Health effects of some major aquatic pollutants in European flounder: Laboratory experiments with emphasis on histopathological and immunological aspects Guy Grinwis Cover illustration: Guy Grinwis, 1967. Health effects of some major aquatic pollutants in European flounder: Laboratory experiments with emphasis on histopathological and immunological aspects Guy Grinwis ISBN-10: 90-393-4268-7 ISBN-13: 978-90-393-4268-8 Printing: Atalanta Drukwerkbemiddeling, Houten The studies described in this thesis were performed as a cooperative effort by the department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, the Dutch National Institute for Public Health and the Environment (RIVM), and the Dutch National Institute for Coastal and Marine Management (RIKZ). Health effects of some major aquatic pollutants in European flounder: Laboratory experiments with emphasis on histopathological and immunological aspects Gezondheidseffecten van enkele belangrijke verontreinigende stoffen in het aquatische milieu in de bot: Laboratorium experimenten met de nadruk op histopathologische en immunologische aspecten (met een samenvatting in het Nederlands) Proefschrift ter verkrijging van de graad van doctor aan de Universiteit Utrecht op gezag van de rector magnificus, prof.dr. W.H. Gispen, ingevolge het besluit van het college voor promoties in het openbaar te verdedigen op maandag 29 mei 2006 des middags te 12.45 uur door Guillaume Cornelis Maria Grinwis geboren op 26 mei 1962 te Utrecht, Nederland. Promotoren: Prof. Dr. J.G. Vos Prof. Dr. J.E. van Dijk Co-promotoren: Dr. A.D. Vethaak Dr. P.W. Wester Contents Chapter 1 Introduction 1 Chapter 2 Short-term toxicity of bis(tri-n-butyltin)oxide in flounder 15 (Platichthys flesus): Pathology and immune function Chapter 3 Chronic aqueous exposure to bis(tri-n-butyltin)oxide (TBTO) 35 causes thymotoxicity in European flounder (Platichthys flesus) Chapter 4 Toxicity of TCDD in European flounder (Platichthys flesus) 49 with emphasis on histopathology and cytochrome P4501A induction in several organ systems Chapter 5 Toxicity of PCB-126 in European Flounder (Platichthys 67 flesus) with emphasis on histopathology and cytochrome P4501A induction in several organs systems Chapter 6 Cytochrome P4501A induction in peripheral blood 81 leukocytes in European flounder (Platichthys flesus): an intravital biomarker of exposure? Chapter 7 Summary and concluding remarks 93 Nederlandse samenvatting 99 Dankwoord 103 Curriculum vitae 106 Color illustrations 107 Chapter 1 Introduction Based on: Toxicology of environmental chemicals in the flounder (Platichthys flesus) with emphasis on the immune system: field, semi-field (mesocosm) and laboratory studies G.C.M. Grinwis, A.D. Vethaak, P.W. Wester, J.G. Vos Toxicology Letters 112–113 (2000) 289–301; with permission from Elsevier Chapter 1 1. General remarks This thesis is part of a large-scale research project in which several research institutes have participated. The primary driving force for this project was provided by reports of epizootics of grossly visible disease signs in fish in the North Sea. Because of concern with the possible contribution of pollution-mediated diseases to fish mortality and population declines, these diseases and abnormalities of marine and estuarine fish populations have received much attention. Moreover, they could be suitable indicators for monitoring anthropogenic environmental stress (Vethaak and ap Rheinallt, 1992). Studies of fish diseases in relation to pollution were designed to answer the following questions: 1. in general terms, are changes in disease patterns associated with changes in environmental quality (field surveys) ? 2. can we identify cause-and-effect relationships between disease patterns and exposure to the complex mixture of chemical pollutants present in the environment (semi-field experiments) ? 3. can we identify cause-and-effect relationships for specific chemical contaminants (laboratory experiments) ? The answers to these questions are highly relevant to the potential use of disease as a biomarker of contaminant effects. The questions mentioned above were addressed in an integrated study strategy (Fig. 1) in which field, semi-field and laboratory studies with the euryhaline fish species European flounder (Platichthys flesus) were carried out in The Netherlands. Each type of study has its strengths and disadvantages regarding the relevance of its results to natural populations and to relationships between pollution and disease (correlative or causal), but combined they are complementary. Both field and semi-field studies have been performed in the past. This thesis reports the results of laboratory experiments, the missing link between correlative and causal evidence. Evidence Control of variables Relevance to natural populations Correlative none only Field study Semi-field moderate moderate study Laboratory study Low (needs Causal high Extrapolation) Fig. 1. Integrated approach to study the causes of wildlife diseases (According to Vethaak, 1993). - 2 -
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