Occupational quantitative exposure to crystalline silica, solvents, pesticides, and risk of clinical forms of systemic sclerosis.

OBJECTIVES: To estimate the association between SSc clinical phenotypes and quantitative occupational exposure to crystalline silica, chlorinated solvents, trichloroethylene, and pesticides using job-exposure matrices. METHODS: In the VISS-EXPOSITION transversal study, data on declarative occupational exposure to crystalline silica, solvents, and pesticides were retrieved. In parallel, the Lifetime Occupational History was evaluated using a questionnaire and cursus laboris for SSc patients followed at Bordeaux University Hospital (France). Using job-exposure matrices, we assessed patients' occupational exposure in relation to relevant clinical phenotypic forms of the disease. RESULTS: Toxic exposure to crystalline silica and pesticides is underestimated by patients. Non-biased job-exposure matrices retrieved more exposed patients than the declarative assessment (10.1% of patients by job-exposure matrices versus 6.3% by declaration for crystalline silica and 25.9% versus 12.2% for pesticides). Patients overestimate their solvent exposure (7.9% for chlorinated solvents and 4.8% for trichlorethylene assessed by job-exposure matrices and 24.4% declarative exposure to solvents at large). Clinical form evaluation revealed a nonsignificant trend toward an increased risk of crystalline silica occupational exposure in the pulmonary fibrotic group of SSc patients (OR 3.12 CI 95% [0.80-12.15]). We also observed a nonsignificant trend toward elevated OR (OR 2.89 CI 95% [0.93-8.95]) for chlorinated solvent occupational exposure and the vascular phenotype of SSc. Of note, pesticide occupational exposure evaluation represents one of the largest to date in SSc patients. CONCLUSION: This study emphasizes that many exposed SSc patients are unaware of their occupational exposure. Job-exposure matrices allow better exposure screening for SSc secondary prevention and occupational exposure compensation. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov, https://www.clinicaltrials.gov, NCT03543956.

Lower limb venous and arterial peripheral diseases and work conditions: systematic review.

OBJECTIVES: The individual peripheral vascular disease risk factors are well documented, but the role of work conditions remains equivocal. This systematic review aims to assess relationships between lower limb peripheral venous diseases (lower limb varicose veins (LLVV), venous thromboembolism (VTE) comprising deep vein thrombosis and pulmonary embolism), peripheral arterial disease (intermittent claudication, aortic dissection, aortic aneurysm) and occupational constraints among working adults. METHODS: Several databases were systematically searched until February 2019 for observational studies and clinical trials. Preferred Reporting Items for Systematic Reviews and Meta-Analyses method was used for article selection. Quality assessment and risk of bias were evaluated using Strengthening the Reporting of Observational Studies in Epidemiology and Newcastle-Ottawa scales. RESULTS: Among the 720 screened articles, 37 remained after full-text evaluation. Among the 21 studies on LLVV, prolonged standing was significantly associated to a higher risk of varicose veins with a threshold probably around >3 to 4 hours/day but exposure duration in years was not sufficiently considered. Seated immobility was often observed in workers, with no sufficient evidence to prove that prolonged sitting at work is related to VTE. Carrying heavy loads, stress at work and exposure to high temperatures have emerged more recently notably in relation to varicose veins but need to be better explored. Only three studies discussed the potential role of work on peripheral arterial disease development. CONCLUSIONS: Although some observational studies showed that prolonged standing can be related to varicose veins and that seated immobility at work could be linked to VTE, very little is known about peripheral arterial disease and occupational constraints. Clinical trials to determine preventive strategies at work are needed. PROSPERO REGISTRATION NUMBER: CRD42019127652.

Maternal cumulative exposure to extremely low frequency electromagnetic fields, prematurity and small for gestational age: a pooled analysis of two birth cohorts.

BACKGROUND: Data on the effects of extremely low frequency electromagnetic fields (ELF-EMF) on pregnancy outcomes are inconclusive. OBJECTIVE: To 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. METHODS: Elfe 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. RESULTS: According 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)). CONCLUSION: Some 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.

Residential proximity to power lines and risk of brain tumor in the general population.

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 at <50 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.

Allergic conditions and risk of glioma and meningioma in the CERENAT case-control study.

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.

Impact of occupational environmental stressors on blood pressure changes and on incident cases of hypertension: a 5-year follow-up from the VISAT study.

BACKGROUND: The role of occupational stressors (OS) on blood pressure (BP) is often suspected, but asserting its impact remains uncertain. Our goal was to evaluate their impact on BP increase and on incident cases of hypertension over a 5-year period. METHODS: One thousand, one hundred and fifty-six men and women from the French prospective VISAT study were followed up over five-years (T1 to T2). Exposures to a large panel of OS (physical, organizational, psychosocial and employment categories) were collected. Linear and logistic regressions were used to assess associations between OS and T2-T1 SBP difference and incident cases of hypertension. They were performed to determine the role of OS first considered separately, then in combination, in crude and adjusted models for main cardiovascular risk factors (gender, age, education, BMI, lifestyle habits and medical history). RESULTS: For initial SBP level < 130 mmHg, carrying loads, intense noise exposure, working more than 48 h/week, active and high strain tended to be associated with an SBP difference increase, while job recognition was associated with a decrease. After adjustment, only significant associations with job strain and job recognition persisted. For initial SBP level ≥ 130 mmHg, being exposed to an active job strain was positively associated with T2-T1 SBP difference only in unadjusted model. Considering all the OS, the recognition of completed tasks had a major protective role. No impact of OS on incident cases of hypertension was observed. CONCLUSION: Associations between OS and SBP were observed mainly when initial SBP is within the normal range, and are mainly explained by cardiovascular factors, requiring physician's particular attention to people exposed to these OS. VISAT study is registered in "LE PORTAIL EPIDEMIOLOGIE - FRANCE- AVIESAN -ID 3666".

Central nervous system tumors and agricultural exposures in the prospective cohort AGRICAN.

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.

Residential proximity to agricultural land and risk of brain tumor in the general population.

The effect of pesticides 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 the results concerning residential exposure are scarce. Our objective was to investigate the association between residential proximity to agricultural pesticides 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 two geographical data sources on agricultural land use to create exposure scores based on crop surface areas near the residence, for open field crops, vineyards and orchards. Conditional logistic regression for matched sets was used to estimate Odds Ratios (ORs) and 95% confidence intervals (95%CI). We found a significant association between meningioma and proximity to open field crops above the 75th percentile (OR 2.30 95%CI 1.04-5.10). Non-significant associations were also found with proximity of vineyards above the 95th percentile (OR 1.90 95%CI 0.41-8.69) and orchards above the 95th percentile (OR 5.50, 95%CI 0.49-61.94). No significant association was found between glioma and proximity to agricultural land. Further investigations are needed, particularly to improve the quality and availability of geographical data on agricultural land use.

Exposure to environmental occupational constraints and all-cause mortality: Results for men and women from a 20-year follow-up prospective cohort, the VISAT study. Be aware of shift-night workers!

Objective: To determine the predictive value of the large panel of occupational constraints (OC) on all-cause mortality with a 20-year follow-up, in general population of workers. Methods: In VISAT prospective cohort study, 3,138 workers (1,605 men; 1,533 women) were recruited during the periodic work health visits conducted by occupational physicians. OC (physical, organizational, psychological and employment categories) were collected through self-questionnaires. Exposure durations of each OC were divided by tertile distribution. Cox-regression models were performed to analyze the associations between all-cause mortality and each OC first separately and simultaneously in a single model. Results: The mortality rates were higher among exposed participants to most of OC compared to those unexposed. Being exposed and longer exposure increased the risks of all-cause mortality for exposures to carrying heavy loads, loud noise, working more than 48 h/week, starting its first job before 18 years old although these risks became non-significant after adjustments for cardiovascular risk factors. Shift work and night work confirmed a high risk of mortality whatever the adjustments and notably when the other occupational exposures were taking into account, with, respectively: HR: 1.38 (1.01-1.91) and 1.44 (1.06-1.95). After adjustments being exposed more than 13 years to a work requiring getting-up before 5:00 a.m. and more than 16 years in rotating shift work significantly increased the risk of mortality by one and a half. Conclusion: The links between each OC and all-cause mortality and the role of individual factors were stressed. For night-shift workers, it is urgent to implement preventive strategies at the workplace.

Comparison of the Effect on Fetal Growth of a Mixture of Atrazine and Nitrates in Drinking Water and of Active Tobacco Exposure during Pregnancy.

Active tobacco exposure during pregnancy is a known determinant of fetal growth. Nitrates and atrazine metabolites in drinking water may affect fetal growth as a mixture of endocrine disruptors (ED). We aimed to determine whether EDC have an additional effect on fetal growth compared to active tobacco exposure. A historic cohort study was carried out with a sample stratified with regard to the maternity unit, drinking water exposure, and year of birth. The women included were living in Deux-Sèvres, had given birth between 2005 and 2010 in three selected maternity units, and ultrasound data were available in their obstetrical records. Mixed linear models were used to analyze fetal weight evolution from the second trimester to the time of birth according to drinking water exposure to EDC mixture and active tobacco exposure. We included 558 mother-neonate couples, of whom 9% were exposed to high doses of the mixture and 21% to active tobacco smoking. There was no difference in fetal weight evolution according to drinking water mixture exposure (0.97 g; 95% CI [-3.01; 4.94]). We could not show a supplementary effect of mixture exposure in drinking-water on fetal growth as compared to active tobacco exposure. Further research is needed, using more precise methods to estimate EDC exposure.

Determinants of non-dietary exposure to agricultural pesticides in populations living close to fields: A systematic review.

BACKGROUND: There is growing evidence in the scientific literature that individuals living near fields are more exposed to agricultural pesticides than people living further away. OBJECTIVE: The main objective of this systematic review was to identify the non-dietary determinants of pesticide exposure related to the drift pathway in residents living in agricultural areas, including spatial indictors related to agricultural activities, hygiene practices, behaviors and sociodemographic parameters. METHODS: Three databases were consulted (PubMed, Web of sciences, Scopus). At least two experts selected the eligible studies. RESULTS: A total of 27 original studies (2002-2020) fulfilled the eligibility criteria of this review. These publications explored pesticide exposure of individuals through measurements in biological samples (n = 13), environmental samples (n = 11) or both (n = 3). Spatial indicators, including residential proximity to fields, crop acreage around the residence and amounts of pesticides applied in the vicinity were identified as determinants of pesticide exposure in many studies (n = 17), including publications considered to be of very good or good quality (n = 12). Season of spraying tended to increase the levels of pesticides measured in five publications out of seven. Meteorological parameters and physical barriers showed an inconsistent and complex influence on the presence and levels of pesticides in urine samples and house dust. Frequent housekeeping reduced the presence of pesticides at home and consequently in biological matrices in three studies out of six. Finally, the effect of the occupants' sociodemographic characteristics, behaviors, and hygiene practices on the exposure measurement was less well documented and results were fairly inconsistent. DISCUSSION AND CONCLUSION: This study consolidates our knowledge of the determinants influencing pesticide exposure levels in people living in agricultural areas. Nevertheless, the available scientific data is still too limited to serve as a basis for developing risk management measures. More research is needed to improve knowledge of the determinants of exposure.

Assessment of residential exposures to agricultural pesticides: A scoping review.

The assessment of residential exposure to agricultural pesticides is a major issue for public health, regulatory and management purposes. In recent years, research into this field has developed considerably. The purpose of this scoping review is to provide an overview of scientific literature characterizing residential exposure to agricultural pesticides and to identify potential gaps in this research area. This work was conducted according to the JBI and PRISMA guidelines. Three databases were consulted. At least two experts selected the eligible studies. Our scoping review enabled us to identify 151 articles published between 1988 and 2019 dealing with the assessment of residential exposure to agricultural pesticides. Of these, 98 (64.9%) were epidemiological studies investigating possible links between pesticide exposure and the onset of adverse health effects, principally cancers and reproductive outcomes. They predominantly used Geographic Information Systems and sometimes surveys or interviews to calculate surrogate exposure metrics, the most common being the amounts of pesticides applied or the surface area of crops around the dwelling. Twenty-six (17.2%) were observational measurement studies conducted to quantify levels of pesticide exposure and identify their possible determinants. These studies assessed exposure by measuring pesticides in biological and environmental matrices, mostly in urines and house dust. Finally, we found only eight publications (5.3%) that quantified the risk to human health due to residential exposure for management purposes, in which exposure was mainly determined using probabilistic models. Pesticide exposure appears to be largely correlated with the spatial organization of agriculture activities in a territory. The determinants and routes of exposure remain to be explored to improve the conduct of epidemiological and risk assessment studies and to help prevent future exposures. Improvement could be expected from small-scale studies combining different methods of exposure assessment.

[Occupational cancers: Risks and prevention]. / Les cancers professionnels : risques et prévention.

Since 2008, cancer became the first cause of death in France, exceeding cardiovascular diseases. The part of occupational cancers is close to 5% of all cancers but may still be widely underestimated. The detection of occupational cancer risk factors remains complicated. Indeed, most occupational risk factors are also present in the general environment. Thus far, 36 substances and 13 activities have been classified as carcinogenic (Group 1) and 37 substances and 6 activities have been classified as probably carcinogenic (Group 2A) by the International Agency for Research on Cancer (IARC). The most common cancer site is the lung, followed by bladder and skin (except melanoma). The most frequently observed occupational exposure was chemicals, building and construction, mining, metal production and coal transformation. Thus far, preventive actions are mandatory in occupational health in France, and are about occupational exposure monitoring, protection of vulnerable populations and reinforced medical supervision. Research must be continued to improve the knowledge on occupational carcinogens, in order to better protect the health of workers.

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.

Association of Occupational Pesticide Exposure With Immunochemotherapy Response and Survival Among Patients With Diffuse Large B-Cell Lymphoma.

Importance: Professional use of pesticides is a risk factor for non-Hodgkin lymphoma. The main biological mechanisms of pesticides and chemotherapy are genotoxicity and reactive oxygen species generation. Cellular adaptation among patients exposed to low doses of genotoxic and oxidative compounds might hinder chemotherapy efficiency in patients with lymphoma. Objective: To examine the association of occupational exposure to pesticides with immunochemotherapy response and survival among patients treated for diffuse large B-cell lymphoma. Design, Setting, and Participants: This retrospective cohort study assessed patients treated from July 1, 2010, to May 31, 2015, for diffuse large B-cell lymphoma, with a 2-year follow-up. The study took place at 6 university and nonuniversity hospitals in Languedoc-Roussillon, France. A total of 404 patients with newly diagnosed diffuse large B-cell lymphoma treated with anthracycline-based immunochemotherapy were included before the study began. Occupational history was reconstructed for 244 patients and analyzed with the PESTIPOP French job-exposure matrix to determine likelihood of occupational exposure to pesticides. Analysis of the data was performed from July 15, 2017, to July 15, 2018. Main Outcomes and Measures: Treatment failure (ie, partial response, stable disease, disease progression, or interruption for toxic effects) rate, 2-year event-free survival, and overall survival between exposed and nonexposed patients after adjustment for confounding factors. Results: A total of 244 patients (mean [SD] age, 61.3 [15.2] years; 153 [62.7%] male) had complete occupational data. Of these patients, 67 (27.4%) had occupational exposure to pesticides, with 38 exposed through agricultural occupations. Occupational exposure was not associated with clinical and biological characteristics at diagnosis. Occupationally exposed patients had a significantly higher treatment failure rate (22.4% vs 11.3%; P = .03; adjusted odds ratio [AOR] for confounding factors, 3.0; 95% CI, 1.3-6.9); this difference was higher among patients with exposing agricultural occupations compared with other patients (29.0% vs 11.7%; AOR, 5.1; 95% CI, 2.0-12.8). Two-year event-free survival was 70% in the occupationally exposed group vs 82% in the unexposed group (adjusted hazard ratio [AHR] for confounding factors, 2.2; 95% CI, 1.3-3.9). Among patients with exposing agricultural occupations compared with other patients, the difference was more pronounced (2-year event-free survival, 56% vs 83%; AHR, 3.5; 95% CI, 1.9-6.5). Similarly, 2-year overall survival was lower in the group of patients with exposing agricultural occupations compared with other patients (81% vs 92%; AHR, 3.9; 95% CI, 1.5-10.0). Conclusions and Relevance: This retrospective study showed that agricultural occupational exposure to pesticides was associated with treatment failure, event-free survival, and overall survival among patients with diffuse large B-cell lymphoma.

Pesticide use in agriculture and Parkinson's disease in the AGRICAN cohort study.

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 < 0.05]. Rotenone, diquat, paraquat and several dithiocarbamates were associated with an increased risk of PD [OR = 1.31 (cuprobam) to 1.57 (rotenone)], especially in farmers with the longest exposure. Conclusions: Our work suggests that the risk of PD is increased in farmers exposed to pesticides on several French crops and livestock, and supports additional evidence of an association of PD with dithiocarbamate fungicides, rotenone and the herbicides diquat and paraquat.

Occupational exposure to pesticides: development of a job-exposure matrix for use in population-based studies (PESTIPOP).

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.

Use of job-exposure matrices to estimate occupational exposure to pesticides: A review.

The health effects of pesticides have been extensively studied in epidemiology, mainly in agricultural populations. However, pesticide exposure assessment remains a key methodological issue for epidemiological studies. Besides self-reported information, expert assessment or metrology, job-exposure matrices still appear to be an interesting tool. We reviewed all existing matrices assessing occupational exposure to pesticides in epidemiological studies and described the exposure parameters they included. We identified two types of matrices, (i) generic ones that are generally used in case-control studies and document broad categories of pesticides in a large range of jobs, and (ii) specific matrices, developed for use in agricultural cohorts, that generally provide exposure metrics at the active ingredient level. The various applications of these matrices in epidemiological studies have proven that they are valuable tools to assess pesticide exposure. Specific matrices are particularly promising for use in agricultural cohorts. However, results obtained with matrices have rarely been compared with those obtained with other tools. In addition, the external validity of the given estimates has not been adequately discussed. Yet, matrices would help in reducing misclassification and in quantifying cumulated exposures, to improve knowledge about the chronic health effects of pesticides.

A French crop-exposure matrix for use in epidemiological studies on pesticides: PESTIMAT.

Pesticide exposure assessment is a key methodological issue for epidemiological studies. The history of pesticide has proven difficult to obtain from individuals' report because of the wide range of active ingredients (AIs). We developed a crop-exposure matrix, which intends to reconstitute parameters of pesticide exposure in France since 1950. PESTIMAT is composed of tables crossing crops and AIs by year and providing the following metrics: (1) probability (proportion of farmers having used the AIs); (2) frequency (number of treatment days); and (3) intensity (application rate of the AIs in kg/ha). Metrics were obtained by the combination of six sources: (i) registration information from the Agriculture Ministry; (ii) information from agricultural bodies on products marketed; (iii) agricultural recommendations by the Plant Health Protection body; (iv) treatment calendars provided by farmers; (v) data from associations of farmers; and (vi) data from the industry. To date, 529 AIs usable between 1950 and 2010 are included in PESTIMAT: 160 fungicides; 160 herbicides; and 209 insecticides. When combined with duration and determinants of intensity, the metrics in PESTIMAT will make it possible to calculate exposure scores and to search for dose-effect relationships, an important criterion for causality judgment in epidemiology.