The concept:

t4 was created with the following aims:

•       to analyze current tools and programs and model/forecast the likely outcome with regard to safety and economic burden (cost/benefit analyses)

•       to compare different approaches on an international scale (especially transatlantic) and support harmonization

•       to further the concept of an evidence-based toxicology (EBT) following the role model of evidence-based medicine

•       to develop and assess the conceptual needs to enable the change of approaches (predictive toxicology, integrated testing, systems toxicology, organotypic, and stem cell cultures)

•       to create and maintain information platforms (AltWeb, ALTEX, TestSmart workshops, etc.) to further the paradigm change in toxicology

Alan Goldberg, Center for Alternatives to Animal Testing (CAAT), Johns Hopkins University, Baltimore, USA (2009-2019);

Thomas Hartung, Doerenkamp-Zbinden Chair for Evidence-based Toxicology, CAAT, Johns Hopkins University, Baltimore, USA, and CAAT-Europe, University of Konstanz, Germany;

Marcel Leist, Doerenkamp-Zbinden Chair for in vitro Toxicology and Biomedicine and CAAT-Europe, University of Konstanz, Germany;

Bas Blaauboer, Doerenkamp-Zbinden Chair on Alternatives to Animal Testing in Toxicological Risk Assessment, IRAS, Utrecht University, The Netherlands (2009-2019)

All reviews and reports may be downloaded from the ALTEX website (www.altex-edition.org) and AltWeb (www.altweb.jhsph.edu). Further in depth reviews of all toxicologically-relevant topics are encouraged. The reviews are commissioned by any t4 member. Interested authors are advised to contact a relevant t4 member directly with a review proposal. Publication is subject to a two-step peer review process. Reviews will be published and made available to the public free of charge. Authors are eligible for an honorarium.

t4 workshop reports:

37.  Golden, E., Allen, D., Amberg, A., Anger, L. T., Baker, E., Baran, S. W., Bringezu, F., Clark, M., Duchateau-Nguyen, G., Escher, S. E., Giri, V., Grevot, A., Hartung, T., Li, D., Lotfi, L., Muster, W., Snyder, K., Wange, R., & Steger-Hartmann, T. (2024). Toward implementing virtual control groups in nonclinical safety studies: Workshop report and roadmap to implementation. ALTEX 41, 282–301. doi:10.14573/altex.2310041

36.  Maertens, A., Antignac, E., Benfenati, E., Bloch, D., Fritsche, E., Hoffmann, S., Jaworska, J., Loizou, G., McNally, K., Piechota, P., Roggen, E. L., Teunis, M., & Hartung, T. (2024). The probable future of toxicology - probabilistic risk assessment. ALTEX 41, 273–281. doi:10.14573/altex.2310301

35.  Knight, J., Hartung, T. and Rovida, C. (2023). 4.2 million and counting... The animal toll for REACH systemic toxicity studies.ALTEX 40, 389–407. doi:10.14573/altex.2303201

34.  Krewski, D., Saunders-Hastings, P., Baan, R. A., Barton-Maclaren, T. S., Browne, P., Chiu, W. A., Gwinn, M., Hartung, T., Kraft, A. D., Lam, J., Lewis, R. J., Sanaa, M., Morgan, R. L., Paoli, G., Rhomberg, L., Rooney, A., Sand, S., Schünemann, H. J., Straif, K., Thayer, K. A., & Tsaioun, K. (2022). Development of an evidence-based risk assessment framework. ALTEX 39, 667–693. doi:10.14573/altex.2004041

33.  Cassotta, M. ., Geerts, H. ., Harbom, L., Outeiro, T. F., Pediaditakis, I., Reiner, O., Schildknecht, S., Schwamborn, J. C., Bailey, J., Herrmann, K., & Hogberg, H. T. (2022). The future of Parkinson's disease research: A new paradigm of human specific investigation is necessary... and possible. ALTEX 39, 694–709. doi:10.14573/altex.2203161

32.  Hoffmann, S., Aiassa, E., Angrish, M., Beausoleil, .C. ., Bois, F. Y. ., Ciccolallo, L., Craig, P. S., de Vries, R. B. M. ., Dorne, J. L. C. M. ., Druwe, I. L., Edwards, S. W. ., Eskes, C., Georgiadis, M., Hartung, T. ., Kienzler, A., Kristjansson, E. A. ., Lam, J. ., Martino, L., Meek, B., Morgan, R. L. ., Munoz-Guajardo, I., Noyes, P. D. ., Parmelli, E. ., Piersma, A., Rooney, A., Sena, E., Sullivan, K., Tarazona, J., Terron, A., Thayer, K., Turner, J., Verbeek, J., Verloo, D., Vinken, M., Watford, S., Whaley, P., Wikoff, D., Willett, K., & Tsaioun, K. (2022).Application of evidence-based methods to construct mechanism-driven chemical assessment frameworks. ALTEX 39, 499–518. doi:10.14573/altex.2202141

31.  Knight, J., Rovida, C., Kreiling, R. et al. (2021). Continuing animal tests on cosmetic ingredients for REACH in the EU. ALTEX 38, 653-668. doi:10.14573/altex.2104221

30.  Whaley, P., Blaauboer, B. J., Brozek, J. et al. (2021). Improving the quality of toxicology and environmental health systematic reviews: What journal editors can do. ALTEX 38, 513-522. doi:10.14573/altex.2106111

29.  Rovida, C., Barton-Maclaren, T., Benfenati, E. et al. (2020). Internationalization of read-across as a validated new approach method (NAM) for regulatory toxicology. ALTEX 37, 579-606. doi:10.14573/altex.191218

28.  Marx, U., Akabane, T., Andersson, T. B., et al. (2020) “Biology-inspired microphysiological systems to advance patient benefit and animal welfare in drug development”, ALTEX - Alternatives to animal experimentation, 37(3), pp. 364-394. doi: 10.14573/altex.2001241.

27.  Beilmann, M., Boonen, H., Czich, A., et al. (2019) “Optimizing drug discovery by investigative toxicology: Current and future trends”, ALTEX - Alternatives to animal experimentation, 36(2), pp. 289-313. doi: 10.14573/altex.1808181.

26.  Pamies, D., Bal-Price, A., Chesné, et al. (2018) “Advanced Good Cell Culture Practice for human primary, stem cell-derived and organoid models as well as microphysiological systems”, ALTEX - Alternatives to animal experimentation, 35(3), pp. 353-378. doi: 10.14573/altex.1710081.

25.  Pamies, D., Bal-Price, A., Chesné, et al. (2018) “Advanced Good Cell Culture Practice for human primary, stem cell-derived and organoid models as well as microphysiological systems”, ALTEX - Alternatives to animal experimentation, 35(3), pp. 353-378. doi: 10.14573/altex.1710081.

24.  Myers, D. K., Goldberg, A. M., Poth, A., et al. (2017) “From in vivo to in vitro: The medical device testing paradigm shift”, ALTEX - Alternatives to animal experimentation, 34(4), pp. 479-500. doi: 10.14573/altex.1608081.

23.  Pamies, D., Bal-Price, A., Simeonov, A., et al. (2017) “Good Cell Culture Practice for stem cells and stem-cell-derived models”, ALTEX - Alternatives to animal experimentation, 34(1), pp. 95-132. doi: 10.14573/altex.1607121.

22.  Aschner, M., Ceccatelli, S., Daneshian, M., et al. (2017) “Reference compounds for alternative test methods to indicate developmental neurotoxicity (DNT) potential of chemicals: Example lists and criteria for their selection and use”, ALTEX - Alternatives to animal experimentation, 34(1), pp. 49-74. doi: 10.14573/altex.1604201.

28.  Zhu, H., Bouhifd, M., Donley, E., et al. (2016) “Supporting read-across using biological data”, ALTEX - Alternatives to animal experimentation, 33(2), pp. 167-182. doi: 10.14573/altex.1601252.

20.  Ball, N., Cronin, M. T. D., Shen, J., et al. (2016) “Toward Good Read-Across Practice (GRAP) guidance”, ALTEX - Alternatives to animal experimentation, 33(2), pp. 149-166. doi: 10.14573/altex.1601251.

19.  Rovida, C., Alépée, N., Api, et al. (2015) “Integrated testing strategies (ITS) for safety assessment”, ALTEX - Alternatives to animal experimentation, 32(1), pp. 25-40. doi: 10.14573/altex.1411011.

18.  Gordon, S., Daneshian, M., Bouwstra, J., et al. (2015) “Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology”, ALTEX - Alternatives to animal experimentation, 32(4), pp. 327-378. doi: 10.14573/altex.1510051.

17.  Bouhifd, M., Beger, R., Flynn, T., et al. (2015) “Quality assurance of metabolomics”, ALTEX - Alternatives to animal experimentation, 32(4), pp. 319-326. doi: 10.14573/altex.1509161.

16.  Alépée, N., Bahinski, A., Daneshian, et al. (2014) “State-of-the-art of 3D cultures (organs-on-a-chip) in safety testing and pathophysiology”, ALTEX - Alternatives to animal experimentation, 31(4), pp. 441-477. doi: 10.14573/altex.1406111.

15.  van Vliet, E., Daneshian, M., Beilmann, M., et al. (2014) “Current approaches and future role of high content imaging in safety sciences and drug discovery”, ALTEX - Alternatives to animal experimentation, 31(4), pp. 479-493. doi: 10.14573/altex.1405271.

14.  Leist, M., Hasiwa, N., Rovida, C., et al. (2014) “Consensus report on the future of animal-free systemic toxicity testing”, ALTEX - Alternatives to animal experimentation, 31(3), pp. 341-356. doi: 10.14573/altex.1406091.

13.  Kleensang, A., Maertens, A., Rosenberg, M., et al. (2014) “Pathways of Toxicity”, ALTEX - Alternatives to animal experimentation, 31(1), pp. 53-61. doi: 10.14573/altex.1309261.

12.  Juberg, D. R., Borghoff, S. J., Becker, R. A., et al. (2014) “Lessons learned, challenges, and opportunities: The U.S. Endocrine Disruptor Screening Program”, ALTEX - Alternatives to animal experimentation, 31(1), pp. 63-78. doi: 10.14573/altex.1309171.

11.   Juberg, D.R., Borghoff S.J., Becker R.A., et al. (2014). Lessons learned, challenges, and opportunities: The U.S. Endocrine Disruptor Screening Program. ALTEX 31(1), 63–78.

10.   Kleensang, A., Maertens, A., Rosenberg, M., et al. (2014). Pathways of Toxicity. ALTEX 31(1), 53–61.

9.   Ramirez, T., Daneshian, M., Hennicke Kamp H., et al. (2013). Metabolomics in toxicology and preclinical research. ALTEX 30(2), 209–225.

8.   Parks Saldutti L., Beyer B.K., Breslin W., et al. (2013). In vitro testicular toxicity models: Opportunities for advancement via biomedical engineering techniques. ALTEX 30(3), 353–377.

7.   Ramirez, T., Daneshian, M., Kamp, H., et al. (2013). Metabolomics in toxicology and preclinical research. ALTEX 30, 208-225.

6.   Blaauboer, B. J., Boekelheide, K., Clewell, H. J., et al. (2012). The use of biomarkers of toxicity for integrating in vitro hazard estimates into risk assessment for humans. ALTEX 29, 411-425.

5.   Saldutti, L.P., Beyer, B.K., Breslin, W., et al. In vitro Testicular Toxicity Models: Opportunities for Advancement via Biomedical Engineering Techniques (2011). Baltimore, Maryland, USA on October 26-27 , submitted.

4.   Zurlo, J. , Bayne, K. A., Brown, D. C., et al. (2011). Critical evaluation of the use of dogs in biomedical research and testing. ALTEX 28, 355-359.

3.   Silbergeld, E. K., Contreras, E. Q., Hartung, T., et al. (2011). Nanotoxicology: “The end of the beginning” – Signs on the roadmap to a strategy for assuring the safe application and use of nanomaterials – t4 workshop report. ALTEX 28, 236-241.

2.   Hasiwa, N., Bailey, J., Clausing, P., et al. (2011). Critical evaluation of the use of dogs in biomedical research and testing in Europe. ALTEX 28, 326-340.

1.   Daneshian, M., Akbarsha, A. M., Blaauboer, B., et al. (2011). A framework program for the teaching of alternative methods (replacement, reduction, refinement) to animal experimentation. ALTEX 28, 341-352.

t4 reports:

19.   Ferrario, D., Brustio, R. and Hartung, T. (2014) “Glossary of reference terms for alternative test methods and their validation”, ALTEX - Alternatives to animal experimentation, 31(3), pp. 319-335. doi: 10.14573/altex.1403311.

18.   Daneshian, M., Botana, L.M., Dechraoui Bottein, MY., (2013). A roadmap for hazard monitoring and risk assessment of marine biotoxins on the basis of chemical and biological test systems. ALTEX 30(4), 487–545.

17.   Hasiwa, N., Daneshian, M., Bruegger, P., et al. (2013). Evidence for the detection of non-endotoxin pyrogens by the whole blood monocyte activation test. ALTEX 30(2), 169–208

16.   Basketter, D.A., Clewell, H., Kimber, I., et al. (2012). A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing. ALTEX, 29:3-89.

15.   Ferrario, D and Rabbit, R. R. (2012). Analysis of the proposed EU Regulation concerning biocide products and its opportunities for alternative approaches and a toxicology for the 21st century. ALTEX 29, 157-172.

14.   Basketter, D. A., Clewell, H., Kimber, I., et al. (2012). A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing. ALTEX 29, 3-91.

13.   Rovida, C., Longo, F., and Rabbit, R. R. (2011). How are reproductive toxicity and developmental toxicity addressed in REACH dossiers? ALTEX 28, 273-294.

12.   Hartung, T., Blaauboer, B. J., Bosgra, S., et al. (2011). An expert consortium review of the EC-commissioned report “Alternative (Non-Animal) Methods for Cosmetics Testing: Current Status and Future Prospects – 2010”. ALTEX 28, 183-209.

11.   Boekelheide, K. and Andersen, M. E. (2010). A mechanistic redefinition of adverse effects – a key step in the toxicity testing paradigm shift. ALTEX 27, 243-252.

10.   Dietrich, D. R. (2010). Courage for simplification and imperfection in the 21st century assessment of “Endocrine disruption”. ALTEX 27, 264-278.

9.    Jaworska, J. and Hoffmann, S. (2010). Integrated Testing Strategy (ITS) – Opportunities to better use existing data and guide future testing in toxicology. ALTEX 27, 231-242.

8.    Hartung T. Vergleichende Analyse der überarbeiteten Richtlinie 2010/63/EU für den Schutz von Labortieren mit der abgelösten Richtlinie 86/609/EEC – ein t4 Bericht. ALTEXethik 2010, 2, 103.

7.    Hartung, T. (2010b). Comparative analysis of the revised Directive 2010/63/EU for the protection of laboratory animals with its predecessor 86/609/EEC – a t4 report. ALTEX 27, 285-303.

6.    Hartung, T. (2010a). Evidence-based toxicology – the toolbox of validation for the 21st century? ALTEX 27, 253-263.

5.    Kuegler, P. B., Zimmer, B., Waldmann, T., et al. (2010). Markers of murine embryonic and neural stem cells, neurons and astrocytes: reference points for developmental neurotoxicity testing. ALTEX 27, 17-42.

4.    Hartung T and Rovida C. Chemical regulators have overreached. Nature 2009, 460:1080-1081.

3.    Rovida C. and Hartung T. Neuevaluierung der erforderlichen Tierzahlen und Kosten der in vivo Tests zur Erfüllung der REACH Vorgaben für Chemikalien – ein Bericht des “transatlantic think tank for toxicology (t4)”. ALTEXethik 2009, 1:115.

2.    Rovida, C. and Hartung, T. (2009). Re-evaluation of animal numbers and costs for in vivo tests to accomplish REACH legislation requirements for chemicals - a report by the transatlantic think tank for toxicology (t4). ALTEX 26, 187-208.

1.    Leist, M., Bremer, S., Brundin, P., et al. (2008). The biological and ethical basis of the use of human embryonic stem cells for in vitro test systems or cell therapy. ALTEX 25, 163-190.