ZusammenfassungDie gesundheitlichen Auswirkungen von Schicht- und Nachtarbeit sind Gegenstand vieler wissenschaftlicher Untersuchungen. Das Spektrum möglicher Erkrankungen und Endpunkte, die mit Schicht- und Nachtarbeit assoziiert sind, reicht von chronischen Erkrankungen wie Krebs, Herz-Kreislauf-Erkrankungen über Schlafstörungen, psychische Belastungen bis hin zu Reproduktionsstörungen und Unfällen. Im Juni 2019 stufte die Internationale Krebsagentur (IARC) Nachtarbeit als wahrscheinlich krebserregend ein (Gruppe 2A) und bestätigte damit ihre Einschätzung aus dem Jahr 2007. Die Expertengruppe der IARC weist dabei auf die immer noch sehr heterogenen Studienergebnisse hin. Während der überwiegende Teil der populationsbasierten Fall-Kontroll-Studien positive Assoziationen zwischen Schichtarbeit und Krebserkrankungen zeigte, wurde in vielen Kohorten-Studien keine Assoziation beobachtet. Die Frage, ob erhöhte Krebsrisiken tatsächlich auf Schicht- oder Nachtarbeit zurückgeführt werden können, kann daher zurzeit nicht zweifelsfrei beantwortet werden. Der folgende Beitrag gibt einen Überblick zu offenen Fragen und Aspekten der Schichtarbeitsforschung am Beispiel von Krebserkrankungen und diskutiert die aktuelle arbeitsmedizinische Einschätzung.
Ziel dieses Projektes war es, verschiedene Aerosole im Expositionslabor des Instituts für Prävention und Arbeitsmedizin der Deutschen Gesetzlichen Unfallversicherung (IPA) mit einem geeigneten Probenahmesystem direkt auf einen Probenträger abzuscheiden. Mittels Rasterelektronenmikroskopie-Aufnahmen sollte analysiert werden, welche morphologische Beschaffenheit ein Aerosol hat, unmittelbar bevor Probanden einer toxikologischen Studie luftgetragene Partikel in verschiedenen Größen inhalieren. Dabei sollten die experimentellen Umgebungsbedingungen identisch mit den Zielbedingungen des beabsichtigten bzw. bereits durchgeführten Studiendesigns sein. Zusätzlich sollte die Frage beantwortet werden, welches Partikelgeneratorsystem für zukünftige Inhalationsstudien im Expositionslabor für eine gewünschte Substanz zur Anwendung kommen kann. Die Untersuchungen umfassten nano-Zinkoxid, mikro-Zinkoxid, mikro-Bariumsulfat und zwei unterschiedliche nano-Titandioxid-Atmosphären. Begleitende Messungen bestätigten, dass es kaum Unterschiede zwischen Soll- und Zielkonzentrationen gab. Auch die zu erwartenden Partikelgrößenverteilungen wurden erreicht – mit Ausnahme eines der beiden Titandioxid-Materialien. Zusätzlich konnte die Frage beantwortet werden, ob es mit einem Suspensionsvernebler-System möglich ist, nanofeine Materialien in die Atmosphärenluft unter Erhalt der ursprünglichen Partikelgröße zu resuspendieren. Allerdings funktionierte diese Methode nicht.
Objectives Workplace measurements in the past have shown that the applicable occupational exposure limits (OELs) are regularly exceeded in practice when high-emission welding processes are applied. The InterWeld pilot study was planned as part of an intervention study to show under which conditions compliance with the OEL is achievable in gas metal arc welding (GMAW) with solid wire. The investigation focussed on local exhaust ventilation, i.e. captor hoods and welding torches with integrated fume extraction.
Methods Forty tests with hand-guided GMAW were configured by experts with regard to all technical parameters and carried out by a professional welder. Effects of protective measures and process parameters on the exposure to respirable welding fumes and airborne manganese (Mn), chromium, nickel, and hexavalent chromium were investigated. Personal sampling was carried out in the welder's breathing zone outside the face shield at high flow rates (10 l min−1) in order to achieve sufficient filter loading. Particle masses and welding fume concentrations were determined by weighing the sampling filters. Metal concentrations were analysed by inductive coupled plasma mass spectrometry. In order to evaluate the effects on exposure, the measurements were performed under similar conditions. The data were analysed descriptively and with mixed linear models. For measurements below the limit of detection, the exposure level was estimated using multiple imputation.
Results Two to five times higher exposures to respirable welding fumes and airborne metals were observed during welding of 10 mm sheets than during welding of 2- or 3-mm sheets. Welding fume and Mn exposure were reduced by 70 and 90% when on-torch extraction or a captor hood was applied. Other airborne metals were reduced to a similar extent. Modifications on welding parameters led to a reduction of exposure against respirable particles by 51 up to 54%.
Conclusions Although proper extraction at the point of origin and lower-emitting process variants ensure a drastic reduction in exposure, compliance with current OELs is not guaranteed. In order to ensure adequate health protection, especially at workplaces where thick sheets with long relative arc times are processed, there is a need for technical development.
AbstractExposure to the bicyclic aromatic hydrocarbon naphthalene occurs in most cases along with other polycyclic aromatic hydrocarbons. Here we report from an investigation of 63 healthy, non-smoking male employees in the abrasives industry where naphthalene is the only relevant chemical exposure. Exposure assessment was performed using a combination of Air and Biological Monitoring over nearly a whole working week (Mo.–Th.). Air measurements were carried out during the shift on Thursday with the GGP mini-sampling system, combining particle and vapour sampling at low flow rates. In urine spot samples, the metabolites 1- and 2-naphthol were measured Mo.–Th. pre- and post-shift (for the reference group only Mo. pre- and Th. post-shift). With regard to naphthalene concentrations measured in air and concentrations of its metabolites (1- and 2-naphthol) in urine, study participants could be divided into a high and a low exposure group, and a reference group. The naphthalene concentration in air was in the range of 0.1–11.6 mg m−3, and naphthol concentrations (sum of 1- and 2-naphthol) in post-shift urine were in the range of <1 to 10 127 µg l−1. Naphthalene concentrations in air and naphthol concentrations in urine were closely correlated, indicating mainly airborne exposure at the investigated workplaces. As expected from toxicokinetic data, internal body burden increased slightly during a working week and did not completely decline over a work-free weekend to background concentrations observed in occupationally not exposed persons. Taking into account the observed increase in pre- and post-shift values during the working week, urine sampling for Biological Monitoring at workplaces should be carried out after several preceding shifts. Our data allow the derivation of biological limit values for the sum of 1- and 2-naphthol in urine corresponding to occupational exposure limits for naphthalene in air.
During the population representative German Environmental Survey of Children and Adolescents (GerES V, 2014-2017) 2256 first-morning void urine samples from 3 to 17 years old children and adolescents were analysed for 21 metabolites of 11 different phthalates (di-methyl phthalate (DMP), di-ethyl phthalate (DEP), butylbenzyl phthalate (BBzP), di-iso-butyl phthalate (DiBP), di-n-butyl phthalate (DnBP), di-cyclohexyl phthalate (DCHP), di-n-pentyl phthalate (DnPeP), di-(2-ethylhexyl) phthalate (DEHP), di-iso-nonyl phthalate (DiNP), di-iso-decyl phthalate (DiDP) and di-n-octyl phthalate (DnOP)). Metabolites of DMP, DEP, BBzP, DiBP, DnBP, DEHP, DiNP and DiDP were found in 97%-100% of the participants, DCHP and DnPeP in 6%, and DnOP in none of the urine samples. Geometric means (GM) were highest for metabolites of DiBP (MiBP: 26.1 μg/L), DEP (MEP: 25.8 μg/L), DnBP (MnBP: 20.9 μg/L), and DEHP (cx-MEPP: 11.9 μg/L). For all phthalates but DEP, GMs were consistently higher in the 3–5 years old children than in the 14-17 years old adolescents. For DEHP, the age differences were most pronounced. All detectable phthalate biomarker concentrations were positively associated with the levels of the respective phthalate in house dust. In GerES V we found considerably lower phthalate biomarker levels than in the preceding GerES IV (2003–2006). GMs of biomarker levels in GerES V were only 18% (BBzP), 23% (MnBP), 23% (DEHP), 29% (MiBP) and 57% (DiNP) of those measured a decade earlier in GerES IV. However, some children and adolescents still exceeded health-based guidance values in the current GerES V. 0.38% of the participants had levels of DnBP, 0.08% levels of DEHP and 0.007% levels of DiNP which were higher than the respective health-based guidance values. Accordingly, for these persons an impact on health cannot be excluded with sufficient certainty. The ongoing and substantial exposure of vulnerable children and adolescents to many phthalates confirms the need of a continued monitoring of established phthalates, whether regulated or not, as well as of potential substitutes. With this biomonitoring approach we provide a picture of current individual and cumulative exposure developments and body burdens to phthalates, thus providing support for timely and effective chemicals policies and legislation.
Objectives Exposure to manganese (Mn) may cause movement disorders, but less is known whether the effects persist after the termination of exposure. This study investigated the association between former exposure to Mn and fine motor deficits in elderly men from an industrial area with steel production.
Methods Data on the occupational history and fine motor tests were obtained from the second follow-up of the prospective Heinz Nixdorf Recall Study (2011–2014). The study population included 1232 men (median age 68 years). Mn in blood (MnB) was determined in archived samples (2000–2003). The association between Mn exposure (working as welder or in other at-risk occupations, cumulative exposure to inhalable Mn, MnB) with various motor functions (errors in line tracing, steadiness, or aiming and tapping hits) was investigated with Poisson and logistic regression, adjusted for iron status and other covariates. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated for substantially impaired dexterity (errors >90th percentile, tapping hits <10th percentile).
Results The median of cumulative exposure to inhalable Mn was 58 µg m–3 years in 322 men who ever worked in at-risk occupations. Although we observed a partly better motor performance of exposed workers at group level, we found fewer tapping hits in men with cumulative Mn exposure >184.8 µg m–3 years (OR 2.15, 95% CI 1.17–3.94). MnB ≥ 15 µg l–1, serum ferritin ≥ 400 µg l–1, and gamma-glutamyl transferase ≥74 U l–1 were associated with a greater number of errors in line tracing.
Conclusions We found evidence that exposure to inhalable Mn may carry a risk for dexterity deficits. Whether these deficits can be exclusively attributed to Mn remains to be elucidated, as airborne Mn is strongly correlated with iron in metal fumes, and high ferritin was also associated with errors in line tracing. Furthermore, hand training effects must be taken into account when testing for fine motor skills.
To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Download ; Previous transcriptome-wide association studies (TWAS) have identified breast cancer risk genes by integrating data from expression quantitative loci and genome-wide association studies (GWAS), but analyses of breast cancer subtype-specific associations have been limited. In this study, we conducted a TWAS using gene expression data from GTEx and summary statistics from the hitherto largest GWAS meta-analysis conducted for breast cancer overall, and by estrogen receptor subtypes (ER+ and ER-). We further compared associations with ER+ and ER- subtypes, using a case-only TWAS approach. We also conducted multigene conditional analyses in regions with multiple TWAS associations. Two genes, STXBP4 and HIST2H2BA, were specifically associated with ER+ but not with ER- breast cancer. We further identified 30 TWAS-significant genes associated with overall breast cancer risk, including four that were not identified in previous studies. Conditional analyses identified single independent breast-cancer gene in three of six regions harboring multiple TWAS-significant genes. Our study provides new information on breast cancer genetics and biology, particularly about genomic differences between ER+ and ER- breast cancer. Keywords: GWAS; TWAS; breast cancer subtype; causal gene. ; Cancer Research UK European Union's Horizon 2020 Research and Innovation Programme European Union (EU) United States Department of Health & Human Services National Institutes of Health (NIH) - USA Cancer UK Genome Canada Canadian Institutes of Health Research (CIHR) Ministere de l'Economie, Science et Innovation du Quebec through Genome Quebec Quebec Breast Cancer Foundation United States Department of Health & Human Services National Institutes of Health (NIH) - USA Post-Cancer GWAS initiative (GAME-ON initiative) Department of Defence Canadian Institutes of Health ...
Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57-1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628-0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs. ; Novartis ; Eli Lilly and Company ; AstraZeneca ; AbbVie ; Pfizer UK ; Celgene ; Eisai ; Genentech ; Merck Sharp and Dohme ; Roche ; Cancer Research UK ; Government of Canada ; Array BioPharma ; Genome Canada ; National Institutes of Health ; European Commission ; Ministère de l'Économie, de l'Innovation et des Exportations du Québec ; Seventh Framework Programme ; Canadian Institutes of Health Research