomes. Les analyses ont montre plusieurs augmentations de risque de tumeurs du SNC chez les agriculteurs, en particulier chez les utilisateurs de pesticides (rapport de risques instantanes = 1,96 [1,11–3,47]). Les associations variaient selon les sous-types de tumeurs et les types de cultures et d’elevages. Les principales augmentations de risque etaient constatees pour les meningiomes chez les eleveurs porcins et chez les cultivateurs de tournesols, de betteraves et de pomme de terre et pour les gliomes chez les cultivateurs de prairies. Dans la plupart des cas, des exces de risque plus eleves etaient observes chez les applicateurs de pesticides. Conclusions Meme si nous ne pouvons pas completement exclure la contribution des autres facteurs agricoles, les expositions aux pesticides constituent notre principale hypothese pour expliquer ces resultats. Des analyses en cours exploreront le role de certaines matieres actives pesticides appartenant a la famille des carbamates dans l’incidence des tumeurs du SNC, grâce a l’utilisation de la matrice PESTIMAT.

PurposeSeveral studies and meta-analyses demonstrated that farmers have an excess risk of Non-Hodgkin Lymphomas (NHL), including Multiple Myeloma (MM). It has been suggested that pesticides could explain these results. Therefore circumstances of pesticide exposures (on crops, seeds or animals) and other farming tasks need to be explored in relation to NHL risk overall and major subtypes. From the large cohort of French farmers AGRICAN, we assessed the risk of NHL by subtypes (1) compared to the general population and (2) among farmers to identify the farm activities and tasks linked to NHLs subtypes.MethodsAGRICAN cohort enrolled more than 1 80 000 adults registered with the Mutualité Sociale Agricole, from 11 areas. Incident NHLs cases were identified by individual cross linkage with cancer registries from enrolment (2005–2007) to 2013. Lifetime work on 13 crops and 5 types of animals and the tasks performed (with duration and size information) were collected by enrollment questionnaire. Standardized incidence ratios (SIR) were calculated. Associations between NHLs and crops, animals and specific tasks were analyzed using Cox models.Results1,133 NHL incident cases were identified (269 MM, 244 chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL-SLL), and 190 diffuse large B-cell lymphoma (DLBCL)). Increased risks were observed for NHL overall and MM (SIR=1.05, and SIR=1.23, respectively). Positive associations were observed with exposure to pesticides i) on crops: DLBCL (grassland), MM (corn, wheat/barley and potato), CLL-SLL (corn, wheat/barley and vineyard) and DLBCL (tobacco), ii) in seed treatment: in CLL-SLL (sunflower, wheat/barley) and in MM (wheat/barley, corn) and iii) for use on animals (MM). Other tasks were linked to NHL risk: hay making (LDGCB) and harvesting corn (MM) and wheat/barley (CLL-SLL).ConclusionOur results supports the role of pesticide exposure on NHL risk, not only on crops. Moreover, specific associations according to NHLs subtypes were observed.

ContextExposure to inorganic arsenicals, including occupational use of pesticides, is carcinogenic to the lung (IARC group 1). However epidemiological data are scarce for agricultural exposures. This work assesses lung cancer (LC) risk, including duration-effect relationships, associated to arsenicals use in farming, by gender and histology.MethodsWe linked data from two French projects: (1) the Agriculture and Cancer (AGRICAN) cohort, a large prospective cohort of farmers and people affiliated to the French agricultural insurance scheme and (2) the Pesticide Matrix (PESTIMAT), a crop-exposure matrix. Incident lung cancer cases were collected and their histological subtype ascertained from cancer registries, from enrolment (2005–2007) to December 31 st 2013. The enrolment questionnaire included items on smoking history, and the involvement in 18 different breedings/crops and specific tasks, including pesticide application, with years of beginning and end. We performed Cox models, with age as timescale, adjusted on gender, smoking, and two activities found to be protective in previous analyses – cattle breeding and corn growing. The reference group included farmers having never applied any pesticide on any crop. We assessed risks for each inorganic compound (lead, sodium, aluminum, copper and calcium arsenate) and for overall exposure.ResultsNearly 10% (n=14 359 people) of the population was potentially exposed to arsenicals, in vineyard growing before 2001, or in fruit-tree or potato growing before 1973. We observed 98 incident LC among exposed people. Only women exhibited a higher risk of LC (HR 3.14 95% CI(1.42–6.96) for exposure to any compound, n=7 exposed cases, all adenocarcinomas), but with no duration-effect relationship. Risks were significantly elevated for lead, copper and sodium arsenate.ConclusionWe found an increased risk of LC, especially adenocarcinomas, among women. At this stage, exposure assessment was broad: the use of an exposure index, based on probability, frequency and intensity of use, will help refine the analyses.