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International audience; Objectives: To investigate the association between exposure to unintentionally emitted carbonaceous nanoscale particles (NPs) and small for gestational age (SGA), as well as head circumference (HC) at birth and at two years of age.Methods: Mothers from the French Longitudinal Study of Children (Elfe cohort) who worked during pregnancy were selected for our study. Data collected at birth and during follow-up (up to two years) were used. The probability and frequency of maternal occupational exposure to unintentionally emitted carbonaceous NPs was estimated using a job exposure matrix (MatPUF). Multivariate logistic regression, linear regression, and mixed models were applied to estimate any associations. Analyses were carried out depending on whether mothers stopped working during the first, second, or third trimester of pregnancy.Results: Maternal occupational exposure to unintentionally emitted carbonaceous NPs was associated with SGA in the overall study population by multivariate analysis (ORa = 1.80, 95% CI: 1.29, 2.46), as well as in sub-groups of mothers who stopped working during the second (ORa = 1.84, 95% CI: 1.13, 3.02) or third (ORa = 1.80, 95% CI: 1.10, 2.95) trimesters. There were no significant associations with HC at birth or two years of age.Conclusions: We found a significant association between occupational exposure to carbonaceous NPs and SGA, with the effect depending on the period of exposure during pregnancy. These results should encourage further studies concerning the adverse effects of exposure to carbonaceous NPs on the development of offspring.

International audience; Objectives: Nanoscale particles (1-100 nm) can be of natural origin, and either intentionally or unintentionally produced by human activities. Toxicological data have suggested a possible carcinogenic effect of such particles. The aim of this study was to estimate the association between occupational exposure to nanoscale particles and risk of lung cancer, pleural mesothelioma and brain tumors in adults.Methods: Three French population-based case-control studies were analyzed: 1) the ICARE study including 2,029 lung cancer cases and 2,591 controls; 2) the PNSM study including 371 pleural mesothelioma cases and 730 controls and 3) the CERENAT study including 257 brain tumor cases and 511 controls. Occupational exposure to unintentionally emitted nanoscale particles (UNPs) was retrospectively assessed by a job exposure matrix providing a probability and a frequency of exposure.Results: In adjusted analyses among men, significant associations between occupational exposure to UNPs and lung cancer (OR=1.51; 95% CI: 1.22-1.86 and brain tumors (OR=1.69; 95% CI: 1.17-2.44) were observed. No increased OR was observed for pleural mesothelioma (OR=0.78; 95% CI: 0.46-1.33).Conclusion: This is the first study showing positive associations between occupational exposure to UNPs and increased risk of lung cancer and brain tumors. These preliminary results should encourage further epidemiological research.

Objectives: To investigate the association between maternal occupational exposures to nanoscale particles (NPs) during pregnancy and small for gestational age (SGA). Methods: This study included 11,224 mothers and singleton birth pairs from the French Longitudinal Study of Children (ELFE cohort), which included infants born after 33 weeks of gestation or more in continental France in 2011. Mothers who did not work during pregnancy were excluded from the analyses. Maternal occupational exposures to NPs was estimated using a job-exposure matrix for the probability (>50%: occupationally exposed group, n = 569; 0%: occupationally non-exposed group, n = 9113; between these two thresholds: uncertain group, n = 1542) and frequency of exposure. Associations were estimated from multivariate logistic regression models for occupationally exposed vs occupationally unexposed groups in a first analysis, and with the frequency-weighted duration of work for the occupationally exposed group only in a second analysis. Results: Among working mothers, 5.1% were occupationally exposed to NPs. Maternal occupational exposures to NPs was associated with SGA (ORa = 1.63, 95% CI: 1.22, 2.18). The frequency-weighted duration of work for the occupationally exposed group (n = 569) was not associated with SGA (ORa = 1.02, 95% CI: 0.97, 1.08) in adjusted analyses. Conclusions: These results, showing a significant association between occupational exposures to NPs and SGA, should encourage further studies to examine the adverse effect of NPs exposure on fetal development. Keywords: Small for gestational age, Occupational exposures, Nanoscale particles, Job-exposure matrix, ELFE cohort

The aim of this study was to investigate the hypothesis of an increased risk of pleural mesothelioma due to co-exposure to asbestos and refractory ceramic fibres (RCF) compared to asbestos exposure alone. Males were selected from a French case-control study conducted in 1987-1993 and from the French National Mesothelioma Surveillance Program in 1998-2006. Two population controls were frequency matched to each case by year of birth. Complete job histories were collected and occupational asbestos and RCF exposures were assessed using job exposure matrices. The dose-response relationships for asbestos exposure were estimated from an unconditional logistic regression model in subjects exposed to asbestos only (group 1) and subjects exposed to both asbestos and RCF (group 2). A total of 988 cases and 1125 controls ever-exposed to asbestos were included. A dose-response relationship was observed in both groups but it was stronger in group 2. In comparison with subjects exposed at the minimum value of the cumulative index of exposure, the odds ratio was 2.6 (95% CI 1.9-3.4) for subjects exposed to 75 fibres · mL(-1) · year(-1) in group 1 increasing to 12.4 (95% CI 4.6-33.7) in group 2. Our results suggest that the pleural carcinogenic effect of occupational asbestos exposure may be modified by additional exposure to RCF.

Aims Unintentional nanoscale particles (UNP) are generated from usual work processes and thus exist since a long time and are more prevalent than the manufactured nanoscale particles. The objective of this study was to develop a job-exposure matrix, a useful tool to estimate prevalence of occupational exposure to UNP for epidemiologic studies. . Methods Work-processes generating UNP and their associated chemical families have been identified through an extensive literature review and the knowledge of an expert’s panel in various domain such as industrial hygiene, toxicology, atmospheric physics and chemistry, epidemiology… These processes were associated to occupations extracted from the ISCO classification edition 1968. A probability and a frequency were assessed for each specific combination “occupation × work-process”. When an occupation was related to several work-processes, the final exposure assessment consisted in the highest probability of exposure and a weighted-frequency of exposure combining assessments from each related work-process. Exposure assessment for some specific occupations could differ according to industries and historical periods. Due to the few available measurement data, intensity could not be assessed at that time. Results Over 50 work-processes generating UNP have been identified and were related with seven UNP chemical families: metal, mineral, carbon, wood, polymer, polycyclic aromatic hydrocarbon (PAH) and other organic. A little less than 50% occupational ISCO codes were unexposed, and 9%, 13% and 31% were possibly, probably and certainly exposed, respectively. Most of occupations were exposed to carbonaceous, PAHs UNP and then to metallic and mineral UNP. Conclusions These results suggest that occupational exposure to UNP might be important at the workplace and might concern a wide variety of workers. In order to assess intensity of exposure, we are currently organising measurement campaigns in French and Canadian workplaces (ExproPNano program).

Introduction Nanoscale particles (1-100 nm) may be naturally occurring; intentionally-produced for commercial purposes or unintentionally-produced by manufacturing processes or human activities. Toxicological data have suggested a possible carcinogenic effect of nanoscale particles and have shown that they have the ability to translocate into different organs including the brain. While epidemiological data on nanoscale particles are very scarce to date, there is some suggestion of their potential role in cancer (e.g. diesel exhaust emissions classified as carcinogenic for humans by IARC). The objective of this study was to estimate the association between occupational exposure to nanoscale particles and risk of brain tumour in adults. Methods The CERENAT study is a multicenter case-control study carried out in four districts of France between 2004 and 2006. From detailed occupational histories, occupational exposure to unintentionally-produced nanoscale particles was retrospectively assessed by the MatPUF job exposure matrix providing a probability and frequency of exposure for each combination occupation × industry according to international and national classifications. Conditional logistic regression was used to estimate ORs and 95% CIs. Results Overall, 596 brain tumour cases and 1192 matched controls were included in this study. Among men, a significant association between occupational exposure to nanoscale particles and brain tumour was observed (OR = 1.5; 95% CI: 1.1–2.2). This increased OR was essentially observed in the highest exposure categories (OR = 1.6; 95% CI: 1.1–2.4 for a total duration of exposure over 30 years) as well as for carbonaceous (OR = 1.5; 95% CI: 1.1–2.3) and HAP nanoscale particles (OR = 1.6; 95% CI: 1.1–2.4). Conclusion Even if these preliminary results should be confirmed by other analyses including the intensity of exposure (on-going work in a further version of the job-exposure matrix), these results should encourage further epidemiological research on nanoscale particles.

Asbestos is the primary cause of pleural mesothelioma (PM). The objective of this study was to elucidate the importance of different temporal patterns of occupational asbestos exposure on the risk of PM using case–control data in male subjects. Cases were selected from a French case–control study conducted in 1987–1993 and the French National Mesothelioma Surveillance Program in 1998–2006. Population controls were frequency matched to cases by year of birth. Occupational asbestos exposure was evaluated with a job–exposure matrix. The dose–response relationships were estimated using restricted cubic spline functions in logistic regression models. A total of 2,466 ever-asbestos-exposed males (1,041 cases and 1,425 controls) were used. After adjustment for intensity and total duration of occupational asbestos exposure, the risk of PM was lower for subjects first exposed after the age of 20 yrs and continued to increase until 30 yrs after cessation of exposure. The effect of total duration of exposure decreased when age at first exposure and time since last exposure increased. These results, based on a large population-based case–control study, underline the need to take into account the temporal pattern of exposure on risk assessment.

Background Occupational exposure to asbestos, widely used in various industries for decades, is the most important risk factor for pleural mesothelioma. We report here the ranking of occupations and industries in France at high risk for this cancer among men and women. Methods A population-based case–control study, conducted from 1998 to 2002, included 462 cases (80.3% men) and 897 controls. Data were collected in face-to-face interviews with a standardized questionnaire. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each occupation and industry; subjects never employed in each category were the reference. Results For men, risks were high for several occupations and industries. Besides the expected high risks for non-metallic mineral product makers and manufacturing asbestos products, occupations such as plumbers (OR ¼ 5.57, 95% CI: 2.90–10.69), sheet-metal workers, welders, metal molders, coremakers, and cabinetmakers were also at high risk. Elevated risks were found in the industries of shipbuilding (OR ¼ 9.13, 95% CI: 5.20– 16.06) and construction, but also in the manufacturing of metal products, chemicals, and railroad and aircraft equipment. The results for women showed increased but not significant risks in several occupational activities. Conclusions This report provides new insight into the epidemiology of mesothelioma, confirming risks for occupational activities reported earlier and pointing out risks in activities never previously reported. It offers guidance to authorities for the compensation of asbestos victims and for prevention in at-risk activities still involving asbestoscontaining products. Am. J. Ind. Med. 53:1207–1219, 2010. 2010 Wiley-Liss, Inc.

Objectives To estimate the proportion of pleural mesothelioma cases that can be attributed to asbestos exposure in France including non-occupational exposure. Methods A population-based case-control study including 437 incident cases and 874 controls was conducted from 1998 to 2002. Occupational and non-occupational asbestos exposure was assessed retrospectively by two expert hygienists. ORs of pleural mesothelioma for asbestos-exposed subjects compared to non-exposed subjects, and population-attributable risk (ARp) of asbestos exposure were estimated using a conditional logistic regression. Results A clear dose-response relationship was observed between occupational asbestos exposure and pleural mesothelioma (OR=4.0 (99% CI 1.9 to 8.3) for men exposed at less than 0.1 f/mL-year vs 67.0 (99% CI 25.6 to 175.1) for men exposed at more than 10 f/mL-year). The occupational asbestos ARp was 83.1% (99% CI 74.5% to 91.7%) for men and 41.7% (99% CI 25.3% to 58.0%) for women. A higher risk of pleural mesothelioma was observed in subjects non-occupationally exposed to asbestos compared to those never exposed. The non-occupational asbestos ARp for these subjects was 20.0% (99% CI −33.5% to 73.5%) in men and 38.7% (99% CI 8.4% to 69.0%) in women. When considering all kinds of asbestos exposure, ARp was 87.3% (99% CI 78.9% to 95.7%) for men and 64.8% (99% CI 45.4% to 84.3%) for women. Conclusions Our study suggests that the overall ARp in women is largely driven by non-occupational asbestos exposure arguing for the strong impact of such exposure in pleural mesothelioma occurrence. Considering the difficulty in assessing domestic or environmental asbestos exposure, this could explain the observed difference in ARp between men and women.

Background More than 80% of mesothelioma cases in men are attributable to occupational asbestos exposure compared to only 40% in women. The objective of the study was to characterize a series of female pleural mesotheliomas according to known and suspected risk factors. Methods From the exhaustive recording of 318 female mesothelioma cases in the French National Mesothelioma Surveillance Program between 1998 and 2009, multiple correspondence analysis and hybrid clustering were performed to characterize these cases according to expert assessed occupational and non-occupational exposure to asbestos and man-made vitreous fibers, X-ray exposure, and history of cancer and non-malignant respiratory diseases. Results Four clusters were identified: (1) occupational exposure to asbestos and man-made vitreous fibers (7.9% of subjects); (2) radiation exposure during radiotherapy (12.9%); (3) increased asbestos exposure (19.8%); and (4) “non-exposure” characteristics (59.4%). Conclusion These results will allow hypotheses to be generated about associations between mesothelioma and non-occupational asbestos exposure, X-ray exposure and history of respiratory disease. Am. J. Ind. Med. 56:1307–1316, 2013. © 2013 Wiley Periodicals, Inc.

International audience; Pleural 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.