Maternal occupational exposure to endocrine-disrupting chemicals during pregnancy and semen parameters in adulthood: results of a nationwide cross-sectional study among Swiss conscripts.

STUDY QUESTION: Is there a relationship between maternal occupational exposure to endocrine-disrupting chemicals (EDCs) during pregnancy and the semen quality of their sons? SUMMARY ANSWER: Our results suggest an association between maternal occupational exposure to potential EDCs, especially to pesticides, phthalates and heavy metals, and a decrease in several semen parameters. WHAT IS KNOWN ALREADY: Sexual differentiation, development and proper functioning of the reproductive system are largely dependent on steroid hormones. Although there is some animal evidence, studies on maternal exposure to EDCs during pregnancy and its effect on the semen quality of sons are scarce and none have focused on maternal occupational exposure. STUDY DESIGN, SIZE, DURATION: A cross-sectional study aiming to evaluate semen quality was carried out among Swiss conscripts aged 18 to 22 years between 2005 and 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: Conscript and parent questionnaires were completed prior to the collection of a semen sample. Semen parameters were categorised according to the guidelines of the World Health Organization (WHO). Data on maternal employment during pregnancy were provided by the parent questionnaire. Maternal occupational exposure to potential EDC categories was defined using a job-exposure matrix (JEM). Logistic regressions were used to analyse the relationship between maternal occupational exposure to EDCs and each semen parameter adjusted for potential confounding factors. Results are presented using odds ratios and 95% confidence intervals. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 1,737 conscripts provided a conscript and parent questionnaire, as well as a semen sample; among these 1,045 of their mothers worked during pregnancy. Our study suggests an association between occupational exposure of mothers during pregnancy to potential EDCs and low semen volume and total sperm count, particularly for exposure to pesticides (OR 2.07, 95% CI 1.11-3.86 and OR 2.14, 95% CI 1.05-4.35), phthalates (OR 1.92, 95% CI 1.10-3.37 and OR 1.89, 95% CI 1.01-3.55), and heavy metals (OR 2.02, 95% CI 1.14-3.60 and OR 2.29, 95% CI 1.21-4.35). Maternal occupational exposure to heavy metals was additionally associated with a low sperm concentration (OR 1.89, 95% CI 1.06-3.37). LIMITATIONS, REASONS FOR CAUTION: Several limitations should be noted, such as the indirect method for maternal occupational exposure assessment during the pregnancy (JEM) and the cross-sectional design of the study. WIDER IMPLICATIONS OF THE FINDINGS: Our observations reinforce the need to inform pregnant women of potential hazards during pregnancy that could impair their child's fertility. Additional studies are needed to confirm the involvement of EDCs. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Swiss Centre for Applied Human Toxicology: SCAHT and the 'Fondation privée des Hôpitaux Universitaires de Genève'. The collection of human biological material used for this study was supported by the FABER Foundation, the Swiss National Science Foundation (SNSF): NFP 50 'Endocrine Disruptors: Relevance to Humans, Animals and Ecosystems', the Medical Services of the Swiss Army (DDPS) and Medisupport. The authors declare they have no competing financial interests. TRIAL REGISTRATION NUMBER: N/A.

Occupational exposure to organic solvent mixtures during pregnancy and the risk of non-syndromic oral clefts.

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.

Risk of lung cancer in workers producing stainless steel and metallic alloys.

OBJECTIVES: The mortality of workers involved in the production of stainless and alloyed steel from 1968 to 1992 was studied, in order to investigate the risk of lung cancer due to exposure to metals, i.e. iron oxides, chromium and/or nickel compounds. METHODS: The study design was a historical cohort mortality study and a nested case-control study concerning lung cancer. Standardized mortality ratios (SMRs) were computed using regional mortality rates as an external reference for comparing observed and expected numbers of deaths, adjusting for age, sex and calendar time. Conditional logistic regression was used to estimate odds ratios (ORs). Occupational exposure was assessed through the complete job histories of cases and controls and a specific job-exposure matrix. RESULTS: The cohort comprised 4,288 male and 609 female workers. The observed overall mortality was significantly lower than expected [649 deaths; SMR = 0.91; 95% confidence interval (CI) 0.84-0.98]. No significant SMR was observed for mortality from lung cancer (54 deaths; SMR = 1.19; CI 0.88-1.55). The case-control study was based on 54 cases and 162 individually matched controls. Smoking habits were available for 71%. No lung cancer excess was observed for exposure to (1) metals and/or their compounds, i.e. iron (OR = 0.94, CI 0.48-1.86), chromium and/or nickel (OR = 1.18, CI 0.62-2.25), and cobalt (OR =0.64, CI 0.33-1.25), (2) acid mists (OR = 0.43, CI 0.17-1.10), and (3) asbestos (OR = 1.00, CI 0.54-1.86). With respect to exposure to polycyclic aromatic hydrocarbons (PAHs) and silica, which are often found together in workplaces, (1) high and statistically significant lung cancer excesses were observed, the ORs being 1.95 (CI 1.03-3.72) and 2.47 (CI 1.28-4.77) respectively, (2) quantitative exposure parameters revealed upward trends reaching statistical significance (P < 0.05), and (3) adjustments for tobacco consumption did not reveal any confounding factors from smoking. CONCLUSION: This study failed to detect any relationship between lung cancer and exposure to iron, chromium, nickel and/or their compounds. High and statistically significant relative risks, along with increasing trends, were observed for simultaneous exposure to PAHs and silica.

Congenital malformation and maternal occupational exposure to glycol ethers. Occupational Exposure and Congenital Malformations Working Group.

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.

[Occupational exposure and malignant hemopathies: a case-control study in Lyon (France)]. / Expositions professionnelles et hémopathies malignes: une enquête cas-témoins réalisée à Lyon (France).

A hospital based case-control study was carried out in Lyon with the aim of assessing the association between haematologic malignancies and occupational exposures to 320 compounds. Job histories were obtained by questionnaire for 118 cases (52 non Hodgkin lymphomas, 48 acute myeloid leukemia, 18 others leukaemias), and 118 controls with diseases other than cancer from the same general hospital; controls were matched for sex, age and nationality. Systematic coding of exposures based on a blind analysis of job histories, was done by a team of experts in chemistry and occupational health. Mantel-Haenszel analysis was performed. Significantly elevated odds-ratio were observed for non Hodgkin lymphomas and exposure to mineral oils (14.86; 2.76-80.0), excavation dusts (3.91; 0.94-15.95), alkali compounds (2.90; 1.09-7.68), inks (2.47; 1.09-5.17). For inks, a dose-response relation was observed. Elevated odds-ratios appeared for acute myeloid leukaemias and arsenic compounds (3.02; 0.90-10.13) and lead compounds (3.70; 1.09-13.44). When regarding industrial activities, two of them are more frequently found: food industries (14 cases/5 controls), public works (12 cases/0 control). When regarding jobs, winding (6 cases/0 control), glass workers (8 cases/1 control) and warehousemen (10 cases and 4 controls) are more often seen among cases.

Bladder cancer and occupational exposures.

OBJECTIVES: A hospital-based case-referent study was carried out in Lyon with the purpose of generating hypotheses about the role of occupational exposures to 320 compounds in bladder carcinogenesis. METHODS: Job histories were obtained by questionnaire for 116 cases and 232 reference patients with diseases other than cancer (one referent from the same hospital ward and one from another ward of the same hospital per case); the referents were matched for gender, hospital, age, and nationality. Systematic coding of exposures, with a blind analysis of job histories, was carried out by a team of experts in chemistry and occupational health. RESULTS: Significantly elevated odds ratios were observed for exposure to pyrolysis and combustion products [odds ratio (OR) 2.3, 95% confidence interval (95% CI) 1.0-4.0] when the general referents were used and for cutting fluids (OR 2.6, 95% CI 1.2-5.4) when tobacco consumption was adjusted for. The latter was highest among the category consisting of blue-collar and unskilled workers, supervisors, and agricultural workers (OR 4.6 95% CI 2.0-10.6), while the odds ratio for the other category was 0.8 (95% CI 0.3-2.7). An elevated odds ratio for exposure to inks was observed for the women (OR 14.0, 95% CI 1.8-106.5) on the basis of 14 exposed cases, but confounding factors could have been responsible for this result. Odds ratios for several other exposures (rubber: OR 5.7, nitrates: OR 8.2, coke dust: OR 3.5, meat additives: OR 3.8) were also elevated, but not significantly so when based on a small number of exposed cases. CONCLUSION: The observations of this investigation should be tested in future studies, in particular since exposures to agents such as cutting fluids or pyrolysis products are ubiquitous in industrial settings and may present an important public health hazard.