OBJECTIVE:To assess the association between parental occupational pesticide exposures at birth and adult testicular germ cell tumour (TGCT) by histological subtype and the agreement between two pesticide job-exposure matrices (JEM). METHODS:TGCT cases (n=454) and matched controls (n=670) aged 18-45 years were recruited from 20 French university hospitals into the TESTIS national case-control study. Paternal and maternal jobs at birth were obtained from interviews of participants and their mothers/relatives and coded into official nomenclatures (International Standard Classification of Occupations, French nomenclature of activity-1999). Two complementary JEMs, ALOHA+ and FRIJEM, assessed occupational exposure to all pesticides, herbicides, insecticides, fungicides with ALOHA+ for each parent by linking job titles to JEM-derived probability and intensity estimates (no/low/high). Cohen's Kappa coefficient (κ) assessed their agreement. ORs and 95% CIs comparing exposure and levels of exposure with no exposure were estimated using conditional logistic regression adjusted for literature-based covariates statistically associated with TGCT and stratified by histological subtypes. RESULTS:Agreement between ALOHA+and FRIJEM was moderate to substantial (κ 0.52-0.80). A statistically non-significant higher TGCT risk was observed for high paternal occupational pesticide exposure with ALOHA+ (OR 1.95, CI 0.98 to 3.84) and FRIJEM (OR 1.70, CI 0.88 to 3.28). With ALOHA+, statistically significant positive associations were seen for high paternal occupational exposure to herbicides (overall: OR 4.23, CI 1.75 to 10.22; seminomas: OR 4.78, CI 1.79 to 12.77; non-seminomas: OR 3.53, CI 1.21 to 10.3) and fungicides (overall: OR 2.09, CI 1.05 to 4.18; seminomas: OR 2.31, CI 1.02 to 5.23). No statistically significant associations were observed for other levels of paternal exposure or pesticide groups nor for maternal exposure. CONCLUSION:Only high paternal occupational exposure to pesticides at birth, especially herbicides and fungicides, was positively associated with TGCT.

BACKGROUND:Despite an incidence increase in recent decades, the etiology of testicular germ cell tumors (TGCT) remains poorly understood. The hypothesis of a two-stage development, combining initial alteration in utero followed by malignant transformation later in life, has been suggested. This study examined the association between cumulative lifetime occupational and para-occupational solvent exposure and TGCT risk. METHODS:The French multicenter case-control study TESTIS included 454 cases and 670 controls. Participants provided information on their occupational history; participants' mothers (N = 547) provided information on their own and the father's occupational history. Solvent exposure was assessed by using the Matgéné job-exposure matrices. The influence of the parental and subject's occupational exposures over the lifetime and at different periods (i.e. fetal life/infancy; childhood; adolescence; subject's exposure) on TGCT was examined. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by using conditional logistic regression models. RESULTS:An OR for TGCT of 1.03 (95% CI 0.59-1.79) was found for the lifetime solvent exposure. When each period was examined individually, the results showed an increased TGCT risk in adult males who were occupationally exposed to trichloroethylene (OR = 3.09; 95% CI 1.25-7.65); fuels and petroleum-based solvents (OR = 1.91; 95% CI 1.21-3.02); diesel, kerosene, and fuel oil (OR = 2.26; 95% CI 1.16-4.41); and ketones and esters (OR = 1.66; 95% CI 1.02-2.71), and suggested a positive association with solvent exposure during adolescence (OR = 1.77; 95% CI 0.95-3.31). CONCLUSION:Overall, this study did not suggest a substantial role of cumulative lifetime solvent exposure and TGCT risk. The results showed an increased TGCT risk associated with solvent exposure during adulthood. Indirect exposure to certain solvents during adolescence might also promote TGCT development.

Research question Does maternal occupational exposure to endocrine-disrupting chemicals (EDCs) during pregnancy affect reproductive hormone levels in adult sons? Design We analyzed data from a cross-sectional study of 2,326 Swiss conscripts collected between 2005 and 2017. At inclusion, the conscripts’ mothers completed a detailed questionnaire about their pregnancy. A job-exposure matrix was used to assess exposure to 10 categories of potential EDCs. Reproductive hormones, such as FSH, LH, total and free testosterone, estradiol and SHBG, were determined in serum samples from all conscripts whose mothers were exposed to EDCs during pregnancy (n=138) and a random sample of non-exposed conscripts (n=276). Multiple linear regression analyses were adjusted for potential confounders. Results Prenatal exposure to phthalates or alkyl phenolic compounds was significantly associated with higher FSH levels (aβ = 0.26; 95% CI = 0.03-0.49, and aβ = 0.22; 95% CI = 0.02-0.42, respectively) and prenatal exposure to pesticides was significantly associated with higher SHBG levels (aβ = 0.22; 95% CI = 0.05-0.38). No statistically significant associations were found between other EDC categories and reproductive hormones. Conclusion Maternal occupational exposure to certain types of EDCs during pregnancy was associated with the levels of reproductive hormones in adult sons. These findings require replication in larger, prospective population studies.

RESEARCH QUESTION:Does maternal occupational exposure to endocrine-disrupting chemicals (EDC) during pregnancy affect reproductive hormone concentrations in adult sons? DESIGN:Data from a cross-sectional study of 2326 Swiss conscripts collected between 2005 and 2017 were analysed. On inclusion, the conscripts' mothers completed a detailed questionnaire about their pregnancy. A job-exposure matrix was used to assess exposure to 10 categories of potential EDC. Reproductive hormones - FSH, LH, total and free testosterone, oestradiol and sex hormone-binding globulin (SHBG) - were determined in serum samples from all conscripts whose mothers were exposed to EDC during pregnancy (n = 138) and a random sample of non-exposed conscripts (n = 276). Multiple linear regression analyses were adjusted for potential confounders. RESULTS:Prenatal exposure to phthalates or alkyl phenolic compounds was significantly associated with higher FSH concentrations (aβ = 0.26, 95% CI 0.03-0.49, and aβ = 0.22, 95% CI 0.02-0.42, respectively) and prenatal exposure to pesticides was significantly associated with higher SHBG concentrations (aβ = 0.22, 95% CI 0.05-0.38). No statistically significant associations were found between other EDC categories and reproductive hormones. CONCLUSIONS:Maternal occupational exposure to certain types of EDC during pregnancy was associated with the concentrations of reproductive hormones in adult sons. These findings require replication in larger, prospective population studies.

INTRODUCTION:The problem of transcoding is recurrent when researchers wish to link occupational data from cohorts to Job-Exposure Matrices (JEMs) which were not set up in the same classifications. The Occupational Asthma-specific JEM (OAsJEM) is a JEM developed for assessing exposure to agents known at risk for asthma for jobs coded with ISCO88 occupation classification. To apply the OAsJEM in the CONSTANCES cohort, in which jobs and industries were coded with French PCS2003 and NAF2008 classifications respectively, we developed a crosswalk to convert jobs from PCS2003 into ISCO88 classification. METHODS:This work was carried out by 2 skilled coders and 1 novice coder who have worked independently by using different tools and transcoding strategies defined a priori. Consensus meetings were organized with skilled coders to define the final crosswalk. This work was elaborated in 2 steps: (i) for 38 ISCO88 codes classified as potentially exposed to cleaning and disinfection products by the OAsJEM, and (ii) for all jobs from the ISCO88 classification. A comparison between the 3 initial coder's crosswalk proposals and the final crosswalk was made for the 38 ISCO codes in step (i). RESULTS:The final crosswalk provided 998 matches between the 482 4-digit PCS2003 codes, 308 4-digit ISCO88 codes, and 31 3-digit ISCO88 codes. Information regarding the NAF2008 industry classification was also used in some cases to improve the final crosswalk. For the selected 38 ISCO88 codes, the final crosswalk provided 110 combinations, but the number of proposed ISCO88-PCS2003 couples by each of the 3 coders varied greatly from 68 to 153. In addition, an important variability between the 3 coders were observed among the number of common combinations between the initial coder's proposals and the final crosswalk (from 47% to 78%). DISCUSSION:We have developed a crosswalk specifically for an application of the OAsJEM in population-based surveys using the PCS2003 occupation classification. The development of this crosswalk is of great interest for the use of OAsJEM on the data of the CONSTANCES cohort and on any other survey with occupational data coded according to the French classifications. This OAsJEM crosswalk could be used by other teams to evaluate occupational exposures known to be at risk of asthma from occupational calendars coded with French classifications.

OBJECTIVES: Etiological factors of testicular germ cell tumors (TGCT) remain largely unknown, but a causal role of occupational exposures to solvents has been suggested. Previous studies analyzing these exposures reported discordant results, potentially related to exposure assessment methods. The aim of this study was to investigate the role of occupational exposure to solvents on the risk of developing TGCT among young men. METHODS: This study examined occupational exposures to solvents and TGCT risk based on the lifetime work histories of 454 cases and 670 controls, aged 18–45 years, of the French national TESTIS case–control study. Solvent exposure was estimated using: (i) exposure assignment by job-exposure matrix (JEM) and (ii) JEM combined with self-reported exposure data from specific questionnaires (SQ) and expert assessment (EA). Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression models. RESULTS: Both approaches (JEM and JEM+SQ+EA) showed a consistent association between TGCT and trichloroethylene exposure (exposed versus not exposed; JEM=OR 1.80 [95% confidence interval (CI) 1.12–2.90] and JEM+SQ+EA= OR 2.59 (95% CI 1.42–4.72). Both approaches also observed positive associations with ketone esters and fuels & petroleum-based solvents. CONCLUSION: The results suggest that some organic solvents might be involved in the pathogenesis of TGCT among occupationally exposed men. The combined use of JEM+SQ+EA seemed to limit misclassification by considering individual exposure variability and is, therefore, an appealing approach to assess occupational exposures in epidemiological studies.

ObjectivesThe impact of chronic occupational exposures to irritants on asthma remains discussed. We studied the associations between occupational exposures and asthma, with specific interest for chronic exposure to irritants, including disinfectants and cleaning products (DCPs) and solvents.MethodsCross-sectional analyses included 115 540 adults (55% women, mean age 43 years, 10% current asthma) working at inclusion in the French population-based CONSTANCES cohort (2012–2020). Current asthma was defined by ever asthma with symptoms, medication or asthma attacks (past 12 months), and the asthma symptom score by the sum of 5 respiratory symptoms (past 12 months). Both lifetime and current occupational exposures were assessed by the Occupational Asthma-specific Job-Exposure Matrix. Associations were evaluated by gender using logistic and binomial negative regressions adjusted for age, smoking status and body mass index.ResultsIn women, associations were observed between current asthma and lifetime exposure to irritants (OR 1.05, 95% CI 1.00 to 1.11), DCPs (1.06, 95% CI 1.00 to 1.12) and solvents (1.06, 95% CI 0.98 to 1.14). In men, only lifetime exposure to DCPs (1.10, 95% CI 1.01 to 1.20) was associated with current asthma. Lifetime exposure to irritants was associated with higher asthma symptom score both in women (mean score ratio: 1.08, 95% CI 1.05 to 1.11) and men (1.11, 95% CI 1.07 to 1.15), especially for DCPs (women: 1.09, 95% CI 1.06 to 1.13, men: 1.21, 95% CI 1.15 to 1.27) and solvents (women 1.14, 95% CI 1.10 to 1.19, men: 1.10, 95% CI 1.05 to 1.15). For current exposures, no consistent associations were observed with current asthma and asthma symptom score.ConclusionsLifetime occupational exposures to irritants were associated with current asthma and higher asthma symptom score. These exposures should be carefully considered in asthma management.

BackgroundTesticular germ cell tumors (TGCT) are the most frequent cancer in young men in developed countries. Parental occupational exposures during early-life periods are suspected to increase TGCT risk. The objective was to estimate the association between parental occupations at birth and adult TGCT.MethodsA case–control study was conducted, including 454 TGCT cases aged 18–45 from 20 French university hospitals, matched to 670 controls based on region and year of birth. Data collected from participants included parental jobs at birth coded according to the International Standard Classification of Occupation—1968 and the French nomenclature of activities—1999. Odds ratios (OR) for TGCT and 95% confidence intervals (CI) were estimated using conditional logistic regression, adjusting for TGCT risk factors.ResultsPaternal jobs at birth as service workers (OR = 1.98, CI 1.18–3.30), protective service workers (OR = 2.40, CI 1.20–4.81), transport equipment operators (OR = 1.96, CI 1.14–3.37), specialized farmers (OR = 2.66, CI 1.03–6.90), and maternal jobs as secondary education teachers (OR = 2.27, CI 1.09–4.76) or in secondary education (OR = 2.35, CI 1.13–4.88) were significantly associated with adult TGCT. The risk of seminoma was increased for the above-mentioned paternal jobs and that of non-seminomas for public administration and defence; compulsory social security (OR = 1.99, CI 1.09–3.65); general, economic, and social administration (OR = 3.21, CI 1.23–8.39) for fathers; and secondary education teacher (OR = 4.67, CI 1.87–11.67) and secondary education (OR = 3.50, CI 1.36–9.01) for mothers.ConclusionSome paternal jobs, such as service workers, transport equipment operators, or specialized farmers, and maternal jobs in secondary education seem to be associated with an increased risk of TGCT with specific features depending on the histological type. These data allow hypotheses to be put forward for further studies as to the involvement of occupational exposures in the risk of developing TGCT, such as exposure to pesticides, solvents, or heavy metals.

L’étiologie des tumeurs germinales du testicule (TGT) est encore inconnue, mais un rôle causal de l’exposition professionnelle aux solvants a été suggéré. Cependant, peu d’études sur ces expositions ont été menées et celles disponibles montrent des résultats discordants, du fait des différences d’exposition dans les populations suivies et des méthodes d’évaluation de l’exposition permettant une évaluation plus ou moins fine. Une mauvaise classification de l’exposition peut conduire à une estimation erronée du risque. Les matrices emplois-expositions (MEE) et les questionnaires spécifiques à une exposition (QS) sont les outils les plus largement utilisés. Notre objectif était d’évaluer le rôle des expositions professionnelles aux solvants sur le risque de développer un TGT, par l’évaluation combinée de deux méthodes, les MEE (approche no 1) et les MEE combinées aux données obtenues via QS (approche no 2). Les 1124 participants de l’étude nationale cas-témoins TESTIS ont fourni des informations sur leurs historiques professionnels qui ont été codés par un hygiéniste industriel selon deux nomenclatures : la CITP68 pour la profession et la NAF93 pour la branche d’activité. L’accord entre les deux méthodes (MEE et MEE-QS) a été testé à l’aide des Kappas de Cohen. L’élaboration de règles de décision pour statuer sur les emplois « discordants », complétées par l’intervention d’un expert a permis d’obtenir une évaluation combinant les deux méthodes. Un score d’exposition cumulé (SEC) a ensuite été calculé sur l’ensemble du parcours professionnel. Le SEC a été catégorisé en « non exposé », « faiblement » et « hautement exposé », en fonction de la médiane parmi les témoins exposés. Les odds ratios (OR) et intervalles de confiance à 95 % ont été estimés pour chaque solvant. Quarante-sept pour cent des hommes étaient exposés à au moins un solvant durant leur carrière professionnelle. Les Kappa de Cohen ont montré une faible concordance entre les deux méthodes (−0,01 à 0,27). Les deux approches ont montré une association positive entre le TGT et l’exposition au trichloroéthylène, et ce risque semblait augmenter avec le niveau d’exposition. Selon l’approche no 1, la catégorie des « faiblement exposés » aux cétones-esters (OR low = 1,74 ; IC95 % : 1,10–2,74), aux carburants et solvants pétroliers (OR low = 1,47 ; IC95 % : 1,05–2,05) a montré une association positive avec le risque de TGT. L’approche no 2 a montré une augmentation du risque pour les mêmes solvants, mais pour la catégorie des plus fortement exposés (OR high = 1,50 ; IC95 % : 1,01–2,24, OR high = 1,61 ; IC95 % : 1,11–2,33, respectivement). L’évaluation de l’exposition professionnelle est une étape critique et complexe dans l’épidémiologique des risques professionnels. Les outils communément utilisés présentent diverses limites. L’OR élevé observé pour la catégorie des faiblement exposés dans l’approche no 1 a été affiné par l’approche no 2. L’utilisation combinée des deux méthodes d’évaluation semble être une approche intéressante pour prendre en compte les expositions spécifiques de certains emplois tout en tenant compte des variations individuelles, et limiter ainsi les erreurs de classement. Cette approche permet également de réduire l’ampleur du travail d’évaluation par expert. Cette étude suggère une augmentation du risque de TGT chez les hommes exposés professionnellement aux solvants.

OBJECTIVES: The etiology of testicular germ cell tumors (TGCT) is suspected to be related to prenatal environmental risk factors. Some solvents have potential endocrine disrupting or carcinogenic properties and may disrupt male genital development in utero. The aim of this study was to examine the association between parental occupational exposure to solvents and TGCT risk among their offspring. METHODS: A French nationwide case–control study, TESTIS included 454 TGCT cases and 670 controls frequency-matched on region and 5-year age strata. Participants were interviewed via telephone and provided information on parental occupations at birth. Job-exposure matrices (JEM) developed in the French Matgéné program were used to assign exposure to five petroleum-based solvents, five solvents or groups of oxygenated solvents, and five chlorinated solvents. Odds ratios (OR) for TGCT and 95% confidence intervals (CI) were estimated using conditional logistic regression, adjusting for TGCT risk factors. RESULTS: Occupational exposure to at least one solvent during the year of their son’s birth was 41% among fathers and 21% among mothers. Paternal exposure to at least one solvent showed OR 0.89 (95% CI 0.68–1.15). Exposure to perchloroethylene (OR 1.41, 95% CI 0.55–3.61), methylene chloride (OR 1.13, 95% CI 0.54–2.34) and diesel/kerosene/fuel oil (OR 1.17, 95% CI 0.80–1.73) disclosed OR >1 but with low precision. Our results suggest a possible modest increase in non-seminoma risk for sons whose fathers were highly exposed to trichloroethylene (OR 1.44, 95% CI 0.79–2.63). Maternal exposure to at least one solvent showed OR 0.90 (95% CI 0.65–1.24). When stratifying by birth year, men born in the 1970s experienced an increased TGCT risk following maternal exposure to fuels and petroleum-based solvents (OR 2.74, 95% CI 1.11–6.76). CONCLUSION: Overall, no solid association was found between parental occupational exposure to solvents and TGCT risk. The association found with maternal occupational exposure to fuels and petroleum solvents among older men needs further investigation.

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.

Background: In developed countries, about 15% of women are occupationally exposed to solvents. Associations between this maternal occupational exposure and intrauterine fetal growth are inconsistent, but almost no existing study has investigated this relation by solvent family (oxygenated, petroleum, and chlorinated), although they may affect fetal growth differently.Objectives: To investigate the relations between maternal occupational solvent exposure, by solvent family, and the risk of neonates born small for gestational age (SGA), or with low birthweight, or with small head circum-ference (HC).Methods: Among the 18,040 women enrolled in the Elfe rather than included in the Elfe birth cohort, we included 13,026 women who worked during pregnancy (72% of the cohort). Information about maternal occupations and industrial activities during pregnancy was collected by questionnaire at the maternity ward, and completed at 2 -month when necessary. Using Matge acute accent ne acute accent job-exposure matrices, we assessed maternal occupational exposure to solvents. Logistic and multiple linear regressions were used to assess the association between maternal occu-pational solvent exposure and SGA status, birth weight, and HC. Analyses were conducted for exposure during pregnancy and also stratified by the trimester that pregnancy leave began.Results: We observed a higher risk of SGA newborns among mothers occupationally exposed during pregnancy to petroleum solvents (ORadjusted = 1.26; 95%CI: 1.01 to 1.57). Among women working until the third trimester of pregnancy, we observed a higher risk of SGA newborns to those occupationally exposed to oxygenated solvents (ORadjusted = 1.75; 95%CI: 1.11 to 2.75), a significantly lower birthweight for infants of mothers exposed to petroleum solvents (beta adjusted =-47.37 g;-89.33 to-5.42), and a lower HC among newborns of those occu-pationally exposed to oxygenated solvents (beta adjusted =-0.28;-0.49 to-0.07) and to chlorinated solvents (beta adjusted =-0.29;-0.53 to-0.05).Discussion: Our results suggest that maternal occupational solvent exposure may influence fetal growth, espe-cially exposure into the third trimester of pregnancy.

Aim The biological mechanisms of work-related asthma induced by irritants remain unclear. We investigated the associations between occupational exposure to irritants and respiratory endotypes previously identified among never asthmatics (NA) and current asthmatics (CA) integrating clinical characteristics and biomarkers related to oxidative stress and inflammation. Methods We used cross-sectional data from 999 adults (mean 45 years old, 46% men) from the case-control and familial Epidemiological study on the Genetics and Environments of Asthma (EGEA) study. Five respiratory endotypes have been identified using a cluster-based approach: NA1 (n=463) asymptomatic, NA2 (n=169) with respiratory symptoms, CA1 (n=50) with active treated adult-onset asthma, poor lung function, high blood neutrophil counts and high fluorescent oxidation products level, CA2 (n=203) with mild middle-age asthma, rhinitis and low immunoglobulin E level, and CA3 (n=114) with inactive/mild untreated allergic childhood-onset asthma. Occupational exposure to irritants during the current or last held job was assessed by the updated occupational asthma-specific job-exposure matrix (levels of exposure: no/medium/high). Associations between irritants and each respiratory endotype (NA1 asymptomatic as reference) were studied using logistic regressions adjusted for age, sex and smoking status. Results Prevalence of high occupational exposure to irritants was 7% in NA1, 6% in NA2, 16% in CA1, 7% in CA2 and 10% in CA3. High exposure to irritants was associated with CA1 (adjusted OR aOR, (95% CI) 2.7 (1.0 to 7.3)). Exposure to irritants was not significantly associated with other endotypes (aOR range: 0.8 to 1.5). Conclusion Occupational exposure to irritants was associated with a distinct respiratory endotype suggesting oxidative stress and neutrophilic inflammation as potential associated biological mechanisms.

This study of endotypes responsible for the development of irritant induced occupational asthma raises questions as to what is meant by a respiratory irritant. Classifying an exposure as irritant usually implies that the effect is nonspecific, that is, all similar asthmatics would react to the exposure whether they have had previous exposure to the agent or not. For instance, sulphur dioxide is a respiratory irritant, the exposure needed to provoke asthma is correlated with the degree of preexisting nonspecific reactivity, as measured with methacholine or histamine. The paper by Andrianjafimasy et al uses a job exposure matrix (JEM) whose list of irritants includes the best known lowmolecularweight respiratory sensitisers, such as isocyanates, acrylates, epoxy resins and amines where there is no evidence of airflow obstruction in previously unexposed, or exposed asymptomatic workers induced by exposures that can cause severe reactions in sensitised individuals. Reactive low molecular weight chemicals may act as haptens, binding to body protein creating neoantigens. The action of biocides denaturing proteins may have a similar effect again leading to specificity in the airway response. The mechanisms, and perhaps susceptibility to reactions with specificity is likely to differ from agents which lack specificity. Labelling a chemical as a sensitiser should lead to better control than adding an irritant label, which risks degrading the significance of the exposure, similar to classifying an exposure as a ‘nuisance’ dust. We believe that labelling a substance as an irritant needs as much evidence as labelling a chemical as a sensitiser. The potential for a lowmolecularweight chemical to act as a sensitiser can often be predicted from its chemical structure. We may need an additional category where the mechanism awaits elucidation, such as exhaust fumes and textile dust where there are studies appearing to show some specificity of the airway responses.

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.

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.

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 MATGÉNÉ 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.

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, ethoxyethoxyacetic 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.