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Klaus Schneider Marco Dilger Claudia Drossard Heidi Ott Eva Kaiser 《Journal of applied toxicology : JAT》2022,42(5):913-926
Frameworks for deriving occupational exposure limits (OELs) and OEL-analogue values (such as derived-no-effect levels [DNELs]) in various regulatory areas in the EU and at national level in Germany were analysed. Reasons for differences between frameworks and possible means of improving transparency and harmonisation were identified. Differences between assessment factors used for deriving exposure limits proved to be one important reason for diverging numerical values. Distributions for exposure time, interspecies and intraspecies extrapolation were combined by probabilistic methods and compared with default values of assessment factors used in the various OEL frameworks in order to investigate protection levels. In a subchronic inhalation study showing local effects in the respiratory tract, the probability that assessment factors were sufficiently high to protect 99% and 95% of the target population (workers) from adverse effects varied considerably from 9% to 71% and 17% to 87%, respectively, between the frameworks. All steps of the derivation process, including the uncertainty associated with the point of departure (POD), were further analysed with two examples of full probabilistic assessments. It is proposed that benchmark modelling should be the method of choice for deriving PODs and that all OEL frameworks should provide detailed guidance documents and clearly define their protection goals by stating the proportion of the exposed population the OEL aims to cover and the probability with which they intend to provide protection from adverse effects. Harmonisation can be achieved by agreeing on the way to perform the methodological steps for deriving OELs and on common protection goals. 相似文献
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Leonie Konczalla Daniel R. Perez Nadine Wenzel Gerrit Wolters-Eisfeld Clarissa Klemp Johanna Lüddeke Annika Wolski Dirk Landschulze Chris Meier Anika Buchholz Dichao Yao Bianca T. Hofmann Julia K. Graß Sarah L. Spriestersbach Katharina Grupp Udo Schumacher Christian Betzel Svetlana Kapis Theresa Nuguid Pablo Steinberg Klaus Püschel Guido Sauter Maximillian Bockhorn Faik G. Uzunoglu Jakob R. Izbicki Cenap Güngör Alexander T. El Gammal 《International journal of cancer. Journal international du cancer》2020,146(6):1618-1630
MALT1 is a key mediator of NF-κB signaling and a main driver of B-cell lymphomas. Remarkably, MALT1 is expressed in the majority of pancreatic ductal adenocarcinomas (PDACs) as well, but absent from normal exocrine pancreatic tissue. Following, MALT1 shows off to be a specific target in cancer cells of PDAC without affecting regular pancreatic cells. Therefore, we studied the impact of pharmacological MALT1 inhibition in pancreatic cancer and showed promising effects on tumor progression. Mepazine (Mep), a phenothiazine derivative, is a known potent MALT1 inhibitor. Newly, we described that biperiden (Bip) is a potent MALT1 inhibitor with even less pharmacological side effects. Thus, Bip is a promising drug leading to reduced proliferation and increased apoptosis in PDAC cells in vitro and in vivo. By compromising MALT1 activity, nuclear translocation of c-Rel is prevented. c-Rel is critical for NF-κB-dependent inhibition of apoptosis. Hence, off-label use of Bip or Mep represents a promising new therapeutic approach to PDAC treatment. Regularly, the Anticholinergicum Bip is used to treat neurological side effects of Phenothiazines, like extrapyramidal symptoms. 相似文献
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Martin R. Späth Malte P. Bartram Nicolàs Palacio-Escat K. Johanna R. Hoyer Cedric Debes Fatih Demir Christina B. Schroeter Amrei M. Mandel Franziska Grundmann Giuliano Ciarimboli Andreas Beyer Jayachandran N. Kizhakkedathu Susanne Brodesser Heike Göbel Jan U. Becker Thomas Benzing Bernhard Schermer Martin Höhne Markus M. Rinschen 《Kidney international》2019,95(2):333-349
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Mitterreiter Johanna Scheiblauer Heinrich Fiedler Sarah Kreß Julia 《Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz》2022,65(2):209-219
Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Infektionen mit den Hepatitisviren B, C und E (HBV, HCV, HEV) sind über das Blut übertragbar... 相似文献
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