25 results on '"Scholze, M."'
Search Results
2. The relationship between the pH value of a hydration solution and the biomechanical properties of Crosado-embalmed human iliotibial bands
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Steel, S., Pearcy, Q., Li, K.C., Scholze, M., and Zwirner, J.
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- 2022
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3. Biomechanics of vascular areas of the human cranial dura mater
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Pearcy, Q., Jeejo, M., Scholze, M., Tomlinson, J., Dressler, J., Zhang, M., and Zwirner, J.
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- 2022
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4. On the correlations of biomechanical properties of super-imposed temporal tissue layers and their age-, sex-, side- and post-mortem interval dependence
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Zwirner, J., Ondruschka, B., Pregartner, G., Berghold, A., Scholze, M., and Hammer, N.
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- 2022
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5. Effect of equal-channel angular pressing on ordering kinetics and twinning in an 18-carat AuCuAg alloy
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Scholze, M., primary, Wagner, M.F.X., additional, Dietrich, D., additional, Elibol, C., additional, Fritsch, S., additional, Illgen, C., additional, Bohne, B., additional, Böhme, M Bohm., additional, Colas, D., additional, and Frint, P., additional
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- 2023
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6. Do state-of-the-art atmospheric CO2 inverse models capture drought impacts on the European land carbon uptake?
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He, W., Jiang, F., Ju, W., Byrne, B., Xiao, J., Nguyen, N., Wu, M., Wang, S., Wang, J., Rödenbeck, C., Li, X., Scholze, M., Monteil, G., Wang, H., Zhou, Y., He, Q., and Chen, J.
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- 2023
7. P15-08 PANORAMIX: Providing risk assessments of complex real-life mixtures for the protection of Europe’s citizens and the environment
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Vinggaard, A.M., primary, Lamoree, M., additional, Escher, B.I., additional, Antignac, J.-P., additional, Scholze, M., additional, Jensen, T.K., additional, Herzler, M., additional, Audebert, M., additional, Hamers, T., additional, Kortenkamp, A., additional, Busquet, F., additional, Piumatti, M., additional, Dervilly, G., additional, Valente, M.J., additional, Cariou, R., additional, Moteau, S., additional, Oelgeschläger, M., additional, Renko, K., additional, Schmeisser, S., additional, Maier, D., additional, and Laursen, L.L., additional
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- 2022
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8. Paving the Road to Flex and Biomass: The Land Surface Carbon Constellation Study
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Rodriguez-Fernandez, N., primary, Barbier, M., additional, Verrelst, J., additional, Lindqvist, H., additional, Bueechi, E., additional, Munoz, P. Reyes, additional, Mialon, A., additional, Vreugdenhil, M., additional, Dorigo, W., additional, Bouvet, A., additional, Kerr, Y., additional, Vossbeck, M., additional, Kaminski, T., additional, and Scholze, M., additional
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- 2022
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9. P25-27 In vitro assessment of PFAS mixtures in a human induced pluripotent stem cell-based 3D model of embryo- and developmental toxicity.
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Treschow, A.F., Scholze, M., Vinggaard, A.M., and Valente, M.J.
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FLUOROALKYL compounds , *MIXTURES , *HUMAN beings - Published
- 2024
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10. Biomechanics of vascular areas of the human cranial dura mater
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Pearcy, Q., primary, Jeejo, M., additional, Scholze, M., additional, Tomlinson, J., additional, Dressler, J., additional, Zhang, M., additional, and Zwirner, J., additional
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- 2021
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11. S01-01 Risk assessment of complex chemical mixtures – an overview of approaches and recent developments.
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Vinggaard, A.M., Escher, B.I., Scholze, M., Valente, M.J., Lamoree, M., Hamers, T., Schmeisser, S., and Herzler, M.
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RISK assessment , *MIXTURES - Published
- 2024
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12. S01-02 Whole mixture assessments of water, food and human blood.
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Escher, B., Antignac, J.-P., Audebert, M., Cenjin, P., Hamers, T., Valente, M. João Portugal Couto, Khoury, L., König, M., Lamoree, M., Lee, J., Ma, Y., Jornet, M. Margalef, Motteau, S., Renko, K., Scholze, M., and Vinggaard, A.M.
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MIXTURES , *HUMAN beings - Published
- 2024
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13. P25-04 Antiandrogenic activity of reconstituted chemical mixtures reflecting real-life co-exposure patterns.
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Valente, M.J., Motteau, S., Margalef, M., König, M., Lee, J., Braun, G., Wojtyisiak, N., Antignac, J.-P., Lamoree, M., Scholze, M., Escher, B.I., and Vinggaard, A.M.
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MIXTURES - Published
- 2024
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14. Two novel in vitro assays to screen chemicals for their capacity to inhibit thyroid hormone transmembrane transporter proteins OATP1C1 and OAT4.
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Wagenaars F, Cenijn P, Chen Z, Meima M, Scholze M, and Hamers T
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- Humans, Fluorocarbons toxicity, Thyroid Hormones metabolism, Caprylates toxicity, Thyroxine metabolism, Biological Transport drug effects, HEK293 Cells, Alkanesulfonic Acids toxicity, Animals, Endocrine Disruptors toxicity, Organic Anion Transporters metabolism, Organic Anion Transporters antagonists & inhibitors, Organic Anion Transporters, Sodium-Independent metabolism
- Abstract
Early brain development depends on adequate transport of thyroid hormones (THs) from the maternal circulation to the fetus. To reach the fetal brain, THs have to cross several physiological barriers, including the placenta, blood-brain-barrier and blood-cerebrospinal fluid-barrier. Transport across these barriers is facilitated by thyroid hormone transmembrane transporters (THTMTs). Some endocrine disrupting chemicals (EDCs) can interfere with the transport of THs by THTMTs. To screen chemicals for their capacity to disrupt THTMT facilitated TH transport, in vitro screening assays are required. In this study, we developed assays for two THTMTs, organic anion transporter polypeptide 1C1 (OATP1C1) and organic anion transporter 4 (OAT4), both known to play a role in the transport of THs across barriers. We used overexpressing cell models for both OATP1C1 and OAT4, which showed an increased uptake of radiolabeled T4 compared to control cell lines. Using these models, we screened various reference and environmental chemicals for their ability to inhibit T4 uptake by OATP1C1 and OAT4. Tetrabromobisphenol A (TBBPA) was identified as an OATP1C1 inhibitor, more potent than any of the reference chemicals tested. Additionally perfluorooctanesulfonic acid (PFOS), perfluoroctanic acid (PFOA), pentachlorophenol and quercetin were identified as OATP1C1 inhibitors in a similar range of potency to the reference chemicals tested. Bromosulfophthalein, TBBPA, PFOA and PFOS were identified as potent OAT4 inhibitors. These results demonstrate that EDCs commonly found in our environment can disrupt TH transport by THTMTs, and contribute to the identification of molecular mechanisms underlying TH system disruption chemicals., (© 2024. The Author(s).)
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- 2024
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15. Screening for endocrine disrupting chemicals inhibiting monocarboxylate 8 (MCT8) transporter facilitated thyroid hormone transport using a modified nonradioactive assay.
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Wagenaars F, Cenijn P, Scholze M, Frädrich C, Renko K, Köhrle J, and Hamers T
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- Biological Transport drug effects, Phenols toxicity, Thyroxine, Humans, Animals, Dogs, Madin Darby Canine Kidney Cells, Toxicity Tests, Endocrine Disruptors isolation & purification, Endocrine Disruptors toxicity, Monocarboxylic Acid Transporters antagonists & inhibitors, Symporters antagonists & inhibitors
- Abstract
Early neurodevelopmental processes are strictly dependent on spatial and temporally modulated of thyroid hormone (TH) availability and action. Thyroid hormone transmembrane transporters (THTMT) are critical for regulating the local concentrations of TH, namely thyroxine (T4) and 3,5,3'-tri-iodothyronine (T3), in the brain. Monocarboxylate transporter 8 (MCT8) is one of the most prominent THTMT. Genetically induced deficiencies in expression, function or localization of MCT8 are associated with irreversible and severe neurodevelopmental adversities. Due to the importance of MCT8 in brain development, studies addressing chemical interferences of MCT8 facilitated T3 uptake are a crucial step to identify TH system disrupting chemicals with this specific mode of action. Recently a non-radioactive in vitro assay has been developed to rapidly screen for endocrine disrupting chemicals (EDCs) acting upon MCT8 mediated transport. This study explored the use of an UV-light digestion step as an alternative for the original ammonium persulfate (APS) digestion step. The non-radioactive TH uptake assay, with the incorporated UV-light digestion step of TH, was then used to screen a set of 31 reference chemicals and environmentally relevant substances to detect inhibition of MCT8-depending T3 uptake. This alternative assay identified three novel MCT8 inhibitors: methylmercury, bisphenol-AF and bisphenol-Z and confirmed previously known MCT8 inhibitors., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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16. M-FISH evaluation of chromosome aberrations to examine for historical exposure to ionising radiation due to participation at British nuclear test sites.
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Lawrence KJ, Scholze M, Seixo J, Daley F, Al-Haddad E, Craenen K, Gillham C, Rake C, Peto J, and Anderson R
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- Humans, Aged, Radiation, Ionizing, Biological Assay, Family, Chromosome Aberrations, Military Personnel
- Abstract
Veterans of the British nuclear testing programme represent a population of ex-military personnel who had the potential to be exposed to ionising radiation through their participation at nuclear testing sites in the 1950s and 1960s. In the intervening years, members of this population have raised concerns about the status of their health and that of their descendants, as a consequence. Radiation dose estimates based on film badge measurements of external dose recorded at the time of the tests suggest any exposure to be limited for the majority of personnel, however, only ∼20% of personnel were monitored and no measurement for internalised exposure are on record. Here, to in-part address families concerns, we assay for chromosomal evidence of historical radiation exposure in a group of aged nuclear test (NT) veterans, using multiplex in situ hybridisation (M-FISH), for comparison with a matched group of veterans who were not present at NT sites. In total, we analysed 9379 and 7698 metaphase cells using M-FISH (24-colour karyotyping) from 48 NT and 38 control veteran samples, representing veteran servicemen from the army, Royal Airforce and Royal Navy. We observed stable and unstable simple- and complex-type chromosome aberrations in both NT and control veterans' samples, however find no significant difference in yield of any chromosome aberration type between the two cohorts. We do observe higher average frequencies of complex chromosome aberrations in a very small subset of veterans previously identified as having a higher potential for radiation exposure, which may be indicative of internalised contamination to long-lived radionuclides from radiation fallout. By utilising recently published whole genome sequence analysis data of a sub-set of the same family groups, we examined for but found no relationship between paternal chromosome aberration burden, germline mutation frequency and self-reported concerns of adverse health in family members, suggesting that the previously reported health issues by participants in this study are unlikely to be associated with historical radiation exposure. We did observe a small number of families, representing both control and NT cohorts, showing a relationship between paternal chromosome aberrations and germline mutation sub-types which should be explored in future studies. In conclusion, we find no cytogenetic evidence of historical radiation exposure in the cohort of nuclear veterans sampled here, offering reassurance that attendance at NTs sites by the veterans sampled here, was not associated with significant levels of exposure to radiation., (Creative Commons Attribution license.)
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- 2024
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17. Drivers of divergent assessments of bisphenol-A hazards to semen quality by various European agencies, regulators and scientists.
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Kortenkamp A, Martin O, Iacovidou E, and Scholze M
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- Adult, Animals, Male, Humans, Phenols toxicity, Benzhydryl Compounds toxicity, Semen Analysis, Semen
- Abstract
The downward revision of the bisphenol A (BPA) Health-based Guidance Value (HBGV) by the European Food Safety Authority (EFSA) has led to disagreements with other regulatory agencies, among them the German Federal Institute for Risk Assessment (BfR). The BfR has recently published an alternative Tolerable Daily Intake (TDI), 1000-times higher than the EFSA HBGV of 0.2 ng/kg/d. While the EFSA value is defined in relation to immunotoxicity, the BfR alternative TDI is based on declines in sperm counts resulting from exposures in adulthood. Earlier, we had used semen quality deteriorations to estimate a BPA Reference Dose (RfD) of 3 ng/kg/d for use in mixture risk assessments of male reproductive health. We derived this estimate from animal studies of gestational BPA exposures which both EFSA and BfR viewed as irrelevant for human hazard characterisations. Here, we identify factors that drive these diverging views. We find that the fragmented, endpoint-oriented study evaluation system used by EFSA and BfR, with its emphasis on data that can support dose-response analyses, has obscured the overall BPA effect pattern relevant to male reproductive effects. This has led to a disregard for the effects of gestational BPA exposures. We also identify problems with the study evaluation schemes used by EFSA and BfR which leads to the omission of entire streams of evidence from consideration. The main driver of the diverging views of EFSA and BfR is the refusal by BfR to accept immunotoxic effects as the basis for establishing an HBGV. We find that switching from immunotoxicity to declines in semen quality as the basis for deriving a BPA TDI by deterministic or probabilistic approaches produces values in the range of 2.4-6.6 ng/kg/d, closer to the present EFSA HBGV of 0.2 ng/kg/d than the BfR TDI of 200 ng/kg/d. The proposed alternative BfR value is the result of value judgements which erred on the side of disregarding evidence that could have supported a lower TDI. The choices made in terms of selecting key studies and methods for dose-response analyses produced a TDI that comes close to doses shown to produce effects on semen quality in animal studies and in human studies of adult BPA exposures., Competing Interests: Declaration of competing interest Andreas Kortenkamp, Martin Scholze and Eleni Iacovidou declare they have no conflicts of interests. Olwenn V Martin reports a relationship with European Chemicals Agency that includes board membership and with the Food Packaging Forum that includes board membership and consulting or advisory services., (Copyright © 2023 The Authors. Published by Elsevier GmbH.. All rights reserved.)
- Published
- 2024
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18. Sample size considerations in soft tissue biomechanics.
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Hammer N, Ondruschka B, Berghold A, Kuenzer T, Pregartner G, Scholze M, Schulze-Tanzil GG, and Zwirner J
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- Humans, Biomechanical Phenomena, Sample Size, Skin, Dura Mater
- Abstract
Biomechanical experiments help link tissue morphology with load-deformation characteristics. A tissue-dependent minimum sample number is indispensable to obtain accurate material properties. Stress-strain properties were retrieved from human dura mater and scalp skin, exemplifying two distinct soft tissues. Minimum sample sizes necessary for a stable estimation of material properties were obtained in a simulation study. One-thousand random samples were sequentially drawn for calculating the point at which a majority of the estimators settled within a corridor of stability at given tolerance levels around a 'complete' reference for the mean, median and coefficient of variation. Stable estimations of means and medians can be achieved below sample sizes of 30 at a ± 20%-tolerance within 80%-conformity for scalp skin and dura. Lower tolerance levels or higher conformity dramatically increase the required sample size. Conformity was barely ever reached for the coefficient of variation. The parameter type appears decisive for achieving conformity. STATEMENT OF SIGNIFICANCE: Biomechanical trials utilizing human tissues are needed to obtain material properties for surgical repair, tissue engineering and modeling purposes. Linking tissue mechanics with morphology helps elucidate form-function relationships, the 'morpho-mechanical link'. For material properties to be accurate, it is vital to examine a minimum number of samples. This number may vary between tissues, and the effects of intrinsic tissue characteristics on data accuracy are unclear to date. This study used data obtained from human dura and skin to compute minimum sample sizes required for estimating material properties at a stable level. It was shown that stable estimations are possible at a ± 20%-tolerance within 80%-conformity below sample sizes of 30. Higher accuracy warrants much higher sample sizes for most material properties., Competing Interests: Declaration of Competing Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2023
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19. Establishment of a human cell-based in vitro battery to assess developmental neurotoxicity hazard of chemicals.
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Blum J, Masjosthusmann S, Bartmann K, Bendt F, Dolde X, Dönmez A, Förster N, Holzer AK, Hübenthal U, Keßel HE, Kilic S, Klose J, Pahl M, Stürzl LC, Mangas I, Terron A, Crofton KM, Scholze M, Mosig A, Leist M, and Fritsche E
- Abstract
Developmental neurotoxicity (DNT) is a major safety concern for all chemicals of the human exposome. However, DNT data from animal studies are available for only a small percentage of manufactured compounds. Test methods with a higher throughput than current regulatory guideline methods, and with improved human relevance are urgently needed. We therefore explored the feasibility of DNT hazard assessment based on new approach methods (NAMs). An in vitro battery (IVB) was assembled from ten individual NAMs that had been developed during the past years to probe effects of chemicals on various fundamental neurodevelopmental processes. All assays used human neural cells at different developmental stages. This allowed us to assess disturbances of: (i) proliferation of neural progenitor cells (NPC); (ii) migration of neural crest cells, radial glia cells, neurons and oligodendrocytes; (iii) differentiation of NPC into neurons and oligodendrocytes; and (iv) neurite outgrowth of peripheral and central neurons. In parallel, cytotoxicity measures were obtained. The feasibility of concentration-dependent screening and of a reliable biostatistical processing of the complex multi-dimensional data was explored with a set of 120 test compounds, containing subsets of pre-defined positive and negative DNT compounds. The battery provided alerts (hit or borderline) for 24 of 28 known toxicants (82% sensitivity), and for none of the 17 negative controls. Based on the results from this screen project, strategies were developed on how IVB data may be used in the context of risk assessment scenarios employing integrated approaches for testing and assessment (IATA)., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ellen Fritsche, Kristina Bartmann, Arif Dönmez and Axel Mosig are shareholders of the company DNTOX that provides DNT-IVB assay services. The authors declare no potential conflicts of interest with respect to the research in this article. All other authors have no conflict of interest to declare., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2023
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20. The impact of biostatistics on hazard characterization using in vitro developmental neurotoxicity assays.
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Keßel HE, Masjosthusmann S, Bartmann K, Blum J, Dönmez A, Förster N, Klose J, Mosig A, Pahl M, Leist M, Scholze M, and Fritsche E
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- Humans, Biostatistics, Toxicity Tests methods, Benchmarking, Research Design, Neurotoxicity Syndromes
- Abstract
In chemical safety assessment, benchmark concentrations (BMC) and their associated uncertainty are needed for the toxicological evaluation of in vitro data sets. A BMC estimation is derived from concentration-response modelling and results from various statistical decisions, which depend on factors such as experimental design and assay endpoint features. In current data practice, the experimenter is often responsible for the data analysis and therefore relies on statistical software, often without being aware of the software default settings and how they can impact the outputs of data analysis. To provide more insight into how statistical decision-making can influence the outcomes of data analysis and interpretation, we have developed an automated platform that includes statistical methods for BMC estimation, a novel endpoint-specific hazard classification system, and routines that flag data sets that are outside the applicability domain for an automatic data evaluation. We used case studies on a large dataset produced by a developmental neurotoxicity (DNT) in vitro battery (DNT IVB). Here we focused on the BMC and its confidence interval (CI) estimation as well as on final hazard classification. We identified five crucial statistical decisions the experimenter must make during data analysis: choice of replicate averaging, response data normalization, regression modelling, BMC and CI estimation, and choice of benchmark response levels. The insights gained are intended to raise more awareness among experimenters on the importance of statistical decisions and methods but also to demonstrate how important fit-for-purpose, internationally harmonized and accepted data evaluation and analysis procedures are for objective hazard classification.
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- 2023
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21. Mixture Risk Assessment of Complex Real-Life Mixtures-The PANORAMIX Project.
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Escher BI, Lamoree M, Antignac JP, Scholze M, Herzler M, Hamers T, Jensen TK, Audebert M, Busquet F, Maier D, Oelgeschläger M, Valente MJ, Boye H, Schmeisser S, Dervilly G, Piumatti M, Motteau S, König M, Renko K, Margalef M, Cariou R, Ma Y, Treschow AF, Kortenkamp A, and Vinggaard AM
- Subjects
- Humans, Risk Assessment methods, European Union, Complex Mixtures toxicity, Environmental Pollution adverse effects, Organic Chemicals toxicity
- Abstract
Humans are involuntarily exposed to hundreds of chemicals that either contaminate our environment and food or are added intentionally to our daily products. These complex mixtures of chemicals may pose a risk to human health. One of the goals of the European Union's Green Deal and zero-pollution ambition for a toxic-free environment is to tackle the existent gaps in chemical mixture risk assessment by providing scientific grounds that support the implementation of adequate regulatory measures within the EU. We suggest dealing with this challenge by: (1) characterising 'real-life' chemical mixtures and determining to what extent they are transferred from the environment to humans via food and water, and from the mother to the foetus; (2) establishing a high-throughput whole-mixture-based in vitro strategy for screening of real-life complex mixtures of organic chemicals extracted from humans using integrated chemical profiling (suspect screening) together with effect-directed analysis; (3) evaluating which human blood levels of chemical mixtures might be of concern for children's development; and (4) developing a web-based, ready-to-use interface that integrates hazard and exposure data to enable component-based mixture risk estimation. These concepts form the basis of the Green Deal project PANORAMIX, whose ultimate goal is to progress mixture risk assessment of chemicals.
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- 2022
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22. No evidence of increased mutations in the germline of a group of British nuclear test veterans.
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Moorhouse AJ, Scholze M, Sylvius N, Gillham C, Rake C, Peto J, Anderson R, and Dubrova YE
- Subjects
- Germ Cells, Germ-Line Mutation, Humans, Mutation, Whole Genome Sequencing, Veterans
- Abstract
The potential germline effects of radiation exposure to military veterans present at British nuclear tests in Australia and the South Pacific is of considerable interest. We analyzed germline mutations in 60 families of UK military personnel comprising 30 control and 30 nuclear test veterans (NTV). Using whole-genome sequencing we studied the frequency and spectra of de novo mutations to investigate the transgenerational effect of veterans' (potential) exposure to radiation at nuclear bomb test sites. We find no elevation in total de novo single nucleotide variants, small insertion-deletions, structural variants or clustered mutations among the offspring of nuclear test veterans compared to those of control personnel. We did observe an elevated occurrence of single base substitution mutations within mutation signature SBS16, due to a subset of NTV offspring. The relevance of this elevation to potential exposure of veteran fathers and, future health risks, require further investigation. Overall, we find no evidence of increased mutations in the germline of a group of British nuclear test veterans. ISRCTN Registry 17461668., (© 2022. The Author(s).)
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- 2022
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23. Combined exposures to bisphenols, polychlorinated dioxins, paracetamol, and phthalates as drivers of deteriorating semen quality.
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Kortenkamp A, Scholze M, Ermler S, Priskorn L, Jørgensen N, Andersson AM, and Frederiksen H
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- Acetaminophen toxicity, Benzhydryl Compounds, Environmental Exposure adverse effects, Environmental Exposure analysis, Humans, Male, Phenols, Semen Analysis, Diethylhexyl Phthalate, Dioxins toxicity, Environmental Pollutants toxicity, Phthalic Acids toxicity
- Abstract
Background: Semen quality in men continues to decline in Western countries, but the contours of the issue remain obscure, in relation to contributing chemicals., Objectives: To obtain more clarity about the chemicals that drive the deterioration of semen quality, we conducted a mixture risk assessment based on European exposures., Methods: We included chemicals capable of affecting semen quality after prenatal exposures, among them androgen receptor antagonists, substances that disrupt prostaglandin signalling, suppress testosterone synthesis, inhibit steroidogenic enzymes or activate the aryl hydrocarbon receptor. We employed the Hazard Index approach (HI), based on risk quotients of exposures in Europe and reference doses for reductions in semen quality. By summing up the risk quotients of the 29 chemicals included in the assessment we examined fold-exceedances of "acceptable" mixture exposures relative to an index value of 1. For bisphenols A, F, S, phthalates DEHP, DnBP, BBzP, DiNP, n-butyl paraben and paracetamol we relied on biomonitoring studies in which these 9 chemicals were measured together in the same subjects. This allowed us to construct personalised Hazard Indices., Results: Highly exposed subjects experienced combined exposures to the 9 chemicals that exceeded the index value of 1 by more than 100-fold; the median was a 17-fold exceedance. Accounting for median background exposures to the remaining 20 chemicals added a Hazard Index of 1.39. Bisphenol A made the largest contribution to the HI, followed by polychlorinated dioxins, bisphenols S and F and DEHP. Eliminating bisphenol A alone would still leave unacceptably high mixture risks. Paracetamol is also a driver of mixture risks among subjects using the drug., Conclusions: Tolerable exposures to substances associated with deteriorations of semen quality are exceeded by a large margin. Bisphenols, polychlorinated dioxins, phthalates and analgesics drive these risks. Dedicated efforts towards lowering exposures to these substances are necessary to mitigate risks., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2022
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24. British nuclear test veteran family trios for the study of genetic risk.
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Rake C, Gilham C, Scholze M, Bukasa L, Stephens J, Simpson J, Peto J, and Anderson R
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- Aged, Child, Cohort Studies, Humans, Male, Radiation, Ionizing, Military Personnel, Radiation Injuries, Veterans
- Abstract
The risk of radiation effects in children of individuals exposed to ionising radiation remains an ongoing concern for aged veterans of the British nuclear testing programme. The genetic and cytogenetic family trio (GCFT) study is the first study to obtain blood samples from a group of British nuclear test veterans and their families for the purposes of identifying genetic alterations in offspring as a consequence of historical paternal exposure to ionising radiation. In this report, we describe the processes for recruitment and sampling, and provide a general description of the study population recruited. In total, blood samples were received from 91 (49 test and 42 control) families representing veteran servicemen from the army, Royal Air Force and Royal Navy. This translated to an overall response rate of 14% (49/353) for test veterans and 4% (42/992) for control veterans (excluding responders known to be ineligible). Due to the lack of dose information available, test veterans were allocated to a three-point exposure rank. Thirty (61%) test veterans were ranked in the lower group. Nineteen (39%) of the 49 test veterans were classified in the mid (5 veterans; 10%)/high (14 veterans; 29%) exposure ranks and included 12 veterans previously identified as belonging to the special groups or listed in health physics documents. An increased number of test veteran families (20%), compared with control families (5%), self-reported offspring with congenital abnormalities ( p = 0.03). Whether this observation in this small group is reflective of the entire UK test veteran cohort or whether it is selection bias requires further work. The cohort described here represent an important and unique family trio grouping whose participation is enabling genetic studies, as part of the GCFT study, to be carried out. The outcomes of these studies will be published elsewhere. ISRCTN Registry: 17461668., (Creative Commons Attribution license.)
- Published
- 2022
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25. Bisphenol A and declining semen quality: A systematic review to support the derivation of a reference dose for mixture risk assessments.
- Author
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Kortenkamp A, Martin O, Ermler S, Baig A, and Scholze M
- Subjects
- Animals, Male, Phenols toxicity, Risk Assessment, Benzhydryl Compounds, Semen Analysis
- Abstract
To support a mixture risk assessment with a focus on male reproductive health, we conducted a systematic review of associations between bisphenol A (BPA) exposures and declines in semen quality, based on animal and epidemiological studies. Contrary to a widely held view that there is "conflicting" evidence of such associations, our review and confidence rating approach reveals that animal studies provide convincing evidence of declines of semen quality after gestational BPA exposures. Many of the reported negative findings can be attributed to deficiencies in study sensitivity, insufficient control of background contamination and probable confounding through hormonal interference due to the use of soy-containing diets. We did not evaluate animal studies of adult BPA exposures. Divergent findings in "medium to high" and "medium" confidence epidemiological studies can be explained in terms of differences in exposure conditions. We attempted the estimation of a BPA reference dose based on animal studies. Due to variations in the no-observed adverse effect levels (NOAELs) in high confidence studies, possible reference doses ranged from 0.0001 to 0.0099 μg/kg/d. In choosing 0.003 μg/kg/d we struck a balance between caution suggested by studies at the lower end of the doses and the weight of evidence from studies with higher NOAELs. This weighting was motivated by the intended use of the value in a mixture risk assessment which meant arriving at a reasonable estimate of BPA exposures likely without effects on semen quality. We realise that our approach does not conform with the standards necessary for deriving tolerable daily intakes (TDIs) for single chemical exposures, which is not our interest here. BPA exposures currently experienced by European populations and beyond are in excess of 0.003 μg/kg/d and even fall in the range where some epidemiological studies observed effects on semen quality as a result of BPA exposures in adulthood., (Copyright © 2022 The Authors. Published by Elsevier GmbH.. All rights reserved.)
- Published
- 2022
- Full Text
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