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Occupational exposure to trichloroethylene (TCE) has been associated with alterations in B-cell activation factors and an increased risk of non-Hodgkin's lymphoma (NHL). Here, we aimed to examine the biological processes influenced by trichloroethylene (TCE) exposure to understand the underlying molecular mechanisms. This cross-sectional molecular epidemiology study included data of 1317 targeted proteins in the serum from 42 TCE exposed and 34 unexposed factory workers in Guangdong, China. We used multivariable linear regressions to identify proteins associated with TCE exposure and examined their exposure-response relationship across categories of TCE exposure (unexposed, low exposed:10 ppm, high exposed: ≥10 ppm). We further examined pathway enrichment of TCE-related proteins to understand their biological response. Occupational exposure to TCE was associated with lower levels of tumor necrosis factor receptor superfamily member 17 (TNFRSF17; β = -0.08; p-value=0.0003) and Kynureninase (KYNU; β = -0.10, p-value = 0.002). These proteins also showed a significant exposure-response relation across the unexposed, low exposed, and high exposed workers (all p-trends0.001, FDR0.20). Pathway analysis of TCE-related proteins showed significant enrichment (FDR0.05) for several inflammatory and immune pathways. TCE exposure was associated with TNFRSF17, a key B-cell maturation antigen that mediates B-cell survival and KYNU, an enzyme that plays a role in T-cell mediated immune response. Given that altered immunity is an established risk factor for NHL, our findings support the biological plausibility of linking TCE exposure with NHL. This article is protected by copyright. All rights reserved.

The emergence of bacterial strains resistant to topical antimicrobials in both human and veterinary medicine has raised concerns over retaining the efficacy of these preparations. Yet, little information is available regarding the use of topical antimicrobials in either sector for planning targeted interventions. This study aims to quantify the use of topical antimicrobials in 44 Dutch companion animal clinics before and during their participation in an antimicrobial stewardship programme (ASP), to explore the effect of the intervention on topical antimicrobial use (AMU). Hence, prescription and clinic animal population data, collected from July 2012 until June 2018 were used. Specifically, the period from July 2012 until June 2015 was defined as pre-intervention period, whereas clinics started to participate in the ASP from March 2016 onwards. As quantification metric, the Defined Daily Dose for Animals (DDDA) was used and a mixed effect times series model with auto-regression was applied to monthly topical AMU data. The intervention effect was modelled using a step function with a change in (linear) time trend and clinic characteristics, as potential determinants of topical AMU, were assessed using a multivariable regression model. A seasonal pattern was identified, in the pre-intervention period, where topical AMU was highest in July-August and lowest in February-March. In addition, total topical AMU appeared to significantly decrease over time in the pre-intervention period and the proportion of dogs in the clinic was positively associated with topical AMU. The intervention effect was significant only for second line and for skin product AMU. This study demonstrates that during participation in an ASP, second line and skin product AMU decreased in Dutch companion animal clinics. Additionally, this study demonstrates the existence of a seasonal effect and a decrease in topical AMU over time already before introduction of a targeted intervention.

It has been suggested that domestic animals can serve as sentinels for human exposures. In this study our objectives were to demonstrate that i) silicone collars can be used to measure environmental exposures of (domestic) animals, and that ii) domestic animals can be used as sentinels for human residential exposure. For this, we simultaneously measured polycyclic aromatic hydrocarbons (PAHs) using silicone bands worn by 30 pet cats (collar) and their owner (wristband). Collars and wristbands were worn for 7 days and analyzed via targeted Gas Chromatography-Mass Spectrometry (GC-MS). Demographics and daily routines were collected for humans and cats. Out of 16 PAHs, 9 were frequently detected (>50% of samples) in both wristbands and collars, of which Phenanthrene and Fluorene were detected in all samples. Concentrations of wristbands and collars were moderately correlated for these 9 PAHs (Median Spearman's r = 0.51 (range 0.16–0.68)). Determinants of PAH concentrations of cats and humans showed considerable overlap, with vacuum cleaning resulting in higher exposures and frequent changing of bed sheets in lower exposures. This study adds proof-of-principle data for the use of silicone collars to measure (domestic) animal exposure and shows that cats can be used as sentinels for human residential exposure.

ObjectivesThere has been concern over the possible risk of autoimmune diseases from exposure to trichloroethylene (TCE), an industrial solvent and common pollutant near hazardous waste sites. Studies of TCE-exposed lupus-prone mouse strains have reported increases in serum antinuclear antibodies (ANAs), a marker of autoimmunity, and autoimmune pathologic changes, while epidemiologic studies have provided limited support for an association between TCE exposure and scleroderma. To investigate exposure-related biologic evidence of autoimmunity in humans, we measured ANA levels in sera from a cross-sectional study of TCE-exposed (n=80) and TCE-unexposed (n=96) workers in Guangdong, China.MethodsFull-shift personal air exposure measurements for TCE were taken prior to blood collection. Serum ANAs were detected by immunofluorescence on HEp-2 cells. We calculated ORs and 95% CI relating levels of TCE exposure (categorised using tertiles as cut-points) and ANA positivity (1+ intensity at 1:320 dilution) using multivariable logistic regression.ResultsSamples from 16 of 176 participants were ANA-positive. We found higher levels of TCE exposure (concentrations>17.27 ppm) to be associated with an elevated odds of ANA positivity (OR 4.7, 95% CI 1.3 to 16.8) compared with unexposed controls. This association remained after excluding two subjects with diagnosed autoimmune disease (OR 4.5, 95% CI 1.2 to 16.2). We did not observe an association with ANAs at lower exposure levels.ConclusionsOur findings, to our knowledge the first direct human evidence of an association between TCE exposure and systemic autoimmunity, provide biologic plausibility to epidemiologic evidence relating TCE and autoimmune disease.

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.

Background: There is a growing interest in the impact of air pollution from livestock farming on respiratory health. Studies in adults suggest adverse effects of livestock farm emissions on lung function, but so far, studies involving children and adolescents are lacking. Objectives: To study the association of residential proximity to livestock farms and modelled particulate matter ≤10 μm (PM10) from livestock farms with lung function in adolescence. Methods: We performed a cross-sectional study among 715 participants of the Dutch prospective PIAMA (Prevention and Incidence of Asthma and Mite Allergy) birth cohort study. Relationships of different indicators of residential livestock farming exposure (distance to farms, distance-weighted number of farms, cattle, pigs, poultry, horses and goats within 3 km; modelled atmospheric PM10 concentrations from livestock farms) with forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) at age 16 were assessed by linear regression taking into account potential confounders. Associations were expressed per interquartile range increase in exposure. Results: Higher exposure to livestock farming was consistently associated with a lower FEV1, but not with FVC among participants living in less urbanized municipalities (2, N = 402). Shorter distances of homes to livestock farms were associated with a 1.4% (0.2%; 2.7%) lower FEV1. Larger numbers of farms within 3 km and higher concentrations of PM10 from livestock farming were associated with a 1.8% (0.8%, 2.9%) and 0.9% (0.4%,1.5%) lower FEV1, respectively. Conclusions: Our findings suggest that higher exposure to livestock farming is associated with a lower FEV1 in adolescents. Replication and more research on the etiologic agents involved in these associations and the underlying mechanisms is needed.

Residential relocation is increasingly used as a natural experiment in epidemiological studies to assess the health impact of changes in environmental exposures. Since the likelihood of relocation can be influenced by individual characteristics that also influence health, studies may be biased if the predictors of relocation are not appropriately accounted for. Using data from Swedish and Dutch adults (SDPP, AMIGO), and birth cohorts (BAMSE, PIAMA), we investigated factors associated with relocation and changes in multiple environmental exposures across life stages. We used logistic regression to identify baseline predictors of moving, including sociodemographic and household characteristics, health behaviors and health. We identified exposure clusters reflecting three domains of the urban exposome (air pollution, grey surface, and socioeconomic deprivation) and conducted multinomial logistic regression to identify predictors of exposome trajectories among movers. On average, 7 % of the participants relocated each year. Before relocating, movers were consistently exposed to higher levels of air pollution than non-movers. Predictors of moving differed between the adult and birth cohorts, highlighting the importance of life stages. In the adult cohorts, moving was associated with younger age, smoking, and lower education and was independent of cardio-respiratory health indicators (hypertension, BMI, asthma, COPD). Contrary to adult cohorts, higher parental education and household socioeconomic position were associated with a higher probability of relocation in birth cohorts, alongside being the first child and living in a multi-unit dwelling. Among movers in all cohorts, those with a higher socioeconomic position at baseline were more likely to move towards healthier levels of the urban exposome. We provide new insights into predictors of relocation and subsequent changes in multiple aspects of the urban exposome in four cohorts covering different life stages in Sweden and the Netherlands. These results inform strategies to limit bias due to residential self-selection in epidemiological studies using relocation as a natural experiment. The EXPANSE project is funded by the European Union’s Horizon 2020 research and innovation programme under grand agreement No 874627. This research has received funding from the EXPOSOME-NL Gravitation program of the Dutch Ministry of Education, Culture, and Science and the Netherlands Organization for Scientific Research (NWO grant number 024.004.017). AS has received funding from the Swiss National Science Foundation (grant number 210781). We acknowledge collaborators involved in the EXPANSE project and those who participated in the cohort data collection and preparation for this research. The AMIGO cohort was funded by the Netherlands Organisation for Health Research and Development (ZonMw) within the Electromagnetic Fields and Health Research programme (grant numbers 85200001 and 85200002). The SDPP cohort was funded by the Stockholm County Council, the Swedish Research Council, the Swedish Diabetes Association, and Novo Nordisk Scandinavia. The PIAMA study was supported by The Netherlands Organization for Health Research and Development; The Dutch Research Council (NWO); The Lung Foundation Netherlands; The Netherlands Ministry of Spatial Planning, Housing, and the Environment; The Netherlands Ministry of Health, Welfare, and Sport; and The National Institute for Public Health and the Environment. The BAMSE study was supported by grants from the Swedish Research Council (2016-03086; 2020-01886), the Swedish Heart-Lung Foundation, Region Stockholm (ALF project, and for cohort and database maintenance).

BACKGROUND: We previously showed that exposure to 5-methylchrysene (5MC) and other methylated polycyclic aromatic hydrocarbons (PAHs) best explains lung cancer risks in a case-control study among non-smoking women using smoky coal in China. Time-related factors (e.g., age at exposure) and non-linear relations were not explored. OBJECTIVE: We investigated the relation between coal-derived air pollutants and lung cancer mortality using data from a large retrospective cohort. METHODS: Participants were smoky (bituminous) or smokeless (anthracite) coal users from a cohort of 42,420 subjects from four communes in XuanWei. Follow-up was from 1976 to 2011, during which 4,827 deaths from lung-cancer occurred. Exposures were predicted for 43 different pollutants. Exposure clusters were identified using hierarchical clustering. Cox regression was used to estimate exposure-response relations for 5MC, while effect modification by age at exposure was investigated for cluster prototypes. A Bayesian penalized multi-pollutant model was fitted on a nested case-control sample, with more restricted models fitted to investigate non-linear exposure-response relations. RESULTS: We confirmed the strong exposure-response relation for 5MC (Hazard Ratio [95% Confidence Interval] = 2.5 [2.4, 2.6] per standard-deviation (SD)). We identified four pollutant clusters, with all but two PAHs in a single cluster. Exposure to PAHs in the large cluster was associated with a higher lung cancer mortality rate (HR [95%CI] = 2.4 [2.2, 2.6] per SD), while exposure accrued before 18 years of age appeared more important than adulthood exposures. Results from the multi-pollutant model identified anthanthrene (ANT) and benzo(a)chrysene (BaC) as risk factors. 5MC remained strongly associated with lung cancer in models that included ANT and BaC and also benzo(a)pyrene (BaP). CONCLUSION: We confirmed the link between PAH exposures and lung cancer in smoky coal users and found exposures before age 18 to be especially important. We found some evidence for the carcinogen 5MC and non-carcinogens ANT and BaC.

Objective: Women of reproductive age are exposed to ubiquitous chemicals such as phthalates, parabens, and per- and polyfluoroalkyl substances (PFAS), which have potential endocrine disrupting properties and might affect fertility. Our objective was to investigate associations between potential endocrine-disrupting chemicals (EDCs) and female fertility in two cohorts of women attending fertility clinics. Methods: In a total population of 333 women in Sweden and Estonia, we studied the associations between chemicals and female fertility, evaluating ovarian sensitivity index (OSI) as an indicator of ovarian response, as well as clinical pregnancy and live birth from fresh and frozen embryo transfers. We measured 59 chemicals in follicular fluid samples and detected 3 phthalate metabolites, di-2-ethylhexyl phthalate (DEHP) metabolites, 1 paraben, and 6 PFAS in >90% of the women. Associations were evaluated using multivariable-adjusted linear or logistic regression, categorizing EDCs into quartiles of their distributions, as well as with Bayesian Kernel Machine Regression. Results: We observed statistically significant lower OSI at higher concentrations of the sum of DEHP metabolites in the Swedish cohort (Q4 vs Q1, β = -0.21, 95% CI: −0.38, −0.05) and methylparaben in the Estonian cohort (Q3 vs Q1, β = -0.22, 95% CI: −0.44, −0.01). Signals of potential associations were also observed at higher concentrations of PFUnDA in both the combined population (Q2 vs. Q1, β = −0.16, 95% CI -0.31, −0.02) and the Estonian population (Q2 vs. Q1, β = −0.27, 95% CI -0.45, −0.08), and for PFOA in the Estonian population (Q4 vs. Q1, β = −0.31, 95% CI -0.61, −0.01). Associations of chemicals with clinical pregnancy and live birth presented wide confidence intervals. Conclusions: Within a large chemical mixture, we observed significant inverse associations levels of DEHP metabolites and methylparaben, and possibly PFUnDA and PFOA, with OSI, suggesting that these chemicals may contribute to altered ovarian function and infertility in women.

Background: Established risk factors for breast cancer include genetic disposition, reproductive factors, hormone therapy, and lifestyle-related factors such as alcohol consumption, physical inactivity, smoking, and obesity. More recently a role of environmental exposures, including air pollution, has also been suggested. The aim of this study, was to investigate the relationship between long-term air pollution exposure and breast cancer incidence. Methods: We conducted a pooled analysis among six European cohorts (n = 199,719) on the association between long-term residential levels of ambient nitrogen dioxide (NO2), fine particles (PM2.5), black carbon (BC), and ozone in the warm season (O3) and breast cancer incidence in women. The selected cohorts represented the lower range of air pollutant concentrations in Europe. We applied Cox proportional hazards models adjusting for potential confounders at the individual and area-level. Results: During 3,592,885 person-years of follow-up, we observed a total of 9,659 incident breast cancer cases. The results of the fully adjusted linear analyses showed a HR (95% confidence interval) of 1.03 (1.00–1.06) per 10 μg/m³ NO2, 1.06 (1.01–1.11) per 5 μg/m³ PM2.5, 1.03 (0.99–1.06) per 0.5 10−5 m−1 BC, and 0.98 (0.94–1.01) per 10 μg/m³ O3. The effect estimates were most pronounced in the group of middle-aged women (50–54 years) and among never smokers. Conclusions: The results were in support of an association between especially PM2.5 and breast cancer. Impact: The findings of this study suggest a role of exposure to NO2, PM2.5, and BC in development of breast cancer.

Background: The link between exposure to ambient air pollution and mortality from cardiorespiratory diseases is well established, while evidence on neurodegenerative disorders including Parkinson's Disease (PD) remains limited. Objective: We examined the association between long-term exposure to ambient air pollution and PD mortality in seven European cohorts. Methods: Within the project ‘Effects of Low-Level Air Pollution: A Study in Europe’ (ELAPSE), we pooled data from seven cohorts among six European countries. Annual mean residential concentrations of fine particulate matter (PM2.5), nitrogen dioxide (NO2), black carbon (BC), and ozone (O3), as well as 8 PM2.5 components (copper, iron, potassium, nickel, sulphur, silicon, vanadium, zinc), for 2010 were estimated using Europe-wide hybrid land use regression models. PD mortality was defined as underlying cause of death being either PD, secondary Parkinsonism, or dementia in PD. We applied Cox proportional hazard models to investigate the associations between air pollution and PD mortality, adjusting for potential confounders. Results: Of 271,720 cohort participants, 381 died from PD during 19.7 years of follow-up. In single-pollutant analyses, we observed positive associations between PD mortality and PM2.5 (hazard ratio per 5 µg/m3: 1.25; 95% confidence interval: 1.01–1.55), NO2 (1.13; 0.95–1.34 per 10 µg/m3), and BC (1.12; 0.94–1.34 per 0.5 × 10-5m-1), and a negative association with O3 (0.74; 0.58–0.94 per 10 µg/m3). Associations of PM2.5, NO2, and BC with PD mortality were linear without apparent lower thresholds. In two-pollutant models, associations with PM2.5 remained robust when adjusted for NO2 (1.24; 0.95–1.62) or BC (1.28; 0.96–1.71), whereas associations with NO2 or BC attenuated to null. O3 associations remained negative, but no longer statistically significant in models with PM2.5. We detected suggestive positive associations with the potassium component of PM2.5. Conclusion: Long-term exposure to PM2.5, at levels well below current EU air pollution limit values, may contribute to PD mortality.

Within the European Human Biomonitoring (HBM) Initiative HBM4EU we derived HBM indicators that were designed to help answering key policy questions and support chemical policies. The result indicators convey information on chemicals exposure of different age groups, sexes, geographical regions and time points by comparing median exposure values. If differences are observed for one group or the other, policy measures or risk management options can be implemented. Impact indicators support health risk assessment by comparing exposure values with health-based guidance values, such as human biomonitoring guidance values (HBM-GVs). In general, the indicators should be designed to translate complex scientific information into short and clear messages and make it accessible to policy makers but also to a broader audience such as stakeholders (e.g. NGO's), other scientists and the general public. Based on harmonized data from the HBM4EU Aligned Studies (2014-2021), the usefulness of our indicators was demonstrated for the age group children (6-11 years), using two case examples: one phthalate (Diisobutyl phthalate: DiBP) and one non-phthalate substitute (Di-isononyl cyclohexane-1,2- dicarboxylate: DINCH). For the comparison of age groups, these were compared to data for teenagers (12-18 years), and time periods were compared using data from the DEMOCOPHES project (2011-2012). Our result indicators proved to be suitable for demonstrating the effectiveness of policy measures for DiBP and the need of continuous monitoring for DINCH. They showed similar exposure for boys and girls, indicating that there is no need for gender focused interventions and/or no indication of sex-specific exposure patterns. They created a basis for a targeted approach by highlighting relevant geographical differences in internal exposure. An adequate data basis is essential for revealing differences for all indicators. This was particularly evident in our studies on the indicators on age differences. The impact indicator revealed that health risks based on exposure to DiBP cannot be excluded. This is an indication or flag for risk managers and policy makers that exposure to DiBP still is a relevant health issue. HBM indicators derived within HBM4EU are a valuable and important complement to existing indicator lists in the context of environment and health. Their applicability, current shortcomings and solution strategies are outlined. The authors received funding from the EUHorizon 2020 framework (grant agreement No 733032). Additional financial support for the conduct of the studies is provided by each participating country. The Norwegian Institute of Public Health (NIPH) has contributed to funding of the Norwegian Environmental Biobank (NEB). The laboratory measurements have partly been funded by the Research Council of Norway through research projects (275903 and 268465). The funding of the German Ministry for the Environment, Nature Conservation, Nuclear Safety and Consumer Protection is gratefully acknowledged. PCB cohort was supported by Ministry of Health of the Slovak Re public, grant no. 2012/47-SZU-11 and by Slovak Research and Development Agency, grant no. APVV-0571-12. PCB cohort follow-up received additional funding from the Ministry of Health of the Slovak Republic, program 07B0103. Riksmaten Adolescents was performed by the Swedish Food Agency with financial support from the Swedish Environmental Protection Agency and the Swedish Civil Contingencies Agency. The BEA study was co-funded by the Spanish Ministry of Agriculture, Fisheries and Food and the Instituto de Salud Carlos III (SEG 1321/15). The CELSPAC study is supported by the MEYS (LM2018121, CZ.02.1.01/0.0/0.0/17_043/0009632 and CZ.02.1.01/0.0/0.0/15_003/0000469) and from the European Union’s Horizon 2020 research and innovation programme under grant agreement (857560). This publication reflects only the author’s view and the European Commission is not responsible for any use that may be made of the information it contains. NIRAS/ONDRAF (Belgian National Agency for Radioactive Waste and enriched Fissile Material), STORA (Study and Consultation Radioactive Waste Dessel) and MONA (Mols Overleg Nucleair Afval) financed the 3xG study. The FLEHS IV study was conducted within the framework of the Flemish Center of Expertise on Environment and Health (FLEHS 2016–2020) and funded by the Flemish Government, Department of Environment & Spatial Development. CROME study is co-funded by the European Commission research funds of Horizon 2020 and LIFE financial instrument of the European Community (LIFE12 ENV/GR/001040). ESTEBAN is funded by Sant´e Publique France and the French ministries of Health and the Environment. The Slovenian SLO-CRP study was co-financed by the Jozef Stefan Institute program P1-0143, and a national project “Exposure of children and adolescents to selected chemicals through their habitat environment” (grant agreement No. C2715-16-634802). The OCC studies were supported by Odense University Hospital, the Region of Southern Denmark, the Municipality of Odense, the Mental Health Service of the Region of Southern Denmark, Odense Patient data Exploratory Network (OPEN), Novo Nordisk Foundation [grant nr. NNF15OC00017734 and NNF19OC0058266], the Danish Council for Independent Research [4004-00352B_FSS]. POLAES study was co-financed by Ministry of Science and Education of Poland (contract no.3764/H2020/2017/2) Sí

INTRODUCTION: Radiofrequency electromagnetic fields originate from a variety of wireless communication sources operating near and far from the body, making it challenging to quantify daily absorbed dose. In the framework of the prospective cohort SCAMP (Study of Cognition, Adolescents and Mobile Phones), we aimed to characterize RF-EMF dose over a 2-year period. METHODS: The SCAMP cohort included 6605 children from greater London, UK at baseline (age 12.1 years; 2014-2016) and 5194 at follow-up (age 14.2; 2016-2018). We estimated the daily dose of RF-EMF to eight tissues including the whole body and whole brain, using dosimetric algorithms for the specific absorption rate transfer into the body. We considered RF-EMF dose from 12 common usage scenarios such as mobile phone calls or data transmission. We evaluated the association between sociodemographic factors (gender, ethnicity, phone ownership and socio-economic status), and the dose change between baseline and follow-up. RESULTS: Whole body dose was estimated at an average of 170 mJ/kg/day at baseline and 178 mJ/kg/day at follow-up. Among the eight tissues considered, the right temporal lobe received the highest daily dose (baseline 1150 mJ/kg/day, follow-up 1520 mJ/kg/day). Estimated daily dose [mJ/kg/day] increased between baseline and follow-up for head and brain related tissues, but remained stable for the whole body and heart. Doses estimated at baseline and follow-up showed low correlation among the 3384 children who completed both assessments. Asian ethnicity (compared to white) and owning a bar phone or no phone (as opposed to a smartphone) were associated with lower estimated whole-body and whole-brain RF-EMF dose, while black ethnicity, a moderate/low socio-economic status (compared to high), and increasing age (at baseline) were associated with higher estimated RF-EMF dose. CONCLUSION: This study describes the first longitudinal exposure assessment for children in a critical period of development. Dose estimations will be used in further epidemiological analyses for the SCAMP study.

We would like to thank ‘the National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands’ for their contribution and ongoing support to the EPIC Study., This work was undertaken during the tenure of a doctoral Fellowship supported by INCa (INCa 2016 − 184), by Fondation ARC pour la recherche sur le cancer (ARC 2019-DOC4) and by IARC. The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition PotsdamRehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (C864/A 14136 to EPIC- Norfolk (DOI https://doi.org/10.22025/2019.10.105.00004); C8221/A29017 to EPIC-Oxford), Medical Research Council (MR/N003284/1 and MC_UU_00006/1 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford). (United Kingdom)., Data Availability For information on how to submit an application for gaining access to EPIC data and/or biospecimens, please follow the instructions at http://epic.iarc.fr/access/index.php., Background: Diet may impact important risk factors for endometrial cancer such as obesity and inflammation. However, evidence on the role of specific dietary factors is limited. We investigated associations between dietary fatty acids and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods: This analysis includes 1,886 incident endometrial cancer cases and 297,432 non-cases. All participants were followed up for a mean of 8.8 years. Multivariable Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of endometrial cancer across quintiles of individual fatty acids estimated from various food sources quantified through food frequency questionnaires in the entire EPIC cohort. The false discovery rate (q-values) was computed to control for multiple comparisons. Results: Consumption of n-6 γ-linolenic acid was inversely associated with endometrial cancer risk (HR comparing 5th with 1st quintileQ5-Q1=0.77, 95% CI = 0.64; 0.92, ptrend=0.01, q-value = 0.15). This association was mainly driven by γ-linolenic acid derived from plant sources (HRper unit increment=0.94, 95%CI= (0.90;0.98), p = 0.01) but not from animal sources (HRper unit increment= 1.00, 95%CI = (0.92; 1.07), p = 0.92). In addition, an inverse association was found between consumption of n-3 α-linolenic acid from vegetable sources and endometrial cancer risk (HRper unit increment= 0.93, 95%CI = (0.87; 0.99), p = 0.04). No significant association was found between any other fatty acids (individual or grouped) and endometrial cancer risk. Conclusion: Our results suggest that higher consumption of γ-linolenic acid and α-linoleic acid from plant sources may be associated with lower risk of endometrial cancer., Institut National du Cancer (INCA) France C864/A 14136, Fondation ARC pour la Recherche sur le Cancer ARC 2019-DOC4, IARC, World Health Organization. International Agency for Research on Cancer (IARC), Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, NIHR Imperial Biomedical Research Centre (BRC), Danish Cancer Society, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (Inserm), Deutsche Krebshilfe. German Cancer Aid, Helmholtz Association, German Institute of Human Nutrition PotsdamRehbruecke (DIfE), Federal Ministry of Education & Research (BMBF), Fondazione AIRC per la ricerca sul cancro, Compagnia di San Paolo, Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund International (WCRF), Netherlands Government, Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skane and Vaesterbotten (Sweden), Cancer Research UK C8221/A29017 MR/N003284/1, UK Research & Innovation (UKRI) Medical Research Council UK (MRC) MC_UU_00006/1 MR/M012190/1 2016 - 184

Chronic lymphocytic leukemia (CLL) is preceded by monoclonal B-cell lymphocytosis (MBL), a CLL precursor state with a prevalence of up to 12% in aged individuals; however, the duration of MBL and the mechanisms of its evolution to CLL remain largely unknown. In this study, we sequenced the B-cell receptor (BcR) immunoglobulin heavy chain (IGH) gene repertoire of 124 patients with CLL and 118 matched controls in blood samples taken up to 22 years prior to diagnosis. Significant skewing in the BcR IGH gene repertoire was detected in the majority of patients, even before the occurrence of lymphocytosis and irrespective of the clonotypic IGH variable gene somatic hypermutation status. Furthermore, we identified dominant clonotypes belonging to major stereotyped subsets associated with poor prognosis up to 16 years before diagnosis in 14 patients with CLL. In 22 patients with longitudinal samples, the skewing of the BcR IGH gene repertoire increased significantly over time to diagnosis or remained stable at high levels. For 14 of 16 patients with available samples at diagnosis, the CLL clonotype was already present in the prediagnostic samples. Overall, our data indicate that the preclinical phase of CLL could be longer than previously thought, even in adverse-prognostic cases.

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.

The European Policy Evaluation Network (PEN), initiated in autumn 2018, aimed at advancing the evidence base for public policies impacting dietary behaviour, physical activity and sedentary behaviours in Europe. This is needed because non-communicable diseases—the leading cause of global mortality—are substantially caused by physical inactivity and unhealthy dietary behaviours, which in turn are driven by upstream factors that have not yet been addressed effectively by prevention approaches. Thus, successful policy interventions are required that target entire populations and tackle the ‘causes of the causes’. To advance our knowledge on the effective implementation of policies and their impact in terms of improving health behaviours, PEN focused on five research tasks: (i) Adaptation and implementation of a Food Environment Policy Index (Food-EPI) and development of a Physical Activity Environment Policy Index (PA-EPI); (ii) Mapping of health-related indicators needed for policy evaluation and facilitating a harmonized pan-European approach for surveillance to assess the impact of policy interventions; (iii) Refining quantitative methods to evaluate the impact of public policies; (iv) Identifying key barriers and facilitators of implementation of policies; and (v) Advance understanding the equity impact of the development, implementation and evaluation of policies aimed at promoting physical activity and a healthy diet. Finally, and in order to provide concrete evidence for policymaking, existing exemplary policies, namely sugar-sweetened beverages taxation, active transport policies and school policies on nutrition and physical activity were assessed in consideration of these five tasks. At the end of the PEN project’s formal runtime, considerable advancements have been made. Here, we present an overview of the most important learnings and outputs.

Assessment of long-term human exposure to spatiotemporally highly variable air pollution requires accounting for human space–time activity. Individual exposure and space–time track data are not available over large populations and for long periods and a modelling approach is required. However, activity-based exposure models face here challenges in setting up the model and overly-large computations. Aiming for long-term and large-population simulations, we propose an activity model which integrates statistical and agent-based modelling by treating mobility-related variables as random variables. Probability distributions for these variables are estimated or derived from mobility datasets containing observed activities. On top of the activity model, we implemented an exposure model. A case-study of exposure assessment was developed using hourly air pollution maps. The activity model can potentially integrate any mobility data and is thus applicable when limited time activity data is available at the individual level.

BACKGROUND: Type 2 diabetes (T2D) is thought to be influenced by environmental stressors such as air pollution and noise. Although environmental factors are interrelated, studies considering the exposome are lacking. We simultaneously assessed a variety of exposures in their association with prevalent T2D by applying penalised regression Least Absolute Shrinkage and Selection Operator (LASSO), Random Forest (RF), and Artificial Neural Networks (ANN) approaches. We contrasted the findings with single-exposure models including consistently associated risk factors reported by previous studies.METHODS: Baseline data (n = 14,829) of the Occupational and Environmental Health Cohort study (AMIGO) were enriched with 85 exposome factors (air pollution, noise, built environment, neighbourhood socio-economic factors etc.) using the home addresses of participants. Questionnaires were used to identify participants with T2D (n = 676(4.6 %)). Models in all applied statistical approaches were adjusted for individual-level socio-demographic variables.RESULTS: Lower average home values, higher share of non-Western immigrants and higher surface temperatures were related to higher risk of T2D in the multivariable models (LASSO, RF). Selected variables differed between the two multi-variable approaches, especially for weaker predictors. Some established risk factors (air pollutants) appeared in univariate analysis but were not among the most important factors in multivariable analysis. Other established factors (green space) did not appear in univariate, but appeared in multivariable analysis (RF). Average estimates of the prediction error (logLoss) from nested cross-validation showed that the LASSO outperformed both RF and ANN approaches.CONCLUSIONS: Neighbourhood socio-economic and socio-demographic characteristics and surface temperature were consistently associated with the risk of T2D. For other physical-chemical factors associations differed per analytical approach.

BACKGROUND: Particulate matter (PM) is classified as a group 1 human carcinogen. Previous experimental studies suggest that particles in diesel exhaust induce oxidative stress, inflammation and DNA damage in kidney cells, but the evidence from population studies linking air pollution to kidney cancer is limited. METHODS: We pooled six European cohorts (N = 302,493) to assess the association of residential exposure to fine particles (PM2.5), nitrogen dioxide (NO2), black carbon (BC), warm season ozone (O3) and eight elemental components of PM2.5 (copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc) with cancer of the kidney parenchyma. The main exposure model was developed for year 2010. We defined kidney parenchyma cancer according to the International Classification of Diseases 9th and 10th Revision codes 189.0 and C64. We applied Cox proportional hazards models adjusting for potential confounders at the individual and area-level. RESULTS: The participants were followed from baseline (1985–2005) to 2011–2015. A total of 847 cases occurred during 5,497,514 person-years of follow-up (average 18.2 years). Median (5–95%) exposure levels of NO2, PM2.5, BC and O3 were 24.1 μg/m3 (12.8–39.2), 15.3 μg/m3 (8.6–19.2), 1.6 10−5 m−1 (0.7–2.1), and 87.0 μg/m3 (70.3–97.4), respectively. The results of the fully adjusted linear analyses showed a hazard ratio (HR) of 1.03 (95% confidence interval [CI]: 0.92, 1.15) per 10 μg/m³ NO2, 1.04 (95% CI: 0.88, 1.21) per 5 μg/m³ PM2.5, 0.99 (95% CI: 0.89, 1.11) per 0.5 10−5 m−1 BCE, and 0.88 (95% CI: 0.76, 1.02) per 10 μg/m³ O3. We did not find associations between any of the elemental components of PM2.5 and cancer of the kidney parenchyma. CONCLUSION: We did not observe an association between long-term ambient air pollution exposure and incidence of kidney parenchyma cancer.

Childhood allergic diseases, including asthma, rhinitis and eczema, are prevalent conditions that share strong genetic and environmental components. Diagnosis relies on clinical history and measurements of allergen-specific IgE. We hypothesize that a multi-omics model could accurately diagnose childhood allergic disease. We show that nasal DNA methylation has the strongest predictive power to diagnose childhood allergy, surpassing blood DNA methylation, genetic risk scores, and environmental factors. DNA methylation at only three nasal CpG sites classifies allergic disease in Dutch children aged 16 years well, with an area under the curve (AUC) of 0.86. This is replicated in Puerto Rican children aged 9–20 years (AUC 0.82). DNA methylation at these CpGs additionally detects allergic multimorbidity and symptomatic IgE sensitization. Using nasal single-cell RNA-sequencing data, these three CpGs associate with influx of T cells and macrophages that contribute to allergic inflammation. Our study suggests the potential of methylation-based allergy diagnosis.

ObjectivesNever-smoking women in Xuanwei (XW), China, have some of the highest lung cancer rates in the country. This has been attributed to the combustion of smoky coal used for indoor cooking and heating. The aim of this study was to evaluate the spectrum of cause-specific mortality in this unique population, including among those who use smokeless coal, considered ‘cleaner’ coal in XW, as this has not been well-characterised.DesignCohort study.SettingXW, a rural region of China where residents routinely burn coal for indoor cooking and heating.ParticipantsAge-adjusted, cause-specific mortality rates between 1976 and 2011 were calculated and compared among lifetime smoky and smokeless coal users in a cohort of 42 420 men and women from XW. Mortality rates for XW women were compared with those for a cohort of predominately never-smoking women in Shanghai.ResultsMortality in smoky coal users was driven by cancer (41%), with lung cancer accounting for 88% of cancer deaths. In contrast, cardiovascular disease (CVD) accounted for 32% of deaths among smokeless coal users, with 7% of deaths from cancer. Total cancer mortality was four times higher among smoky coal users relative to smokeless coal users, particularly for lung cancer (standardised rate ratio (SRR)=17.6). Smokeless coal users had higher mortality rates of CVD (SRR=2.9) and pneumonia (SRR=2.5) compared with smoky coal users. These patterns were similar in men and women, even though XW women rarely smoked cigarettes. Women in XW, regardless of coal type used, had over a threefold higher rate of overall mortality, and most cause-specific outcomes were elevated compared with women in Shanghai.ConclusionsCause-specific mortality burden differs in XW based on the lifetime use of different coal types. These observations provide evidence that eliminating all coal use for indoor cooking and heating is an important next step in improving public health particularly in developing countries.

Current-use pesticides (CUP) are extensively applied in both agricultural and urban settings. Exposure occurs mainly via the dietary pathway; however, other pathways such as inhalation or skin contact are also important. In this study, urinary levels of 12 CUP metabolites were investigated among 110 parent-child pairs during two seasons of 2020. Metabolites of pyrethroids (3-PBA, t/c-DCCA), chlorpyrifos (TCPY), and tebuconazole (TEB-OH) were detected in more than 60% of the samples. Chlorpyrifos metabolite was found at the highest concentration and tebuconazole was detected in almost all samples. CUP urinary metabolite levels were significantly higher in children in comparison to adults, except for tebuconazole, which was similar in both groups. In children, winter samples had significantly higher concentrations of pyrethroid and chlorpyrifos metabolites in comparison to the summer samples, but in adults, only chlorpyrifos metabolite concentrations were higher in the winter. No association between CUP urinary metabolite levels and proximity/surface of agricultural areas around residences was observed. Based on our findings, we suspect that CUP exposure is mainly driven by diet and that the effect of environmental exposure is less significant. Daily Intakes were estimated with three possible scenarios considering the amount of the metabolite excreted in urine and were compared to Acceptable Daily Intake values. Using a realistic scenario, exposure to chlorpyrifos exhibited the highest health risk, but still within a safe level. The Acceptable Daily Intake was exceeded only in one child in the case of cypermethrin. The cumulative risk assessment of pesticide mixtures having an effect on the nervous system, based on the total margin of exposure calculations, did not indicate any risk. The overall risk associated with pesticide exposure in the observed population was low. However, the risk observed using the worst-case scenario suggests the need for continuous evaluation of human exposure to such compounds, especially in children.

RATIONALE: Evidence regarding the role of long-term exposure to ultrafine particles (OBJECTIVES: We examined the association between exposure to UFP and asthma development in the Dutch PIAMA (Prevention and Incidence of Asthma and Mite Allergy) birth cohort and assessed whether there is an association with UFP, independent of other air pollutants.METHODS: Data from birth up to age 20 years from 3687 participants were included. Annual average exposure to UFP at the residential addresses was estimated with a land-use regression model. Overall and age-specific associations of exposure at the birth address and current address at the time of follow-up)with asthma incidence were assessed using discrete-time hazard models adjusting for potential confounders. We investigated both single- and two-pollutant models accounting for co-exposure to other air pollutants (PM2.5 and PM10 mass concentrations, nitrogen dioxide, and PM2.5 absorbance).MEASUREMENTS AND MAIN RESULTS: A total of 812 incident asthma cases were identified. Overall, we found that higher UFP exposure was associated with higher asthma incidence (adjusted odds ratio (95% confidence interval) 1.08 (1.02,1.14) and 1.06 (1.00, 1.12) per interquartile range increase in exposure at the birth address and current address at the time of follow-up, respectively). Age-specific associations were not consistent. The association was no longer significant after adjustment for other traffic-related pollutants (nitrogen dioxide and PM2.5 absorbance).CONCLUSIONS: Our findings support the importance of traffic-related air pollutants for asthma development through childhood and adolescence, but provide little support for an independent effect of UFP.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Limited evidence suggests ALS diagnosis may be associated with air pollution exposure and specifically traffic-related pollutants. METHODS: In this population-based case-control study, we used 3,937 ALS cases from the Danish National Patient Register diagnosed during 1989-2013 and matched on age, sex, year of birth, and vital status to 19,333 population-based controls free of ALS at index date. We used validated predictions of elemental carbon (EC), nitrogen oxides (NO x ), carbon monoxide (CO), and fine particles (PM 2.5 ) to assign 1-, 5-, and 10-year average exposures pre-ALS diagnosis at study participants' present and historical residential addresses. We used an adjusted Bayesian hierarchical conditional logistic model to estimate individual pollutant associations and joint and average associations for traffic-related pollutants (EC, NO x , CO). RESULTS: For a standard deviation (SD) increase in 5-year average concentrations, EC (SD = 0.42 µg/m 3 ) had a high probability of individual association with increased odds of ALS (11.5%; 95% credible interval [CrI] = -1.0%, 25.6%; 96.3% posterior probability of positive association), with negative associations for NO x (SD = 20 µg/m 3 ) (-4.6%; 95% CrI = 18.1%, 8.9%; 27.8% posterior probability of positive association), CO (SD = 106 µg/m 3 ) (-3.2%; 95% CrI = 14.4%, 10.0%; 26.7% posterior probability of positive association), and a null association for nonelemental carbon fine particles (non-EC PM 2.5 ) (SD = 2.37 µg/m 3 ) (0.7%; 95% CrI = 9.2%, 12.4%). We found no association between ALS and joint or average traffic pollution concentrations. CONCLUSIONS: This study found high probability of a positive association between ALS diagnosis and EC concentration. Further work is needed to understand the role of traffic-related air pollution in ALS pathogenesis.

Background: The NORMAN Association (https:// www. norman-​netwo rk. com/) initiated the NORMAN Suspect List Exchange (NORMAN-SLE; https:// www. norman-​netwo rk. com/ nds/ SLE/) in 2015, following the NORMAN collaborative trial on non-target screening of environmental water samples by mass spectrometry. Since then, this exchange of information on chemicals that are expected to occur in the environment, along with the accompanying expert knowledge and references, has become a valuable knowledge base for “suspect screening” lists. The NORMAN-SLE now serves as a FAIR (Findable, Accessible, Interoperable, Reusable) chemical information resource worldwide. Results: The NORMAN-SLE contains 99 separate suspect list collections (as of May 2022) from over 70 contributors around the world, totalling over 100,000 unique substances. The substance classes include per- and polyfluoroalkyl substances (PFAS), pharmaceuticals, pesticides, natural toxins, high production volume substances covered under the European REACH regulation (EC: 1272/2008), priority contaminants of emerging concern (CECs) and regulatory lists from NORMAN partners. Several lists focus on transformation products (TPs) and complex features detected in the environment with various levels of provenance and structural information. Each list is available for separate download. The merged, curated collection is also available as the NORMAN Substance Database (NORMAN SusDat). Both the NORMAN-SLE and NORMAN SusDat are integrated within the NORMAN Database System (NDS). The individual NORMAN-SLE lists receive digital object identifiers (DOIs) and traceable versioning via a Zenodo community (https:// zenodo. org/ commu nities/ norman-​sle), with a total of > 40,000 unique views, > 50,000 unique downloads and 40 citations (May 2022). NORMAN-SLE content is progressively integrated into large open chemical databases such as PubChem (https:// pubch em. ncbi. nlm. nih. gov/) and the US EPA’s CompTox Chemicals Dashboard (https:// compt ox. epa. gov/ dashb oard/), enabling further access to these lists, along with the additional functionality and calculated properties these resources offer. PubChem has also integrated significant annotation content from the NORMAN-SLE, including a classification browser (https:// pubch em. ncbi. nlm. nih. gov/ class ifica tion/# hid= 101). Conclusions: The NORMAN-SLE offers a specialized service for hosting suspect screening lists of relevance for the environmental community in an open, FAIR manner that allows integration with other major chemical resources. These efforts foster the exchange of information between scientists and regulators, supporting the paradigm shift to the “one substance, one assessment” approach. New submissions are welcome via the contacts provided on the NORMAN-SLE website (https:// www. norman-​netwo rk. com/ nds/ SLE/)., NORMAN Association, Luxembourg National Research Fund A18/BM/12341006, European Union's Horizon 2020 research and innovation programme 101036756, National Center for Biotechnology Information of the National Library of Medicine (NLM), National Institutes of Health (NIH), National Health and Medical Research Council (NHMRC) of Australia EL1 2009209, Australian Research Council DP190102476 Queensland Department of Health, Instituto de Salud Carlos III European Commission CP19/00060 European Union through Fondo Europeo de Desarrollo Regional (FEDER), Federal Ministry of Education & Research (BMBF) FKz: 02WRS1495 A/B/E, FWO 11G1821N, NIH via grant NIH NIGMS R01GM092218 NIH via grant NIH NCI 1R03CA222452-01, Vanderbilt Chemical Biology Interface training program 5T32GM065086-16, Netherlands Organization for Scientific Research (NWO) 15747, SOLUTIONS project (European Union's Seventh Framework Programme for research, technological development and demonstration) 603437, HBM4EU (European Union's Horizon 2020 research and innovation programme 733032, German Research Foundation (DFG) 441958208, NaToxAq (European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie Grant 722493, German Federal Ministry for the Environment, Nature Conservation and Nuclear Safety (BMU) (FKZ) 3716 67 416 0, German Federal Ministry for the Environment, Nature Conservation, Nuclear Safety and Consumer Protection (BMUV) Project (FKZ) 3719 65 408 0, EU Cohesion Funds within the project Monitoring and assessment of water body status 310011A366, Swiss Federal Office for the Environment (FOEN), Canadian Institutes of Health Research (CIHR) Genome Canada, MAVA foundation, Valery Foundation, National Science Foundation (NSF) RUI-1306074 National Natural Science Foundation of China (NSFC) 22193051 21906177, China Postdoctoral Science Foundation 2019M650863, Environmental Protection Administration, Executive Yuan, R.O.C. Taiwan (Taiwan EPA) 108C002871, Swiss Federal Office for the Environment, United States Environmental Protection Agency, Center for Forestry Research & Experimentation (CIEF), European Commission 2019/040, Marie Sklodowska-Curie grant 859891 European Commission European Commission Joint Research Centre 308610 289511, Joint Programming Initiative FOODBALL 2014-17 MCIN/AEI RYC2020-028901-I, ESF investing in your future, August T Larsson Guest Researcher Programme from the Swedish University of Agricultural Sciences, German Federal Ministry of Education and Research within the RiSKWa program 02WRS1273 02WRS1354, RECETOX research infrastructure (the Czech Ministry of Education, Youth and Sports) LM2018121, CETOCOEN PLUS project CZ.02.1.01/0.0/0.0/15_ 003/0000469 CETOCOEN EXCELLENCE Teaming 2 project - Czech ministry of Education, Youth and Sports CZ.02.1.01/0.0/0.0/1 7_043/0009632

Background: Early-life respiratory tract infections might affect chronic obstructive respiratory diseases, but conclusive studies from general populations are lacking. Our objective was to examine if children with early-life respiratory tract infections had increased risks of lower lung function and asthma at school age. Methods: We used individual participant data of 150 090 children primarily from the EU Child Cohort Network to examine the associations of upper and lower respiratory tract infections from age 6 months to 5 years with forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, forced expiratory flow at 75% of FVC (FEF75%) and asthma at a median (range) age of 7 (4-15) years. Results: Children with early-life lower, not upper, respiratory tract infections had a lower school-age FEV1, FEV1/FVC and FEF75% (z-score range: -0.09 (95% CI -0.14- -0.04) to -0.30 (95% CI -0.36- -0.24)). Children with early-life lower respiratory tract infections had a higher increased risk of school-age asthma than those with upper respiratory tract infections (OR range: 2.10 (95% CI 1.98-2.22) to 6.30 (95% CI 5.64-7.04) and 1.25 (95% CI 1.18-1.32) to 1.55 (95% CI 1.47-1.65), respectively). Adjustment for preceding respiratory tract infections slightly decreased the strength of the effects. Observed associations were similar for those with and without early-life wheezing as a proxy for early-life asthma. Conclusions: Our findings suggest that early-life respiratory tract infections affect development of chronic obstructive respiratory diseases in later life, with the strongest effects for lower respiratory tract infections. A comprehensive list of grant funding is available on the ALSPAC website (www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). BAMSE: BAMSE was funded by the Swedish Research Council, the Swedish Heart Lung Foundation, ALF Region Stockholm and SFO Epidemiology Karolinska Institutet. E. Mélen is supported by a European Research Council grant (TRIBAL, 757919). BiB (Born in Bradford): BiB is only possible because of the enthusiasm and commitment of the children and parents in BiB. We are grateful to all the participants, practitioners and researchers who have made BiB happen. The BiB study presents independent research commissioned by the National Institute for Health Research Collaboration for Applied Health Research and Care (NIHR CLAHRC) and the Programme Grants for Applied Research funding scheme (RP-PG-0407-10044). Core support for BiB is also provided by the Wellcome Trust (WT101597MA). BILD: This study was funded by the Swiss National Science Foundation (320030_163311). CoNER: Funds were obtained from the special programme (Programmi speciali – Art.12 bis, comma 6 D.lgs.229/99 Sanitaria e della Vigilanza sugli Enti) funded by the Italian Ministry of Health. Approval for the study was obtained from the Ethics Committee of the S. Orsola-Malpighi Teaching Hospital in April 2004 (52/2004/U/Tess). COPSAC 2000 and COPSAC 2010: All funding received by COPSAC is listed on www.copsac.com. The Lundbeck Foundation (R16-A1694), Ministry of Health (903516), Danish Council for Strategic Research (0603-00280B) and Capital Region Research Foundation have provided core support to the COPSAC research centre. We express our deepest gratitude to the children and families of the COPSAC 2000 and COPSAC 2010 cohort studies for all their support and commitment. We acknowledge and appreciate the unique efforts of the COPSAC research team. DNBC (Danish National Birth Cohort): The authors would like to thank the participants, the first Principal Investigator of DNBC, Jørn Olsen, the scientific managerial team and DNBC secretariat for being, establishing, developing and consolidating the DNBC. The DNBC was established with a significant grant from the Danish National Research Foundation. Additional support was obtained from the Danish Regional Committees, Pharmacy Foundation, Egmont Foundation, March of Dimes Birth Defects Foundation, Health Foundation and other minor grants. The DNBC Biobank has been supported by the Novo Nordisk Foundation and Lundbeck Foundation. Follow-up of mothers and children has been supported by the Danish Medical Research Council (SSVF 0646, 271-08-0839/06-066023, O602-01042B, 0602-02738B), Lundbeck Foundation (195/04, R100-A9193), Innovation Fund Denmark 0603-00294B (09-067124), Nordea Foundation (02-2013-2014), Aarhus Ideas (AU R9-A959-13-S804), University of Copenhagen Strategic Grant (IFSV 2012) and Danish Council for Independent Research (DFF-4183-00594, DFF-4183-00152). A. Pinot de Moira is funded by a Lundbeck Foundation grant (R264-2017-3099). EDEN: We thank the EDEN mother–child cohort study group (I. Annesi-Maesano, J.Y. Bernard, J. Botton, M.A. Charles, P. Dargent-Molina, B. de Lauzon-Guillain, P. Ducimetière, M. de Agostini, B. Foliguet, A. Forhan, X. Fritel, A. Germa, V. Goua, R. Hankard, B. Heude, M. Kaminski, B. Larroque†, N. Lelong, J. Lepeule, G. Magnin, L. Marchand, C. Nabet, F. Pierre, R. Slama, M.J. Saurel-Cubizolles, M. Schweitzer and O. Thiebaugeorges). We thank all funding sources for the EDEN study (not allocated for the present study but for the cohort): Foundation for Medical Research (FRM), National Agency for Research (ANR), National Institute for Research in Public health (IRESP: TGIR cohorte santé 2008 programme), French Ministry of Health (DGS), French Ministry of Research, INSERM Bone and Joint Diseases National Research (PRO-A) and Human Nutrition National Research Programs, Paris-Sud University, Nestlé, French National Institute for Population Health Surveillance (InVS), French National Institute for Health Education (INPES), the European Union FP7 programmes (FP7/2007-2013, HELIX, ESCAPE, ENRIECO, MeDALL projects), Diabetes National Research Program (in collaboration with the French Association of Diabetic Patients (AFD)), French Agency for Environmental Health Safety (now ANSES), Mutuelle Générale de l'Education Nationale complementary health insurance (MGEN), French national agency for food security, and French speaking association for the study of diabetes and metabolism (ALFEDIAM). The funding source had no involvement in the conception of the present study. FLEHS: This study was conducted within the framework of the Flemish Centre of Expertise on Environment and Health, funded by the Dept of the Environment of the Flemish Government, Flemish Agency of Care and Health, and Flemish Dept of Economy, Science and Innovation. GASPII: The GASPII cohort was funded by the Italian Ministry of Health (2001), the research leading to these results has received funding from the European Community's Seventh Framework Program under grant agreement 261357 (MeDALL). Generation R: This study was funded by Erasmus MC Rotterdam, Erasmus University Rotterdam and the Netherlands Organisation for Health Research and Development. V.W.V. Jaddoe received a grant from the European Research Council (ERC-2014-CoG-648916). L. Duijts received funding from cofunded ERA-Net on Biomarkers for Nutrition and Health (ERA HDHL), Horizon 2020 (696295; 2017), the Netherlands Organisation for Health Research and Development (ZonMw; 529051014; 2017), Science Foundation Ireland (SFI/16/ERA-HDHL/3360), and European Union (ALPHABET project). The project received funding from the European Union's Horizon 2020 research and innovation programme (LIFECYCLE, 733206, 2016; EUCAN-Connect 824989; ATHLETE, 874583). The researchers are independent from the funders. The study sponsors had no role in the study design, data analysis, interpretation of data or writing of this report. Generation XXI: Generation XXI was supported by the European Regional Development Fund (ERDF) through the Operational Programme Competitiveness and Internationalization and national funding from the Foundation for Science and Technology (FCT), Portuguese Ministry of Science, Technology and Higher Education, and by the Unidade de Investigação em Epidemiologia – Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (UIDB/04750/2020), Administração Regional de Saúde Norte (Regional Dept of Ministry of Health) and Fundação Calouste Gulbenkian. A.C. Santos is founded by FCT Investigator contracts IF/01060/2015. GINI: The GINIplus study was mainly supported for the first 3 years by the Federal Ministry for Education, Science, Research and Technology (interventional arm) and Helmholtz Zentrum München (former GSF) (observational arm). The 4- and 6-year follow-up examinations of the GINIplus study were covered from the respective budgets of the five study centres (Helmholtz Zentrum München (former GSF), Research Institute at Marien-Hospital, Wesel, LMU Munich, TU Munich and from 6 years onwards also from IUF – Leibniz Research Institute for Environmental Medicine at the University of Düsseldorf). HUMIS: We thank all mothers for participating in the HUMIS study. HUMIS was funded by a grant from the Norwegian Research Council (226402). The HUMIS study was approved by the Norwegian Data Inspectorate (2002/1398) and by the Regional Ethics Committee for Medical Research in Norway (S-02122), and the specific use in the current study was approved by the Ethics Committee as well (2010/1259/REK sør-øst). INMA: Gipuzkoa: This study was funded by grants from Instituto de Salud Carlos III (FIS-PI09/00090, FIS-PI18/01142 including FEDER funds), CIBERESP, Dept of Health of the Basque Government (2013111089) and annual agreements with the municipalities of the study area (Zumarraga, Urretxu, Legazpi, Azkoitia y Azpeitia and Beasain). Menorca: This study was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176; CB06/02/0041; 97/0588; 00/0021-2, PI061756; PS0901958, PI14/00677 including FEDER funds), CIBERESP, Beca de la IV convocatoria de Ayudas a la Investigación en Enfemerdades Neurodegeneratives de La Caixa, and EC contract QLK4-CT-200-00263. Sabadell: This study was funded by grants from Instituto de Salud Carlos III (Red INMA G03/176; CB06/02/0041; PI041436; PI081151 including FEDER funds), Generalitat de Catalunya-CIRIT 1999SGR 00241 and Fundació La marató de TV3 (090430). ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya. M. Casas holds a Miguel Servet fellowship (CP16/00128) funded by Instituto de Salud Carlos III and cofunded by the European Social Fund “Investing in your future”. Valencia: This study was funded by grants from the European Union (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1), Spain: Instituto de Salud Carlos III (Red INMA G03/176, CB06/02/0041; FIS-FEDER: PI03/1615, PI04/1509, PI04/1112, PI04/1931, PI05/1079, PI05/1052, PI06/1213, PI07/0314, PI09/02647, PI11/01007, PI11/02591, PI11/02038, PI13/1944, PI13/2032, PI14/00891, PI14/01687, PI16/1288, PI17/00663; Miguel Servet-FEDER CP11/00178, CP15/00025, CPII16/00051), Generalitat Valenciana: FISABIO (UGP 15-230, UGP-15-244, UGP-15-249), and Alicia Koplowitz Foundation 2017. Isle of Wight: This study was funded by grants from the National Institutes of Health USA (R01HL082925), Asthma UK (364), Isle of Wight NHS Trust and the British Medical Association. KOALA: The collection of data relevant for this study was funded by grants from the Netherlands Organisation for Health Research and Development (ZonMw; 2100.0090) and the Netherlands Asthma Foundation (3.2.03.48, 3.2.07.022). The researchers are independent from the funders. The funders had no role in the study design, data analysis, interpretation of data or writing of this report. We thank the children and parents for their participation in the KOALA study. LRC (Leicestershire Respiratory Cohorts): This study was funded by grants from the Swiss National Science Foundation (SNF: 320030-182628, 320030-162820, 3233-069348, 3200-069349) and Asthma UK 07/048. Lifeways Cross-Generation Cohort Study: This study was funded by the Health Research Board, Ireland, and the Irish Dept of Health and Children's Health Promotion Policy Unit. LISA: The LISA study was mainly supported by grants from the Federal Ministry for Education, Science, Research and Technology and in addition from Helmholtz Zentrum München (former GSF), Helmholtz Centre for Environmental Research – UFZ, Leipzig, Research Institute at Marien-Hospital Bad Honnef for the first 2 years. The 4-, 6-, 10- and 15-year follow-up examinations of the LISA study were covered from the respective budgets of the involved partners (Helmholtz Zentrum München (former GSF), Helmholtz Centre for Environmental Research – UFZ, Leipzig, Research Institute at Marien-Hospital Wesel, Pediatric Practice, Bad Honnef, IUF – Leibniz Research Institute for Environmental Medicine at the University of Düsseldorf) and in addition by a grant from the Federal Ministry for Environment (IUF Düsseldorf, FKZ 20462296). Further, the 15-year follow-up examination of the LISA study was supported by the Commission of the European Communities, the Seventh Framework Program: MeDALL project. This project has received funding from the European Research Council under the European Union’s Horizon 2020 research and innovation programme (949906). LucKi: LucKi is supported by Child and Youth Health Care Zuyderland, Public Health Service South Limburg and Maastricht University. We thank all parents and children for their participation in LucKi. LUKAS: This study was funded by research grants from the Academy of Finland (139021, 287675, 296814, 296817, 308254); Juho Vainio Foundation; EVO/VTR funding; Päivikki and Sakari Sohlberg Foundation; Farmers’ Social Insurance Institution (Mela); Finnish Cultural Foundation; Foundation for Pediatric Research; European Union QLK4-CT-2001-00250; and Finnish Institute for Health and Welfare, Finland. MAS-90: This study was funded by grants from the German Federal Ministry of Education and Research (MBMF; 07015633m 07ALE27, 01EE9405/5, 01EE9406) and the German Research Foundation (DFG; KE1462/2-1). Millennium Cohort Study: This study was funded by the Economic and Social Research Council and a consortium of UK government funders. We are grateful to the participating families and the Centre for Longitudinal Studies (CLS), UCL Institute of Education, for the use of these data and to the UK Data Service for making them available. However, neither CLS nor the UK Data Service bear any responsibility for the analysis or interpretation of these data. This work was supported by the Welcome Trust (187389/B/08/Z). MoBa: The Norwegian Mother, Father and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and Ministry of Education and Research. We are grateful to all the participating families in Norway who take part in this ongoing cohort study. This research was supported by the Research Council of Norway through its Centres of Excellence funding scheme (262700). NINFEA: The authors are grateful to all the participants of the NINFEA cohort. The NINFEA study was partially funded by the Compagnia San Paolo Foundation. This research was partially funded by the European Union's Horizon 2020 research and innovation programme (LIFECYCLE, 733206). PELAGIE: We are grateful to the families who participated and continue to participate in the study. The cohort is supported by INSERM and received funding from the French National Research Agency, Fondation de France, French Agency for Food, Environmental and Occupational Health & Safety, National Institute for Public Health Surveillance (InVS), French Ministry of Labour, and French Ministry of Ecology. PIAMA: This study was funded by the Netherlands Organisation of Health Research and Development, Netherlands Organisation for Scientific Research, Netherlands Asthma Fund, Netherlands Ministry of Spatial Planning, Housing and the Environment, and Netherlands Ministry of Health, Welfare and Sport. REPRO_PL: This study was funded by the National Science Center Poland (DEC-2014/15/B/N27/00998). Rhea: This study was funded by the European Union Social Fund and the Hellenic Ministry of Health (“Program of prevention and early diagnosis of obesity and neurodevelopment disorders in preschool age children in the prefecture of Heraklion, Crete, Greece”; MIS 349580, NSRF 2007–2013). Additional funding from the National Institute of Environmental Health Sciences (NIEHS) supported L. Chatzi (R01ES030691, R01ES029944, R01ES030364, R21ES029681, R21ES028903, P30ES007048). STEPS: This study was funded by the University of Turku, Abo Akademi University, Turku University Hospital, Academy of Finland (123571, 140251, 277535) and Foundation for Pediatric Research Finland. SWS: This study was funded by the Medical Research Council, British Heart Foundation, Arthritis Research UK, Food Standards Agency, NIHR Southampton Biomedical Research Centre and the European Union's Seventh Framework Programme (FP7/2007–2013), project EarlyNutrition (289346), and the European Union's Horizon 2020 research and innovation programme (LIFECYCLE, 733206). WHISTLER: The WHISTLER birth cohort was supported with a grant from the Netherlands Organisation for Health Research and Development (2001-1-1322) and by an unrestricted grant from GlaxoSmithKline Netherlands. GlaxoSmithKline had no role in study design, in the collection, analysis and interpretation of data, in the writing of the report, and in the decision to submit the report for publication. WHISTLER-Cardio was supported with an unrestricted strategic grant from the University Medical Center Utrecht (UMCU).

Previous European land-use regression (LUR) models assumed fixed linear relationships between air pollution concentrations and predictors such as traffic and land use. We evaluated whether including spatially-varying relationships could improve European LUR models by using geographically weighted regression (GWR) and random forest (RF). We built separate LUR models for each year from 2000 to 2019 for NO2, O3, PM2.5 and PM10 using annual average monitoring observations across Europe. Potential predictors included satellite retrievals, chemical transport model estimates and land-use variables. Supervised linear regression (SLR) was used to select predictors, and then GWR estimated the potentially spatially-varying coefficients. We developed multi-year models using geographically and temporally weighted regression (GTWR). Five-fold cross-validation per year showed that GWR and GTWR explained similar spatial variations in annual average concentrations (average R2 = NO2: 0.66; O3: 0.58; PM10: 0.62; PM2.5: 0.77), which are better than SLR (average R2 = NO2: 0.61; O3: 0.46; PM10: 0.51; PM2.5: 0.75) and RF (average R2 = NO2: 0.64; O3: 0.53; PM10: 0.56; PM2.5: 0.67). The GTWR predictions and a previously-used method of back-extrapolating 2010 model predictions using CTM were overall highly correlated (R2 > 0.8) for all pollutants. Including spatially-varying relationships using GWR modestly improved European air pollution annual LUR models, allowing time-varying exposure-health risk models.

Background: Exposure to ambient air pollution, even at low levels, is a major environmental health risk. The peripheral blood transcriptome provides a potential avenue for the elucidation of ambient air pollution related biological perturbations. We assessed the association between long-term estimates for seven priority air pollutants and perturbations in peripheral blood transcriptomics data collected in the Dutch National Twin Register (NTR) and Netherlands Study of Depression and Anxiety (NESDA) cohorts. Methods: In both the discovery (n = 2438) and replication (n = 1567) cohort, outdoor concentration of 7 air pollutants (NO2, NOx, particulate matter (PM2.5, PM2.5abs, PM10, PMcoarse), and ultrafine particles) was predicted with land use regression models. Gene expression was assessed by Affymetrix U219 arrays. Multi-variable univariate mixed-effect models were applied to test for an association between the air pollutants and the transcriptome. Functional analysis was conducted in DAVID. Results: In the discovery cohort, we observed for 335 genes (374 probes with FDR < 5 %) a perturbation in peripheral blood gene expression that was associated with long-term average levels of PM2.5. For 69 genes pooled effect estimates from the NTR and NESDA cohorts were significant. Identified genes play a role in biological pathways related to cell signaling and immune response. Sixty-two out of 69 genes had a similar direction of effect in an analysis in which we regressed the probes on differential PM2.5 exposure within monozygotic twin pairs, indicating that the observed differences in gene expression were likely driven by differences in air pollution, rather than by confounding by genetic factors. Conclusion: Our results indicate that PM2.5 can elicit a response in cell signaling and the immune system, both hallmarks of environmental diseases. The differential effect that we observed between air pollutants may aid in the understanding of differential health effects that have been observed with these exposures.

We investigated whether exposure to carcinogenic diesel engine exhaust (DEE) was associated with altered adduct levels in human serum albumin (HSA) residues. Nano-liquid chromatography-high resolution mass spectrometry (nLC-HRMS) was used to measure adducts of Cys34 and Lys525 residues in plasma samples from 54 diesel engine factory workers and 55 unexposed controls. An untargeted adductomics and bioinformatics pipeline was used to find signatures of Cys34/Lys525 adductome modifications. To identify adducts that were altered between DEE-exposed and unexposed participants, we used an ensemble feature selection approach that ranks and combines findings from linear regression and penalized logistic regression, then aggregates the important findings with those determined by random forest. We detected 40 Cys34 and 9 Lys525 adducts. Among these findings, we found evidence that 6 Cys34 adducts were altered between DEE-exposed and unexposed participants (i.e., 841.75, 851.76, 856.10, 860.77, 870.43, and 913.45). These adducts were biologically related to antioxidant activity.

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.

BackgroundExposure to extremely low frequency magnetic fields (ELF-MFs) and electric shocks is a common occupational risk factor in many workplaces. Recent investigations have highlighted a possible association between such exposures and lymphoma risk. This study was carried out to further explore the association between occupational exposure to ELF-MFs and electric shocks and risk of lymphoma in a large Nordic census-based cohort.MethodsWe included cases of non-Hodgkin's lymphoma (NHL, n=68 978), chronic lymphocytic leukaemia (CLL, n=20 615) and multiple myeloma (MM, n=35 467) diagnosed between 1961 and 2005 in Finland, Iceland, Norway and Sweden. Cases were matched to five controls by year of birth, sex and country. Lifetime occupational ELF-MF and electric shock exposures were assigned to jobs reported in population censuses using job-exposure matrices. The risk of cancer was assessed based on cumulative exposure to ELF-MF and electric shocks. ORs with 95% CIs were estimated using logistic models adjusted for occupational co-exposures relevant to lymphomas.ResultsLess than 7% of the cases experienced high levels of ELF-MF. We observed no increased risks among workers exposed to high levels of ELF-MF for NHL (OR: 0.93; CI 0.90 to 0.97), CLL (OR: 0.98; CI 0.92 to 1.05) or MM (OR: 0.96; CI 0.90 to 1.01).ConclusionOur results do not provide support for an association between occupational exposure to ELF-MFs and electric shocks and lymphoma risk.

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.

Supplementary data are available online at https://www.sciencedirect.com/science/article/pii/S1438463923000263?via%3Dihub#appsec1 . Copyright © 2023 The Authors. Unintentional chemical mixtures that are present in the environment are of societal concern as the (environmental) chemicals contained therein, either singly or in combination, may possess properties that are hazardous (toxic) for human health. The current regulatory practice, however, is still largely based on evaluating single chemical substances one-by-one. Over the years various research efforts have delivered tools and approaches for risk assessment of chemical mixtures, but many of these were not considered sufficiently mature for regulatory implementation. This is (partly) due to mixture risk assessment (MRA) being very complex because of the large number of chemicals present in the environment. A key element in risk assessment is information on actual exposures in the population of interest. To date, information on actual personal (internal) mixture exposures is largely absent, severely limiting MRA. The use of human biomonitoring data may improve this situation. Therefore, we investigated within the European Human Biomonitoring Initiative (HBM4EU) various approaches to assess combined exposures and MRA. Based on the insights and lessons learnt in the context of the HBM4EU project, conclusions as well as recommendations for policy development regarding chemical mixtures and for further research were drafted. These conclusions and recommendations relate to both exposure and adverse health effects in humans. The recommendations were discussed with stakeholders in a workshop held in October 2021. There was considerable support and agreement with the spirit, scope and intention of the draft recommendations. Here we describe the lessons learnt on mixture risk assessment through the HBM4EU project and present the final recommendations. Overall, HBM4EU results demonstrated the potential of human biomonitoring as an instrument to obtain insight into the real-life mixtures the human population is exposed to. Also, HBM4EU results demonstrated that chemical mixtures are of public health concern. In the majority of the cases, it was possible to identify risk drivers, i.e. chemicals that contribute more strongly than others to the health risk. The novel approaches to identify co-occurrence patterns demonstrated clusters of co-occurring chemicals; chemicals in these mixture clusters are regulated independently under different legislative frameworks. Moreover, HBM4EU data and expertise can support a science-based derivation of a Mixture Assessment Factor and gauge potential impacts on the population's exposure to chemicals. While further expansion is needed on various aspects of the mixture activities carried out in the context of HBM4EU, application of available methodologies for mixture risk assessment should already be implemented to the degree possible. This research has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 733032 HBM4EU.

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.

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.

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.

The COVID-19 pandemic raised a need to characterise the biochemical response to SARS-CoV-2 infection and find biological markers to identify therapeutic targets. In support of these aims, we applied a range of LC-MS platforms to analyse over 100 plasma samples from patients with varying COVID-19 severity and with detailed clinical information on inflammatory responses (>30 immune markers). The first publication in a series reports the results of quantitative LC-MS/MS profiling of 56 amino acids and derivatives. A comparison between samples taken from ICU and ward patients revealed a notable increase in ten post-translationally modified amino acids that correlated with markers indicative of an excessive immune response: TNF-alpha, neutrophils, markers for macrophage, and leukocyte activation. Severe patients also had increased kynurenine, positively correlated with CRP and cytokines that induce its production. ICU and ward patients with high IL-6 showed decreased levels of 22 immune-supporting and anti-oxidative amino acids and derivatives (e.g., glutathione, GABA). These negatively correlated with CRP and IL-6 and positively correlated with markers indicative of adaptive immune activation. Including corresponding alterations in convalescing ward patients, the overall metabolic picture of severe COVID-19 reflected enhanced metabolic demands to maintain cell proliferation and redox balance, alongside increased inflammation and oxidative stress.

BACKGROUND: Air pollution has been associated with carotid intima-media thickness test (CIMT), a marker of subclinical atherosclerosis. To our knowledge, this is the first study to report an association between ambient air pollution and CIMT in a younger adolescent population.OBJECTIVE: To investigate the associations beyond standard mean regression by using quantile regression to explore if associations occur at different percentiles of the CIMT distribution.METHODS: We measured CIMT cross-sectionally at the age of 16 years in 363 adolescents participating in the Dutch PIAMA birth cohort. We fit separate quantile regressions to examine whether the associations of annual averages of nitrogen dioxide (NO2), fine particulate matter (PM2.5), PM2.5 absorbance (a marker for black carbon), PMcoarse and ultrafine particles up to age 14 assigned at residential addresses with CIMT varied across deciles of CIMT. False discovery rate corrections (FDR, p < 0.05 for statistical significance) were applied for multiple comparisons. We report quantile regression coefficients that correspond to an average change in CIMT (µm) associated with an interquartile range increase in the exposure.RESULTS: PM2.5 absorbance exposure at birth was statistically significantly (FDR < 0.05) associated with a 6.23 µm (95% CI: 0.15, 12.3) higher CIMT per IQR increment in PM2.5 absorbance in the 10th quantile of CIMT but was not significantly related to other deciles within the CIMT distribution. For NO2 exposure we found similar effect sizes to PM2.5 absorbance, but with much wider confidence intervals. PM2.5 exposure was weakly positively associated with CIMT while PMcoarse and ultrafine did not display any consistent patterns.CONCLUSIONS: Early childhood exposure to ambient air pollution was suggestively associated with the CIMT distribution during adolescence. Since CIMT increases with age, mitigation strategies to reduce traffic-related air pollution early in life could possibly delay atherosclerosis and subsequently CVD development later in life.

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.

Allergies are major noncommunicable diseases associated with significant morbidity, reduced quality of life, and high healthcare costs. Despite decades of research, it is still unknown if early-life exposure to indoor allergens plays a role in the development of IgE-mediated allergy and asthma. The objective of this study is to contribute to the identification of early-life risk factors for developing allergy. We addressed whether two different sources of house dust mite Der p 1 allergen exposure during early life, i.e., human milk and dust, have different relationships with IgE levels and asthma outcomes in children. We performed longitudinal analyses in 249 mother–child pairs using data from the PIAMA birth cohort. Asthma symptoms and serum total and specific IgE levels in children were available for the first 16 years of life. Der p 1 levels were measured in human milk and dust samples from infant mattresses. We observed that infant exposure to Der p 1 through human milk was associated with an increased risk of having high levels of serum IgE (top tertile > 150 kU/mL) in childhood as compared to infants exposed to human milk with undetectable Der p 1 [adjusted OR (95% CI) 1.83 (1.05–3.20) p = 0.0294]. The Der p 1 content in infant mattress dust was not associated with increased IgE levels in childhood. The risk of asthma and Der p 1 sensitization was neither associated with Der p 1 in human milk nor with Der p 1 in dust. In conclusion, high levels of IgE in childhood were associated with Der p 1 exposure through human milk but not exposure from mattress dust. This observation suggests that human milk is a source of Der p 1 exposure that is relevant to allergy development and fosters the need for research on the determinants of Der p 1 levels in human milk.

Recent urban debates on the governance of sustainability transformations have witnessed an 'infrastructural turn'. Previously blacked-boxed, the role of infrastructures in sustainability transformations has been foregrounded by both growing academic scholarship and major investments in new infrastructural programs. How these changes are, and could be, governed remains somewhat opaque however, with traditional forms of knowledge and practices in need of urgent revision. To nuance public and academic debates, this paper synthesizes emerging approaches to the governance of transformative infrastructural change, revealing their underlying logics and potential contributions. These include appraisal of; alternative infrastructural pathways via 'futuring', their enactment via experimentation processes, supported by cross-domain coordination and new assessment methods. Such approaches may open new directions toward urban sustainability but also surface tensions and contradictions inherent to the governance of infrastructures.

Climate change, urbanisation, chemical pollution and disruption of ecosystems, including biodiversity loss, affect our health and wellbeing. Research is crucial to be able to respond to the current and future challenges that are often complex and interconnected by nature. The HERA Agenda, summarised in this commentary, identifies six thematic research goals in the environment, climate and health fields. These include research to 1) reduce the effects of climate change and biodiversity loss on health and environment, 2) promote healthy lives in cities and communities, 3) eliminate harmful chemical exposures, 4) improve health impact assessment and implementation research, 5) develop infrastructures, technologies and human resources and 6) promote research on transformational change towards sustainability. Numerous specific recommendations for research topics, i.e., specific research goals, are presented under each major research goal. Several methods were used to define the priorities, including web-based surveys targeting researchers and stakeholder groups as well as a series of online and face-to-face workshops, involving hundreds of researchers and other stakeholders. The results call for an unprecedented effort to support a better understanding of the causes, interlinkages and impacts of environmental stressors on health and the environment. This will require breakdown of silos within policies, research, actors as well as in our institutional arrangements in order to enable more holistic approaches and solutions to emerge. The HERA project has developed a unique and exciting opportunity in Europe to consensuate priorities in research and strengthen research that has direct societal impact

The impact of COVID-19 on population health is recognised as being substantial, yet few studies have attempted to quantify to what extent infection causes mild or moderate symptoms only, requires hospital and/or ICU admission, results in prolonged and chronic illness, or leads to premature death. We aimed to quantify the total disease burden of acute COVID-19 in the Netherlands in 2020 using the disability-adjusted life-years (DALY) measure, and to investigate how burden varies between age-groups and occupations. Using standard methods and diverse data sources (mandatory notifications, population-level seroprevalence, hospital and ICU admissions, registered COVID-19 deaths, and the literature), we estimated years of life lost (YLL), years lived with disability, DALY and DALY per 100,000 population due to COVID-19, excluding post-acute sequelae, stratified by 5-year age-group and occupation category. The total disease burden due to acute COVID-19 was 286,100 (95% CI: 281,700-290,500) DALY, and the per-capita burden was 1640 (95% CI: 1620-1670) DALY/100,000, of which 99.4% consisted of YLL. The per-capita burden increased steeply with age, starting from 60 to 64 years, with relatively little burden estimated for persons under 50 years old. SARS-CoV-2 infection and associated premature mortality was responsible for a considerable direct health burden in the Netherlands, despite extensive public health measures. DALY were much higher than for other high-burden infectious diseases, but lower than estimated for coronary heart disease. These findings are valuable for informing public health decision-makers regarding the expected COVID-19 health burden among population subgroups, and the possible gains from targeted preventative interventions.

Humans are exposed to a mixture of pesticides through diet as well as through the environment. We conducted a suspect-screening based study to describe the probability of (concomitant) exposure to a set of pesticide profiles in five European countries (Latvia, Hungary, Czech Republic, Spain and the Netherlands). We explored whether living in an agricultural area (compared to living in a peri-urban area), being a a child (compared to being an adult), and the season in which the urine sample was collected had an impact on the probability of detection of pesticides (-metabolites). In total 2088 urine samples were collected from 1050 participants (525 parent-child pairs) and analyzed through harmonized suspect screening by five different laboratories. Fourty pesticide biomarkers (either pesticide metabolites or the parent pesticides as such) relating to 29 pesticides were identified at high levels of confidence in samples across all study sites. Most frequently detected were biomarkers related to the parent pesticides acetamiprid and chlorpropham. Other biomarkers with high detection rates in at least four countries related to the parent pesticides boscalid, fludioxonil, pirimiphos-methyl, pyrimethanil, clothianidin, fluazifop and propamocarb. In 84% of the samples at least two different pesticides were detected. The median number of detected pesticides in the urine samples was 3, and the maximum was 13 pesticides detected in a single sample. The most frequently co-occurring substances were acetamiprid with chlorpropham (in 62 urine samples), and acetamiprid with tebuconazole (30 samples). Some variation in the probability of detection of pesticides (-metabolites) was observed with living in an agricultural area or season of urine sampling, though no consistent patterns were observed. We did observe differences in the probability of detection of a pesticide (metabolite) among children compared to adults, suggesting a different exposure and/or elimination patterns between adults and children. This survey demonstrates the feasibility of conducting a harmonized pan-European sample collection, combined with suspect screening to provide insight in the presence of exposure to pesticide mixtures in the European population, including agricultural areas. Future improvements could come from improved (harmonized) quantification of pesticide levels. This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 733032 HBM4EU, No 857560 and No 857340. P.C., O.M. & L.S. acknowledge the RECETOX research infrastructure supported by the Ministry of Education, Youth and Sports of the Czech Republic (LM2018121) and the Ministry of Education, Youth and Sports of the Czech Republic (CZ.02.1.01/0.0/0.0/17_043/0009632). This publication reflects only the author’s view and the European Commission is not responsible for any use that may be made of the information it contains. BG was supported by the Margarita Salas postdoctoral contract MGS/2021/25 (UP2021-021) financed by the European UnionNextGenerationEU. Sí

BackgroundChildren are born with a burden of persistent organic pollutants (POPs) which may have endocrine disrupting properties and have been postulated to contribute to the rise in childhood obesity. The current evidence is equivocal, which may be because many studies investigate the effects at one time point during childhood. We assessed associations between prenatal exposure to POPs and growth during infancy and childhood.MethodsWe used data from two Belgian cohorts with cord blood measurements of five organochlorines [(dichlorodiphenyldichloroethylene (p,p’-DDE), hexachlorobenzene (HCB), polychlorinated biphenyls (PCB-138, -150, -180)] (N = 1,418) and two perfluoroalkyl substances [perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS)] (N = 346). We assessed infant growth, defined as body mass index (BMI) z-score change between birth and 2 years, and childhood growth, characterized as BMI trajectory from birth to 8 years. To evaluate associations between POP exposures and infant growth, we applied a multi-pollutant approach, using penalized elastic net regression with stability selection, controlling for covariates. To evaluate associations with childhood growth, we used single-pollutant linear mixed models with random effects for child individual, parametrized using a natural cubic spline formulation.ResultsPrenatal exposures to p,p’-DDE and PCB-153 were selected in elastic net models for infant growth analysis, but the selections were unstable. No clear association between any of the exposures and longer-term childhood growth trajectories was observed. We did not find evidence of effect modification by child sex.ConclusionOur results suggest that prenatal exposure to PCB-153 and p,p’-DDE may affect infant growth in the first two years, with little evidence of more persistent effects.

BACKGROUND: Few epidemiological studies so far have investigated the role of long-term exposure to ultrafine particles (UFP) in inhalant and food allergy development. OBJECTIVES: The purpose of this study was to assess the association between UFP exposure and allergic sensitization to inhalant and food allergens in children up to 16 years old in the Netherlands. METHODS: 2295 participants of a prospective birth cohort with IgE measurements to common inhalant and food allergens at ages 4, 8, 12 and/or 16 were included in the study. Annual average UFP concentrations were estimated for the home addresses at birth and at the time of the IgE measurements using land-use regression models. Generalized estimating equations were used for the assessment of overall and age-specific associations between UFP exposure and allergic sensitization. Additionally, single- and two-pollutant models with NO 2, PM 2.5, PM 2.5 absorbance and PM 10 were assessed. RESULTS: We found no significant associations between UFP exposure and allergic sensitization to inhalant and food allergens (OR (95% CI) ranging from 1.02 (0.95-1.10) to 1.05 (0.98-1.12), per IQR increment). NO 2, PM 2.5, PM 2.5 absorbance and PM 10 showed significant associations with sensitization to food allergens (OR (95% CI) ranging from 1.09 (1.00-1.20) to 1.23 (1.06-1.43) per IQR increment). NO 2, PM 2.5, PM 2.5 absorbance and PM 10 were not associated with sensitization to inhalant allergens. For NO 2, PM 2.5 and PM 2.5 absorbance, the associations with sensitization to food allergens persisted in two-pollutant models with UFP. CONCLUSION: This study found no association between annual average exposure to UFP and allergic sensitization in children up to 16 years of age. NO 2, PM 2.5, PM 2.5 absorbance and PM 10 were associated with sensitization to food allergens.

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.