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Testicular cancer is the most common cancer in young men. Its causes are largely unknown, although prenatal occupational and environmental exposures have been suggested. We investigated paternal occupational exposure to heavy metals and welding fumes and the risk of testicular germ cell tumors (TGCT) in their offspring. A total of 454 cases and 670 controls were included from a French nationwide case–control study. The INTEROCC job exposure matrix was used to assign occupational exposures (cadmium, chromium, iron, nickel, lead, and welding fumes) to the fathers’ jobs. Odds ratios (ORs) for TGCT were estimated using conditional logistic regression models for frequency-matched sets. Three complementary analytical approaches were used: (1) single-agent analysis, (2) analysis by groups, and (3) principal component analysis (PCA). The proportion of paternal exposure to different heavy metals and welding fumes ranged from 0.7% (cadmium) to 11.3% (lead). Based on PCA, three principal components explained 93.5% of the cumulative variance. No associations were found between heavy metals or welding fumes and TGCT. In this study, paternal occupational exposure to heavy metals or welding fumes was not associated with TGCT development in their sons.

ObjectiveTesticular germ cell tumours (TGCT) are the most common cancer in men of working age and its incidence has increased notably over the past 40 years. Several occupations have been identified as potentially associated with TGCT risk. The aim of this study was to further explore the relationship between occupations, industries and TGCT risk in men aged 18–45 years.MethodsThe TESTIS study is a multicenter case–control study conducted between January 2015 and April 2018 in 20 of 23 university hospital centers in metropolitan France. A total of 454 TGCT cases and 670 controls were included. Full job histories were collected. Occupations were coded according to the International Standard Classification of Occupation 1968 version (ISCO-1968) and industry according to the 1999 version of Nomenclature d’Activités Française (NAF-1999). For each job held, ORs and 95% CIs were estimated using conditional logistic regression.ResultsA positive association was observed between TGCT and occupation as agricultural, animal husbandry worker (ISCO: 6–2; OR 1.71; 95% CI (1.02 to 2.82)), as well as salesman (ISCO: 4–51; OR 1.84; 95% CI (1.20 to 2.82)). An increased risk was further observed among electrical fitters and related, electrical and electronics workers employed for 2 years or more (ISCO: 8–5; OR≥2 years1.83; 95% CI (1.01 to 3.32)). Analyses by industry supported these findings.ConclusionsOur findings suggest that agricultural, electrical and electronics workers, and salesmen workers experience an increased risk of TGCT. Further research is needed to identify the agents or chemicals in these high-risk occupations which are relevant in the TGCT development.Trial registration numberNCT02109926.

The biological mechanisms involved in asthma caused by occupational irritants remain poorly understood. Occupational exposure to irritants may be associated to a specific asthma endotype. We aimed to study the associations between occupational exposure to irritants and asthma profiles identified by a cluster analysis integrating clinical characteristics and biomarkers related to oxidative stress and inflammation. We analyzed data from 997 adults from the second phase of the EGEA study (mean age: 45 years, 46% men). Exposure to irritants at the current job was assessed by a new asthma-specific job exposure matrix (http://oasjem.vjf.inserm.fr/), with 3 levels of exposure (no/medium/high). Logistic regression models adjusted for age, sex and smoking were used to study the associations between occupational exposure to irritants and each profile (P). Predominant characteristics of the profiles were: P1 asymptomatic (n=463); P2 respiratory symptoms without asthma (n=167); P3 adult-onset asthma, poor lung function, respiratory symptoms, highest oxidative stress-related biomarker and neutrophil levels (n=50); P4 paucigranulocytic asthma, normal lung function (n=203); P5 childhood-onset asthma, highest IgE level (n=114). In P1, 9% had high exposure to irritants, 10% in P2, 22% in P3, 8% in P4 and 12% in P5. High exposure to irritants was associated with P3 (vs. P1, Odds Ratio (OR) [95%CI]=2.8 [1.2-6.5]). Occupational exposure to irritants was not associated with other profiles (OR range:0.9-1.3). Results suggest that occupational exposure to irritants was related to an asthma endotype characterized by poor lung function, respiratory symptoms, oxidative stress and neutrophilic inflammation.

Background/aim Occupational exposure is a risk factor for asthma. However, its impact on asthma control, the main target of asthma management, has rarely been studied. The healthy worker effect (HWE) can affect occupational studies. We aimed to investigate the effect of occupational exposures on asthma control in a longitudinal study, taking into account a potential HWE by a marginal structural model (MSM). Methods Analyses were conducted in EGEA (Epidemiological study on the Genetics and Environment of Asthma), a case-control and family-based study (EGEA1: 1991–1995), with 2 follow-ups (EGEA2: 2003–2007; EGEA3: 2011–2013). Occupational exposure (no, ‘irritants and/or low level of chemicals/allergens’, ‘known asthmagens’) was defined using an asthma-specific job-exposure matrix. Asthma control was defined using international guidelines (GINA 2014); subjects with partly controlled/uncontrolled asthma were compared to those with controlled or non-current asthma. Associations between occupational exposures and asthma control were evaluated among subjects with asthma using (1) a standard pooled multinomial logistic model and (2) a MSM to control the HWE modelled as a time-varying confounding situation. Results Asthma was partly controlled or uncontrolled in 39% of person-periods (n=822). Occupational exposure to ‘irritants and/or low level of chemicals/allergens’ and to ‘known asthmagens’ was observed in 14% and 13% of all person-periods, respectively. In the standard analysis, after adjustment for age, sex, smoking status and time period, no statistically significant association was found between exposure to ‘irritants and/or low level of chemicals/allergens’ (OR [95% CI]: 0.91 [0.58–1.41]) or ‘known asthmagens’ (1.27 [0.79–2.04]) and partly controlled/uncontrolled asthma. Using the MSM, the association remained similar for exposure to ‘irritants and/or low level of chemicals/allergens’ (0.86 [0.55–1.35]) whereas the association increased for ‘known asthmagens’ (1.55 [0.96–2.52], p=0.08). Conclusion No significant association between occupational exposure and asthma control was observed; however after correcting for a HWE using a MSM, a positive association between exposure to known asthmagens and partly controlled or uncontrolled asthma was suggested. Results support the presence of a healthy worker effect in the study and the deleterious effect of exposure to asthmagens on asthma control.

International audience; OBJECTIVES: To describe urine levels of metabolites of glycol ethers and chlorinated solvents in a sample of pregnant women from the general population, to study their occupational and non-occupational determinants and to compare them with the results of indirect assessment methods of solvent exposure. METHODS: A sample of 451 pregnant women was randomly selected from a general population cohort. At inclusion, the women in this sample completed a self-administered questionnaire about their social and medical characteristics, occupation and exposure to different products at work and in non-occupational activities. Occupational exposure to solvents was assessed from the woman's self-report and from a job-exposure matrix. Eight alkoxycarboxylic acids and trichloroacetic acid and trichloroethanol were measured with chromatography in urine samples collected at inclusion. Associations between metabolite levels and job titles, exposure to products used at work, and solvent exposure were studied. RESULTS: The different glycol ether metabolites were detected in 5.3%-96.4% of the urine samples, trichloroacetic acid in 6.4% and trichloroethanol in 5.5%. Nurses had butoxyacetic acid and phenoxyacetic acid in their urine most often, whereas methoxyethoxyacetic acid was the most frequent among nursing aides. Among cleaners, ethoxyacetic acid and ethoxyethoxyacetic acid were the most frequent. The occupation of hairdresser was associated with urinary excretion of ethoxyacetic acid, ethoxyethoxyacetic acid, butoxyacetic acid and phenoxyacetic acid. Among the women classified as exposed to solvents, the agents identified most often were ethoxyacetic acid, ethoxy-ethoxyacetic acid, butoxyacetic acid, phenoxyacetic acid, trichloroacetic acid and trichloroethanol. Ethoxyethoxyacetic acid was the only metabolite associated with non-occupational exposure. CONCLUSIONS: Metabolites of glycol ethers and chlorinated solvents were present at low levels in the urine of pregnant women. Most metabolites were associated with occupational exposure.

International audience; OBJECTIVES: To examine the association between maternal occupational exposure to mixtures of organic solvents during pregnancy and the risk of non-syndromic oral clefts. METHODS: A case-control study (164 cleft lip with/without cleft palate (CL/P), 76 cleft palate (CP), 236 controls) was conducted in France to investigate the role of maternal occupational exposure to organic solvents at the beginning of pregnancy in the risk of non-syndromic oral clefts. An expert chemist, guided by a detailed description of the women's occupational tasks, assessed exposure for each. Analysis of the findings used logistic regression. RESULTS: In the control group, 39% of the women who reported working during pregnancy were exposed to at least one type of organic solvent. The risk of oral clefts was associated with oxygenated (for CL/P: OR = 1.8, 95% CI 1.1 to 2.9; and for CP, OR = 1.4, 95% CI 0.7 to 2.7), chlorinated (OR = 9.4, 95% CI 2.5 to 35.3; OR = 3.8, 95% CI 0.7 to 20.7), and petroleum (OR = 3.6, 95% CI 1.5 to 8.8; OR = 1.2, 95% CI 0.3 to 4.9) solvents. The risk of oral clefts increased linearly with level of exposure within the three subgroups of oxygenated solvents we considered (aliphatic alcohols, glycol ethers, and other oxygenated solvents, including esters, ketones, and aliphatic aldehydes). CONCLUSIONS: Results suggest that maternal occupational exposure to organic solvents during pregnancy may play a role in the aetiology of oral clefts. The limited number of subjects and the problem of multiple exposures require that these results be interpreted cautiously.

Objectives: Trichloroethylene (TCE) is suspected of association with elevated risk of cervical cancer. A case–control study was performed in a geographical area in which occupational TCE exposure is high. The study objective was to analyze the correlation between occupational TCE exposure and cervical cancer (including precancerous conditions). Methods: Case and control subjects were recruited by gynecologists. General and occupational data were collected by telephonic interviews. An industrial hygienist assessed occupational TCE exposure on a task-exposure matrix. Analysis focused on occupational TCE exposure at various levels and on cumulative dose. Multivariate analysis was performed to take account of the various risk factors. Results: In total, 67 case and 67 age-matched control subjects were included. Mean age was 36 years in both groups. Five of the possible general risk factors correlated significantly with cervical dysplasia or cancer: number of partners, history of genital or anal wart, interval between first period and first sexual relation, parity, and body mass index, the last three showing inverse correlation. Elevated risk was found in women who had had jobs as manual workers according to the PCS French classification (professions and socioprofessional categories), and production and related workers according to ISCO classification (International Standard Classification of Occupations), with odds ratios (ORs), adjusted on general and medical risk factors, of 7.68 [95% confidence interval (CI): 1.39–42.54] and 7.48 (1.30–43.24), respectively, among skilled service sector workers; the adjusted OR was close to significance, at 4.67 (95% CI: 0.92–23.67). No occupational sectors were significantly associated with elevated risk. In all, 17 (25.4%) case and 15 (22.4%) control subjects were exposed to TCE: raw OR = 1.17 (95% CI: 0.54–2.52), adjusted OR = 1.51 (95% CI: 0.42–5.41). There was no significant correlation between cumulative dose and exposure time. Conclusions: The study found no significantly increased risk of cervical dysplasia or cancer associated with occupational TCE exposure.

Objectives Matgene is a program to develop job-exposure matrices (JEMs) adapted to the general population in France for the period since 1950. The aim is to create retrospective exposure assessment tools for estimating the prevalence of occupational exposure to various agents that can then be correlated to health-related parameters. Methods JEMs were drawn up by a team of six industrial hygienists who based their assessments on available occupational measurement, economic and statistical data, and several thousand job descriptions from epidemiological studies performed in France since 1984. Each JEM is specific to one agent, assessing exposure for a set of homogeneous combinations (occupation × activity × period) according to two occupational classifications (ISCO 1968 and PCS 1994) and one economic activities classification (NAF 2000). The cells of the JEM carry an estimate of the probability and level of exposure. Level is estimated by the duration and intensity of exposure-linked tasks or by description of the tasks when exposure measurement data are lacking for the agent in question. The JEMs were applied to a representative sample of the French population in 2007, and prevalence for each exposure was estimated in various population groups. All documents and data are available on a dedicated website. Results By the end of 2010, 18 JEMs have been developed and eight are under development, concerning a variety of chemical agents: organic and mineral dust, mineral fibers, and solvents. By implementation in the French population, exposure prevalences were calculated at different dates and for complete careers, and attributable risk fractions were estimated for certain pathologies. Some of these results were validated by comparison with those of other programs. Discussion Initial Matgene JEMs results are in agreement with the French and international literature, thus validating the methodology. Exposure estimates precision, however, vary between agents and according to the amount of exposure measurement data available. These JEMs are important epidemiological tools, and improving their quality will require investment in occupational health data harvesting, especially in the case of low-level exposures.

Objectives Investigating the role of occupational exposure to solvents in the occurrence of lymphoid neoplasms (LNs) in men. Methods The data were generated by a French hospital-based case-control study, conducted in six centres in 2000–2004. The cases were incident cases aged 18–75 years with a diagnosis of LN. During the same period, controls of the same age and gender as the cases were recruited in the same hospitals, mainly in the orthopaedic and rheumatological departments. Exposure to solvents was assessed using standardised occupational questionnaires and case-by-case expert assessment. Specific quantification of benzene exposure was attempted. The analyses included 491 male patients (244 cases of non-Hodgkin9s lymphoma (NHL), 87 of Hodgkin9s lymphoma, 104 of lymphoproliferative syndrome and 56 of multiple myeloma) and 456 male controls. Unconditional logistic regressions were used to estimate OR and 95% CI. Results Solvent exposure, all solvents considered together, was marginally associated with NHL (OR=1.4 (1.0 to 2.0) p=0.06), but not with other LNs. No association with the main chemical series of solvents was observed. There was no trend with the average intensity or frequency of exposure. Exposure to pure benzene was not significantly related to NHL (OR=3.4 (0.8 to 15.0)). The highest maximum intensities of benzene exposure were associated with diffuse large cell lymphoma (OR=2.1 (1.0 to 4.6)). Conclusion The results of the present study provide estimates compatible with the hypothesis that exposures to pure benzene and high benzene intensities may play a role in some NHL. There was no evidence for a role of other organic solvents in the occurrence of LN.

Objectives To use job-exposure matrices (JEM), as a tool to describe trends of occupational exposure to carcinogenic chemicals present in the French workplace. Method MATGENE JEMs assess for each job and a given period in France, several exposure indices such as probability, intensity and frequency of exposure. Linking these matrices with job information data coming from French population allow to estimate the prevalence of workers exposed to several chemicals for a given year. To study the evolution of exposure to carcinogens, prevalence of exposure in France for the years 1999 and 2007 were estimated from the population census of 1999 and from a representative sample of the population in 2007. Results French available JEMs assess the exposure of workers since the 1950s for various occupational carcinogens: crystalline silica, benzene, trichlorethylene, perchlorethylene, leather dust, asbestos and refractory ceramic fibres (RCF). A significant decrease in the prevalence of exposure between 1999 and 2007 was observed among men for silica with 7.4% and 5.6% respectively, asbestos with 6.3% and 1.1% and RCF with 0.5% and 0.3%. For women, a significant decrease was also noticed for exposure to asbestos and leather dust. For solvents, the prevalence of exposure remained stable in both men and women. Conclusions The proportion of workers exposed to carcinogens, particularly to asbestos, has decreased in France since 1999. However a substantial number of workers are still exposed. As complete occupational histories are available in the 2007 population sample, the JEMs will also be used to estimate lifetime exposure prevalence and the associated disease burden.

Glycol ethers are found in a wide range of domestic and industrial products, many of which are used in women's work environments. Motivated by concern about their potential reproductive toxicity, we have evaluated the risk of congenital malformations related to glycol ether exposure during pregnancy as part of a multicenter case-control study, conducted in six regions in Europe. The study comprised 984 cases of major congenital malformations and 1,134 controls matched for place and date of birth. Interviews of the mothers provided information about occupation during pregnancy, sociodemographic variables, and other potential risk factors (medical history, tobacco, alcohol, drugs). A chemist specializing in glycol ethers evaluated exposure during pregnancy, using the job description given by the mother, without knowledge of case or control status. We classified malformations into 22 subgroups. The overall odds ratio (OR) of congenital malformation associated with glycol ether exposure was 1.44 [95% confidence interval (CI) = 1.10-1.90], after adjustment for several potential confounders. The association with exposure to glycol ethers appeared particularly strong in three subgroups: neural tube defects (OR = 1.94; 95% CI = 1.16-3.24), multiple anomalies (OR = 2.00; 95% CI = 1.24-3.23), and cleft lip (OR = 2.03; 95% CI = 1.11-3.73). In this last subgroup, risk, especially of an isolated defect, tended to increase with level of exposure.