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Lermen, Dominik; Weber, Till; Göen, Thomas; Bartel-Steinbach, Martina; Gwinner, Frederik; Mueller, Sabine C.; Conrad, André; Rüther, Maria; von Briesen, Hagen; Kolossa-Gehring, Marike International Journal of Hygiene and Environmental Health 231 (2021), 113665; online 19 November 2020 Lead is a ubiquitous pollutant with well-known effects on human health. As there is no lower toxicological threshold for lead in blood and since data gaps on lead exposure still exist in many European countries, HBM data on lead is of high importance. To address this, the European Human Biomonitoring Initiative HBM4EU classified lead as a priority substance. The German Environmental Specimen Bank (German ESB) has monitored lead exposure since more than 35 years. Using data from the early 1980s to 2019 we reveal and discuss long-term trends in blood lead levels (BLLs) and current internal exposure of young adults in Germany. BLLs in young adults decreased substantially in the investigated period. As results from the ESB sampling site Muenster demonstrate, the geometric mean of BLLs of young adults decreased from 1981 (78,7 μg/L) to 2019 (10.4 μg/L) by about 87%. Trends in human exposure closely correlate with air lead levels (ALLs) provided by the European Monitoring and Evaluation Programme (EMEP). Hence, the decrease of BLLs largely reflects the drop in air lead pollution. Known associations of sex, smoking, alcohol consumption, and housing situation with BLLs are confirmed with data of the German ESB. Although internal lead exposure in Germany decreased substantially, the situation might be different in other European countries. Since 2010, BLLs of young adults in Germany levelled out at approximately 10 μg/L. The toxicity of lead even at low levels is known to cause adverse health effects especially in children following exposure of the child or the mother during pregnancy. To identify current exposure sources and to minimize future lead exposure, continuous monitoring of lead intake and exposure levels is needed. doi: 10.1016/j.ijheh.2020.113665
In dem vorliegenden Projekt wurden die Auswirkungen wiederholter Exposition mit unterschiedlich starken statischen Magnetfeldern bis zu einer Flussdichte von 7 Tesla auf die Spermiogenese bei männlichen adulten Mäusen sowie auf Schwangerschaft und Embryogenese bei weiblichen Mäusen untersucht. Zudem wurde die Fertilität männlicher und weiblicher Mäuse, die während ihrer gesamten Embryonalentwicklung in utero täglich diesen statischen Magnetfeldern ausgesetzt worden waren, getestet. Es wurden 6 Versuchsgruppen untersucht: 1) Käfigkontrollen, 2) scheinexponierte Kontrollen, 3) Exposition am Bore-Eingang und 4) im Isozentrum des 1,5T-MRT, 5) Exposition am Bore-Eingang und 6) im Isozentrum des 7T-MRT. Insgesamt wurden in dieser Studie 895 adulte Mäuse, 944 Jungtiere und 2007 Embryonen analysiert. ABSTRACT In the present study, the effects of repeated exposure to strong static magnetic fields up to a flux density of 7 Tesla on spermatogenesis in adult male mice as well as on pregnancy and embryogenesis in female mice were studied. In addition, the fertility of male and female mice which were exposed daily to these static magnetic fields throughout their entire embryonic development in utero was investigated. Six experimental groups were examined: 1) cage controls, 2) sham-exposed controls, 3) exposure at the bore entrance and 4) in the isocenter of a 1.5T MRI, 5) exposure at the bore entrance and 6) in the isocenter of a 7T MRI. Overall, 895 adult mice, 944 offspring, and 2007 embryos were analyzed in this study.
Deutsch: Die wachsende Zahl von Geräten, die hochfrequente elektromagnetische Felder (HF-EMF) aussenden, führt seit langem zu Bedenken hinsichtlich möglicher Wirkungen auf die menschliche Fruchtbarkeit. Zur Bewertung der wissenschaftlichen Evidenz zu diesem Thema erstellten die Forschenden im Auftrag der WHO eine systematische Übersichtsarbeit zur Wirkung von HF-EMF auf Schwangerschaft und die Gesundheit der Nachkommen. Es zeigten sich statistisch signifikante Effekte, die jedoch mit einiger Unsicherheit behaftet waren. Die eingesetzten Expositionsniveaus lagen weit über den Grenzwerten und sind damit nicht für realistische Expositionsszenarien relevant.
Basierend auf epidemiologischen Studien, in denen sich konsistente Hinweise auf eine statistische Assoziation zwischen niederfrequenten Magnetfeldern und Leukämie im Kindesalter fanden, wurden niederfrequente Magnetfelder von der IARC (International Agency for Research on Cancer) 2002 als "möglicherweise krebserregend" (Gruppe 2 b) eingestuft. Ein ursächlicher Zusammenhang konnte jedoch bisher in experimentellen Studien nicht bestätigt werden. In der vorliegenden Studie wurden in weiblichen CD1-Mäusen Wirkungen einer bereits im Mutterleib beginnenden, bis zum Alter von 18 Monaten fortgesetzten Exposition gegenüber niederfrequenten Magnetfeldern untersucht. Endpunkte waren unter anderem die Ausbildung von Reflexen sowie Einflüsse auf das blutbildende System und das Immunsystem. Am Ende des Expositionszeitraums wurden umfangreiche histologische Untersuchungen zur Tumorbildung an relevanten Organen (u.a. Thymus, Milz, Lymphknoten, Knochenmark) vorgenommen. In keiner der untersuchten Dosisgruppen (10 µT, 1 mT und 10 mT) zeigten sich Einflüsse der Magnetfeldexposition auf den Reproduktionserfolg der Muttertiere, auf die körperliche Entwicklung der Nachkommen sowie auf ihr Verhalten. Die histopathologische Untersuchung der Tiere nach 18 Monaten Exposition zeigte keine statistisch signifikanten Unterschiede in den Tumorraten zwischen der Scheinexposition und den verschiedenen Expositionsgruppen. An einem Testzeitpunkt im Alter von 90 Tagen (nicht jedoch nach 28 Tagen oder nach 18 Monaten) wurde eine verminderte Anzahl von CD8+ zytotoxischen T-Zellen in der mittleren und hohen Dosisgruppe beobachtet. Dieser Effekt war nicht sehr ausgeprägt aber signifikant. Bei den hämatologischen Untersuchungen nach 18-monatiger Exposition zeigten sich erhöhte Lymphozytenwerte im peripheren Blut aller drei Magnetfeld-exponierter Gruppen bei gleichzeitiger Abnahme der Anzahl segment-kerniger Granulozyten. Ob diese Effekte funktionelle Auswirkungen haben, konnte in dieser Studie nicht weiter untersucht werden. Gegen gravierende Wirkungen spricht jedoch der fehlende Effekt auf die histologischen Befunde. Der Abschlussbericht umfasst inklusive der Einzeltierbefunde 1688 Seiten (9 MB). Der Bericht wird in zwei Abschnitte geteilt. Band I enthält den Hauptbericht nebst Abschlussbericht des technischen Partners IMST (102 Seiten, 2 MB), Band II die Anhänge (Tabellarische Gruppenauswertungen sowie Einzeltier-Sektionsbefunde, 1586 Seiten, 7 MB) //ABSTRACT// Based on epidemiological studies showing a statistical association between 50 Hz magnetic fields and risk of childhood leukaemia, the International Agency for Research on Cancer (IARC) found limited evidence in humans for the carcinogenicity of extremely low frequency magnetic fields in relation to childhood leukaemia (group 2 b). In experimental animals evidence is inadequate. In the present study, possible effects of an exposure to low-frequency magnetic fields on the development of juvenile animals and the maturation of the hematopoietic and immune system as well as on the central nervous system were assessed in a mouse model (female CD-1 mice) in vivo. Three dose groups (10 µT, 1mT, 10mT) of free moving CD-1 mice in group housing were exposed for 20 hrs per day, starting at gestation day 10 and continued until the age of 18 months. Two additional groups of animals were either sham exposed or cage controls. Neither adverse influences on the reproductive success of the exposed maternal animals nor on the physical development of the juvenile animals or their behaviour were observed. However, at age 90 days, a reduced number of CD8+ cytotoxic T-cells were seen in peripheral blood and spleen in the middle and high dose groups. Although the effect was relatively moderate, it was significant. The effect was not detected at age 28 days or after 18 months of exposure. In the haematological assessment after 18 months of exposure, increased lymphocyte counts and decreased counts of banded neutrophiles were seen in peripheral blood from all 3 exposure groups. Whether the observed reduction of CTL has a functional effect can not be concluded from the study. Severe consequences seem to be unlikely, because the results of the extensive histopathological examination of relevant organs (e.g. thymus, spleen, lymph nodes, bone marrow) did not display any exposure related alterations, especially neither for neoplastic nor for non-neoplastic lesions of the haematopoietic or immune system. The final report consists of 1688 pages (9 MB). The report is divided into two sections. Section I includes the main part and the final report of the technical partner IMST (102 pages, 2 MB. Summary and conclusion are available in English, pages 79 -81). Section II includes the Annexes (group summaries, intergroup comparisons, clinical observations, 1586 pages, 7 MB).
In den letzten Jahrzehnten wurde die Kernspintechnologie zunehmend auch bei schwangeren Frauen und in der Gynäkologie zur Diagnostik fetaler Erkrankungen und Störungen benutzt. Diese Technologie gilt generell als sicher. Dennoch erfordert die Entwicklung zunehmend leistungsfähigerer Tomographen mit höheren Feldstärken zur Verbesserung der Diagnostik auch immer wieder eine erneute Evaluation der biologischen Sicherheit. Entsprechende Studien mit Nagern bieten die Möglichkeit, sowohl akute als auch Langzeiteffekte einer Magnetfeldexposition in systematischer Weise zu untersuchen. Dabei können insbesondere Verhaltensanalysen dazu beitragen, auch subtilere Effekte einer Magnetfeldexposition auf das sich entwickelnde fetale Gehirn nachzuweisen. In der vorliegenden Studie wurde das Verhalten von adulten Mäusen untersucht, die während der gesamten Schwangerschaft in utero täglich einem statischen Magnetfeld von 7 Tesla Feldstärke ausgesetzt waren. In zahlreichen standardisierten, gut validierten Verhaltenstests sowohl für emotionales Verhalten wie auch für Lernen und Gedächtnis konnten wir keine Verhaltensauffälligkeiten nachweisen. Unsere Ergebnisse bestärken damit die allgemeine Sichtweise auf die MRT als sichere bildgebende Methode in der Schwangerschaft. Nichtsdestotrotz ist angesichts der technischen Weiterentwicklung in klinischer und experimenteller Bildgebung eine fortlaufende Risikoseinschätzung essenziell. / - / In the past three decades, magnetic resonance imaging (MRI) has been increasingly used in obstetrics to aid diagnostics of maternal and fetal conditions and has generally been considered a safe imaging method. However, the development of higher-performance systems employing, for example, stronger fields to improve the technique’s diagnostic potential, necessitates an ongoing safety evaluation. Rodent studies provide an excellent opportunity to investigate not only acute but also long-term effects of magnetic field exposure in a systematic manner, and a behavioral analysis might help to uncover subtler effects which might result from magnetic field exposure of the vulnerable developing brain. We conducted a comprehensive investigation of emotional and cognitive behavior in adult mice which had been repeatedly exposed to a 7 Tesla static magnetic field in utero. Using well-validated tests, we did not observe any adverse behavioral alterations regarding emotional behavior as well as spatial and emotional learning.
Mit der schnell fortschreitenden technischen Entwicklung werden Menschen in immer stärkerem Maße magnetischen Feldern ausgesetzt. Aufgrund dieser zunehmenden Bedeutung steigt auch die Notwendigkeit der Risikoabschätzung solcher Expositionen. Zu den Risiken statischer Magnetfelder für die verschiedenen Aspekte der Gesundheit des Menschen sind daher in den letzten Jahren eine Reihe von Übersichtsarbeiten erschienen (Feychting 2005, WHO 2006, Health Protection Agency 2008). Die vorliegende Übersicht fokussiert sich speziell auf die bisher durchgeführten wissenschaftlichen Untersuchungen zur Auswirkung statischer Magnetfelder auf die Fertilität und Fortpflanzung.
A number of prospective cohort studies are ongoing worldwide to investigate the impact of foetal and neonatal exposures to chemical substances on child health. To assess multiple exposure (mixture) effects and low prevalence health outcomes it is useful to pool data from several studies and conduct mega-data-analysis. To discuss a path towards data harmonization, representatives from several large-scale birth cohort studies and a biomonitoring programme formed a collaborative group, the Environment and Child Health International Birth Cohort Group (ECHIBCG). In this study, an intra-laboratory trial was performed to harmonize existing blood lead measurements within the groups' studies. Then, decentralized analyses were conducted in individual countries' laboratories to evaluate blood lead levels (BLL) in each study. The measurements of pooled BLL samples in French, German and three Japanese laboratories resulted in an overall mean blood lead concentration of 8.66 ng¯1 (95% confidence interval: 8.59-8.72 ng¯1) with 3.0% relative standard deviation. Except for China's samples, BLL from each study were comparable with mean concentrations below or close to 10ng¯1. The decentralized multivariate analyses revealed that all models had coefficients of determination below 0.1. Determinants of BLL were current smoking, age >35 years and overweight or obese status. The three variables were associated with an increase in BLL in each of the five studies, most strongly in France by almost 80% and the weakest effect being in Norway with only 15%; for Japan, with the far largest sample (~18,000), the difference was 36%. This study successfully demonstrated that the laboratory analytical methods were sufficiently similar to allow direct comparison of data and showed that it is possible to harmonize the epidemiological data for joint analysis. This exercise showed the challenges in decentralized data analyses and reinforces the need for data harmonization among studies. © 2019 The Authors. Published by Elsevier GmbH.
Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk-outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk-outcome pairs, and new data on risk exposure levels and risk-outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46ââą 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017. Findings In 2017, 341 million (95% uncertainty interval [UI] 333-350) deaths and 121 billion (114-128) DALYs were attributable to GBD risk factors. Globally, 610% (596-624) of deaths and 483% (463-502) of DALYs were attributed to the GBD 2017 risk factors. When ranked by risk-attributable DALYs, high systolic blood pressure (SBP) was the leading risk factor, accounting for 104 million (939-115) deaths and 218 million (198-237) DALYs, followed by smoking (710 million [683-737] deaths and 182 million [173-193] DALYs), high fasting plasma glucose (653 million [523-823] deaths and 171 million [144-201] DALYs), high body-mass index (BMI; 472 million [299-670] deaths and 148 million [986-202] DALYs), and short gestation for birthweight (143 million [136-151] deaths and 139 million [131-147] DALYs). In total, risk-attributable DALYs declined by 49% (33-65) between 2007 and 2017. In the absence of demographic changes (ie, population growth and ageing), changes in risk exposure and risk-deleted DALYs would have led to a 235% decline in DALYs during that period. Conversely, in the absence of changes in risk exposure and risk-deleted DALYs, demographic changes would have led to an 186% increase in DALYs during that period. The ratios of observed risk exposure levels to exposure levels expected based on SDI (O/E ratios) increased globally for unsafe drinking water and household air pollution between 1990 and 2017. This result suggests that development is occurring more rapidly than are changes in the underlying risk structure in a population. Conversely, nearly universal declines in O/E ratios for smoking and alcohol use indicate that, for a given SDI, exposure to these risks is declining. In 2017, the leading Level 4 risk factor for age-standardised DALY rates was high SBP in four super-regions: central Europe, eastern Europe, and central Asia; north Africa and Middle East; south Asia; and southeast Asia, east Asia, and Oceania. The leading risk factor in the high-income super-region was smoking, in Latin America and Caribbean was high BMI, and in sub-Saharan Africa was unsafe sex. O/E ratios for unsafe sex in sub-Saharan Africa were notably high, and those for alcohol use in north Africa and the Middle East were notably low. Interpretation By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning. © 2018 The Author(s). Published by Elsevier Ltd.
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