Pathology

The Department of Pathology offers a broad spectrum of pathology services to industry, research institutions and universities doing research, development and testing of pharmaceuticals and chemicals in animals. The scientific staff working in this Department are certified veterinary pathologists who have many years of experience in toxicologic pathology of the respiratory tract, tumor histopathology, immunohistochemical characterization, and investigation of age-dependent lesions. They competently evaluate toxicity and carcinogenicity studies as well as cell proliferation assays. Furthermore, electron microscopic investigations can be performed by using transmission and scanning electron microscopes. All studies are conducted in compliance with the GLP guidelines. In addition, the Department performs peer reviews and organizes pathology working groups and panel sessions, for which a multi-headed microscope for 21 observers, equipped with an additional video system, is available.

Overview of our services

Histopathological examination of organs and tissues from toxicity and carcinogenicity studies, data acquisition and analysis by using the Provantis pathology program, statistics (SAS), and preparation of reports 

Histopathological evaluation of carcinogenicity and toxicity studies in rodents and dogs 

Morphological examinations to determine the toxicological potential of nanoparticles (light microscopic and ultrastructural)

Histopathological evaluation of transgenic mice 

Morphometrical evaluation of tissues, organs, and human bronchial biopsies 

Evaluation of assays regarding cell proliferation, apoptosis, and oxidative damage 

Histopathological evaluation for the pathology databases RITA (Registry of Industrial Toxicology Animal-data) and CEPA (Cell Proliferation and Apoptosis). These databases are operated in collaboration with the Working Group on Databases and Information Systems

Electron microscopic examinations (TEM, SEM)

Methods

Trimming of organs and tissues from toxicity and carcinogenicity studies according to the internal standard operating procedure or the client's wishes

Paraffin and plastic embedding of tissues and biopsies

Routine and special fixation and histochemical staining methods  

Immunohistochemical techniques for marking tumors, hormones, intermediate filaments, inflammatory cells, and oxidative damage (including markers of cell proliferation and cell cycle, demonstration of apoptosis, demonstration of hormone receptors and neuroendocrine peptides, and demonstration of changes in the cytoskeleton and the extracellular matrix)  

Microphotography and photo documentation

Morphometry and image analysis

Evaluation and immunohistochemical examination of human bronchial biopsies (quantification of inflammatory cell markers and goblet cells)  

Electron microscopy (TEM and SEM), EDX, and immune electron microscopy (analysis by using a CCD camera and a morphometry program)

Projects

Histological evaluation of toxicity and carcinogenicity studies 

Histological evaluation of the respiratory tract after inhalation/intratracheal instillation of different fiber and particle types 

Histological evaluation of the carcinogenic potential of electromagnetic fields in rats and mice 

Histological, immunohistochemical, and morphometric analyses of the effects of different types of fibers on peritoneal cells 

Multigenerational studies 

Determination of cell proliferation in the respiratory tract after inhalation of different types of fibers

Immunohistochemical investigation and quantitative analysis of human bronchial biopsies

Pathology database RITA (Registry of Industrial Toxicology Animal-data) and cell proliferation database CEPA (Cell Proliferation and Apoptosis) in collaboration with the Working Group on Databases and Information Systems

Pathogenetic and immunobiological investigations on the carcinogenicity of particles

Genotoxic mechanisms of action of fine and ultrafine particulate matter in the lung

Electron microscopy to demonstrate inhaled or instilled nanoparticles in the respiratory tract

Electron microscopy to investigate nanoparticle behavior after cellular uptake in different cell culture systems

Peer review of carcinogenicity studies 

Histopathological investigations within the DFG Collaborative Research Center (SFB 587) "Immune Reactions of the Lung in Infection and Allergy"

Cellular and subcellular effects in rat lung epithelial cells after inhalation of fine and nano-scale titanium dioxide particles (doctoral thesis in collaboration with the Hannover University of Veterinary Medicine)

Electron microscopy to investigate translocation of fine and nano-scale titanium dioxide particles from the nose to the brain (doctoral thesis in collaboration with the Hannover University of Veterinary Medicine and the Center for Systems Neuroscience (ZSN))

Special equipment

Multi-headed microscope for 21 observers connected to a video system

Mirax scan system for digital imaging of histological slides

Special image analysis software (AxioVision and AnalySIS)

Publications

2013

Rittinghausen, Susanne ; Bellmann, Bernd ; Creutzenberg, Otto ; Ernst, Heinrich ; Kolling, Angelika ; Mangelsdorf, Inge ; Kellner, Rupert ; Beneke, Sascha ; Ziemann, Christina: Evaluation of immunohistochemical markers to detect the genotoxic mode of action of fine and ultrafine dusts in rat lungs. In: Toxicology 303 (2013), S. 177-186

Gerhauser, I.; Wohlsein, P.; Ernst, H.; Germann, P.-G.; Baumgärtner, W.: Vacuolation and mineralisation as dominant age-related findings in hamster brains. In: Experimental and Toxicologic Pathology 65 (2013), Nr. 4, S. 375-381

McInnes, E. F. ; Ernst, H.; Germann, P.-G.: Spontaneous neoplastic lesions in control syrian hamsters in 6-, 12-, and 24-month short-term and carcinogenicity studies. In: Toxicologic Pathology 41 (2013), Nr. 1, S. 86-97

2012

Kuper, C. F.; Ernst, H.; Oostrum, L. C. M. van; Rittinghausen, S.; Penninks, A. H.; Ganderup, N.-C.; Wolterbeek, A. P. M.: Nasal passages of Göttingen minipigs from the neonatal period to young adult. In: Toxicologic Pathology 40 (2012), Nr. 4, S. 656-666

Eydner, M.; Jacobsen, B.; Thomann, M.; Rittinghausen, S.; Fehr, M.; Baumgärtner, W.: Spontaneously occurring multicentric basal cell carcinoma and keratoacanthomas in a multimammate mouse (Mastomys spp.). In: Journal of veterinary diagnostic investigation 24 (2012), Nr. 4, S. 696-701

2011

Kolling, A.; Ernst, H.; Rittinghausen, S.; Heinrich, U.: Relationship of pulmonary toxicity and carcinogenicity of fine and ultrafine granular dusts in a rat bioassay. In: Inhalation Toxicology 23 (2011), Nr. 9, S. 544-554

Nolte, T.; Rittinghausen, S.; Kellner, R.; Karbe, E.; Kittel, B.; Rinke, M.; Deschl, U.: RITA - Registry of Industrial Toxicology Animal data: The application of historical control data for Leydig cell tumors in rats. In: Experimental and Toxicologic Pathology 63 (2011), Nr. 7-8, S. 645-656

2010

Nolte, T.; Rittinghausen, S.; Kellner, R.; Karbe, E.; Kittel, B.; Rinke, M.; Deschl, U.: RITA-Registry of Industrial Toxicology Animal data: The application of historical control data for Leydig cell tumors in rats. In: Experimental and Toxicologic Pathology (2010), 9. Juni (Online-Veröffentlichung vor Druck) 

2009

Renne, R.; Brix, A.; Harkema, J.; Herbert, R.; Kittel, B.; Lewis, D.;March, T.; Nagano, K.; Pino, M.; Rittinghausen, S.; Rosenbruch, M.; Tellier, P.; Wohrmann, T.: Proliferative and nonproliferative lesions of the rat and mouse respiratory tract. In: Toxicological Pathology 37 (2009)

Vahle, J.; Bradley, A.; Harada, T.; Herbert, R.; Kaufmann, W.; Kellner, R.; Mann, P.; Pyrah, I.; Rittinghausen, S.; Tanaka, T.: The international nomenclature project: an update. In: Toxicological Pathology 37 (2009)

Bellmann, B.; Creutzenberg, O.; Ernst, H.; Muhle, H.: Rat inhalation test with particles from biomass combustion and biomass co-firing exhaust. In: Journal of Physics: Conference Series [Elektronische Ressource] 151 (2009), 012067, 5 p.

Creutzenberg, O.; Ziemann, C.; Hansen, T.; Ernst, H.; Jackson, P.; Cartlidge, D.; Brown, R.: In vivo study with quartz-containing ceramic dusts: Inflammatory effects of two factory samples in lungs after intratracheal instillation in a 28-day study with rats. In: Journal of Physics: Conference Series [Elektronische Ressource] 151 (2009), 012031, 5 p.

2008

Creutzenberg, O.; Ziemann, C.; Hansen, T.; Ernst, H.; Jackson, P.; Brown, R.: Quartz-containing ceramic dusts: in vivo study on inflammatory effects of two factory samples in lungs after intratracheal instillation in a 28-day study with rats. In: The Toxicologist 102 (2008), 1, p. 105, abstract 514

Kolling, A.; Ernst, H.; Rittinghausen, S.; Heinrich, U.; Pott, F.: Comparison of primary lung tumor incidences in the rat evaluated by the standard microscopy method and by multiple step sections. In: Experimental and Toxicologic Pathology Online First 60 (2008), No.4-5, p. 281-288

Schmiedl, A.; Lempa, T.; Hoymann, H.G.; Rittinghausen, S.; Popa, D.; Tschernig, T.; Fehrenbach, H.; Pabst, R.; Hoeper, M.M.; Hohlfeld, J.M.: Elastase-induced lung emphysema in rats is not reduced by hematopoietic growth factors when applied preventionally. In: Virchows Archiv 425 (2008), No.6, S.675-688

Ziemann, C.; Hansen, T.; Ernst, H.; Jackson, P.; Brown, R.; Creutzenberg, O.: In vitro and in vivo screening of the cytotoxic, pro-inflammatory and genotoxic potential of quartz-containing ceramic dusts. In: Naunyn-Schmiedebergs Archives of Pharmacology 377 (2008), Suppl.1, p. 72, Abstract 355

2006

Heikkinen, P.; Ernst, H.; Huuskonen, H.; Komulainen, H.; Kumlin, T.; Mäki-Paakkanen, J.; Puranen, L.; Juutilainen, J.: No effects of radiofrequency radiation on 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone-induced tumorigenesis in female Wistar rats. In: Radiation research 166 (2006), 2, p. 397-408

Mohr, U.; Ernst, H.; Roller, M.; Pott, F.: Pulmonary tumor types induced in Wistar rats of the so-called »19-dust study«. In: Experimental and Toxicologic Pathology 58 (2006), 1, p. 13-20