Advances in Biochemical Engineering/Biotechnology 157 Series Editor: T. Scheper Georg Reifferscheid Sebastian Buchinger Editors In vitro Environmental Toxicology - Concepts, Application and Assessment 157 Advances in Biochemical Engineering/Biotechnology Series editor T. Scheper, Hannover, Germany Editorial Board S. Belkin, Jerusalem, Israel T. Bley, Dresden, Germany J. Bohlmann, Vancouver, Canada M.B. Gu, Seoul, Korea W.-S. Hu, Minneapolis, MN, USA B. Mattiasson, Lund, Sweden J. Nielsen, Gothenburg, Sweden H. Seitz, Potsdam, Germany R. Ulber, Kaiserslautern, Germany A.-P. Zeng, Hamburg, Germany J.-J. Zhong, Shanghai, China W. Zhou, Shanghai, China Aims and Scope This book series reviews current trends in modern biotechnology and biochemical engineering. Its aim is to cover all aspects of these interdisciplinary disciplines, where knowledge, methods and expertise are required from chemistry, biochemis- try, microbiology, molecular biology, chemical engineering and computer science. Volumes are organized topically and provide a comprehensive discussion of devel- opments in the field over the past 3–5 years. The series also discusses new discoveries and applications. Special volumes are dedicated to selected topics which focus on new biotechnological products and new processes for their synthe- sis and purification. In general, volumes are edited by well-known guest editors. The series editor and publisher will, however, always be pleased to receive suggestions and supplemen- tary information. Manuscripts are accepted in English. In references, Advances in Biochemical Engineering/Biotechnology is abbreviated as Adv. Biochem. Engin./Biotechnol. and cited as a journal. More information about this series at http://www.springer.com/series/10 Georg Reifferscheid • Sebastian Buchinger Editors In vitro Environmental Toxicology - Concepts, Application and Assessment With contributions by S. Belkin Á A. Brinke Á M. Brinkmann Á S. Buchinger Á N. Egetenmeyer Á T. Elad Á B.I. Escher Á N. Haase Á M. Heringa Á H. Hollert Á A. Jahnke Á C. Kienle Á Y. Oda Á J. Oehlmann Á T.G. Preuss Á S. Scha¨fer Á W. Schulz Á K.E.C. Smith Á P. Steinberg Á G.D.A. Umbuzeiro Á E.L.M. Vermeirssen Á M. Wagner Á S.C. Weiss Á G. Witt Á E. Zeiger Editors Georg Reifferscheid Sebastian Buchinger Federal Institute of Hydrology Federal Institute of Hydrology Koblenz, Germany Koblenz, Germany ISSN 0724-6145 ISSN 1616-8542 (electronic) Advances in Biochemical Engineering/Biotechnology ISBN 978-3-319-45906-6 ISBN 978-3-319-45908-0 (eBook) DOI 10.1007/978-3-319-45908-0 Library of Congress Control Number: 2017938647 © Springer International Publishing AG 2017 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Printed on acid-free paper This Springer imprint is published by Springer Nature The registered company is Springer International Publishing AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland Preface In recent years, considerable technological progress has been made in the develop- ment of in vitro bioanalytical methods and instruments for the elucidation of toxic effects of compounds of both natural and anthropogenic origin. Such methods, which are progressively applied in toxicologyand environmental science, allow the detection of cytotoxicity as well as the investigation of specific, sublethal effects of chemicals and chemical mixtures of different complexity. In toxicology, in vitro bioanalytical tools have so far mainly been used to generate scientific knowledge, to elucidate the chemical causes of effects, and to provide data in support of environmental monitoring. It is widely accepted that in vitro methods add substantial value to the field of ecotoxicology because of their efficiency, their high throughput capacity, and their ability to obtain mechanistic information about toxicity and basic data on possible toxicological risks in different environmental compartments. However, the use and interpretation of test results in regulation is challenging and still under discussion. Although reduction, replacement, and refinement of in vivo toxicologyis always being called for by society and regulatory stakeholders, one main reason for regulatory obstruction is that options for in vitro/in vivo extrapolation of effects are still missing. This book gives an overview of the current state of the art of in vitro bioassays in the field of (eco)toxicology with special focus on effects of very high concern and reasonable areas of application. Furthermore, selected chapters address topics related to the application of in vitro bioassays in environmental sciences, such as passive sampling/passive dosing and effect-directed analysis. A special chapter describes the possibilities of linking results of in vitro assays to in vivo effects by making use of physiologically-based pharmacokinetic modeling. According to the basic test principles, the underlying concepts of the various techniques are shown. v vi Preface The book exemplifies the use of in vitro approaches in different fields of application. It discusses the potential, current limitations, research needs,and reg- ulatory perspectives of some selected bioanalytical tools and of in vitro bioassays in general. Georg Reifferscheid Sebastian Buchinger Contents Endocrine Disruption and In Vitro Ecotoxicology: Recent Advances and Approaches .......................................... 1 Martin Wagner, Cornelia Kienle, Etie¨nne L.M. Vermeirssen, and Jorg€ Oehlmann In Vitro Genotoxicity Testing: Significance and Use in Environmental Monitoring .............................................. 59 Gisela De Aragao Umbuzeiro, Minne Heringa, and Errol Zeiger In Vitro–In Vivo Carcinogenicity ............................. 81 Pablo Steinberg Advanced Approaches to Model Xenobiotic Metabolism in Bacterial Genotoxicology In Vitro .................................... 97 Yoshimitsu Oda Reporter Gene Assays in Ecotoxicology ........................ 135 Tal Elad and Shimshon Belkin Toxicogenomics in Environmental Science ...................... 159 Alexandra Brinke and Sebastian Buchinger Coupling of In Vitro Bioassays with Planar Chromatography in Effect-Directed Analysis .................................. 187 Stefan C. Weiss, Nicole Egetenmeyer, and Wolfgang Schulz Combining Passive Sampling with Toxicological Characterization of Complex Mixtures of Pollutants from the Aquatic Environment . 225 Annika Jahnke, Gesine Witt, Sabine Scha¨fer, Nora Haase, and Beate I. Escher vii viii Contents Defining and Controlling Exposure During In Vitro Toxicity Testing and the Potential of Passive Dosing ........................... 263 Kilian E.C. Smith and Sabine Scha¨fer Advancing In Vitro–In Vivo Extrapolations of Mechanism-Specific Toxicity Data Through Toxicokinetic Modeling .................. 293 Markus Brinkmann, Thomas G. Preuss, and Henner Hollert Index .................................................. 319 Adv Biochem Eng Biotechnol (2017) 157: 1–58 DOI: 10.1007/10_2016_2 © Springer International Publishing Switzerland 2017 Published online: 3 February 2017 Endocrine Disruption and In Vitro Ecotoxicology: Recent Advances and Approaches Martin Wagner, Cornelia Kienle, Etie¨nne L.M. Vermeirssen, and Jorg€ Oehlmann Abstract Endocrine-disrupting chemicals (EDCs) are man-made compounds interfering with hormone signaling. Omnipresent in the environment, they can cause adverse effects in a wide range of wildlife. Accordingly, Endocrine Disrup- tion is one focal area of ecotoxicology. Because EDCs induce complex response patterns in vivo via a wide range of mechanisms of action, in vitro techniques have been developed to reduce and understand endocrine toxicity. In this review we revisit the evidence for endocrine disruption in diverse species and the underlying molecular mechanisms. Based on this, we examine the battery of in vitro bioassays currently in use in ecotoxicological research and discuss the following key ques- tions. Why do we use in vitro techniques? What endpoints are we looking at? Which applications are we using in vitro bioassays for? How can we put in vitro data into a broader context? And finally, what is the practical relevance of in vitro data? In critically examining these questions, we review the current state-of-the-art of in vitro (eco)toxicology, highlight important limitations and challenges, and discuss emerging trends and future research needs. Keywords Bioanalytical