Publications

P.R.I.T.® technologies have already been used successfully to explore a broad range of different problems. We will be happy to provide you with details from projects that do not fall under confidentiality agreements.

Investigation of airborne substances in-vitro, ex-vivo, in-vivo, and in man with all methods available has been the focus of research activities at the Fraunhofer ITEM since the institute was founded in 1981.

The patented P.R.I.T.® technologies as one of the institute’s latest continuous development projects have already been put to use in different studies and tests. Please see below for references.

Webinar#

Inhalation Toxicity Testing In Vitro: Applications and Capabilities Using a Human Lung Cell Line and an Optimized Methodological Approach

Fraunhofer Webinar

List of Publications#

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Scientific Reports volume 10, Article number: 6257 (2020), "Intermittent exposure to whole cigarette smoke alters the differentiation of primary small airway epithelial cells in the air-liquid interface culture", Julia A. Gindele1,2, Tobias Kiechle1, Kerstin Benediktus1, Gerald Birk3, Michael Brendel4, Fabian Heinemann3, Christian T. Wohnhaas5,6, Michelle LeBlanc7, Haijun Zhang7, Yael Strulovici-Barel7, Ronald G. Crystal7, Matthew J. Thomas1, Birgit Stierstorfer3, Karsten Quast & Jürgen Schymeinsky1,2
1Immunology & Respiratory Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riß, Germany;
2Department of General Physiology, University of Ulm, Ulm, Germany;
3Drug Discovery Sciences, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riß, Germany;
4Non-Clinical Statistics Biberach, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riß, Germany;
5Global Computational Biology and Digital Sciences, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riß, Germany;
6Department of Biology, University of Konstanz, Konstanz, Germany;
7Department of Genetic Medicine, Weill Cornell Medical College, New York, USA;

 

EU-ToxRisk Symposium (2020), Egmont aan Zee (Netherlands), "Hazard assessment of diacetyl and structurally related diketones – a read-across approach", Tanja Hansen1,*, Matthias Wehr1, Britta Anna Kühne1, Detlef Ritter1, Jan Knebel1, Johannes Schimming2, Jan Boei2, Pieter S. Hiemstra2, Harry Vrieling2, Sylvia E. Escher1
1Fraunhofer ITEM, Hannover, Germany;
2Leiden University Medical Center, Leiden, The Netherlands;
3Leiden Academic Centre for Drug Research, Leiden University;

 

Lung Research (DZL) Hannover, Germany,
3Division of Cardiac, Thoracic, Transplantation, and Vascular Surgery, Hannover Medical School, Member of the German Center for Lung Research (DZL) Hannover, Germany,
4KRH Klinikum Siloah-Oststadt-Heidehaus, Hannover Germany,
5Biomedical Research in Endstage and Obstructive Lung Disease (BREATH)

 

Models of Lung Disease Workshop 2020, Hannover (Germany), "Development of alternative in vitro and ex vivo models for testing of inhalable antibiotics – InhalAb.", S. Wronski1, K. Schwarz1, D. Ritter1, J. Knebel1, K. Blümlein1, N. Sonnenschein1, S. Cleeves1, L. Müller1, N. Nowak1, M. Niehof1, K. Sewald1, T. Hansen1 A. Braun1
1Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, Member of the German Center for Lung Research (DZL), Biomedical Research in Endstage and Obstructive Lung Disease (BREATH) research network, Member of Fraunhofer international Consortium for Anti-Infective Research (iCAIR), Hannover, Germany

 

Models of Lung Disease Workshop 2020, Hannover (Germany), "Cigarette smoke exposure disrupts epithelial barrier function and impairs antiviral immune response to influenza infection", S. Böhlen1,5, O. Danov1,5, H. Obernolte1,5, D. Ritter1, J. Knebel1, P. Braubach2,5, D. Jonigk2,5, G. Warnecke3,5, H.-G. Fieguth4, A. Braun1,5 S. Wronski1,5, K. Sewald1,5,
1Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, Member of Fraunhofer international Consortium for Anti-Infective Research (iCAIR), Member of the German Center for Lung Research (DZL) Hannover, Germany,
2Institute for Pathology, Hannover Medical School, Member of the German Center for

 

 

Journal of the European Society of Toxicology in Vitro "Toxicology in Vitro", Volume 63, 2020, "In vitro inhalation cytotoxicity testing of therapeutic nanosystems for pulmonary infection", Detlef Rittera, Jan Knebela, Monika Niehofa, Iraida Loinazb, Marco Marradib, Raquel Graciab, Yvonne te Welscherc, Cornelus F. van Nostrumc, Chiara Falcianid,f, Alessandro Pinid,f, Magnus Strandhe, Tanja Hansena
aPreclinical Pharmacology and In-vitro Toxicology, Fraunhofer ITEM, Hannover, Germany
bCIDETEC Nanomedicine, San Sebastián, Spain
cUtrecht University, Utrecht, the Netherlands
dSetLance, Siena, Italy
eAdenium Biotech ApS, Copenhagen, Denmark
fDepartment of Medical Biotechnology, University of Siena, Italy

 

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37th AAAR Annual Conference, October 2019, Oregon USA,"An alternative model for testing of acute respiratory local toxic and physiological effects based on in vitro and isolated perfused lung (IPL) technologies", Detlef Ritter, Jan Knebel, Sabrina Wilde, Tanja Hansen, Katharina Schwarz
Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, Hannover, Germany

 

SOT 58th Annual Meeting and ToxExpo, March 2019, Baltimore (USA),"Pathophysiological changes in the extracellular matrix but not inflammation were induced by cigarette smoke as early events in fresh human lung tissue", H. Obernolte1,4, D. Ritter1,4, J. Knebel1,4, M. Niehof1,4, P. Braubach2,4, D. Jonigk2,4, G. Warnecke2,4, P. Zardo2,4, H.-G. Fieguth3, O. Pfennig3, A. Braun1,4, K. Sewald1,4
1Fraunhofer Institute for Toxicology and Experimental Medicine, Nikolai-Fuchs-Str. 1, 30625 Hannover, Germany
2Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany
3KRH clinics, Stadionbrücke 4, 30459 Hannover, Germany
4Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Centre for Lung Research (DZL), Carl-Neuberg-Str. 1, 30625 Hannover, Germany.

 

EU-ToxRisk Symposium (2019), Egmont aan Zee (Netherlands),"CS8: The popcorn lung – overview and experimental challenges", T. Hansen1, J. Boei2, H. Vrieling2, J. Schimming3, S. Klima4, S. Escher1, K. Sewald1, J. Knebel1, D. Ritter1
1Department of Preclinical Pharmacology and In Vitro Toxicology, Fraunhofer ITEM, Hannover, Germany
2Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
3Division of Toxicology, Leiden University, The Netherlands
4In vitro Toxicology and Biomedicine, Faculty of Science, University of Konstanz

 

EU-ToxRisk Symposium (2019), Egmont aan Zee (Netherlands),"CS8: In vitro testing of diacetyl and analogues at ALI conditions", T. Hansen1, B. Kühne1, J. Boei2, H. Vrieling2, P.S. Hiemstra2, J. Knebel1, D. Ritter1
1Department of Preclinical Pharmacology and In Vitro Toxicology, Fraunhofer ITEM, Hannover, Germany
2Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands

 

Models of Lung Disease Workshop 2019, Hannover (Germany),"Development of alternative in vitro and ex vivo models for testing of inhalable antibiotics – InhalAb.", S. Wronski1, K. Schwarz1, D. Ritter1, J. Knebel1, K. Blümlein1, S. Gerling1, N. Sonnenschein1, O. Danov1, S. Cleeves1, L. Quercini2, N. Krämer1, L. Müller1, M. Niehof1, C. Hesse1, K. Sewald1, T. Hansen1, A. Braun1
1Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, Member of the German Center for Lung Research (DZL), Biomedical Research in Endstage and Obstructive Lung Disease (BREATH) research network, Member of Fraunhofer international Consortium for Anti-Infective Research (iCAIR), Hannover, Germany
2University of Siena, Department of Medical Biotechnology, Siena, Italy

 

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20th International Congress on In Vitro Toxicology (ESTIV 2018), 15-18 October 2018, Berlin, Germany. "Popcorn lung: Diacetyl exposure of primary human bronchial epithelial cells using a relevant air-liquid setup", D. Ritter1, J. Knebel1, J.Boei2, H.Vrieling2, B.Kühne1, P.S.Hiemstra3, T.Hansen1
1Preclinical Pharmacology and In-vitro Toxicology, Fraunhofer ITEM, Hannover, Germany;
2Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands;
3Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands

 

LIVE 2018 Lung In vitro Event for innovative and predictive models, Nice FRANCE, 5.-6. July 2018, "The human epithelial lung cell line A549 as a suitable tool in in vitro inhalation toxicity testing", D. Ritter, J. Knebel
Preclinical Pharmacology and In-vitro Toxicology, Fraunhofer ITEM, Hannover, Germany

 

EUROTOX 54th Congress of the European Societies of Toxicology, Brussels (Belgium), Toxicology Letters, Volume 295, Supplement 1, October 2018, Pages 69ff. "Cytotoxicity Testing of Therapeutic Nanosystems for Pulmonary Infection using an air-lifted interface in-vitro test system ", J. Knebel1, D. Ritter1, M.Niehof1, T.Hansen1, M.Strandh2, C.Falciani3, M.Flores4, Y.te Welscher5, C.F. van Nostrum5, R.Gracia6, M.Marradi6, I.Loinaz6
1Preclinical Pharmacology and In-vitro Toxicology, Fraunhofer ITEM, Hannover, Germany;
2Adenium Biotech, Copenhagen, Denmark;
3SetLance, Siena, Italy;
4Ingeniatrics Tecnologias, S.L., Sevilla, Spain;
5Utrecht University, Utrecht, The Netherlands;
6CIDETEC Nanomedicine, San Sebastián, Spain

 

WEBINAR: "Inhalation Toxicity Testing In Vitro: Applications and Capabilities Using a Human Lung Cell Line and an Optimized Methodological Approach", Detlef Ritter, Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, Hannover, July 2018

Webinars on Inhalation Toxicity Testing

 

APPLIED IN VITRO TOXICOLOGY, Mary Ann Liebert Inc., Volume 4, Number 2, 2018 "Development and Evaluation of an In Vitro Test System for Toxicity Screening of Aerosols Released from Consumer Products and First Application to Aerosols from a Hair Straightening Process", D. Ritter1, A Bitsch1, M. Elend1, S. Schuchardt1, T.Hansen11, C. Brodbeck2, A. Fuchs3, C. Gronewold3*, R. Fautz3

1Fraunhofer Institute for Toxicology and Experimental Medicine ITEM - Hannover, Germany
2Fraunhofer Institute for Algorithms and Scientific Computing SCAI - Sankt Augustin - Germany
3Safety and Toxicology, KAO Germany GmbH, Darmstadt, Germany
*Current affiliation: Regulatory Affairs—Pharma Polymers, Evonik Nutrition & Care GmbH, Darmstadt, Germany

 

APPLIED IN VITRO TOXICOLOGY, Mary Ann Liebert Inc., Volume 4, Number 2, 2018 "Air–Liquid Interface In Vitro Models for Respiratory Toxicology Research: Consensus Workshop and Recommendations ", Ghislaine Lacroix1, Wolfgang Koch2, Detlef Ritter2, Arno C. Gutleb3, Søren Thor Larsen4, Thomas Loret1, Filippo Zanetti5, Samuel Constant6, Savvina Chortarea7,8, Barbara Rothen-Rutishauser7, Pieter S. Hiemstra9, Emeric Frejafon1, Philippe Hubert1, Laura Gribaldo10, Peter Kearns11, Jean-Marc Aublant12, Silvia Diabate13, Carsten Weiss13, Antoinette de Groot14, Ingeborg Kooter15

1 Chronic Risks Division, Institut National de l’Environnement industriel et des RISques, Verneuil-en-Halatte, France
2In vitro und Mechanistische Toxikologie, Fraunhofer ITEM, Hannover, Germany
3Environmental Research and Innovation (ERIN) Department, Luxembourg Institute of Science and Technology, Esch-sur-Alzette, Luxembourg
4Inhalation Toxicology Group, National Research Centre for the Working Environment, Copenhagen, Denmark
5Systems Toxicology Department, Philip Morris International R&D, Neuchaˆtel, Switzerland
6Epithelix Sarl, Plan-les-Outes, Switzerland
7BioNanomaterials, Adolphe Merkle Institute, University of Fribourg, Fribourg, Switzerland
8Laboratory for Materials-Biology Interactions, EMPA, Swiss Federal Laboratories for Materials, Science and Technology, St Gallen, Switzerland
9Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands
10Directorate F-Health, Consumers and Reference Materials Chemicals Safety and Alternative Methods Unit (F.3), EURL ECVAM, JRC, Ispra, Italy
11Environment, Health and Safety Division, OECD, Paris, France
12European Affairs and Standardization, Laboratoire National de Me´trologie et d’Essais, Paris, France
13Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, Karlsruhe, Germany
14Toxicological and Environmental Risk Assessment (TERA) Department, Solvay, Brussels, Belgium
15Department of Circular Environment and Environment (CEE), TNO, Utrecht, The Netherlands

 

SOT 57th Annual Meeting and ToxExpo, March 2018, San Antonio (USA), "Acute inhalation toxicity in-vitro and ex-vivo test battery prior to regulatory OECD 403 studies", T. Hansen1, D. Ritter1, J. Knebel1, D. Walter1, K. Schwarz2
Fraunhofer Institute for Toxicology and Experimental Medicine - Hannover, Germany
1Department Preclinical Pharmacology and In-Vitro Toxicology
2Department Aerosol research

 

17th Fraunhofer Seminar Translational Airway Research "Models of Lung Disease",January 2018, Hannover (Germany), "Early biomarkers indicate COPD induced by whole cigarette smoke in live lung tissue", H. Obernolte1, D. Ritter1, J. Knebel1, P. Braubach2, D. Jonigk2, G. Warnecke2, P. Zardo2, H.-G. Fieguth3, O. Pfennig3, A. Braun1, K. Sewald1
1Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, Hannover
2Medical University Hannover
1,2Member at the German Center for Lung Research (DZL), Biomedical Research in Endstage and Obstructive Lung Disease (BREATH) Research Network, Member of the Cluster of Excellence Regenerative Biology to Reconstructive Therapy (REBIRTH), Hannover
3KRH Kliniken, Germany

 

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Scientific Computing and Algorithms in Industrial Simulations, Projects and Products of Fraunhofer SCAI " Applying CFD for the Design of an Air-Liquid Interface In-Vitro Testing Method for Inhalable Compounds ", Springer 2017; pages 229-243 C. Brodbeck2, K. Wolf2, D. Ritter1, J. Knebel1
1Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, Hannover, Germany
2Fraunhofer Institute for Algorithms and Scientific Computing SCAI - Sankt Augustin, Germany

Springer

 

EUROTOX 2017 53rd Congress of the European Societies of Toxicology, Bratislava (Slovakia), "Effect of (Co‐) exposures of Printex90 and formaldehyde on a cell‐based assay system under air‐lifted Interphase (ALI) conditions", J. Knebel1, D. Ritter1, K.Schwarz1, T.Hansen1
Fraunhofer Institute for Toxicology and Experimental Medicine - Hannover, Germany

 

10th World Congress on Alternatives and Animals in the Life Sciences (WC10), Seattle (USA), "Cigarette smoke induces biomarkers of COPD in fresh human lung tissue", H. Obernolte1, D. Ritter1, J. Knebel1, P. Braubach2, D. Jonigk2, G. Warnecke2, P. Zardo2, H.-G. Fieguth3, O. Pfennig3, A. Braun1, K. Sewald1
1Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, Hannover, Germany
2Medical School Hannover, Germany
1,2Member of the German Center for Lung Research (DZL), Biomedical Research in Endstage and Obstructive Lung Disease (BREATH) research network, Member of the Cluster of Excellence Regenerative Biology to Reconstructive Therapy (REBIRTH), Hannover, Germany
3KRH clinics, Germany

 

ECOPA SSCT Workshop 2017, Helsinki (Finland), "Improvements for testing of airborne materials using a cell-based in vitro approach for a more reliable data collection ", J. Knebel1, D. Ritter1, T. Hansen1, C. Brodbeck2
1Fraunhofer Institute for Toxicology and Experimental Medicine ITEM - Hannover, Germany
2Fraunhofer Institute for Algorithms and Scientific Computing SCAI - Sankt Augustin, Germany

 

Nanocluster Meeting 2017 Karlsruhe (Germany), " Effekt von Carbon Black Nanopartikeln (CBNP) auf gesunde und vorgeschädigte Lungenzellen und PCLS ", O. Danov, J. Knebel, O. Creutzenberg, A. Braun, K. Sewald und T. Hansen (only German)
Fraunhofer Institute for Toxicology and Experimental Medicine - Hannover, Germany

 

Fraunhofer InnoVisions "Kubus gegen Tierversuche" (only German)

 

SOT 56th Annual Meeting and ToxExpo 2017, Baltimore (USA), "Characterization of Ci-huAEC airway epithelial cells for air-liquid exposure experiments", J. Knebel1, D. Ritter1, L.Schulz1, M.Niehof1, C. Ziemann1, T.May2, T. Hansen1
1Fraunhofer Institute for Toxicology and Experimental Medicine - Hannover, Germany
2InSCREENex GmbH - Braunschweig - Germany

 

Models of Lung Disease Workshop 2017, Hannover (Germany), "Cigarette Smoke induced Inflammation and Cytotoxicity in viable lung tissue", H. Obernolte1, D. Ritter1, J. Knebel1, P. Braubach2, D. Jonigk2, G. Warnecke2, M. Krüger2, H.-G. Fieguth3, O. Pfennig3, A. Braun1, K. Sewald1
1Fraunhofer Institute for Toxicology and Experimental Medicine ITEM, Hannover, Germany
2Medical School Hannover, Germany
1,2Member of the German Center for Lung Research (DZL), Biomedical Research in Endstage and Obstructive Lung Disease (BREATH) research network, Member of the Cluster of Excellence Regenerative Biology to Reconstructive Therapy (REBIRTH), Hannover, Germany
3KRH clinics, Germany

 

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EUROTOX September 2016, Sevilla, Spain, C. Brodbeck, D. Ritter, J. Knebel, "Use of Computational Fluid Dynamics for optimization of cell-based in vitro methods in inhalation research", Postersession

EMBL Microfluidics July 2016, Heidelberg, Germany, C. Brodbeck, D. Ritter, J. Knebel, "Applying CFD for the Design of an Air-Liquid Interface In-Vitro Testing Method for Inhalable Compounds", Postersession

55th Annual Meeting of the Society of Toxicology 2016, New Orleans (USA), Postersession, D. Ritter, A. Bitsch, M. Elend, S. Schuchardt, T. Hansen, C. Brodbeck, J. Knebel, A. Fuchs, C,. Gronewold, R. Fautz, "Development of an experimental cell-based approach to evaluate biological effects of aerosols from the application of hair-straightening products in vitro using relevant product application and cell exposure conditions"

Workshop "From Mice to Men: Road to Human Relevant Alternative Methods for Safety Assessment" of the BIO.NRW.academy, Henkel Düsseldorf, Postersession, C. Brodbeck, D. Ritter, J. Knebel, "Evaluation of biological effects of airborne material using an improved cell-based in vitro approach", May 2016

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54th Annual Meeting of the Society of Toxicology 2015, San Diego (USA), Luncheon Seminar, A. Braun, D. Ritter, K. Sewald, D. Walter, A. Bitsch, "Alternative Methods in inhalation toxicology"

54th Annual Meeting of the Society of Toxicology 2015, San Diego (USA), Postersession, D. Ritter, E. Krakor, J. Knebel "Acute inhalation toxicity of volatile organic compounds - application of an improved cell-based in vitro procedure"

NAFEMS World Congress 2015, San Diego (USA), Präsentation und Paper "Improvements of an Air-Liquid Interface In-Vitro Testing Method for Inhalable Compounds using CFD-Methods", D.Ritter, J. Knebel, C. Brodbeck [abstract]

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Advances in Toxicology 2014, Ritter, D., Knebel, J, "Investigations of the biological effects of airborne and inhalable substances by cell-based in vitro methods: fundamental improvements to the ALI concept", Advances in Toxicology Volume 2014, Article ID 185201, 11 pages

Advances in Aerosol Dosimetry Research 2014, Irvine (USA), Präsentation, D. Ritter, J. Knebel. "Current developments in the field of testing inhalable compounds in vitro based on the air-lifted-interface (ALI) technique"

8th International Symposium on Modern Principles of air Monitoring and Biomonitoring, Airmon 2014, Marseille (Frankreich), Postersession, D. Ritter, C. Brodbeck, J.Knebel "Biological monitoring of inhalable substances in vitro - development of an improved test method based on the air-liquid-interface (ALI) cell culture technique"

9th World Congress on Alternatives and Animal Use in the Life Sciences 2014, Prag (Tschechien), Postersession "Fundamental improvements of the Air-Liquid Interface technique for use in in-vitro inhalation toxciology", J. Knebel, D.Ritter, C. Brodbeck

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Annual Conference 2013 of the Association of inhalation toxicologists, Hannover (Deutschland), Präsentation, D. Ritter "In vitro human cell culture systems and air liquid interface techniques"

European Aerosol Conference 2013, Prag (Tschechien), Postersession "Influence of the Geometry of an Aerosol Conducting System on the Deposition of Particles from Inhalable Aerosols on Cellular Surfaces In-Vitro"

Scandinavian Society for Cell Toxicology (SSCT) Workshop 2013, Charlottenlund (Dänemark), Postersession "Biological effects of inhalable compounds – improvements of the in vitro testing method", D.Ritter, J. Knebel, C. Brodbeck, Pasi Jalava