Education:

Career:

Staff member of Utrecht University, in the Dept. of Veterinary Pharmacology and Toxicology (from 1973). In 1989 this department has allocated its toxicological research activities in the Research Institute of Toxicology (RITOX). After a merger (2001), RITOX now forms the Division of Toxicology at the Institute for Risk Assessment Sciences.

Supervision given to PhD students (17) and to >100 undergraduate students.

The year 1979 spent as a postdoctoral fellow, MRC Toxicology Unit, Carshalton, Surrey, UK.

Head of the research group on biochemical toxicology (1980-1997).

Deputy Director of RITOX: (1993-1998).

Chairman, Board of the GraduateSchool Environmental Chemistry and Toxi­cology (1994-1997).

Seconded (80%) to Association of Universities in the Netherlands (VSNU). Tasks: general research policy of universities; programme manager for the quality assess­ment of research programme (February 1997 - January 2000).

July 2008-present: appointed to the endowed chair “Alternatives to animal testing in toxicological risk assessment” with financial support of the Doerenkamp-Zbinden Foundation.

Present position:

Professor of Toxicology (Doerenkamp-Zbinden Chair on Alternatives to Animal Testing in Toxicological Risk Assessment) located at the Division of Toxicology, IRAS, UtrechtUniversity.

Research and teaching in molecular, biochemical and cellular toxicology, biotransformation and biokinetic modelling.

Director of the Programme for Postdoctoral Education in Toxicology in the Nether­lands (a co-operation of eight universities, located at WageningenUniversity) (since 1 January 2003).

Editor of Toxicology In Vitro.

Editorial Board Member for Alternatives to Laboratory Animals, Human and Experimental Toxicology, ALTEX.

Other previous commitments:

Chairman Working group Toxicology, BION (part of the Dutch research granting organisation NWO). Chairman Steering Committee on Toxicology, NWO. Secretary Section Animal Physiology, BION/SLW-NWO.

Member of review panels for EU-DGXII programmes.

External examiner for PhDs at other Dutch universities and in the UK, Belgium, Ireland, Sweden, Thailand and Australia.

Member of scientific and/or organizing committees for a number of international scientific meetings (the International INVITOX workshops; the Second World Congress on Alternatives and Animal Use in the Life Sciences, 20-24 October 1996, Utrecht, The Netherlands, etc).

Member of the Scientific Advisory Committee for the European Centre for Validation of Alternative Methods (ECVAM), Ispra, Italy (1993-2002).

Member of a number of task forces and expert groups in the field of QSARs, metabolism and biokinetis at the European Centre for the Validation of Alternative Methods (ECVAM), JRC, of the European Commission.

Member of the EUROTOX subcommittees for education and for registration (the ERT).

Member of the Steering Committee, Managing Committee and work package leader for the EU-granted programme “A-Cute-Tox”.

Participant (or chairman) of a number of ECVAM workshops (see bibliography).

Member of the NWO-scientific committee for the Platform for Alternatives to Animal Experimentation (1994-2000).

Chairman of the animal experiments ethical committee of NVI/RIVM (1995-2008).

Member of the Dutch Health Council (1981-2008) and of a number of subcommittees of this Council (Chairman of Committee for Compounds Toxic to Reproduction).

Member of the Dutch board for the authorisation of plant protection agents and biocides (CTGB) (2000-2009).

Member of the ZON Programme committee for Alternatives to Animal Experimentation (2000-2011)

Activities in the field of alternatives to animal testing

Over the years a large number of activities have been performed and initiatives have been taken in the area of the 3Rs.

 Research:

During the year 1979, a Post-doctoral year was spent at the MRC Toxicology Unit of the UK, at that time at Carshalton, Surrey, UK. The research performed was focused on the development and use of hepatocytes primary cultures in the study of toxicity and biotransformation.

After returning to UtrechtUniversity, a leading role was taken in the establishment of a cell- and tissue culture laboratory, focusing on hepatocytes cultures. One activity also included the use of human hepatocytes and also macaque monkey hepatocytes (derived from livers that were a left-over from animals used for vaccine production). These activities allowed the evaluation of the risk of compounds for which animal experiments were less meaningful, (e.g. for peroxisome proliferators).

Another activity was the study of effects on human skin cells, either derived from hair follicle preparations or from hospital material.

From 2005-2011, I was involved in the EU-funded A-Cute-Tox programme, being a member of the steering committee, the management board and the work package leader for kinetics and for the development of the testing strategy.

I am involved in a number of other projects on the integration of toxicodynamic and biokinetic information, aiming at estimating toxic effects in organisms on the basis of in vitro and in silico data and models (e.g. 2 ZonMw projects, the Predict-iv. EG FP7 programme and the CEFIC LRI programme).

For the present research activities please see below: the Chair Group.

 National and international organisational and initiating activities:

I was involved in a group that organised workshops on the use of cell cultures in toxicology, later known as the INVITOX workshops. There have been 17 of these workshops and I was involved in all of them, either as a member of the scientific committee, or as organiser (1996), or as editor of the proceedings. Since 2002 the workshops are under the umbrella of ESTIV, the European Society for Toxicology in Vitro, and are now called ESTIV congresses.  We are now planning the 2014 event, to be held in the Netherlands, and I am a member of the local organising committee.

In the 80s, I have taken the initiative for an in vitro specialty section in the Netherlands Society of Toxicology (NVT), and was its chairman for the first 5 years.

Since the end of the 80s, I became a member of the European Research Group on Alternatives to Toxicity Testing (ERGATT), an informal group of scientists from different European  Countries. The principal objective of ERGATT was to stimulate innovative concepts and new practical approaches in toxicology and toxicity testing, in the belief that greater understanding of mechanisms of toxicity will be the basis of a much-needed improvement in the safety evaluation of chemical compounds, chemical formulations and other agents. ERGATT considers that reduction, refinement and replacement of animal experimentation should be the major objectives in toxicology and toxicity testing, and that in vitro systems represent the most promising replacement alternative approach. The first priority of ERGATT was therefore the development, validation, evaluation and promotion of in vitro methods in toxicology and toxicity testing. From June 1993 I served as ERGATT’s secretary. ERGATT is now hibernating, many of the activities being taken over by e.g. ECVAM (see below).

One of ERGATT’s major achievements is its role in the discussion on the principles and the practical aspects of the validation of alternative methods in research. A number of workshops have been held and the reports had considerable impact. On the basis of this work, the European Commission has established the European Centre for Validation of Alternative Methods (ECVAM) in 1991.

Representing ERGATT, I have been a member of the ECVAM Scientific Advisory Committee (ESAC) from 1993 to 2002.

During this period I was involved in over ten workshops and task forces organized by ECVAM and published in its series of Workshop reports, e.g. on the use of hepatocytes, on biokinetic modelling, validation, metabolism, repeated dose toxicity, the blood-brain barrier, in vitro biokinetics.  

Another important ERGATT initiative was the work on the development of non-animal alternatives for toxicity testing in the form of combining information from different areas of testing. During 1993-1999 I co-ordinated the so-called ECITTS programme (ECITTS = ERGATT-CFN Integrated Toxicity Testing Scheme). In this programme we showed the proof of concept­/principle, that it is possible to estimate toxicity in vivo doses on the basis of integrating knowledge from different domains, viz. QSARs, in vitro toxicity testing and kinetic modelling exercises.

I was a member of the organizing committees for the first two World Congresses on Alternatives and Animal Experimentation (1993: Baltimore; 1996: Utrecht). At the Utrecht conference I also was a member of the local organizing committee. I organized sessions at the next two Congresses (Bologna 1999, New Orleans 2003).

Member of the NWO-scientific committee for the Platform for Alternatives to Animal Experimentation (1994-2000).

Member of the ZON Programme committee for Alternatives to Animal Experimentation (2000-2011), and later of different Advisory Groups for ZONMw.

In 2006 I was co-founder of the Dutch-Belgian Society for In Vitro Methods (INVITROM), for which I had the honour of being its first president, until 2012. Because we attracted many members from outside Belgium and the Netherlands, the name was recently changed to International Society for In Vitro Methods (INVITROM).

I am a member of the ILSI-HESI group RISK21, which group is focusing in the implementation of the NRC-US Report: Toxicity testing in the 21^st century: a vision and a strategy. Recently, ILSI-Europe started a discussion group in implementing innovative strategies in the evaluation of food safety. I was asked to chair this group.

Since 2008 I am a member of TRAIN (Three-Rs Alternatives Initiating Network), a group of professionals involved in the area of animals and alternatives in research.

Member of the Transatlantic Think Tank for Toxicology and in that capacity organiser or participant of a number of Workshops related to the implementation of the aforementioned NRC report. This resulted in a series of publications.

At the request of the ASAT (Assuring Safety without Animal Testing) we organised three workshops, one of which was on the issue of chemicals influencing the thyroid hormone function. The resulting publication is now under discussion at the OECD (nr: 174 in the bibliography, see below).

 Editorial activities

Since 1994 I am the Editor of Toxicology In Vitro. The work also includes the co-editing of meeting proceedings (e.g. INVITOX/ESTIV).

Editorial Board Member for Alternatives to Laboratory Animals, Human and Experimental Toxicology, ALTEX.

 The Doerenkamp-Zbinden Chair

 Starting in July 2008, the Doerenkamp-Zbinden Chair Group was installed, which was placed within the Division of Toxicology at the Institute for Risk Assessment Sciences at UtrechtUniversity. At this Division of Toxicology research is mainly focused on understanding the toxicity of foreign compounds. During the last decades this work is nearly completely carried out on in vitro alternatives. The Chair Group now consists of me as the chair holder, a junior researcher, five PhD students and two technicians.

The vision: The work in the group is focusing on the need to improve the toxicological risk assessment process, thereby acknowledging the need to reduce and replace the use of animal-based models. This requires a shift in the paradigm of toxicity testing from a system that is based on determining apical endpoints (clinical, clinical-chemical and histopathological parameters) in animal studies towards the interpretation of mechanisms of toxicity linked to changes in biological pathways in cellular systems. Using these data as the basis for a quantitative extrapolation from in vitro dose metrics to in vivo exposure scenarios in a transparent, robust and reliable system will then give improved predictions of toxicological risk. When cellular systems derived from human tissues are employed, thus avoiding the problems with interspecies extrapolations, such systems can be better used for predicting human health risks.

The mission: The chair group’ work will focus on the construction of strategies that aim at: development, implementation and acceptance of non-animal methods in toxicological risk assessment. Emphasis is on those parts of the risk assessment where many animals are being used for regulatory purposes, with special attention for diminishing the need to use companion animals.

Ongoing projects:

1. Improving quantitative in vitro-in vivo extrapolation by using alternative dose metrics in vitro
2. The role of facilitated transport by serum protein in in vitro intrinsic clearance
3. The development of in vitro assays to test for sex steroid hormone production interference
4. The development of in vitro models to study the hypothalamus pituitary gonadal (HPG) axis
5. An in vitro model to study the regulation of alkaline phosphatase induction in the liver
6. The effect of the displacement of chemicals from serum constituents on in vitro mixture toxicity
7. Data on in vitro metabolism and mechanisms of action in combination with kinetic modeling: integrating in risk assessment
8. Profiling the toxicity of new drugs: a non animal-based approach integrating toxico-dynamics and biokinetics
9. Factors stimulating or obstructing the acceptance and implementation of the 3rs in the regulatory process.

Teaching:

In the area of teaching, lectures has been given for veterinary, biomedical and biology students, as well as in the Postgraduate Education in Toxicology course on Risk Assessment. We also participated in the teaching programme on alternative methods at the Utrecht University of Applied Sciences (Hogeschool Utrecht).

A special mentioning deserves our involvement in the international TRISK programme for educating Risk Assessment experts. For this programme we developed a special course on “In vitro-in vivo extrapolations of toxicological risk assessment”, given in January 2011 inUtrecht. This was a choice course for the 26 TRISK participants, 5 attended plus 8 other participants.

Together with partners in the Hamner Institutes (RTP, NC, USA) a continuing education course on “In vitro-in vivo-extrapolations” was given at the 50^th SOT meeting in WashingtonDC, USA.).

Other output:

Group members have contributed to congresses (e.g. EUROTOX, SOT, ESTIV, NVT, SETAC) in the form of keynote lectures, oral presentations and poster presentations.

 Awards:

 1. Dr. Bas J. Blaauboer was named 2006 American Industrial Health Council Visiting Scholar at the CIIT Centers for Health Research, Research Triangle Park, NC, USA. This selection specifically acknowledges Dr. Blaauboer’s significant contributions in using quantitative modeling techniques along with in vitro toxicity studies to draw inferences about dose-response characteristics of chemicals in humans.

2. Best publication in ALTEX 2007: Schiffelers M-JWA, Blaauboer BJ, Fentener van Vlissingen JM, Kuil J, Remie R, Thuring JWGM, Vaal MA, Hendriksen CFM (2007). Factors Stimulating or Obstructing the Implementation of the 3Rs in the Regulatory Process. Alternatives to Animal Experimentation 24, 271-278.

3. Best publication on Risk Assessment 2010 of the SOT RA Specialty Section: Louisse, J., De Jong, E., van de Sandt, H., Blaauboer, B.J., Woutersen, R.A., Piersma, A.H., Rietjens, I.M.C.M, Verwei, M., (2010) The use of in vitro toxicity data and physiologically based kinetic modeling to predict dose-response curves for in vivo developmental toxicity of glycol ethers in rat and man. Toxicological Sciences, 118: 470–484.

 Memberships of scientific societies:

- The Dutch Society of Toxicology (NVT)

- The British Toxicology Society (BTS) (since 2008 Fellow of the BTS)

- EUROTOX individual member

- The (US) Society of Toxicology (SOT)

- European Tissue Culture Society  (ETCS) (board member)

- European Society for Toxicology in Vitro (ESTIV) (honorary member)

- Dutch-Belgian Society for In Vitro Methods (INVITROM) (now called  The International Society for In Vitro Methods) (board president from 2006-2012)

Bibliography

I am author or co-author of over 160 publications (peer-reviewed papers or book chapters), reports and editorials.