@article{AllanBossdorfDormannetal.2014, author = {Allan, Eric and Bossdorf, Oliver and Dormann, Carsten F. and Prati, Daniel and Gossner, Martin M. and Tscharntke, Teja and Bl{\"u}thgen, Nico and Bellach, Michaela and Birkhofer, Klaus and Boch, Steffen and B{\"o}hm, Stefan and B{\"o}rschig, Carmen and Chatzinotas, Antonis and Christ, Sabina and Daniel, Rolf and Diek{\"o}tter, Tim and Fischer, Christiane and Friedl, Thomas and Glaser, Karin and Hallmann, Christine and Hodac, Ladislav and H{\"o}lzel, Norbert and Jung, Kirsten and Klein, Alexandra-Maria and Klaus, Valentin H. and Kleinebecker, Till and Krauss, Jochen and Lange, Markus and Morris, E. Kathryn and M{\"u}ller, J{\"o}rg and Nacke, Heiko and Pasalic, Esther and Rillig, Matthias C. and Rothenwoehrer, Christoph and Schally, Peter and Scherber, Christoph and Schulze, Waltraud X. and Socher, Stephanie A. and Steckel, Juliane and Steffan-Dewenter, Ingolf and T{\"u}rke, Manfred and Weiner, Christiane N. and Werner, Michael and Westphal, Catrin and Wolters, Volkmar and Wubet, Tesfaye and Gockel, Sonja and Gorke, Martin and Hemp, Andreas and Renner, Swen C. and Sch{\"o}ning, Ingo and Pfeiffer, Simone and K{\"o}nig-Ries, Birgitta and Buscot, Francois and Linsenmair, Karl Eduard and Schulze, Ernst-Detlef and Weisser, Wolfgang W. and Fischer, Markus}, title = {Interannual variation in land-use intensity enhances grassland multidiversity}, series = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {111}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, number = {1}, publisher = {National Acad. of Sciences}, address = {Washington}, issn = {0027-8424}, doi = {10.1073/pnas.1312213111}, pages = {308 -- 313}, year = {2014}, abstract = {Although temporal heterogeneity is a well-accepted driver of biodiversity, effects of interannual variation in land-use intensity (LUI) have not been addressed yet. Additionally, responses to land use can differ greatly among different organisms; therefore, overall effects of land-use on total local biodiversity are hardly known. To test for effects of LUI (quantified as the combined intensity of fertilization, grazing, and mowing) and interannual variation in LUI (SD in LUI across time), we introduce a unique measure of whole-ecosystem biodiversity, multidiversity. This synthesizes individual diversity measures across up to 49 taxonomic groups of plants, animals, fungi, and bacteria from 150 grasslands. Multidiversity declined with increasing LUI among grasslands, particularly for rarer species and aboveground organisms, whereas common species and belowground groups were less sensitive. However, a high level of interannual variation in LUI increased overall multidiversity at low LUI and was even more beneficial for rarer species because it slowed the rate at which the multidiversity of rare species declined with increasing LUI. In more intensively managed grasslands, the diversity of rarer species was, on average, 18\% of the maximum diversity across all grasslands when LUI was static over time but increased to 31\% of the maximum when LUI changed maximally over time. In addition to decreasing overall LUI, we suggest varying LUI across years as a complementary strategy to promote biodiversity conservation.}, language = {en} } @misc{WeisserStueblerMatheisetal.2017, author = {Weisser, Karin and St{\"u}bler, Sabine and Matheis, Walter and Huisinga, Wilhelm}, title = {Towards toxicokinetic modelling of aluminium exposure from adjuvants in medicinal products}, series = {Regulatory toxicology and pharmacology : official journal of the International Society for Regulatory Toxicology and Pharmacology}, volume = {88}, journal = {Regulatory toxicology and pharmacology : official journal of the International Society for Regulatory Toxicology and Pharmacology}, publisher = {Elsevier}, address = {San Diego}, issn = {0273-2300}, doi = {10.1016/j.yrtph.2017.02.018}, pages = {310 -- 321}, year = {2017}, abstract = {As a potentially toxic agent on nervous system and bone, the safety of aluminium exposure from adjuvants in vaccines and subcutaneous immune therapy (SCIT) products has to be continuously reevaluated, especially regarding concomitant administrations. For this purpose, knowledge on absorption and disposition of aluminium in plasma and tissues is essential. Pharmacokinetic data after vaccination in humans, however, are not available, and for methodological and ethical reasons difficult to obtain. To overcome these limitations, we discuss the possibility of an in vitro-in silico approach combining a toxicokinetic model for aluminium disposition with biorelevant kinetic absorption parameters from adjuvants. We critically review available kinetic aluminium-26 data for model building and, on the basis of a reparameterized toxicokinetic model (Nolte et al., 2001), we identify main modelling gaps. The potential of in vitro dissolution experiments for the prediction of intramuscular absorption kinetics of aluminium after vaccination is explored. It becomes apparent that there is need for detailed in vitro dissolution and in vivo absorption data to establish an in vitro-in vivo correlation (IVIVC) for aluminium adjuvants. We conclude that a combination of new experimental data and further refinement of the Nolte model has the potential to fill a gap in aluminium risk assessment. (C) 2017 Elsevier Inc. All rights reserved.}, language = {en} } @article{HetheyHartungWangorschetal.2021, author = {Hethey, Christoph Philipp and Hartung, Niklas and Wangorsch, Gaby and Weisser, Karin and Huisinga, Wilhelm}, title = {Physiology-based toxicokinetic modelling of aluminium in rat and man}, series = {Archives of toxicology : official journal of EUROTOX}, volume = {95}, journal = {Archives of toxicology : official journal of EUROTOX}, number = {9}, publisher = {Springer}, address = {Berlin ; Heidelberg}, issn = {0340-5761}, doi = {10.1007/s00204-021-03107-y}, pages = {2977 -- 3000}, year = {2021}, abstract = {A sufficient quantitative understanding of aluminium (Al) toxicokinetics (TK) in man is still lacking, although highly desirable for risk assessment of Al exposure. Baseline exposure and the risk of contamination severely limit the feasibility of TK studies administering the naturally occurring isotope Al-27, both in animals and man. These limitations are absent in studies with Al-26 as a tracer, but tissue data are limited to animal studies. A TK model capable of inter-species translation to make valid predictions of Al levels in humans-especially in toxicological relevant tissues like bone and brain-is urgently needed. Here, we present: (i) a curated dataset which comprises all eligible studies with single doses of Al-26 tracer administered as citrate or chloride salts orally and/or intravenously to rats and humans, including ultra-long-term kinetic profiles for plasma, blood, liver, spleen, muscle, bone, brain, kidney, and urine up to 150 weeks; and (ii) the development of a physiology-based (PB) model for Al TK after intravenous and oral administration of aqueous Al citrate and Al chloride solutions in rats and humans. Based on the comprehensive curated Al-26 dataset, we estimated substance-dependent parameters within a non-linear mixed-effect modelling context. The model fitted the heterogeneous Al-26 data very well and was successfully validated against datasets in rats and humans. The presented PBTK model for Al, based on the most extensive and diverse dataset of Al exposure to date, constitutes a major advancement in the field, thereby paving the way towards a more quantitative risk assessment in humans.}, language = {en} }