Report on the SSCT-Swetox workshop: Mechanisms, markers and models - the 3M strategy in risk assessment.
Session 3: In vitro/ in silico analysis for risk assessment
Session 4: 3D and ex vivo tissue models
Session 5: In vitro tests for Human Biomonitoring
The main goal of the EU project ACuteTox (2005-2010), under the title „Optimisation and pre-validation of an in vitro test strategy for predicting human acute toxicity“, was to develop in vitro and in silico methods which could replace animal tests of chemicals. In the project a set of 97 selected reference chemicals were tested in a large amount of in vitro assays, and the results were compared with animal (LD50) and human (blood concentrations measurements in victims of poisoning) data. Therefore one part of the project was creation of a human in vivo database, which is now available at the ACuteTox home page: www.acutetox.eu In the human in vivo database over 2800 human cases are compiled. Tables with sub-lethal, lethal and post-mortem doses at the acute poisoning, with/without time information, are presented. Each case of poisoning is provided by age and sex of a victim, type of poisoning (intentional or unintentional), toxic dose of chemical, time from exposure to sampling (if available), blood concentration of chemical, symptoms and signs of poisoning, as well as the treatment of a poisoned person (if available).Human blood concentration data have been collected from clinical and forensic medical case reports. Among sources of information were the monographs from the MEMO database created by Dr. Björn Ekwall (1940-2000) and his colleagues in the Multicentre Evaluation of In Vitro Cytotoxicity (MEIC) study. Unfortunately, MEMO database is not any more available at the internet , but most of the data are included in the ACuteTox database. Other sources were papers in the international journals, Swedish Poison Informatrion Centre, poison information centers in other countries, several databases, e.g. Poisindex, Thomson Micromedex, HSDB, ChemIDPlus etc.
Availability of human poisoning data was limited by lack of the data concerning of acute exposure (i.e. accidental ingestion, suicidal overdose, etc.) and/or lack in many cases of clinical/forensic monitoring of a victim/patient with reported blood concentration measurments. For these reasons eleven chemicals (of 97) remain without any reported acute poisoning cases.
In the database you can find also references to all cases of poisoning, as well as „summary descriptions“ of all 97 chemicals. In summary descriptions the most important knowledge are summarized, e.g. human toxicity data (acute lehal doses, lowest lehal doses, blood concentrations, etc.), kinetic data, metabolism and excretion, toxicological mechanisms of action, target organs etc.).The authors do hope that human in vivo database will be useful not only for cell toxicologists developing new in vitro assays, but also for medical doctors dealing with human poisoning.
Read more about the human in vivo database in Kolman, A. & Clemedsson, C. (2013) Human in vivo database now on ACuteTox home page. Toxicology in vitro 27, 2350-2351.Ada Kolman firstname.lastname@example.org
Cecilia Clemedson email@example.com
Riksorganisation) is celebrating 55 years
Swedish Animal Friends National Organisation was founded June 8, 1957, in Örebro. Today
it consists of 14 sections located in different cities in Sweden. Three first sections were
established already in 1952 in Malmö, Helsingborg and Göteborg. Later, similar sections were
opened in Stockholm, Uppsala, Karlstad, Borlänge, Karlskrona, Norrtälje and several other
places. In 1957 all these sections were united under the name „Animal Friends National
Organisation”, which is a non-profit body fighting for animal protection and financing its
activities by collecting money from private persons and several companies/organisations.
The main tasks of Animal Friends are described on their home page:
I will not recapitulate here all tasks, but I wish to point out the most important goals which are
common for the Björn Ekvall Memorial Foundation (BEMF) and the Animal Friends:
„to disclose facts about the painful animal experiments and work for a law supporting
alternative research; to be opinion leaders for better animal welfare laws and better animal
The Björn Ekwall Memorial Foundation (BEMF) celebrated in 2011 its 10th Anniversary.
During the past decade, the Björn Ekwall Memorial Award was given to twelve outstanding
scientists who significantly contributed to the field of cell toxicology by development,
implementation and validation of non-animal alternative toxicity tests or by other research
leading to reduction and/or replacement of animal experiments. The BEMF support of
distinguished scientists in the field of in vitro toxicology and alternative methods contributes
to the acceptance of non-animal methods in toxicology.
To be able to hand out the prize every year, the BEMF is dependent on financial support from
companies, organisations and private donors. The Swedish Animal Friends National
Organisation is one of the most significant donators to the BEMF (donations years 2009, 2011
and 2012). Without this generous help we couldn’t be able yearly reward scientists for their
achievements in non-animal toxicological research. Our deep gratitude is going to this
organisation and its members.
Ada Kolman, PhD, assoc. Professor
President of the Björn Ekwall Memorial Foundation
Dr. Tuula Heinonen
Dr. Tuula Heinonen (Ph.D., Adjunct Professor, Director of FICAM) from the School of Medicine, University of Tampere, Tampere, Finland has been selected for the Björn Ekwall Memorial Award 2014 in recognition of her achievements in promotion and implementation of alternative methods by developing human cell based tissue/organ models, as well as by establishing the Finnish Centre for Alternative Methods (FICAM).
Dr. Heinonen defended her PhD thesis in 1982 in the field of toxicology, at the University of Turku; in 1993 she became Adjunct Professor in biochemistry at the University of Helsinki, and in 1984 adjunct professor in toxicology at the University of Turku. Dr. Heinonen has worked as scientist at the Institute of Occupational Health (1979-83) and as toxicologist and in leading research positions in pharmaceutical industry (1983-2007). She has worked in the University of Tampere from 2007 on first in Cell Research Center, and after the establishment of FICAM in 2008 as director of it. Dr. Heinonen and her group will develop human cell based tissue models for biomedical research and toxicology. The focus of Dr. Heinonen is on the development and validation of better methods for prediction of human effects by using human cell based tissue models instead of animal experiments. The first validated model developed by Dr Heinonen’s group is angiogenesis model applicable for both biomedical and toxicological purposes.
The Björn Ekwall Memorial Award 2014 will be handed over at the occasion of the 9th World Congress on Alternatives and Animal Use in Life Sciences, which will be held in Prague, Czech Republic, 24 - 28 August, 2014.
At the meeting, Dr. Heinonen will deliver the Björn Ekwall Memorial Lecture on the 27th of August at 6 p.m. The title of the lecture is: Better science with human-based organ and tissue models.
Professor Per Artursson (M Sci Pharm, PhD) at Uppsala University, Department of Pharmaceutics, receives the 2013 Björn Ekwall Memorial Award in recognition of his scientific achievements in the field of drug design and delivery and for the innovative design and successful implementation of in vitro methods in pharmacy and toxicology.
During the course of this research Dr. Artursson has developed a number of new, scientifically sound and animal saving, in vitro models based on advanced cell and molecular biology. These models have been adopted by the drug industry for prediction of drug absorption in the drug discovery process. Dr Artursson has also been important for the development of in vitro and in silico methods e.g. through his participation in large international studies like MEIC and ACuteTox.The Björn Ekwall Memorial Award 2013 will be handed over at the occasion of the 29th Workshop of SSCT, 25-27 September 2013, Vilvorde Course Center, Charlottenlund, Denmark. At the meeting, Professor Artursson will deliver the Björn Ekwall Memorial Lecture.
Professor Dr. med. Horst Spielmann, has significantly contributed to the field of in vitro toxicology by developing of non-animal tests aiming reduction of animal experiments. The alternative models for toxicity testing developed by H. Spielmann are used world-wide, e.g. use of mouse fibroblasts for the estimation of phototoxicity and chemical toxicity, or human keratinocyte cultures for the test on irritation by chemicals. He also developed the embryonic stem cell test (EST), which is an in vitro embryotoxicity test using two permanent mouse cell lines: 3T3 fibroblasts and embryonic stem cells. These tests have been evaluated statistically and are reproducible. H. Spielmann was a collaborator of Dr. Björn Ekwall during several years. He participated in the MEIC program being head of one of the laboratories at ZEBET that provided data for the MEIC reference chemicals. He was an associate editor of ATLA, which published all papers about MEIC project.
The Björn Ekwall Memorial Award will be handed over at the occasion of the ESTIV 2012 meeting in Lisbon, Portugal, October 16-19, 2012. At the meeting, Professor Spielmann will deliver the Björn Ekwall Memorial Lecture with the title: Today Björn Ekwall would endorse the concept "Toxicology in the 21st Century.
The presentation will be published in ATLA in the beginning of 2013. See the slides from the presentation: Björn Ekwall Memorial Lecture
Dr. Päivi Myllynen (University of Oulu, Finland) has significantly contributed to the field of in vitro toxicology by evaluating placental transfer and metabolism of environmental contaminants and food-borne carcinogens in the human placental perfusion model.
Dr. Myllynen has built her scientific career with great determination and enthusiasm. She completed her Ph.D. thesis in 2003 and acts today as a senior lecturer at the Department of Pharmacology and Toxicology, Institute of Biomedicine, university of Oulu. In addition to the constantly increasing scientific publication activity, she has already started her own research group of younger scientists and doctoral students.
The Björn Ekwall Memorial Award will be handed over at the occasion of the 28thAnnual Workshop of the Scandinavian Society for Cell Toxicology, Tampere, Finland, September 21-23, 2011.
Richard Clothier substantially contributed to the field of in vitro toxicology by developing alternative assays for replacing animal toxicity testing. As an expert in national and international trials, he also significantly contributed to the further advancement of the acceptance of alternative assays for toxicity through his commitment to a number of studies including: FRAME study in 1983-1986, the EC/HO and COLIPA international validation study on alternatives to the Draize eye irritation test, EU/COLIPA international validation study on the in vitro 3T3 NRU test for phototoxicity and others. For many years Dr. Clothier collaborated with Dr. Björn Ekwall on the MEIC programme aimed at the evaluation of ability of in vitro basal cytotoxicity assays to predict human acute systemic toxicity. Dr. Clothier was one of the scientific leaders of the integrated EU sponsored ACuteTox project, and he contributed to its in vitro-in vivo evaluation of the data.
Dr. Clothier was a co-founder (1983) of the FRAME Alternative Laboratory (FAL) at the University of Nottingham, in the Medical School, and was a director of the FAL from 1997 to 2005. Since 2005 he is an Associate Professor at the University of Nottingham. R. Clothier has been a FRAME Trustee since 1983.
London, UK, November 4, 2010
In recognition of her outstanding contribution in the field of in vitro toxicology, promoting implementation of alternative methods for estimation of molecular mechanisms of toxicity Dr. Annalaura Stammati is the recipient of the Björn Ekwall Memorial Award for the year of 2009.
Annalaura Stammati is a research director at the Istituto Superiore di Sanitŕ (ISS), Rome, Italy; and since 2004 she is the director of the Toxicity Mechanisms Unit in the Department of Environment and Primary Prevention. With her team, she significantly contributed to the study of the toxicity of synthetic and natural compounds using different cell lines. In the last years the research was focused on compounds toxic for the gastro-intestinal tract, also investigating their absorption, by using in vitro intestinal models. This non animal-based approach integrating toxicodynamics and biokinetics should lead to the development of a strategy for measuring the real exposure of cells to chemicals and to the prediction of biokinetics in humans. A. Stammati has significantly contributed to the advancement of the acceptance of alternative methods to laboratory animal models through her commitment in national and international expert committees, e.g since 2002 she is a member of the Scientific Advisory Committee of ECVAM (Ispra); she is an expert in OECD Test Guidelines Program (since 1998), and in the Italian delegation in the Committee of Experts on Cosmetic Products (2005-2007). She also funded IPAM, the Italian Platform on Alternative Methods in 2003. During her almost 40 years long career, she was the scientific leader of the Italian unit in many national and international projects and responsible for the education of numerous students and post-graduate students in the field of in vitro toxicology. A. Stammati was one of the closest co-workers of Dr. Björn Ekwall; she participated in the MEIC project from the very beginning, and was a co-author of several MEIC publications.
Lazně Sedmihorky, Czech Republic, September 18, 2009
In recognition of his outstanding contribution in the field of in vitro toxicology, particularly promoting implementation of alternative methods for estimation of neurotoxicity Professor Erik Walum is the recipient of the Björn Ekwall Memorial Award for the year of 2008.
Erik Walum (Biovitrum AB, Sweden) is one of the most significant pioneers in the field of in vitro neurotoxicology. His research has mainly been focused on the influence of toxic substances on neuronal differentiation and degeneration, protection against neurotoxic insult and nerve-glia co-operation. Erik Walum's ideas about mechanism-based toxicity, starting in the early eighties, are still outstanding. Several of the methods that were developed under his guidance have been evaluated, with great success, in international collaborations. Erik Walum has significantly contributed to the advancement of the acceptance of alternative methods to laboratory animal models through his commitment in national and international expert committees such as the Swedish board for laboratory animals (CFN), the European Research Group for Alternative Toxicity Testing (ERGATT) and the European Scientific Advisory Committee (ESAC) of the European Centre for Validation of Alternative Methods (ECVAM). Erik Walum has fostered a large number of students in the field of in vitro toxicology, particularly neurotoxicology, and he supervised 5 students to higher academic degrees at Stockholm university. Together with Björn Ekwall, he founded the Scandinavian Society for Cell Toxicology (SSCT) and he had a fundamental role in the early days of the MEIC project.
Djurönäset, Stockholm, Sweden, September 27, 2008
Dr Rodger Dean Curren
In recognition of his outstanding contribution in the field of in vitro toxicology, particularly promoting the development, optimization, validation and acceptance of alternative (non-animal) testing and research methods, Dr Rodger Dean Curren is the recipient of the Björn Ekwall Memorial Award for the year of 2007.
After he defended his PhD thesis in 1975 in the field of microbiology, Dr. Curren devoted his scientific research to studies of mutagenic and carcinogenic effects of toxic chemicals in several human and animal cell models. He made important contributions in the development and implementation of non-animal ocular and dermal irritation tests. Dr. Curren has contributed significantly to elaboration of criteria for validation of alternative toxicological methods and for their use in the cosmetic and chemical industries. Dr. Curren was also an active collaborator of Dr. Björn Ekwall in the MEIC project.
Dr. Curren is at present time the President of the Institute for In Vitro Sciences, Inc, Gaithersburg, Maryland, the U.S.A., which is an internationally recognized Non-Profit Institute founded to promote the development of alternative methods in toxicity testing. Dr. Curren was 1995-2002 a member of the Pre-validation Task Force for ECVAM (European Center for the Validation of Alternative Methods), a member of the Scientific Advisory Committee on Alternative Toxicological Methods for NIEHS, ICCVAM and NICEATM (2002-2005), and a member of the Advisory Board for EU ACuteTox project (2006). He is a member of the Steering Committee for COLIPA’s 3D skin genotoxicity project, as well as a member of other scientific bodies.
Salzau, Germany, September 21, 2007
In recognition of her enthusiastic work in the MEIC, EDIT and the ACuteTox project, together with her invaluable efforts for the Scandinavian Society for Cell Toxicology, Cecilia Clemedson is the recipient of the Björn Ekwall Memorial Award for the year of 2006.
After receiving her PhD degree at the Department of Neurochemistry and Neurotoxicology at Stockholm University in 1992, Cecilia Clemedson continued her carrier by working on the validation of in vitro cytotoxicity methods for the use in the estimation of acute systemic toxicity. During many years, she was Björn Ekwall’s closest collaborator in the MEIC project. After Björn Ekwall’s death in 2000, she carried on with the EDIT project and the idea to find an alternative strategy to traditional toxicity testing. Cecilia Clemedson is presently the scientific coordinator of the EU-funded ACuteTox project (Optimisation and pre-validation of an in vitro test strategy for predicting human acute toxicity), which is the largest validation project in the world for acute systemic toxicity, comprising 35 partners in 13 countries. Cecilia Clemedson has implemented Björn Ekwall’s and her own ideas very successfully within the framework of her private companies, i.e. her driving force has been - and still is – an excellent contribution to the projects under her guidance.
Grinda, Stockholm, September 8, 2006
Toila, Estonia, October 22, 2005
Professor Hanna Tähti
In recognition of her pioneering work in the field of in vitro neurotoxicology and her enthusiastic efforts for the Scandinavian Society for Cell Toxicology,Professor Hanna Tähti is the recipient of the Björn Ekwall Memorial Award for the year of 2004.
Professor Hanna Tähti started in the eighties to investigate the effects of organic solvents on acetylcholine esterase activity in erythrocytes. By that, she definitely left the rats as the experimental model behind and focused on the development of simple as well as sophisticated in vitro models of the central nervous system and corneal, retinal and blood-brain barriers. She has educated many students and encouraged them to explore new techniques and scientifically demanding matters the field of in vitro neurotoxicology. Professor Hanna Tähti is a devoted member of the Scandinavian Society for Cell Toxicology.
Zegrze, Poland, September 10, 2004
Dr Per Kjellstrand (1941 - 2010)
In recognition of his pioneering work in the field of in vitro screening of complex materials for acute toxicity, Dr Per Kjellstrand is the recipient of the Björn Ekwall Memorial Award for the year of 2003.
Dr. Kjellstrand early realised the necessity to develop rapid and reproducible methods for detection of the toxic activities for large sets of compounds. In the eighties, he introduced cell-based techniques for high throughput toxicity screening into the industrial laboratory, which now have replaced the traditional acute toxicity tests. The world-widely used methods for detection of toxic activity of dialysis fluids and equipment were developed in Dr. Kjellstrand’s department. Dr. Kjellstrand was also one of the first researchers to take part in the MEIC project, which later confirmed the usefulness of simple in vitro methods as alternatives to acute animal toxicity tests.
Murikka, Finland, September 20, 2003
In recognition of her pioneering work in the field of in vitro hepatotoxicity, Dr Maria José Gómez-Lechón is the first recipient of the Björn Ekwall Memorial Award.
Dr. Gómez-Lechón has developed many different hepatic cellular models including primary human hepatocyte cultures, three-dimensional cultures, co-cultures of hepatocytes and non-parenchymal cells and genetically engineered cell lines which express different biotransformation enzymes. On an early stage, she realised the applicability of cultured hepatocytes for toxicity and biotransformation studies and has propagated for their use as alternatives to animal experiments. Dr. Gómez-Lechón was one of the first researchers to take part in the MEIC project (Multicentre Evaluation of In Vitro Cytotoxicity Programme, 1989-1999). By testing the MEIC chemicals in 15 different in vitro test systems, she was the one that contributed the most to the accomplishment of the MEIC project.
Oxford, UK, September 23, 2002