Qualitative and Semiquantitative Assessment of Exposure to Engineered Nanomaterials within the French EpiNano Program: Inter- and Intramethod Reliability Study

The relatively recent development of industries working with nanomaterials has created challenges for exposure assessment. In this article, we propose a relatively simple approach to assessing nanomaterial exposures for the purposes of epidemiological studies of workers in these industries. This method consists of an onsite industrial hygiene visit of facilities carried out individually and a description of workstations where nano-objects and their agglomerates and aggregates (NOAA) are present using a standardized tool, the Onsite technical logbook. To assess its reliability, we implemented this approach for assessing exposure to NOAA in workplaces at seven workstations which synthesize and functionalize carbon nanotubes. The prediction of exposure to NOAA using this method exhibited substantial agreement with that of the reference method, the latter being based on an onsite group visit, an expert’s report and exposure measurements (Cohen kappa = 0.70, sensitivity = 0.88, specificity = 0.92). Intramethod comparison of results for exposure prediction showed moderate agreement between the three evaluators (two program team evaluators and one external evaluator) (weighted Fleiss kappa = 0.60, P = 0.003). Interevaluator reliability of the semiquantitative exposure characterization results was excellent between the two evaluators from the program team (Spearman rho = 0.93, P = 0.03) and fair when these two evaluators’ results were compared with the external evaluator’s results. The project was undertaken within the framework of the French epidemiological surveillance program EpiNano. This study allowed a first reliability assessment of the EpiNano method. However, to further validate this method a comparison with robust quantitative exposure measurement data is necessary

Attributable risk in men in two French case-control studies on mesothelioma and asbestos

International audiencePleural mesothelioma is a primary tumor of the pleura that is mainly due to asbestos exposure. To study the relationship between mesothelioma and occupational asbestos exposure in France, two case-control studies (A and B) were conducted. A substantial difference in the attributable risk in the population (AR) was observed among men: 44.5% (95% CI: [32.6-56.4]) in study A and 83.2% (95% CI: [76.8-89.6]) in study B. As different exposure assessment expert methods were used, the main objective of this work was to re-estimate the AR men in two case-control studies according to a common standardized exposure assessment by using a Job Exposure Matrix (JEM) and to assess the role of subjects' selection. The initial observed AR difference was maintained: 36.3% (95% CI: [24.3-50.3]) in study A and 69.7% (95% CI: [51.7-83.2]) in study B. Further investigations highlighted the potential selection bias introduced in both studies, especially among controls. The AR could be underestimated in study A and overestimated in study B. After weighting subjects according to distribution of socio-economic status in the general population for controls and according to distribution of socio-economic status of cases registered by the French National Mesothelioma Surveillance Program, re-estimated AR values were 52.4% in study A and 70.2% in study B. These results provide additional information to describe the relationship between pleural mesothelioma and occupational asbestos exposure, but also confirm the importance of subjects' recruitment in case control studies, particularly control selection

Integrated approach to assess individual exposure to ultrafine particles (UFPs) in epidemiological studies

Les particules ultrafines ou PUF (< 100 nm) sont émises non intentionnellement par de nombreuses sources suggérant leur présence dans tout l’environnement. Si leur potentiel de toxicité a bien été démontré, les preuves de leur impact sanitaire chez l’Homme sont limitées face à la complexité de mesurer les PUF. Dans ce contexte, nous proposons de développer une démarche globale pour évaluer les expositions aux PUF dans tous les milieux en s’appuyant sur la mesure indirecte des expositions (non instrumentale). Des méthodes d’évaluation ont été construites sous la forme d’une matrice emplois-exposition (MatPUF), et d’une matrice activité-environnement exposition (MA2E) en s’appuyant sur l’identification des procédés émetteurs de PUF. Elles fournissent pour chaque individu l’exposition moyenne passée ou actuelle dans ses emplois et au cours de ses activités au domicile. L’exposition peut être ajustée au plus près de la situation réelle de chaque individu par la mise à disposition de questionnaires. En complément de ces méthodes indirectes, une approche d’analyse et de traitement des données de mesure en temps réel a été proposée pour affiner les connaissances sur les expositions professionnelles. A l’issue de la thèse, les données d’exposition aux PUF dans le milieu ambiant seront apportées dans le cadre d’une collaboration avec le réseau de la surveillance de la qualité de l’air. A terme, une démarche intégrée d’évaluation des expositions individuelles aux PUF sera mise à disposition des épidémiologistes et permettra d’améliorer les connaissances sur l’impact sanitaire de ces particules.Ultrafine particles or UFPs (< 100 nm) are emitted unintentionally from numerous sources, suggesting their presence in all environment. While their potential toxicity has been well demonstrated, evidence of their impact on human health is limited by the complexity of measuring UFPs. In this context, we propose to develop a global approach to assessing exposure to UFPs in all environments, based on indirect exposure measurements (non-instrumental). Assessment methods have been developed in the form of a jobs-exposure matrix (MatPUF), and an activity-environment-exposure matrix (MA2E), based on the identification of UFP-emitting processes. For each individual, they provide average exposure at work and during activities at home. Exposure can be adjusted as closely as possible to the actual situation of each individual, using questionnaires. As a complement to these indirect methods, an approach to analyzing and processing real time measurement data has been proposed to refine our knowledge of occupational exposures. At the end of the thesis, data on exposure to UFPs in the ambient environment will be provided as part of a collaboration with the air quality monitoring network. Ultimately, an integrated approach to assessing individual exposure to UFPs will be available to epidemiologists, improving knowledge of the health impact of these particles

Rev Epidemiol Sante Publique

Introduction Nanoscale particles (NPs) are sized between 1 and 100nm. Based on experimental animal studies on NPs and epidemiological studies on air pollution particles, maternal inhalation of NPs may constitute a hazard to fetal development. It is plausible that NPs may translocate from the respiratory tract to the placenta and fetus, but also adverse effects may occur following a maternal systemic inflammatory response. The aim of this study was to investigate the association between maternal occupational exposure to unintentional nanoscale particles (UNP) during pregnancy and small for gestational age (SGA) within the ELFE cohort. Methods Analyzes were based on data from ELFE cohort that included 18,329 infants born at 33 weeks of amenorrhea or more in France in 2011. Sociodemographic characteristics, detailed information on jobs held by mothers during pregnancy, lifestyle and clinical data were collected through a standardized questionnaire administered at birth. Medical files were consulted to supplement relevant maternal and newborn medical information. Mothers who did not work during pregnancy were excluded from analyses. Maternal occupational exposure to UNP was characterized with a job-exposure matrix by frequency and probability of exposure. Mothers who, during pregnancy, held jobs with a probability of exposure greater than 50% were considered to be exposed. Odd ratios (OR) and 95% confidents intervals (CI) were estimated from logistic regression models adjusted for smoking, marital status, maternal education, monthly household income, high blood pressure during pregnancy, gestational diabetes and alcohol consumption during pregnancy. Results The study sample included 11,224 mother-child pairs. Among mothers who worked during pregnancy, 5.07% were exposed to UNP. Maternal occupational exposure to UNP was significantly associated with SGA (OR=1.63, 95% CI: 1.22, 2.18) in adjusted analyzes. In a sub-analysis conducted in exposed mothers group (n=569), the total duration of work during pregnancy weighted by the frequency of exposure was not associated with SGA (OR=1.02, 95% CI: 0.97, 1.08) in adjusted analyzes. Conclusion This is the first epidemiological study showing a significant association between maternal occupational exposure to UNP and SGA. These results are consistent with those of the toxicological studies that demonstrated the toxicity of NPs on pregnancy. This preliminary research needs to be deepened by further epidemiological studies