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German Social Accident Insurance (DGUV) between 2007 and 2011, Olsson A, Guha N, Bouaoun L, Kromhout H, Peters S, Siemiatycki J, Ho V, Gustavsson P, Boffetta P, Vermeulen R, Behrens T, Brüning T, Kendzia B, Guénel P, Luce D, Karrasch S, Wichmann HE, Consonni D, Landi MT, Caporaso NE, Merletti F, Mirabelli D, Richiardi L, Jöckel KH, Ahrens W, Pohlabeln H, Tardón A, Zaridze D, Field JK, Lissowska J, Świątkowska B, McLaughlin JR, Demers PA, Bencko V, Foretova L, Janout V, Pándics T, Fabianova E, Mates D, Forastiere F, Bueno-de-Mesquita B, Schüz J, Straif K

BACKGROUND: Several studies have confirmed associations between air pollution and overall mortality, but it is unclear to what extent these associations reflect causal relationships. Moreover, few studies to our knowledge have accounted for complex mixtures of air pollution. In this study, we evaluate the causal effects of a mixture of air pollutants on overall mortality in a large, prospective cohort of Dutch individuals. METHODS: We evaluated 86,882 individuals from the LIFEWORK study, assessing overall mortality between 2013 and 2017 through national registry linkage. We predicted outdoor concentration of five air pollutants (PM2.5, PM10, NO2, PM2.5 absorbance, and oxidative potential) with land-use regression. We used logistic regression and mixture modeling (weighted quantile sum and boosted regression tree models) to identify potential confounders, assess pollutants' relevance in the mixture-outcome association, and investigate interactions and nonlinearities. Based on these results, we built a multivariate generalized propensity score model to estimate the causal effects of pollutant mixtures. RESULTS: Regression model results were influenced by multicollinearity. Weighted quantile sum and boosted regression tree models indicated that all components contributed to a positive linear association with the outcome, with PM2.5 being the most relevant contributor. In the multivariate propensity score model, PM2.5 (OR=1.18, 95% CI: 1.08-1.29) and PM10 (OR=1.02, 95% CI: 0.91-1.14) were associated with increased odds of mortality per interquartile range increase. CONCLUSION: Using novel methods for causal inference and mixture modeling in a large prospective cohort, this study strengthened the causal interpretation of air pollution effects on overall mortality, emphasizing the primary role of PM2.5 within the pollutant mixture.

Objective To evaluate the performance of three measurement strategies to test compliance with occupational exposure limits of similarly exposed groups (SEGs): the old and new versions of EN689, and the BOHS-NVvA guidance on measuring compliance. Methods Respirable dust exposures concentrations (n = 1383) measured within the member companies of IMA-Europe were used to compare compliance decisions between the three measurement strategies. A total of 210 SEGs of which 158 with repeated measurements were analysed. An R studio OHcomplianceStrategies package was created for the purpose. Results The old EN689 strategy resulted in the highest number of compliant SEGs in the preliminary tests and statistical test (49–52% and 83%) with lower percentages of compliance with the new EN689 standard (32–44% and 71%). The percentage of non-compliant SEGs was relatively similar between the old and new EN689 for the preliminary tests (1–12% versus 6–11%). However, the new EN689 declared almost twofold more SEGs non-compliant when applying the statistical test (29% versus 17%). The BOHS-NVvA individual test showed results in between the 26% non-compliant SEGs. Conclusion This study showed differences in compliance decisions between the old and new EN689, with the new EN689 being considerably more stringent and resulting in more non-compliant SEGs.

ObjectiveUnprecedented SARS-CoV-2 infections in farmed minks raised immediate concerns regarding transmission to humans and initiated intensive environmental investigations to assess occupational and environmental exposure.MethodsAir sampling was performed at infected Dutch mink farms, at farm premises and at nearby residential sites. A range of other environmental samples were collected from minks’ housing units, including bedding materials. SARS-CoV-2 RNA was analysed in all samples by quantitative PCR.ResultsInside the farms, considerable levels of SARS-CoV-2 RNA were found in airborne dust, especially in personal inhalable dust samples (approximately 1000–10 000 copies/m3). Most of the settling dust samples tested positive for SARS-CoV-2 RNA (82%, 75 of 92). SARS-CoV-2 RNA was not detected in outdoor air samples, except for those collected near the entrance of the most recently infected farm. Many samples of minks’ housing units and surfaces contained SARS-CoV-2 RNA.ConclusionsInfected mink farms can be highly contaminated with SARS-CoV-2 RNA. This warns of occupational exposure, which was substantiated by considerable SARS-CoV-2 RNA concentrations in personal air samples. Dispersion of SARS-CoV-2 to outdoor air was found to be limited and SARS-CoV-2 RNA was not detected in air samples collected beyond farm premises, implying a negligible risk of environmental exposure to nearby communities. Our occupational and environmental risk assessment is in line with whole genome sequencing analyses showing mink-to-human transmission among farm workers, but no indications of direct zoonotic transmission events to nearby communities.

In the Dutch national surveillance system, an increasing number of reports were received in the summer of 2017 from farmers about unusual behavior of their cows. The cows were grouping during the day in summer in one part of the barn and did not move for several hours, which, according to the farmers, led to reduced food and water intake and lying time and resulted in decreased milk production and increased risk of lameness. Many farmers perceived magnetic fields from, for instance, high-voltage lines, automated milking systems, or solar panels as possible causes for the behavior of their cows. Our aim for the study was to study potential factors such as magnetic fields and other factors such as barn climate and insect burden for adverse grouping behavior of dairy cows in the barn. For each case herd, 2 control herds were selected in the same postal area code. A case was a herd in which cattle grouped at least on 7 occasions in a month for several hours. In a control herd, the cows were in the barn during the same time period as in the matching case herd but did not show adverse grouping behavior. A questionnaire was administered by telephone in 31 case herds and 62 control herds. The questionnaire gathered information on behavior of the cows and potential risk factors. In addition, data on the distance of the herd to high-voltage lines was obtained. From a total of 74 variables, all variables with a P-value ≤0.10 were included in full multivariable logistic regression model. Backward selection was carried out at P ≤ 0.10. The grouping behavior of the cows started in most herds in June, was seen only during the day, and lasted mostly 6 to 8 h, with cows often grouped in the northern part of the barn. Identified risk factors appeared to be recently constructed barns, measured stray voltage in barns, and presence of fans in barns. Given the cross-sectional design of the case-control study, causality for these risk factors leading to adverse behavior of the cows could not be proven. Dissemination of the results to farmers hopefully results in measures that can prevent the unusual grouping behavior of cows.

Background Occupational epidemiological studies on pesticide use commonly rely on self-reported questionnaire or interview data to assess exposure. Insight into recall accuracy is important, as misclassification of exposures due to imperfect recall can bias risk estimates. Methods We assessed the ability of workers in three UK cohorts (Prospective Investigation of Pesticide Applicators’ Health [PIPAH], Pesticide Users’ Health Study [PUHS], and Study of Health in Agricultural Work [SHAW]) to remember their working history related to pesticide exposure over time periods ranging from 3 to 14 years prior. During 2019–2020, cohort participants were re-surveyed using a similar questionnaire to that used previously. We compared recall of responses at follow-up to those reported at baseline related to crops/areas of work, use of personal protective equipment (PPE) items, hygiene habits, frequency of pesticide use, and application method. To assess the extent of recall, we used sensitivity, specificity, the percentage of overall agreement, and area under the curve (AUC) values. We also examined the presence of over or underestimation of recalled years, and days and hours per year, of working with pesticides using geometric mean ratios (GMR) and regression analysis to investigate any trends based on demographic characteristics. Results There were 643 individuals who completed both the baseline and follow-up surveys in the three cohorts with response rates ranging from 17 to 46%. There was a strong correlation (rho = 0.77) between the baseline and recalled years working with pesticides, though higher values were reported at follow-up (GMR = 1.18 [95% confidence interval: 1.07–1.30]) with no consistent differences by demographic characteristics. There was stronger agreement in the recalled days compared to hours per year in two of the cohorts. Recall for a number of exposure determinants across short and longer periods entailed overall agreement of >70%, though with some differences: for example, sensitivity for long-term recall of crops was poor ( Conclusion Results indicate that recall ability may deteriorate over a longer period. Although low-response rates may require these findings to be interpreted with caution, recall for a number of exposure determinants appeared reliable, such as crops and hygiene practices within 3 years, as well as days per year working with pesticides.

Background: Pesticides can be transported from the site of application to homes via different routes and lead to exposure of residents, raising concerns regarding health effects. We built a deterministic model framework (OBOmod) to assess exposure of residents living near fields where pesticides are applied. Methods: OBOmod connects five independent models operating on an hourly timescale and high spatial resolution (meters). Models include descriptions of spray drift, volatilization, atmospheric transport and dispersion, exchange between outdoor and indoor air and exchange between indoor air and dust. Fourteen bulb field applications under different weather conditions and comprising 12 pesticides were simulated. Each simulation included the first seven days after the application. The concentrations computed with OBOmod were compared with those measured in outdoor and indoor air and the amounts measured in indoor dust samples. Results: Model evaluation indicated suitability of the developed framework to estimate outdoor and indoor air concentrations. For most pesticides, model accuracy was good. The framework explained about 30% to 95% of the temporal and spatial variability of air concentrations. For 20% of the simulations, the framework explained more than 35% of spatial variability of concentrations in dust. In general, OBOmod estimates remained within one order of magnitude from measured levels. Calculations showed that in addition to spray drift during application, volatilization from the field after spraying and pesticides in house dust are important routes for residents' exposure to pesticides. Conclusions: Our framework covers many processes needed to calculate exposure of residents to pesticides. The evaluation phase shows that, with the exception of the dust model, the framework can be used in support of health and epidemiological studies, and can serve as a tool to support development of regulations and policy making regarding pesticide use.

BackgroundMillions of workers worldwide are exposed to diesel engine exhaust (DEE), a known genotoxic carcinogen. Alu retroelements are repetitive DNA sequences that can multiply and compromise genomic stability. There is some evidence linking altered Alu repeats to cancer and elevated mortality risks. However, whether Alu repeats are influenced by environmental pollutants is unexplored. In an occupational setting with high DEE exposure levels, we investigated associations with Alu repeat copy number.MethodsA cross-sectional study of 54 male DEE-exposed workers from an engine testing facility and a comparison group of 55 male unexposed controls was conducted in China. Personal air samples were assessed for elemental carbon, a DEE surrogate, using NIOSH Method 5040. Quantitative PCR (qPCR) was used to measure Alu repeat copy number relative to albumin (Alb) single-gene copy number in leucocyte DNA. The unitless Alu/Alb ratio reflects the average quantity of Alu repeats per cell. Linear regression models adjusted for age and smoking status were used to estimate relations between DEE-exposed workers versus unexposed controls, DEE tertiles (6.1–39.0, 39.1–54.5 and 54.6–107.7 µg/m3) and Alu/Alb ratio.ResultsDEE-exposed workers had a higher average Alu/Alb ratio than the unexposed controls (p=0.03). Further, we found a positive exposure–response relationship (p=0.02). The Alu/Alb ratio was highest among workers exposed to the top tertile of DEE versus the unexposed controls (1.12±0.08 SD vs 1.06±0.07 SD, p=0.01).ConclusionOur findings suggest that DEE exposure may contribute to genomic instability. Further investigations of environmental pollutants, Alu copy number and carcinogenesis are warranted.

Wireless phones (both mobile and cordless) emit not only radiofrequency (RF) electromagnetic fields (EMF) but also extremely low frequency (ELF) magnetic fields, both of which should be considered in epidemiological studies of the possible adverse health effects of use of such devices. This paper describes a unique algorithm, developed for the multinational case-control MOBI-Kids study, that estimates the cumulative specific energy (CSE) and the cumulative induced current density (CICD) in the brain from RF and ELF fields, respectively, for each subject in the study (aged 10-24 years old). Factors such as age, tumour location, self-reported phone models and usage patterns (laterality, call frequency/duration and hands-free use) were considered, as was the prevalence of different communication systems over time. Median CSE and CICD were substantially higher in GSM than 3G systems and varied considerably with location in the brain. Agreement between RF CSE and mobile phone use variables was moderate to null, depending on the communication system. Agreement between mobile phone use variables and ELF CICD was higher overall but also strongly dependent on communication system. Despite ELF dose distribution across the brain being more diffuse than that of RF, high correlation was observed between RF and ELF dose. The algorithm was used to systematically estimate the localised RF and ELF doses in the brain from wireless phones, which were found to be strongly dependent on location and communication system. Analysis of cartographies showed high correlation across phone models and across ages, however diagonal agreement between these cartographies suggest these factors do affect dose distribution to some level. Overall, duration and number of calls may not be adequate proxies of dose, particularly as communication systems available for voice calls tend to become more complex with time. Funding for the coordination of the MOBI-Kids study was obtained from the European Commission's Seventh Framework Programme under grant agreements number 226873 and 603794, and from the Spanish Ministry of Science and Innovation (MINECO). In Spain, additional funding was obtained from the Spanish Health Research Fund (FIS) of the National Institute for Health Carlos III, and from the Junta de Andalucía, Consejería de Salud. Proyecto PI-0317-2010. ISGlobal also acknowledges support from the Spanish Ministry of Science, Innovation and Universities through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), support from the Generalitat de Catalunya through the CERCA Program and support from the Secretariat of Universities and Research of the Department of Business and Knowledge of the Generalitat of Catalonia through AGAUR (the Catalan Agency for Management of University and Research Grants) (Project 2017 SGR 1487). Australian participation in MOBI-Kids was supported by the Australian National Health and Medical Research Council with a five-year research grant (grant number: 546130). Austrian participation in MOBI-Kids was partly supported by a grant from the Ministry of Science. In Canada, participation in MOBI-Kids was supported by a university-industry partnership grant from the Canadian Institutes of Health Research (CIHR), reference number 110835, with the Canadian Wireless Telecommunications Association (CWTA) serving as the industrial partner. CWTA provides technical information on wireless telecommunications in Canada and facilitates access to billing records from Canadian network operators, but has no involvement in the design, conduct, analysis, or interpretation of the MOBI-KIDS study. French participation was also supported by the French National Agency for Sanitary Safety of Food, Environment and Labour (ANSES, contract FSRF2008-3 and 2013/2/007), French National Cancer Institute (INCa), Pfizer Foundation and League against cancer. The German study centre received additional funding from the Federal Office for Radiation Protection (BfS) under grant number 3609S30010. In Greece, the study was partially supported by the Hellenic Society for Social Pediatrics and Health Promotion, ELKE (Special Account for Research Grants of the National and Kapodistrian University of Athens) and GGET (General Secretariat for Research and Technology). Mobi-Kids India was supported by Board of Research in Nuclear Sciences (BRNS, sanction no: 2013/38/01-BRNS). Italian participation was partially supported by a Ministry of Health grant (RF-2009-1546284). MOBI-Kids Korea was supported by the ICT R&D program (2017-0-00961 and 2019-0-00102) of MSIT/IITP, Korea. Mobi-Kids Japan was supported by Research on biological electromagnetic environment (Grant Number: JPMI10001) of Ministry of Internal Affairs and Communications Japan. New Zealand participation was supported by the Health Research Council (HRC 12/380) and Cure Kids (grant number 3536). The Netherland’s participation in MOBI-KIDS was partly supported by The Netherlands Organisation for Health Research and Development (ZonMw) within the program Electromagnetic Fields and Health Research under grant number 85800001, and by the ODAS foundation, a private foundation supporting activities in the field of pediatric oncology and visual disabilities.

BACKGROUND: Mechanistic data is increasingly used in hazard identification of chemicals. However, the volume of data is large, challenging the efficient identification and clustering of relevant data. OBJECTIVES: We investigated whether evidence identification for hazard assessment can become more efficient and informed through an automated approach that combines machine reading of publications with network visualization tools. METHODS: We chose 13 chemicals that were evaluated by the International Agency for Research on Cancer (IARC) Monographs program incorporating the key characteristics of carcinogens (KCCs) approach. Using established literature search terms for KCCs, we retrieved and analyzed literature using Integrated Network and Dynamical Reasoning Assembler (INDRA). INDRA combines large-scale literature processing with pathway databases and extracts relationships between biomolecules, bioprocesses, and chemicals into statements (e.g., "benzene activates DNA damage"). These statements were subsequently assembled into networks and compared with the KCC evaluation by the IARC, to evaluate the informativeness of our approach. RESULTS: We found, in general, larger networks for those chemicals which the IARC has evaluated the evidence to be strong for KCC induction. Larger networks were not directly linked to publication count, given that we retrieved small networks for several chemicals with little support for KCC activation according to the IARC, despite the significant volume of literature for these specific chemicals. In addition, interpreting networks for genotoxicity and DNA repair showed concordance with the IARC KCC evaluation. DISCUSSION: Our method is an automated approach to condense mechanistic literature into searchable and interpretable networks based on an a priori ontology. The approach is no replacement of expert evaluation but, instead, provides an informed structure for experts to quickly identify which statements are made in which papers and how these could connect. We focused on the KCCs because these are supported by well-described search terms. The method needs to be tested in other frameworks as well to demonstrate its generalizability. https://doi.org/10.1289/EHP9112.

[EN] Objective: To investigate the association of estimated all-day and evening whole-brain radiofrequency electromagnetic field (RF-EMF) doses with sleep disturbances and objective sleep measures in preadolescents. Methods: We included preadolescents aged 9-12 years from two population-based birth cohorts, the Dutch Generation R Study (n = 974) and the Spanish INfancia y Medio Ambiente Project (n = 868). All-day and evening overall whole-brain RF-EMF doses (mJ/kg/day) were estimated for several RF-EMF sources including mobile and Digital Enhanced Cordless Telecommunications (DECT) phone calls (named phone calls), other mobile phone uses, tablet use, laptop use (named screen activities), and far-field sources. We also estimated all-day and evening whole-brain RF-EMF doses in these three groups separately (i.e. phone calls, screen activities, and far-field). The Sleep Disturbance Scale for Children was completed by mothers to assess sleep disturbances. Wrist accelerometers together with sleep diaries were used to measure sleep characteristics objectively for 7 consecutive days. Results: All-day whole-brain RF-EMF doses were not associated with self-reported sleep disturbances and objective sleep measures. Regarding evening doses, preadolescents with high evening whole-brain RF-EMF dose from phone calls had a shorter total sleep time compared to preadolescents with zero evening whole-brain RF-EMF dose from phone calls [-11.9 min (95%CI -21.2; -2.5)]. Conclusions: Our findings suggest the evening as a potentially relevant window of RF-EMF exposure for sleep. However, we cannot exclude that observed associations are due to the activities or reasons motivating the phone calls rather than the RF-EMF exposure itself or due to chance finding. This work was supported by the European Union Seventh Framework Program (FP7/2007-2013 No. 603794 GERoNiMO project) . Arno Thielens is a postdoctoral fellow of the Research Foundation Flanders (FWO) under grant agreement no. 12U1417N. INMA-Sabadell: This study was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176; CB06/02/0041; PI041436; PI081151 incl. FEDER funds; PI12/01890 incl. FEDER funds; CP13/00054 incl. FEDER funds, MS13/00054, CPII18/00018; PI17/01340 incl. FEDER funds) , CIBERESP, Generalitat de Catalunya-CIRIT 1999SGR 00241, Generalitat de Catalunya-AGAUR (2009 SGR 501, 2014 SGR 822) , Fundacio La Marato de TV3 (090430) , Spanish Ministry of Economy and Competitiveness (SAF2012-32991 incl. FEDER funds) , French Agency for Food, Environmental and Occupational Health & Safety (EST-2016 RF-21, EST/2013/2/22) , EU Commission (261357, 308333, 603794 and 634453) .We also acknowledge support from the Spanish Ministry of Science and Innovation and State Research Agency through the "Centro de Excelencia Severo Ochoa 2019-2023" Program (CEX2018-000806-S) , and support from the Generalitat de Catalunya through the CERCA Program". INMA-Gipuzkoa: This study was funded by grants from Instituto de Salud Carlos III (FIS-PI13/02187) , CIBERESP, Department of Health of the Basque Government (2015111065) , and the Provincial Government of Gipuzkoa (DFG15/221) and annual agreements with the municipal-ities of the study area (Zumarraga, Urretxu, Legazpi, Azkoitia y Azpeitia y Beasain) . The Generation R Study: The general design of the Generation R Study is supported by the Erasmus Medical Center-Rotterdam, the Erasmus University Rotterdam, the Netherlands Organization for Health Research and Development, the Netherlands Organization for Scientific Research, and the Dutch Ministry of Health, Welfare and Sport, and the Stichting Trombosedienst and Artsenlaboratorium Rijnmond. This study was funded by a grantfromthe Netherlands organization for Health Research and Development (85500036) . Henning Tiemeier was sup-ported by a grant of the Netherlands Organization for Scientific Research (NWO/ZonMW grant 016.VICI.170.200) and of Erasmus Medical Center Efficiency Grant (MRC-2013-169) .

Background: Epidemiological studies have associated biomass combustion with (respiratory) morbidity and mortality, primarily in indoor settings. Barbecuing results in high outdoor air pollution exposures, but the health effects are unknown. Objective: The objective was to investigate short-term changes in respiratory health in healthy adults, associated with exposure to barbecue fumes. Methods: 16 healthy, adult volunteers were exposed to barbecue smoke in outdoor air in rest during 1.5 h, using a repeated-measures design. Major air pollutants were monitored on-site, including particulate matter

OBJECTIVES: Congenital heart defects (CHD) are the most prevalent congenital anomalies. This study aims to examine the association between maternal occupational exposures to organic and mineral dust, solvents, pesticides, and metal dust and fumes and CHD in the offspring, assessing several subgroups of CHD. METHODS: For this case–control study, we examined 1174 cases with CHD from EUROCAT Northern Netherlands and 5602 controls without congenital anomalies from the Lifelines cohort study. Information on maternal jobs held early in pregnancy was collected via self-administered questionnaires, and job titles were linked to occupational exposures using a job exposure matrix. RESULTS: An association was found between organic dust exposure and coarctation of aorta [adjusted odds ratio (OR_adj) 1.90, 95% confidence interval (CI) 1.01–3.59] and pulmonary (valve) stenosis in combination with ventricular septal defect (OR_adj 2.68, 95% CI 1.07–6.73). Mineral dust exposure was associated with increased risk of coarctation of aorta (OR_adj 2.94, 95% CI 1.21–7.13) and pulmonary valve stenosis (OR_adj 1.99, 95% CI 1.10–3.62). Exposure to metal dust and fumes was infrequent but was associated with CHD in general (OR_adj 2.40, 95% CI 1.09–5.30). Exposure to both mineral dust and metal dust and fumes was associated with septal defects (OR_adj 3.23, 95% CI 1.14–9.11). Any maternal occupational exposure was associated with a lower risk of aortic stenosis (OR_adj 0.32, 95% CI 0.11–0.94). CONCLUSIONS: Women should take preventive measures or avoid exposure to mineral and organic dust as well as metal dust and fumes early in pregnancy as this could possibly affect foetal heart development.

ObjectivesThe aim of this study was to assess the association between maternal occupational exposure to solvents and gastroschisis in offspring.MethodsWe used data from the National Birth Defects Prevention Study, a large population-based case-control study of major birth defects conducted in 10 US states from 1997 to 2011. Infants with gastroschisis were ascertained by active birth defects surveillance systems. Control infants without major birth defects were selected from vital records or birth hospital records. Self-reported maternal occupational histories were collected by telephone interview. Industrial hygienists reviewed this information to estimate exposure to aromatic, chlorinated and petroleum-based solvents from 1 month before conception through the first trimester of pregnancy. Cumulative exposure to solvents was estimated for the same period accounting for estimated exposure intensity and frequency, job duration and hours worked per week. ORs and 95% CIs were estimated to assess the association between exposure to any solvents or solvent classes, and gastroschisis risk.ResultsAmong 879 cases and 7817 controls, the overall prevalence of periconceptional solvent exposure was 7.3% and 7.4%, respectively. Exposure to any solvent versus no exposure to solvents was not associated with gastroschisis after adjusting for maternal age (OR 1.00, 95% CI 0.75 to 1.32), nor was an association noted for solvent classes. There was no exposure-response relationship between estimated cumulative solvent exposure and gastroschisis after adjusting for maternal age.ConclusionOur study found no association between maternal occupational solvent exposure and gastroschisis in offspring. Further research is needed to understand risk factors for gastroschisis.

The specific absorption rate (SAR) induced by wireless radiofrequency (RF) systems depends on different parameters. Previously, SAR was mainly assessed under conditions of a single frequency and technology and for a limited number of localized RF sources. The current and emerging mobile systems involve a wider range of usage scenarios and are frequently used simultaneously, leading to combined exposures for which almost no exposure evaluation exists. The aim and novelty of this study is to close this gap of knowledge by developing new methods to rapidly evaluate the SAR induced by RF systems in such scenarios at frequencies from 50 MHz to 5.5 GHz. To this aim, analytical methods for SAR estimation in several usage scenarios were derived through a large-scale numerical study. These include subject-specific characteristics, properties of the RF systems and provide an estimation of the SAR in the whole body, tissues and organs, and different brain regions.

Effect-directed analysis (EDA) aims at the detection of bioactive chemicals of emerging concern (CECs) by combining toxicity testing and high-resolution mass spectrometry (HRMS). However, consolidation of toxicological and chemical analysis techniques to identify bioactive CECs remains challenging and laborious. In this study, we incorporate state-of-the-art identification approaches in EDA and propose a robust workflow for the high-throughput screening of CECs in environmental and human samples. Three different sample types were extracted and chemically analyzed using a single high-performance liquid chromatography HRMS method. Chemical features were annotated by suspect screening with several reference databases. Annotation quality was assessed using an automated scoring system. In parallel, the extracts were fractionated into 80 micro-fractions each covering a couple of seconds from the chromatogram run and tested for bioactivity in two bioassays. The EDA workflow prioritized and identified chemical features related to bioactive fractions with varying levels of confidence. Confidence levels were improved with the in silico software tools MetFrag and the retention time indices platform. The toxicological and chemical data quality was comparable between the use of single and multiple technical replicates. The proposed workflow incorporating EDA for feature prioritization in suspect and nontarget screening paves the way for the routine identification of CECs in a high-throughput manner., A comprehensive workflow was developed that incorporates effect-directed analysis in suspect and nontarget screening for feature prioritization, allowing for the high-throughput identification of bioactive chemicals of emerging concern.

ObjectivesThere is rising concern regarding possible health effects from exposure to pesticides in residents living near agricultural land. Some studies indicated increased risks of reporting symptoms of anxiety and depression among agricultural workers but less is known about the mental and perceived health of rural residents. We aimed to study possible associations between self-reported psychological distress (SPD) and self-perceived health (SPH) in residents near pesticide-treated agricultural land.MethodsUsing the Public Health Monitor national survey from 2012, we selected 216 932 participants who lived in rural and semi-urban areas of the Netherlands and changed addresses at most once in the period 2009–2012. Psychological distress (PD) was assessed via the Kessler Psychological Distress scale (K10) and participants were asked to assess their own health. We estimated the area of specific crop groups cultivated within buffers of 50 m, 100 m, 250 m and 500 m around each individual’s residence for the period 2009–2012. Association between these exposure proxies and the outcomes was investigated using logistic regression, adjusting for individual, lifestyle and area-level confounders.ResultsOverall, results showed statistically non-significant OR across all buffer sizes for both SPD and SPH, except for the association between SPH and ‘all crops’ (total area of all considered crop groups) with OR (95% CI) ranging from 0.77 (0.63 to 0.93) in 50 m to 1.00 (1.00 to 1.00) in 500 m. We observed that most ORs were below unity for SPH.ConclusionsThis study provides no evidence that residential proximity to pesticide treated-crops is associated with PD or poorer perceived health.

International audience; The implementation of One Health/EcoHealth/Planetary Health approaches has been identified as key (i) to address the strong interconnections between risk for pandemics, climate change and biodiversity loss and (ii) to develop and implement solutions to these interlinked crises. As a response to the multiple calls from scientists on that subject, we have here proposed seven long-term research questions regarding COVID-19 and emerging infectious diseases (EIDs) that are based on effective integration of environmental, ecological, evolutionary, and social sciences to better anticipate and mitigate EIDs. Research needs cover the social ecology of infectious disease agents, their evolution, the determinants of susceptibility of humans and animals to infections, and the human and ecological factors accelerating infectious disease emergence. For comprehensive investigation, they include the development of nature-based solutions to interlinked global planetary crises, addressing ethical and philosophical questions regarding the relationship of humans to nature and regarding transformative changes to safeguard the environment and human health. In support of this research, we propose the implementation of innovative multidisciplinary facilities embedded in social ecosystems locally: ecological health observatories and living laboratories. This work was carried out in the frame of the European Community project HERA (www. HERAresearchEU.eu), which aims to set priorities for an environment, climate and health research agenda in the European Union by adopting a systemic approach in the face of global environmental change

In recent decades, the possibility that use of mobile communicating devices, particularly wireless (mobile and cordless) phones, may increase brain tumour risk, has been a concern, particularly given the considerable increase in their use by young people. MOBI-Kids, a 14-country (Australia, Austria, Canada, France, Germany, Greece, India, Israel, Italy, Japan, Korea, the Netherlands, New Zealand, Spain) case-control study, was conducted to evaluate whether wireless phone use (and particularly resulting exposure to radiofrequency (RF) and extremely low frequency (ELF) electromagnetic fields (EMF)) increases risk of brain tumours in young people. Between 2010 and 2015, the study recruited 899 people with brain tumours aged 10 to 24 years old and 1,910 controls (operated for appendicitis) matched to the cases on date of diagnosis, study region and age. Participation rates were 72% for cases and 54% for controls. The mean ages of cases and controls were 16.5 and 16.6 years, respectively; 57% were males. The vast majority of study participants were wireless phones users, even in the youngest age group, and the study included substantial numbers of long-term (over 10 years) users: 22% overall, 51% in the 20-24-year-olds. Most tumours were of the neuroepithelial type (NBT; n = 671), mainly glioma. The odds ratios (OR) of NBT appeared to decrease with increasing time since start of use of wireless phones, cumulative number of calls and cumulative call time, particularly in the 15-19 years old age group. A decreasing trend in ORs was also observed with increasing estimated cumulative RF specific energy and ELF induced current density at the location of the tumour. Further analyses suggest that the large number of ORs below 1 in this study is unlikely to represent an unknown causal preventive effect of mobile phone exposure: they can be at least partially explained by differential recall by proxies and prodromal symptoms affecting phone use before diagnosis of the cases. We cannot rule out, however, residual confounding from sources we did not measure. Overall, our study provides no evidence of a causal association between wireless phone use and brain tumours in young people. However, the sources of bias summarised above prevent us from ruling out a small increased risk. Funding for the coordination of the MOBI-Kids study was obtained from the European Community's Seventh Framework Programme under grant agreements number 226873 and 603794, and from the Spanish Ministry of Science and Innovation (MINECO). In Spain, additional funding was obtained from the Spanish Health Research Fund (FIS) of the National Institute for Health Carlos III, and from the Junta de Andalucía, Consejería de Salud. Proyecto PI-0317-2010. ISGlobal also acknowledges support from the Spanish Ministry of Science, Innovation and Universities through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), support from the Generalitat de Catalunya through the CERCA Program and support from the Secretariat of Universities and Research of the Department of Business and Knowledge of the Generalitat of Catalonia through AGAUR (the Catalan Agency for Management of University and Research Grants) (Project 2017 SGR 1487). Australian participation in MOBI-Kids was supported by the Australian National Health and Medical Research Council with a five-year research grant (grant number: 546130). Austrian participation in MOBI-Kids was partly supported by a grant from the Ministry of Science. In Canada, participation in MOBI-Kids was supported by a university-industry partnership grant from the Canadian Institutes of Health Research (CIHR), reference number 110835, with the Canadian Wireless Telecommunications Association (CWTA) serving as the industrial partner. CWTA provides technical information on wireless telecommunications in Canada and facilitates access to billing records from Canadian network operators, but has no involvement in the design, conduct, analysis, or interpretation of the MOBI-KIDS study. French participation was also supported by the French National Agency for Sanitary Safety of Food, Environment and Labour (ANSES, contract FSRF2008-3), French National Cancer Institute (INCa), Pfizer Foundation and League against cancer. The German study centre received additional funding from the Federal Office for Radiation Protection (BfS) under grant number 3609S30010. In Greece, the study was partially supported by the Hellenic Society for Social Pediatrics and Health Promotion, ELKE (Special Account for Research Grants of the National and Kapodistrian University of Athens) and GGET (General Secretariat for Research and Technology). Mobi-Kids India was supported by Board of Research in Nuclear Sciences (BRNS, sanction no: 2013/38/01-BRNS).

OBJECTIVES: To evaluate smallholder farmers' recall of pesticide use and exposure determinants over a two-year period in a low-income country context. METHODS: The Pesticide Use in Tropical Settings (PESTROP) study in Uganda consists of 302 smallholder farmers who were interviewed in 2017. In the same season in 2019, these farmers were re-questioned concerning pesticide use (e.g., use of active ingredients) and exposure information (e.g., crops, personal protective equipment [PPE], hygienic behaviours) they had previously provided. The extent of recall bias was assessed by comparing responses at follow-up in 2019 with practices and behaviours reported from the baseline interview in 2017. RESULTS: An 84% (n = 255) follow-up response rate was attained. We found instances of better recall (e.g., overall agreement >70% and Area Under the Curve (AUC) values > 0.7) for the use of some active ingredients, commonly used PPE items, and washing clothes after application, whereas only 13.3% could correctly recall their three major crops. We observed a trend where more individuals reported the use of active ingredients, while fewer reported the use of PPE items, two years later. In general, we found better agreement in the recall of years working with pesticides compared to hours per day or days per week in the field, with no apparent systematic over or under reporting by demographic characteristics. CONCLUSIONS: While some of these findings provide consistency with those from high-income countries, more research is needed on recall in poorly educated agriculture communities in low- and middle-income settings to confirm these results.

Indoor dust has been postulated as an important matrix for residential pesticide exposure. However, there is a lack of information on presence, concentrations and determinants of multiple pesticides in dust in residential homes close to treated fields. Our objective was to characterize the spatial and temporal variance of pesticides in house dust, study the use of doormats and floors as proxies for pesticides in indoor dust and identify determinants of occurrence and concentrations. Homes within 250 m from selected bulb fields were invited to participate. Homes within 20 km from these fields but not having agricultural fields within 500 m were selected as controls. House dust was vacuumed in all homes from floors (VFD) and from newly placed clean doormats (DDM). Sampling was done during two periods, when pesticides are used and not-used. For determination of 46 prioritized pesticides, a multi-residue extraction method was used. Most statistical analyses are focused on the 12 and 14 pesticides that were detected in >40% of DDM and VFD samples, respectively. Mixed models were used to evaluate relationships between possible determinants and pesticides occurrence and concentrations in DDM and VFD. 17 pesticides were detected in more than 50% of the homes in both matrixes. Concentrations differed by about a factor five between use and non-use periods among homes within 250 m of fields and between these homes and controls. For 7 pesticides there was a moderate to strong correlation (Spearman rho 0.30–0.75) between concentrations in DDM and VFD. Distance to agricultural fields and air concentrations were among the most relevant predictors for occurrence and levels of a given pesticide in DDM. Concentrations in dust are overall higher during application periods and closer to fields (

On the African continent, ongoing agriculture intensification is accompanied by the increas-ing use of pesticides, associated with environmental and public health concerns. Using a systematic literature review, we aimed to map current geographical research hotspots and gaps around environmental and public health risks research of agriculture pesticides in Sub-Saharan Africa (SSA). Studies were included that collected primary data on past and current-used agricultural pesticides and assessed their environmental occurrence, related knowledge, attitude and practice, human exposure, and environmental or public health risks between 2006 and 2021. We identified 391 articles covering 469 study sites in 37 countries in SSA. Five geographical research hotspots were identified: two in South Africa, two in East Africa, and one in West Africa. Despite its ban for agricultural use, organochlorine was the most studied pesticide group (60%; 86% of studies included DDT). Current-used pesticides in agriculture were studied in 54% of the study sites (including insecticides (92%), herbicides (44%), and fungicides (35%)). Environmental samples were collected in 67% of the studies (e.g., water, aquatic species, sediment, agricultural produce, and air). In 38% of the studies, human subjects were investigated. Only few studies had a longitudinal design or assessed pesticide’s environmental risks; human biomarkers; dose-response in human subjects, including children and women; and interventions to reduce pesticide exposure. We established a research database that can help stakeholders to address research gaps, foster research collaboration between environmental and health dimensions, and work towards sustainable and safe agriculture systems in SSA. ISSN:1660-4601 ISSN:1661-7827

Background Poorly educated smallholder farmers in low-income countries are highly exposed to pesticides. This can result in adverse mental health issues, of which sleep problems might be an underlying indicator. We aim to examine the association between sleep problems and pesticide exposure among smallholder farmers in Uganda. Methods A cross-sectional survey with 253 smallholder farmers was conducted between October and December 2019. Sleep problems were assessed during the week before the visit using the Medical Outcomes Study Sleep Scale (MOS-SS). Exposure to pesticides was assessed as application days of any pesticide and as use of 2,4-D, glyphosate, mancozeb, organophosphates & carbamates, pyrethroids and other pesticides during the week and year prior to the visit. Associations were assessed using adjusted multivariable logistic regression models. Results Increased odds ratio (OR) for the sleep problem index 6-items (OR [95% Confidence Interval] 1.99 [1.04; 3.84] and 3.21 [1.33; 7.82]), sleep inadequacy (1.94 [1.04; 3.66] and 2.49 [1.05–6.22]) and snoring (3.17 [1.12; 9.41] and 4.07 [1.04; 15.14]) were observed for farmers who respectively applied pesticides up to two days and three or more days in the past week compared to farmers who did not apply during the past week. Gender-stratified analyses showed a higher OR for female applicators (4.27 [1.76–11.16]) than for male applicators (1.82 [0.91–3.79]) for the association between the sleep problem index 6-items and pesticide use in the week before the visit. Increased ORs were also observed for the association between the sleep problem index 6-item and mancozeb exposure during the past year 2.28 [1.12–4.71] and past week 2.51 [0.86–7.55] and glyphosate exposure during the past week 3.75 [1.24–11.8] compared to non-applicators. Discussion Our findings suggest an increased risk of sleep problems among smallholder farmers in a pesticide-exposure-dependent way in a low-income context. Further gender-stratified, longitudinal investigations are warranted to confirm these findings., Environment International, 158, ISSN:0160-4120, ISSN:1873-6750

International audience; The current epidemics of cardiovascular and metabolic noncommunicable diseases have emerged alongside dramatic modifications in lifestyle and living environments. These correspond to changes in our “modern” postwar societies globally characterized by rural-to-urban migration, modernization of agricultural practices, and transportation, climate change, and aging. Evidence suggests that these changes are related to each other, although the social and biological mechanisms as well as their interactions have yet to be uncovered. LongITools, as one of the 9 projects included in the European Human Exposome Network, will tackle this environmental health equation linking multidimensional environmental exposures to the occurrence of cardiovascular and metabolic noncommunicable diseases.

Background: The aim of the EU-funded HERA (health and environment research agenda) project is to set priorities for the future European research agenda in the environment, climate and health nexus. We report results from a European researcher's perspective and identify research areas that have been inadequately investigated to date. Methods: An online survey was completed by European researchers to assess, evaluate and visualise research gaps. These research gaps were identified for 21 predefined areas within 3 main categories: i) classical environment and health paradigm; ii) problem or sector-based research areas and approaches and iii) holistic research areas and concepts. All research gaps were then evaluated by expert groups with the pre-defined criteria and systematically summarized. For areas identified within the survey as under-reported, additional input was sought from a range of key selected experts. The EU project database Cordis was utilized to verify that these areas were under-researched. Results: Between May and July 2019, 318 respondents from 38 countries reported 624 research gaps. The main areas for attention identified were: urban environments; chemicals; and climate change, (combined n = 313 gaps). Biodiversity loss and health; transport, mobility, sustainable solutions and health; energy transition and health; waste and the circular economy and health; ethics and philosophy and health were areas that were acknowledged as under-researched (combined n = 27 gaps). These under-researched areas were identified as having certain commonalities, they: i) mostly fell in the category "problem or sector based approaches"; ii) they are essential for developing and implementing solutions; and iii) require trans-disciplinary and cross-sectoral collaboration. Conclusions: Currently attention is given to topical and highly researched areas in environmental health. In contrast, this paper identifies key topics and approaches that are under-researched, yet, are critical for the implementation of the EU Green Deal, related strategies and action plans, and require further investigation and investment. The findings reveal the imperative to foster solutions-oriented, trans-disciplinary and participatory research and its implementation through changes in research funding and research structures. The HERA project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement N◦ 825417. MK acknowledges support from the Spanish State Research Agency and Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and the Generalitat de Catalunya through the CERCA Program.

Highlights • AGRICOH analyzed cancer incidence in >248,000 agricultural workers from 6 countries. • Cancer overall occurred less in agricultural workers than in the general population. • An excess was found for multiple myeloma, melanoma of the skin, and prostate cancer. • Direction of risk was largely consistent across cohorts with a few deviations. • A large deficit of larynx and lung cancers was observed in nearly all cohorts., Background Agricultural work can expose workers to potentially hazardous agents including known and suspected carcinogens. This study aimed to evaluate cancer incidence in male and female agricultural workers in an international consortium, AGRICOH, relative to their respective general populations. Methods The analysis included eight cohorts that were linked to their respective cancer registries: France (AGRICAN: n = 128,101), the US (AHS: n = 51,165, MESA: n = 2,177), Norway (CNAP: n = 43,834), Australia (2 cohorts combined, Australian Pesticide Exposed Workers: n = 12,215 and Victorian Grain Farmers: n = 919), Republic of Korea (KMCC: n = 8,432), and Denmark (SUS: n = 1,899). For various cancer sites and all cancers combined, standardized incidence ratios (SIR) and 95% confidence intervals (CIs) were calculated for each cohort using national or regional rates as reference rates and were combined by random-effects meta-analysis. Results During nearly 2,800,000 person-years, a total of 23,188 cancers were observed. Elevated risks were observed for melanoma of the skin (number of cohorts = 3, meta-SIR = 1.18, CI: 1.01–1.38) and multiple myeloma (n = 4, meta-SIR = 1.27, CI: 1.04–1.54) in women and prostate cancer (n = 6, meta-SIR = 1.06, CI: 1.01–1.12), compared to the general population. In contrast, a deficit was observed for the incidence of several cancers, including cancers of the bladder, breast (female), colorectum, esophagus, larynx, lung, and pancreas and all cancers combined (n = 7, meta-SIR for all cancers combined = 0.83, 95% CI: 0.77–0.90). The direction of risk was largely consistent across cohorts although we observed large between-cohort variations in SIR for cancers of the liver and lung in men and women, and stomach, colorectum, and skin in men. Conclusion The results suggest that agricultural workers have a lower risk of various cancers and an elevated risk of prostate cancer, multiple myeloma (female), and melanoma of skin (female) compared to the general population. Those differences and the between-cohort variations may be due to underlying differences in risk factors and warrant further investigation of agricultural exposures.

Background: Trihalomethanes (THMs) and nitrate are widespread chemicals in drinking water associated with colorectal cancer risk but mechanisms are not well understood. Objectives: We explored the association between exposure to THMs and nitrate in drinking water and inflammation markers, and the link with colorectal cancer risk. Methods: A subset of 198 colorectal cancer cases and 205 controls from the multicase-control study MCC-Spain were included. Average concentration of THMs (chloroform, bromodichloromethane, dibromochloromethane, bromoform) and nitrate in tap water at the residence was estimated from age 18 until 2 years before the interview ("long term") and for a recent period (3 years before diagnosis). Serum levels of EGF, eotaxin, G-CSF, IL-17E, IL-1rA, IL-8, IP-10, MDC, MPO, periostin, VEGF, and C-reactive protein (CRP) were measured. We estimated the linear association between inflammation markers and exposure among controls, and the odds ratio of colorectal cancer associated with THM and nitrate exposure, and inflammation markers. A mediation analysis was conducted to identify inflammation markers in the pathway between THM/nitrate exposure and colorectal cancer. Results: Serum concentrations of EGF, IL-8, IL-17E and eotaxin increased with recent residential levels of brominated THMs, chloroforom and/or total THM. No associations were observed for nitrate and for long-term residential THM levels. All residential exposures except chloroform were positively associated with colorectal cancer. Serum concentrations of VEGF and periostin were positively associated with colorectal cancer, while EGF was inversely associated. One protein-exposure combination (periostin-recent ingested brominated THMs) slightly mediated the association with colorectal cancer risk. Discussion: Results suggest that estimated THM exposure is involved in inflammation processes. However, the study design was limited to stablish etiologically relevant associations between the protein levels and colorectal cancer risk. The lack of association between nitrate exposure and inflammation markers suggests other biological mechanisms are involved in the link with colorectal cancer. Acknowledgements: We acknowledge support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. This work was funded by the 7th Framework Programme EXPOSOMICS Project (grant agreement 308610), the Acci´on Transversal del C´ancer del Consejo de Ministros del 11/10/2007, and the Instituto de Salud Carlos III-FEDER (PI08/1770, PI08/0533, PI11/00226) FIS grants.

Background: Particulate matter (PM) air pollution exposure has been linked to lung function in adolescents, but little is known about the relevance of specific PM components and ultrafine particles (UFP).Objectives: To investigate the associations of long-term exposure to PM elemental composition and UFP with lung function at age 16 years.Methods: For 706 participants of a prospective Dutch birth cohort, we assessed associations of forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) at age 16 with average exposure to eight elemental components (copper, iron, potassium, nickel, sulfur, silicon, vanadium and zinc) in PM2.5 and PM10, as well as UFP during the preceding years (age 13-16 years) estimated by land-use regression models. After assessing associations for each pollutant individually using linear regression models with adjustment for potential confounders, independence of associations with different pollutants was assessed in two-pollutant models with PM mass and NO2, for which associations with lung function have been reported previously.Results: We observed that for most PM elemental components higher exposure was associated with lower FEV1, especially PM10 sulfur [e.g. adjusted difference -2.23% (95% confidence interval (CI) -3.70 to -0.74%) per interquartile range (IQR) increase in PM10 sulfur]. The association with PM10 sulfur remained after adjusting for PM10 mass. Negative associations of exposure to UFP with both FEV1 and FVC were observed [-1.06% (95% CI: -2.08 to -0.03%) and -0.65% (95% CI: -1.53 to 0.23%), respectively per IQR increase in UFP], but did not persist in two-pollutant models with NO2 or PM2.5.Conclusions: Long-term exposure to sulfur in PM10 may result in lower FEV1 at age 16. There is no evidence for an independent effect of UFP exposure.

The outline of a framework for assessing privacy risks in multi-omic research and databases provided by Dupras and Bunnik is a valuable contribution to the literature on the ethics of omics data. T...

Assessment of occupational pesticide exposure in epidemiological studies of chronic diseases is challenging. Biomonitoring of current pesticide levels might not correlate with past exposure relevant to disease aetiology, and indirect methods often rely on workers’ imperfect recall of exposures, or job titles. We investigated how the applied exposure assessment method influenced risk estimates for some chronic diseases. In three meta-analyses the influence of exposure assessment method type on the summary risk ratio (sRR) of prostate cancer (PC) (25 articles), non-Hodgkin’s lymphoma (NHL) (29 articles) and Parkinson’s disease (PD) (32 articles) was investigated. Exposure assessment method types analysed were: group-level assessments (eg, job titles), self-reported exposures, expert-level assessments (eg, job-exposure matrices) and biomonitoring (eg, blood, urine). Additionally, sRRs were estimated by study design, publication year period and geographic location where the study was conducted. Exposure assessment method types were not associated with statistically significant different sRRs across any of the health outcomes. Heterogeneity in results varied from high in cancer studies to moderate and low in PD studies. Overall, case–control designs showed significantly higher sRR estimates than prospective cohort designs. Later NHL publications showed significantly higher sRR estimates than earlier. For PC, studies from North America showed significantly higher sRR estimates than studies from Europe. We conclude that exposure assessment method applied in studies of occupational exposure to pesticides appears not to have a significant effect on risk estimates for PC, NHL and PD. In systematic reviews of chronic health effects of occupational exposure to pesticides, epidemiological study design, publication year and geographic location, should primarily be considered.

High-resolution air quality (AQ) maps based on street-by-street measurements have become possible through large-scale mobile measurement campaigns. Such campaigns have produced data-only maps and have been used to produce empirical models [i.e., land use regression (LUR) models]. Assuming that all road segments are measured, we developed a mixed model framework that predicts concentrations by an LUR model, while allowing road segments to deviate from the LUR prediction based on between-segment variation as a random effect. We used Google Street View cars, equipped with high-quality AQ instruments, and measured the concentration of NO2on every street in Amsterdam (n = 46.664) and Copenhagen (n = 28.499) on average seven times over the course of 9 and 16 months, respectively. We compared the data-only mapping, LUR, and mixed model estimates with measurements from passive samplers (n = 82) and predictions from dispersion models in the same time window as mobile monitoring. In Amsterdam, mixed model estimates correlated rs(Spearman correlation) = 0.85 with external measurements, whereas the data-only approach and LUR model estimates correlated rs= 0.74 and 0.75, respectively. Mixed model estimates also correlated higher rs= 0.65 with the deterministic model predictions compared to the data-only (rs= 0.50) and LUR model (rs= 0.61). In Copenhagen, mixed model estimates correlated rs= 0.51 with external model predictions compared to rs= 0.45 and rs= 0.50 for data-only and LUR model, respectively. Correlation increased for 97 locations (rs= 0.65) with more detailed traffic information. This means that the mixed model approach is able to combine the strength of data-only mapping (to show hyperlocal variation) and LUR models by shrinking uncertain concentrations toward the model output.

Background Epidemiological studies have demonstrated a positive association between chronic lymphocytic leukaemia (CLL) and non-melanoma skin cancer (NMSC). We hypothesized that shared genetic risk factors between CLL and NMSC could contribute to the association observed between these diseases. Methods We examined the association between (i) established NMSC susceptibility loci and CLL risk in a meta-analysis including 3100 CLL cases and 7667 controls and (ii) established CLL loci and NMSC risk in a study of 4242 basal cell carcinoma (BCC) cases, 825 squamous cell carcinoma (SCC) cases and 12802 controls. Polygenic risk scores (PRS) for CLL, BCC and SCC were constructed using established loci. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results Higher CLL-PRS was associated with increased BCC risk (OR4th-quartile-vs-1st-quartile = 1.13, 95% CI: 1.02–1.24, Ptrend = 0.009), even after removing the shared 6p25.3 locus. No association was observed with BCC-PRS and CLL risk (Ptrend = 0.68). These findings support a contributory role for CLL in BCC risk, but not for BCC in CLL risk. Increased CLL risk was observed with higher SCC-PRS (OR4th-quartile-vs-1st-quartile = 1.22, 95% CI: 1.08–1.38, Ptrend = 1.36 × 10–5), which was driven by shared genetic susceptibility at the 6p25.3 locus. Conclusion These findings highlight the role of pleiotropy regarding the pathogenesis of CLL and NMSC and shows that a single pleiotropic locus, 6p25.3, drives the observed association between genetic susceptibility to SCC and increased CLL risk. The study also provides evidence that genetic susceptibility for CLL increases BCC risk.

Background and aimOccupational exposures are important, preventable causes of COPD. We previously found an increased risk of COPD among six occupations by analysing lifetime job histories and lung function data in the population-based UK Biobank cohort. We aimed to build on these findings and elucidate the underlying potential causal agents to focus preventive strategies.MethodsWe applied the ALOHA+job exposure matrix (JEM) based on the International Standard Classification of Occupations V.1988 codes, where exposure to 12 selected agents was rated as 0 (no exposure), 1 (low) or 2 (high). COPD was spirometrically defined as FEV1/FVC less than the lower limit of normal. We calculated semiquantitative cumulative exposure estimates for each agent by multiplying the duration of exposure and squared intensity. Prevalence ratio (PR) and 95% CI for COPD were estimated using robust Poisson regression adjusted for centre, sex, age, smoking and coexposure to JEM agents. Only associations confirmed among never-smokers and never-asthmatics were considered reliable.ResultsOut of 116 375 participants with complete job histories, 94 514 had acceptable/repeatable spirometry and smoking data and were included in the analysis. Pesticide exposure showed increased risk of COPD for ever exposure (PR=1.13, 95% CI 1.01 to 1.28) and high cumulative exposure (PR=1.32, 95% CI 1.12 to 1.56), with positive exposure–response trends (p trend=0.004), which were confirmed among never-smokers (p trend=0.005) and never-asthmatics (p trend=0.001).ConclusionIn a large population-based study, occupational exposure to pesticides was associated with risk of COPD. Focused preventive strategies for workers exposed to pesticides can prevent the associated COPD burden.

Moisture-damaged buildings are associated with respiratory symptoms and underlying diseases among building occupants, but the causative agent(s) remain a mystery. We first identified specific fungal and bacterial taxa in classrooms with moisture damage in Finnish and Dutch primary schools. We then investigated associations of the identified moisture damage indicators with respiratory symptoms in more than 2700 students. Finally, we explored whether exposure to specific taxa within the indoor microbiota may explain the association between moisture damage and respiratory health. Schools were assessed for moisture damage through detailed inspections, and the microbial composition of settled dust in electrostatic dustfall collectors was determined using marker-gene analysis. In Finland, there were several positive associations between particular microbial indicators (diversity, richness, individual taxa) and a respiratory symptom score, while in the Netherlands, the associations tended to be mostly inverse and statistically non-significant. In Finland, abundance of the Sphingomonas bacterial genus and endotoxin levels partially explained the associations between moisture damage and symptom score. A few microbial taxa explained part of the associations with health, but overall, the observed associations between damage-associated individual taxa and respiratory health were limited.

BACKGROUND: We investigated whether associations between prevalent diabetes and cancer risk are pertinent to older adults and whether associations differ across subgroups of age, body weight status or levels of physical activity. METHODS: We harmonised data from seven prospective cohort studies of older individuals in Europe and the United States participating in the CHANCES consortium. Cox proportional hazard regression was used to estimate the associations of prevalent diabetes with cancer risk (all cancers combined, and for colorectum, prostate and breast). We calculated summary risk estimates across cohorts using pooled analysis and random-effects meta-analysis. RESULTS: A total of 667,916 individuals were included with an overall median (P25–P75) age at recruitment of 62.3 (57–67) years. During a median follow-up time of 10.5 years, 114,404 total cancer cases were ascertained. Diabetes was not associated with the risk of all cancers combined (hazard ratio (HR) = 0.94; 95% confidence interval (CI): 0.86–1.04; I(2) = 63.3%). Diabetes was positively associated with colorectal cancer risk in men (HR = 1.17; 95% CI: 1.08–1.26; I(2) = 0%) and a similar HR in women (1.13; 95% CI: 0.82–1.56; I(2) = 46%), but with a confidence interval including the null. Diabetes was inversely associated with prostate cancer risk (HR = 0.81; 95% CI: 0.77–0.85; I(2) = 0%), but not with postmenopausal breast cancer (HR = 0.96; 95% CI: 0.89–1.03; I(2) = 0%). In exploratory subgroup analyses, diabetes was inversely associated with prostate cancer risk only in men with overweight or obesity. CONCLUSIONS: Prevalent diabetes was positively associated with colorectal cancer risk and inversely associated with prostate cancer risk in older Europeans and Americans.

Purpose Workers on offshore petroleum installations are at risk of being exposed to benzene which is carcinogenic to humans. The present study aimed to assess the time trend of full-shift benzene exposure from 2002 to 2018 in order to characterize benzene exposure among laboratory technicians, mechanics, process operators, and industrial cleaners, and to examine the possible determinants of benzene exposure. Methods A total of 924 measurements of benzene exposure from the Norwegian petroleum offshore industry were included. The median sampling duration was 680 min, ranging from 60 to 940 min. The overall geometric mean (GM) and 95% confidence interval, time trends, and determinants of exposure were estimated using multilevel mixed-effects tobit regression analyses. Time trends were estimated for sampling duration below and above 8 h, both overall and for job groups. The variability of exposure between installation and workers was investigated in a subset of data containing worker identification. Results The overall GM of benzene exposure was 0.004 ppm. When adjusting for job group, design of process area, season, wind speed, and sampling duration, industrial cleaners had the highest exposure (GM = 0.012). Laboratory technicians, mechanics, and process operators had a GM exposure of 0.004, 0.003, and 0.004 ppm, respectively. Overall, the measured benzene exposure increased by 7.6% per year from 2002 to 2018. Mechanics had an annual increase of 8.6% and laboratory technicians had an annual decrease of 12.6% when including all measurements. When including only measurements above 8 h, mechanics had an increase of 16.8%. No statistically significant time trend was found for process operators. Open process area, high wind speed, and wintertime were associated with reduced exposure level. Conclusions An overall increase in measured exposure was observed from 2002 to 2018. The increase may reflect changes in measurement strategy from mainly measuring on random days to days with expected exposure. However, the time trend varied between job groups and was different for sampling duration above or below 8 h. Industrial cleaners had the highest exposure of the four job groups while no differences in exposure were observed between laboratory technicians, mechanics, and process operators. The design of the process area, job group, wind speed, and season were all significant determinants of benzene exposure.

Pooling metabolomics data across studies is often desirable to increase the statistical power of the analysis. However, this can raise methodological challenges as several preanalytical and analytical factors could introduce differences in measured concentrations and variability between datasets. Specifically, different studies may use variable sample types (e.g., serum versus plasma) collected, treated, and stored according to different protocols, and assayed in different laboratories using different instruments. To address these issues, a new pipeline was developed to normalize and pool metabolomics data through a set of sequential steps: (i) exclusions of the least informative observations and metabolites and removal of outliers, imputation of missing data, (ii) identification of the main sources of variability through principal component partial R-square (PC-PR2) analysis, (iii) application of linear mixed models to remove unwanted variability, including samples’ originating study and batch, and preserve biological variations while accounting for potential differences in the residual variances across studies. This pipeline was applied to targeted metabolomics data acquired using Biocrates AbsoluteIDQ kits in eight case-control studies nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Comprehensive examination of metabolomics measurements indicated that the pipeline improved the comparability of data across the studies. Our pipeline can be adapted to normalize other molecular data, including biomarkers as well as proteomics data, and could be used for pooling molecular datasets, for example in international consortia, to limit biases introduced by inter-study variability. This versatility of the pipeline makes our work of potential interest to molecular epidemiologists.

Background Large nation- and region-wide epidemiological studies have provided important insights into the health effects of long-term exposure to outdoor air pollution. Evidence from these studies for the long-term effects of ultrafine particles (UFP), however is lacking. Reason for this is the shortage of empirical UFP land use regression models spanning large geographical areas including cities with varying topographies, peri-urban and rural areas. The aim of this paper is to combine targeted mobile monitoring and long-term regional background monitoring to develop national UFP models. Method We used an electric car to monitor UFP concentrations in selected cities and towns across the Netherlands over a 14-month period in 2016–2017. Routes were monitored 3 times and concentrations were averaged per road segment. In addition, we used kriging maps based on regional background monitoring (20 sites; 3 × 2 weeks) over the same period to assess annual average regional background concentrations. All road segments were used to model spatial variation of UFP with three different land-use (regression) approaches: supervised stepwise regression, LASSO and random forest. For each approach, we also tested a deconvolution method, which segregates the average concentration at each road segment into a local and background signal. Model performance was evaluated with short-term (400 sites across the Netherlands; 3 × 30 minutes) and external longer-term measurements (42 sites in two major cities; 3 × 24 hours). We also compared predictions of all six models at 1000 random addresses spread over the country. Results We found similar predictive performance for the six models, with validation R2 values from 0.25 to 0.35 for short-term measurements and 0.52 to 0.60 for longer-term external measurements. Models with and without deconvolution had similar predictive performance. All models based on the deconvolution method included a regional background kriging map as important predictor. Correlations between predictions at random addresses were high with Pearson correlations from 0.84 to 0.99. Models overestimated exposure at the short-term and long-term sites by about 20–30% in all cases, with small differences between regions and road types. Conclusion We developed robust nation-wide models for long-term UFP exposure combining mobile monitoring with long-term regional background monitoring. Minor differences in predictive performance between different algorithms were found, but the deconvolution approach is considered more physically realistic. The models will be applied in Dutch nation-wide health studies.

Studies of the health effects of ultrafine particles (UFPs) in large nationwide cohorts are currently hampered by a lack of knowledge about spatial and spatiotemporal variations in regional background UFPs. We measured the UFP (10–300 nm) at 20 regional background locations (3 × 2 weeks) across the Netherlands and a reference site continuously over a total period of 14 months in 2016–2017. We compared the overall averages for each site and used kriging to create a regional background spatial map of the Netherlands. Spatiotemporal variability was analyzed by correlating time-series of 2 and 24 h average concentrations. The overall average measured UFP concentrations at the 20 locations ranged from 3814 to 7070 particles/cm3. We found the spatial correlation in the UFP concentrations up to 180 km and clear differences between the north and the more populated southern parts of the country. The average temporal correlation between 2 and 24 h average UFP concentrations was 0.50 (IQR: 0.36–0.61) and 0.58 (IQR: 0.44–0.75), respectively. Temporal correlation declined weakly with a distance between sites, from 0.58 for sites within 80 km of each other to 0.47 for sites farther away. The substantial spatial variation in the regional background UFP concentrations suggests that regional variation may contribute importantly to exposure contrast in nationwide health studies of UFP.

Rationale: PM2.5-induced adverse effects on respiratory health may be driven by epigenetic modifications in airway cells. The potential impact of exposure duration on epigenetic alterations in the airways is not yet known.Objectives: We aimed to study associations of fine particulate matter PM2.5 exposure with DNA methylation in nasal cells.Methods: We conducted nasal epigenome-wide association analyses within 503 children from Project Viva (mean age 12.9 y), and examined various exposure durations (1-day, 1-week, 1-month, 3-months and 1-year) prior to nasal sampling. We used residential addresses to estimate average daily PM2.5 at 1 km resolution. We collected nasal swabs from the anterior nares and measured DNA methylation (DNAm) using the Illumina Methylation EPIC BeadChip. We tested 719,075 high quality autosomal CpGs using CpG-by-CpG and regional DNAm analyses controlling for multiple comparisons, and adjusted for maternal education, household smokers, child sex, race/ethnicity, BMI z-score, age, season at sample collection and cell-type heterogeneity. We further corrected for bias and genomic inflation. We tested for replication in a cohort from the Netherlands (PIAMA).Results: In adjusted analyses, we found 362 CpGs associated with 1-year PM2.5 (FDR < 0.05), 20 CpGs passing Bonferroni correction (P < 7.0 x 10(-8)) and 10 Differentially Methylated Regions (DMRs). In 445 PIAMA participants (mean age 16.3 years) 11 of 203 available CpGs replicated at P < 0.05. We observed differential DNAm at/ near genes implicated in cell cycle, immune and inflammatory responses. There were no CpGs or regions associated with PM2.5 levels at 1-day, 1-week, or 1-month prior to sample collection, although 2 CpGs were associated with past 3-month PM2.5.Conclusion: We observed wide-spread DNAm variability associated with average past year PM2.5 exposure but we did not detect associations with shorter-term exposure. Our results suggest that nasal DNAm marks reflect chronic air pollution exposure.

Air pollution is now recognised by governments, international institutions and civil society as a major global public health risk factor. The health burden of air pollution is large: 509 000 premature deaths every year in Europe [1] and serious aggravations of heart and lung diseases that affect millions of patients, both children and adults. The European Environmental Agency estimated that in 2018 there were 417 000 premature deaths attributable to particulate matter with diameter, The potential role of air pollution in the worsening of health impacts of COVID-19, and the influence of the pandemic on air pollution levels in Europe is explored. This editorial outlines the major lessons learned to chart a healthy post-pandemic course. https://bit.ly/3hmbaya

Simple Summary Occupational cancers can be prevented by eliminating hazardous substances or by reducing workers’ exposures. Characterizing the extent of exposure to carcinogens in workplaces and industries is a crucial first step to exposure control. Iran is one of the most industrialized countries in the Middle East, yet lacks an overview of the extent of exposure to carcinogens and comprehensive risk management. This review provides an overview of studies conducted to date and demonstrates the need for interdisciplinary collaboration to inform occupational research and exposure control in Iran and beyond. Abstract Introduction: The extent of exposure to occupational carcinogens is not well characterized in Iran, and little is known about the burden of occupational cancer. Objectives: This study aimed to describe exposure to occupational carcinogens and occupational epidemiology studies in Iran. Methods: Relevant studies up to January 2021 in Iran were identified through three databases (PubMed, Web of Science, and Google Scholar). Results: Forty-nine publications from 2009 to 2020 (one cohort, 11 case-control, 34 exposure monitoring studies, and three cancer burden studies) were included. The exposure monitoring studies were conducted mainly in the petroleum industry, metal industry, manufacturing of electronics, manufacturing of plastics, construction industry, and service industry. A few of the case-control studies also reported increased risk of cancers in relation to work in those industries. Conclusions: Occupational cancer epidemiology in Iran is at an early stage. Both epidemiological and exposure monitoring studies are generally limited in size to provide robust evidence of occupational cancer risks. A coherent strategy to estimate the occupational cancer burden in Iran should start with conducting epidemiological studies along with systematic monitoring of occupational carcinogens for use in hazard control and research.

Objectives To assess whether adolescents with asthma experience a lower mental well-being and lower general health than their peers without asthma.Study design Data from the Prevention and Incidence of Asthma and Mite Allergy study were used. At the ages of 11, 14, 17, and 20 years, 2651, 2522, 2094, and 2206 participants, respectively, completed questionnaires. Their parents completed questionnaires at the ages of 11 (n = 2660), 14 (n = 2338), and 17 years (n = 1872). Asthma was defined according to the Mechanisms of the Development of Allergy criteria. Mental well-being was measured using the Mental Health Index-5 and was reported by the adolescents. General health, measured on a 4-point Likert scale, was reported by the adolescents and their parents. We estimated associations of asthma with mental wellbeing and perceived general health using generalized estimating equations.Results At ages 11, 14, 17, and 20 years, 6.7%, 6.9%, 5.0%, and 6.6%, respectively, of the adolescents had asthma. Adolescents with asthma did not score differently on the Mental Health Index than their peers without asthma. Adolescents with asthma were less likely to experience good or excellent health than their peers without asthma (aOR, 0.37; 95% CI, 0.26-0.51 for intermittent asthma and 0.33; 95% CI, 0.25-0.41 for persistent asthma). These results remain similar across the different ages.Conclusions The mental well-being of adolescents with asthma is similar to that of their peers without asthma, although adolescents with asthma are less likely to perceive a good or excellent general health.

Introduction: Lung cancer survivors are at high risk of developing a second primary lung cancer (SPLC). However, SPLC risk factors have not been established and the impact of tobacco smoking remains controversial. We examined the risk factors for SPLC across multiple epidemiologic cohorts and evaluated the impact of smoking cessation on reducing SPLC risk.Methods: We analyzed data from 7059 participants in the Multiethnic Cohort (MEC) diagnosed with an initial primary lung cancer (IPLC) between 1993 and 2017. Cause-specific proportional hazards models estimated SPLC risk. We conducted validation studies using the Prostate, Lung,Colorectal, and Ovarian Cancer Screening Trial (N = 3423 IPLC cases) and European Prospective Investigation into Cancer and Nutrition (N = 4731 IPLC cases) cohorts and pooled the SPLC risk estimates using random effects meta analysis.Results: Overall, 163 MEC cases (2.3%) developed SPLC. Smoking pack-years (hazard ratio [HR] = 1.18 per 10 pack years, p < 0.001) and smoking intensity (HR = 1.30 per 10 cigarettes per day, p < 0.001) were significantly associated with increased SPLC risk. Individuals who met the 2013 U.S. Preventive Services Task Force's screening criteria at IPLC diagnosis also had an increased SPLC risk (HR = 1.92; p < 0.001). Validation studies with the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial and European Prospective Investigation into Cancer and Nutrition revealed consistent results. Meta-analysis yielded pooled HRs of 1.16 per 10 pack-years (p(meta) < 0.001), 1.25 per 10 cigarettes per day (p(meta) < 0.001), and 1.99 (p(meta) < 0.001) for meeting the U.S. Preventive Services Task Force's criteria. In MEC, smoking cessation after IPLC diagnosis was associated with an 83% reduction in SPLC risk (HR = 0.17; p < 0.001).Conclusions: Tobacco smoking is a risk factor for SPLC. Smoking cessation may reduce the risk of SPLC. Additional strategies for SPLC surveillance and screening are warranted. (C) 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).