Research title: 

3 Rs and Replacement: Research with in vitro models for Risk assessment

Tutor: Prof. Francesca Caloni


Contact details

Prof Francesca Caloni

Department of Veterinary Medicine (DIMEVET)

University of Milan, Via Celoria 10, 20133 Milan, Italy

Tel. +39 02 50317884

e-mail: francesca.caloni@unimi.


State of the art

Research is looking on the one hand to the protection of animals used for scientific purposes (Directive 2010/63 EU) with the application of 3Rs (Reduce, Refine, Replace), and on  the other hand to a predictive interdisciplinary science both for risks linked to the environment and to human and animal health. The project will be focused on the evaluation of in vitro adverse effects  of Contaminants of Emerging Concern (CECs) (OECD, 2012), natural or synthetic, alone or mixture, using in vitro models through the concept of  Integrated Approaches to Testing and Assessment, IATA.




Aims of the project 

The research activity of the project will be focused on the evaluation of the effects of Contaminants of Emerging Concern, CECs, using in vitro models. Bioavailability, mechanism of action, mode of action, metabolism, transport, and toxicity of some CECs, natural or synthetic, alone or in mixture, will be investigated using alternative methods of Replacement with an integrated testing approach. Predictive 3D in vitro models, in vitro co-cultures and species-specific in vitro barrier (i.e. alveolar, dermal, intestinal), through specific endpoints (cytotoxicity, barrier integrity, marker release), will be useful tools for toxicological studies.  Epithelial cells (i.e. alveolar, intestinal) will be cultured on semi-permeable inserts in order to evaluate absorption profile, and the possible involvement of transporters (i.e. PgP, MDR). In vitro testing strategy, based on the use of complementary cell-based assays for the definition of hepatoxicity, neurotoxicity, Endocrine Disruptors (ED) effects (EATS mechanism),will be also applied with an interdisciplinary collaboration.


Recent publications of the tutor in the field 

1T. Coccini, F.Caloni, L.J., Ramirez Cando, U. De Simone Cytotoxicity and proliferative capacity impairment induced on human brain cell cultures after short- and long-term exposure to magnetite nanoparticles. Journal of Applied Toxicology, 2017, 37(3): 361-373. doi: 10.1002/jat.3367

2. M.C.,Perego, L.F.Schutz, F. Caloni, C. Cortinovis, M. Albonico, L.J. Spicer  Evidence for direct effects of glyphosate on ovarian function:  glyphosate influences steroidogenesis and proliferation of bovine granulosa but not theca cells in vitro, 2016, Journal of Applied Toxicology doi: 10.1002/jat.3417

3. F. Pizzo, F. Caloni, N.B. Schreiber, C. Cortinovis, L.J. Spicer In vitro effects of deoxynivalenol and zearalenone major metabolites alone and combined, on cell proliferation, steroid production and gene expression in bovine small-follicle granulosa cells. Toxicon, 2016, 109:70-83, doi: 10.1016/j.toxicon.2015.11.018.

4. S. Gordon, M. Daneshian, J. Bouwstra, F. Caloni, S. Constant, D.E. Davies, G. Dandekar, C.A. Guzman, E. Fabian, E. Haltner, T. Hartung, N. Hasiwa, P. Hayden, H. Kandarova, S. Khare, H.F. Krug, C. Kneuer, M. Leist, G. Lian, U. Marx, M. Metzger, K. Ott, P. Prieto, M.S. Roberts, E.L. Roggen, T. Tralau, C. van den Braak, H. Walles, C.M. Lehr. Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology. ALTERNATIVES TO ANIMAL EXPERIMENTATION ALTEX, 2015, 32(4):327-378. doi: 10.14573/altex.1510051.

5. C. Rovida, N. Alépée, A.M. Api, D.A. Basketter, F. Bois, F. Caloni, E. Corsini, M. Daneshian, C. Eskes, J. Ezendam, H. Fuchs, P. Hayden, C. Hegele-Hartung, S. Hoffmann, B. Hubesch, M.N. Jacobs, J. Jaworska, A. Kleensang, N. Kleinstreuer, J. Lalko, R. Landsiedel, F. Lebreux, T. Luechtefeld, M. Locatelli, A. Mehling, A. Natsch, J.W. Pitchford, D. Prater, P. Prieto, A. Schepky, G. Schuurmann, L. Smirnova, C. Toole, E. van Vlie, D. Weisensee, T. Hartung Integrated Testing Strategies (ITS) for Safety Assessment. ALTERNATIVES TO ANIMAL EXPERIMENTATION ALTEX, 2015, 32(1): 25-40. doi: