Publications

Gerlowski, L.E. & Jain, R.K. (1983). Physiologically based pharmacokinetic modeling: principles and applications. Journal of Pharmaceutical Sciences 72, 1103-1127.

Nestorov, I. (2003). Whole body pharmacokinetic models. Clinical Pharmacokinetics 42, 883-908.

Rowland, M., Balant, L. & Peck, C. (2004). Physiologically based pharmacokinetics in drug development and regulatory science: A workshop report. AAPS PharmSci 6, 6-10.

Price, P.S., Conolly, R.B., Chaisson, C.F., Gross, E.A., Young, J.S., Mathis, E.T. & Tedder, D.T. (2003). Modeling inter-individual variation in physiological factors used in PBPK models of humans. Critical Reviews in Toxicology 33, 469-503.

Fiserova-Bergerova, V. (1995). Extrapolation of physiological parameters for physiologically based simulation models. Toxicology Letters 79, 77-86.

Blaauboer, B.J., Bayliss, M.K., Castell, J.V., Evelo, C.T.A., Frazier, J.M., Groen, K., Gülden, M., Guillouzo, A., Hissink, A.M., Houston, J.B., Johanson, G., de Jongh, J., Kedderis, G.L., Reinhardt, C.A., van de Sandt, J.J. & Semino, G. (1996). The use of biokinetics and in vitro methods in toxicological risk evaluation. The report and recommendations of ECVAM Workshop 15. ATLA 24, 473-497.

Blaauboer, B.J. (2002). The necessity of biokinetic information in the interpretation of in vitro toxicity data. ATLA 30 Suppl. 2, 85-91.

Boobis, A., Gundert-Remy, U., Kremers, P., Macheras, P. & Pelkonen, O. (2002). In silico prediction of ADME and pharmacokinetics. Report of an expert meeting organised by COST B15. European Journal of Pharmaceutical Sciences 17, 183-193.

De Jongh, J., Nordin-Andersson, M., Ploeger, B. & Forsby, A. (1999). Estimation of systemic toxicity of acrylamide by integration of in vitro toxicity data with kinetic simulations. Toxicology & Applied Pharmacology 158, 261-268.

Gubbels-van Hal, W.M., Blaauboer, B.J., Barentsen, H.M., Hoitink, M.A., Meerts, I.A. & van der Hoeven, J.C. (2005). An alternative approach for the safety evaluation of new and existing chemicals, an exercise in integrated testing. Regulatory Toxicology & Pharmacology 42, 284-295.

Blaauboer, B.J. (2003). The integration of data on physico-chemical properties, in vitro-derived toxicity data and physiologically based kinetic and dynamic as modelling a tool in hazard and risk assessment. A commentary. Toxicology Letters 138, 161-171.

Blaauboer, B.J. (2003). Biokinetic and toxicodynamic modelling and its role in toxicological research and risk assessment. ATLA 31, 277-281.

Verwei, M., van Burgsteden, J.A., Krul, C.A.M., van de Sandt, J.J.M. & Freidig, A.P. (2006). Prediction of in vivo embryotoxic effect levels with a combination of in vitro studies and PBPK modelling. Toxicology Letters 165, 79-87.

Haddad, S., Beliveau, M., Tardif, R. & Krishnan, K. (2001). A PBPK modeling-based approach to account for interactions in the health risk assessment of chemical mixtures. Toxicological Sciences 63, 125-131.

Jones, H.M., Parrott, N., Jorga, K. & Lavé, T. (2006). A novel strategy for physiologically based predictions of human pharmacokinetics. Clinical Pharmacokinetics 45, 511-542.

Nestorov, I.A., Aarons, L.J., Arundel, P.A. & Rowland, M. (1998). Lumping of whole-body physiologically based pharmacokinetic models. Journal of Pharmacokinetics & Biopharmaceutics 26, 21-46.

Rostami-Hodjegan, A. & Tucker, G.T. (2007). Simulation and prediction of in vivo drug metabolism in human populations from in vitro data. Nature Reviews Drug Discovery 6, 140-148.

Tucker, G.T., Houston, J.B., & Huang, S.M. (2001). Optimizing drug development: strategies to assess drug metabolism/transporter interaction potential - towards a consensus. British Journal of Clinical Pharmacology 52, 107-117.

Barton, H.A., Chiu, W.A., Setzer, R.W., Andersen, M.E., Bailer, A.J., Bois, F.Y., DeWoskin, R.S., Hays, S., Johanson, G., Jones, N., Loizou, G., MacPhail, R.C., Portier, C.J., Spendiff, M. & Tan, Y-M. (2007). Characterizing uncertainty and variability in physiologically based pharmacokinetic (PBPK) models: State of the science and needs for research and implementation. Toxicological Sciences 99, 395-402.

International Workshop on the Development of Good Modelling Practice for PBPK Models. Mediterranean Agronomic Institute of Chania, Crete, Greece. April 26-28, 2007. Available at: http://www.hsl.gov.uk/ news/news_pbpk.htm (Accessed 11.09.07).

COST Action B25 (2006). Physiologically-based Pharmaco-Toxicokinetics and Dynamics. Strasbourg, France: COST-ESF. Available at: http://www.cost.esf.org/index.php?id=383 (Accessed 11.09.07).

Pfaller, W., Balls, M., Clothier, R.D., Coecke, S., Dierickx, P., Ekwall, B., Hanley, B.A., Hartung, T., Prieto, P., Ryan, M.P., Schmuck, G., Sladowski, D., Vericat, J-A., Wendel, A., Wolf, A. & Zimmer, J. (2001). Novel advanced in vitro methods for long-term toxicity testing. The report and recommendations of ECVAM Workshop 45. ATLA 29, 393-426.

Clark, L.H., Setzer, R.W. & Barton, H.A. (2004). Framework for evaluation of physiologically based pharmacokinetic models for use in safety or risk assessment. Risk Analysis 24, 1697-1718.

US Environmental Protection Agency (2006). Approaches for the Application of Physiologically Based Pharmacokinetic (PBPK) Models and Supporting Data in Risk Assessment, EPA/600/R-05/043F, 123pp. Washington, DC, USA: EPA National Center for Environmental Assessment. Available at: http:// cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=157668 (Accessed 11.09.07).

Crespi, C.L. (1995). Xenobiotic-metabolizing human cells as tools for pharmacological and toxicological research. Advances in Drug Research 26, 179­235.

Phillips, I.R. & Shephard, E.A., eds (1998). Cytochrome P450 Protocols. Methods in Molecular Biology 107, 439­468.

Castell, J.V. & Gómez-Lechón, M.J., eds (1997). In vitro Methods in Pharmaceutical Research. 467pp. London, UK: Academic Press.

Plant, N. (2003). Strategies for using in vitro screens in drug metabolism. Drug Discovery Today 9, 328­336.

Ekins, S. (2000). Present and future in vitro approaches for drug metabolism. Journal of Pharmacological and Toxicological Methods 44, 313­324.

Kim, R.B. (2002). Transporters and xenobiotic disposition. Toxicology 181­182, 291­297.

Bailey, M.J. & Dickinson, R.G. (2003). Acyl glucuronide reactivity in perspective: biological consequences. Chemico-Biological Interaction 145, 117­137.

Anders, M.W. (2004). Glutathione-dependent bioactivation of haloalkanes and haloalkenes. Drug Metabolism Reviews 36, 583­594.

Banoglu, E. (2000). Current status of the cytosolic sulfotransferases in the metabolic activation of promutagens and procarcinogens. Current Drug Metabolism 1, 1­30.

Morisseau, C. & Hammock, B.D. (2004). Epoxide hydrolases: mechanisms, inhibitor designs and biological roles. Annual Reviews of Pharmacology and Toxicology 45, 311­333.

Hotchkiss, S.A.M. (1992). Skin as a xenobiotic metabolizing organ. In Progress in Drug Metabolism, Vol. 13 (ed. G.G. Gibson), pp. 217­262. London, UK: Taylor & Francis.

Howes, D., Guy, R., Hadgraft, J., Heylings, J., Hoeck, U., Kemper, F., Maibach, H., Marty, J-P., Merk, H., Parra, J., Rekkas, D., Rondelli, I., Schaefer, H., Täuber, U. & Verbiese, N. (1996). Methods for assessing percutaneous absorption. The report and recommendations of ECVAM workshop 13. ATLA 24, 81­106.

Combes, R.D. (1992). The in vivo relevance of in vitro genotoxicity assays incorporating enzyme activation systems. In Progress in Drug Metabolism, Vol. 13 (ed. G.G. Gibson), pp. 295­321. London, UK: Taylor & Francis.

Ding, X. & KIaminsky, L.S. (2003). Human extrahepatic cytochromes P450: function in xenobiotic metabolism and tissue toxicity in the respiratory and gastrointestinal tracts. Annual Reviews of Pharmacology and Toxicology 43, 149­173.

Pelkonen, O. & Raunio, H. (1997). Metabolic activation of toxins: tissue-specific expression and metabolism in target organs. Environmental Health Perspectives 105, 767­774.

Evans, W.E. & Relling, M.V. (1999). Pharmacogenomics: translating functional genomics into rational therapeutics. Science, New York 286, 487­491.

Kalow, W. & Tyndale, R.F. (1992). Debrisoquine/ sparteine monoxygenase and other P450s in the brain. In Pharmacogenetics of Drug Metabolism (ed. W. Kalow), pp. 649­656. New York, NY, USA: Pergamon Press.

Strazielle, N., Khuth, S.T. & Ghersi-Egea, J.F. (2004). Detoxification systems, passive and specific transport for drugs at the blood-CSF barrier in normal and pathological situations. Advanced Drug Delivery Reviews 56, 1717­1740.

Henderson, C.J. & Wolf, C.R. (2003). Transgenic analysis of human drug-metabolizing enzymes: preclinical drug development and toxicology. Molecular Interventions 3, 331­343.

Bigger, C.A.H., Tomaszewski, J.E., Dipple, A. & Lake, R.S. (1980). Limitations of metabolic activation systems used with in vitro tests for carcinogens. Science, New York 209, 503­505.

Pacifici, G.M. & Pelkonen, O., eds (2001). Interindividual Variability in Human Drug Metabolism, pp. 358­394. London, UK: Taylor & Francis.

Pelkonen, O., Mäenpää, J., Taavitsainen, P., Rautio, A. & Raunio, H. (1998). Inhibition and induction of human cytochrome P450 (CYP) enzymes. Xenobiotica 28, 1203­1253.

Ingelman-Sundberg, M. (2004). Human drug metabolising cytochrome P450 enzymes: properties and polymorphisms. Naunyn-Schmiedeberg's Archives of Pharmacology 369, 89­104.

Rendic, S. (2002). Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metabolism Reviews 34, 83­448.

Miller, M.S., Juchau M.R., Guengerich, F.P., Nebert, D.W. & Raucy, J.L. (1996) Drug metabolic enzymes in developmental toxicology. Fundamental and Applied Toxicology 34, 165­176.

Morgan, E.T. (2001). Regulation of cytochrome P450 by inflammatory mediators. Drug Metabolism and Disposition 29, 207­212.

Baillie, T.A., Cayen, M.N., Fouda, H., Gerson, R.J., Green, J.D., Grossman, S.J., Klunk, L.J., Le Blanc, B., Perkins D.G. & Shipley L.A. (2002). Contemporary issues in toxicology. Toxicology and Applied Pharmacology 182, 188­196.

Williams, D.P. & Park, B.K. (2003). Idiosyncratic toxicity: the role of toxicophores and bioactivation. Drug Discovery Today 8, 1044­1050.

Lin, J.H. & Lu, A.Y.H. (1997). Role of pharmacokinetics and metabolism in drug discovery and development. Pharmacological Reviews 49, 403­449.

Leahy, D.E., Duncan, R., Ahr, H.J., Bayliss, M.K., de Boer, A.G., Darvas, F., Fentem, J.H., Fry, J.R., Hopkins, R., Houston, J.B., Karlsson, J., Kedderis, G.L., Pratten, M.K., Prieto, P., Smith, D.A. & Straughan, D.W. (1997). Pharmacokinetics in early drug research. The report and recommendations of ECVAM Workshop 22. ATLA 25, 17­31.

Van de Waterbeemd, H. & Gifford, E. (2003). ADMET in silico modelling: towards prediction paradise? Nature Reviews -- Drug Discovery 2, 192­204.

Worth, A.P. & Balls, M., eds (2002). Alternative (non-animal) methods for chemicals testing: current status and future prospects. A report prepared by ECVAM and the ECVAM Working Group on Chemicals. ATLA 30, Suppl. 1, 1­125.

De Silva, O., Basketter, D.A., Barratt. M.D., Corsini, E., Cronin, M.T.D., Das, P.K., Degwert, J., Enk, A., Garrigue, J.L., Hauser, C., Kimber, I., Lepoittevin, J-P., Peguet, J. & Ponec, M. (1995). Alternative methods for skin sensitisation testing: the report and recommendations of ECVAM workshop 19. ATLA 24, 683­705.

Kimber, I. (2000). Skin sensitisation: immunological mechanisms and novel approaches to predictive testing. In Progress in the Reduction, Refinement and Replacement of Animal Experimentation (ed. M. Balls, A-M. van Zeller & M.E. Halder), pp. 613­622. Amsterdam, The Netherlands: Elsevier.

Casati, S., Aeby, P., Basketter, D.A., Cavani, A., Gennari, A., Gerberick, G.F., Griem., P., Hartung, T., Kimber, I., Lepoittevin, J-P., Meade, B.J., Pallardy, M., Rougier, N., Rousset, F., Rubinstenn, G., Sallusto, F., Verheyen, G.R. & Zuang, V. (2005). Dendritic cells as a tool for the predictive identification of skin sensitisation hazard. The report and recommendations of ECVAM Workshop 51. ATLA 33, 47­62.

Coecke, S., Eskes, C., Gartlon, J., Kinsner, A., Price, A., van Vliet, E., Prieto, P., Boveri, M., Pellizzer, C., Wendel, A. & Hartung, T. (2005). The value of alternative testing for neurotoxicity in the context of regulatory needs. Environmental Toxicology and Pharmacology, in press.

Park, B.K., Kitteringham, N.R., Maggs, J.L., Pirmohamed, M. & Williams, D.P. (2005). The role of metabolic activation in drug-induced hepatotoxicity. Annual Reviews of Pharmacology and Toxicology 45, 177­202.

Zucco, F., De Angelis, I., Testai, E. & Stammati, A. (2003). Toxicology investigations with cell culture systems: 20 years after. Toxicology in Vitro 18, 15­163.

Lee, Y.C., Shlyankevich, M., Jeong, H.K., Douglas, J.S. & Surh, Y.J., (1995). Bioactivation of 5-hydroxylmethyl-2-furaldehyde to an electrophilic and mutagenic allylic sulfuric acid ester. Biochemical and Biophysical Research Communications 209, 996­1002.

Bogni, A., Monshouwer, M., Moscone, A., Hidestrand, M., Ingelman-Sundberg, M., Hartung, T. & Coecke, S. (2005). Substrate specific metabolism by polymorphic cytochrome P450 2D6 alleles. Toxicology in Vitro 19, 621­629.

Coecke, S., Bogni, A., Langezaal, I., Worth, A., Hartung, T. & Monshouwer, M. (2001). The use of genetically engineered cells for assessing CYP2D6related polymorphic effects. Toxicology in Vitro 15, 553­556.

Glatt, H., Gemperlein, I., Turchi, G., Heinritz, H., Doehmer, J. & Oesch, F. (1988). Search for cell culture systems with diverse xenobiotic-metabolizing activities and their use in toxicological studies. Molecular Toxicology 1, 313­334.

Freshney, I.R. (2000). Culture of Animal Cells: A Manual of Basic Techniques, 4th edn, 608pp. Chichester, UK: John Wiley & Sons.

Clarke, S.E. (1998). In vitro assessment of human cytochrome P450. Xenobiotica 28, 1167­1202.

Guengerich, F.P. (2000). Metabolism of chemical carcinogens. Carcinogenesis 21, 345­351.

Freyberger, A. & Scholz, G. (2004). Endocrine toxicology -- contributions of in vitro methods to the 3R concept. ALTEX 21, 20­27.

Anon. (2005). Guidance for Industry Safety Testing of Drug Metabolites. US Food and Drug Administration. Rockville, MD, USA: FDA. Website http://www.fda.gov/cder/guidance/6366dft.htm#_ Toc101751578 (Accessed 30.09.05).

Clark, A.M. & Hufford, C.D. (1991). The use of microorganisms for the study of drug metabolism: an update. Medicinal Research Reviews 11, 473­501.

Pelkonen, O. & Raunio, H. (2005). In vitro screening of drug metabolism during drug development: Can we trust the predictions? Expert Opinion on Drug Metabolism & Toxicology 1, 49­60.

Elliott, B.M., Combes, R.D., Elcombe, C., Gatehouse, D., Gibson, G.G. & Wolf, C.R. (1992). Alternatives to Aroclor 1254 for genotoxicity assays -- Report of the UKEMS Working Party on Enzyme Inducers. Mutagenesis 7, 175­177.

García Franco, S., Domínguez, G. & Pico, J.C. (1999). Alternatives in the induction and preparation of Phenobarbital/naphthoflavone-induced S9 and their activation profiles. Carcinogenesis 14, 323­326.

Judson, P.N., Marchant, C.A. & Vessey, J.D. (2003). Using argumentation for absolute reasoning about the potential toxicity of chemicals. Journal of Chemical Information and Computer Sciences 43, 1364­1370.

Cervenková, K., Belejová, M., Veselý, J., Chmela, Z., Rypka, M., Ulrichová, J., Modrianský, M. & Maurel, P. (2001). Cell suspensions, cell cultures, and tissue slices important metabolic in vitro systems. Biomedical Papers 145, 57­60.

Coecke, S., Rogiers, V., Bayliss, M., Castell, J., Doehmer, J., Fabre, G., Fry, J., Kern, A. & Westmoreland, C. (1999). The use of long-term hepatocyte cultures for detecting induction of drug metabolising enzymes: the current status. ECVAM Hepatocytes and Metabolically Competent Systems Task Force report 1. ATLA 27, 579­638.

Aninat, C., Piton, A., Glaise, D., Le Charpentier, T., Langouët, S., Morel, F., Guguen-Guillouzo, C. & Guillouzo, A. (2006). Expression of cytochromes P450, conjugating enzymes and nuclear receptors in human hepatoma Hepa RG cells. Drug Metabolism and Disposition 34, 75­83.

Glatt, H., Gemperlein, I., Setiabudi, F., Platt, K.L. & Oesch, F. (1990). Expression of xenobiotic-metabolizing enzymes in propagatable cell cultures and induction of micronuclei by 13 compounds. Mutagenesis 5, 241­249.

Urani, C., Doldi, M., Crippa, S. & Camatini, M. (1998). Human-derived cell lines to study xenobiotic metabolism. Chemosphere 37, 2785­2795.

Gómez-Lechón, M.J., Donato, T., Jover, R., Rodriguez, C., Ponsoda, X., Glaise, D., Castell, J.V. & Gugen-Guillouzo, C. (2001). Expression and induction of a large set of drug-metabolizing enzymes by the highly differentiated human hepatoma cell line BC2. European Journal of Biochemistry 268, 1448­1459.

Fabre, N., Arrivet, E., Trancard, J., Bichet, N., Roome, N.O., Prenez, A. & Vericat, J-A. (2003). A new hepatoma cell line for toxicity testing at repeated doses. Cell Biology and Toxicology 19, 71­82.

Ringel, M., von Mach, M.A., Santos, R., Feilen, P.J., Brulport, M., Hermes, M., Bauer, A.W., Schormann, W., Tanner, B., Schon, M.R., Oesch, F. & Hengstler, J.G. (2005). Hepatocytes cultured in alginated microspheres: an optimized technique to study enzyme induction. Toxicology 206, 153­167.

Choi, S.H., Nishikawa, M., Sakoda, A. & Sakai, Y. (2004). Feasibility of a simple double-layered coculture system incorporating metabolic processes of the intestine and live tissue: application the analysis of benzo[a]pyrene toxicity. Toxicology in Vitro 18, 393­402.

Bruinink, A., Yu, D. & Maier, P. (2002). Short-term assay for the identification of neurotoxic compounds and their liver derived stable metabolites. Toxicology in Vitro 16, 717­724.

Coecke, S., Eskes, C., Gartlon, J., Vliet, E.V., Kinsner, A., Bogni, A., Raimondo, L., Parissis, N. & Langezaal, I. (2002). Metabolism and neurotoxicity: the significance of genetically engineered cell lines and new three-dimensional cell cultures. ATLA 30, Suppl. 2, 115­118.

Bremer, S., Pellizzer, C., Coecke, S., Paparella, M. & Catalani, P. (2002). Detection of the embryotoxic potential of cyclophosphamide by using a combined system of metabolic competent cells and embryonic stem cells. ATLA 30, 77­85.

Combes, R., Balls, M., Bansil, L., Barratt, M., Bell, D., Botham, P., Broadhead, C., Clothier, R., George, E., Fentem, J., Jackson, M., Indans, I., Laozou, G., Navaratnam, V., Pentreath, V., Phillips, B., Stemplewski, H. & Stewart, J. (2002). An assessment of progress in the use of alternatives in toxicity testing since the publication of the report of the Second FRAME Toxicity Committee (1991). ATLA 30, 365­406.

Bach, P.H., Vickers, A.E.M. & Fisher, R. (1996). The use of tissue slices for pharmacotoxicology studies. The report and recommendations of ECVAM workshop 20. ATLA 24, 893­923.

Hawksworth, G.M., Bach, P.H., Nagelkerke, J.F., Dekant, W., Diezi, J.E., Harpur, E., Lock, E.A., MacDonald, C., Morin, J-P., Pfaller, W., Rutten, A.A.J.J.L., Ryan, M.P., Toutain, H.J. & Trevisan, A. (1995). Nephrotoxicity testing in vitro. The report and recommendations of ECVAM workshop 10. ATLA 23, 713­727.

Gebhardt, R., Lippert, C., Schneider, A. & Doehmer, J. (1999). Improved determination of drug metabolism by perifusion of recombinant V79 cells carrying human CYP3A4. Toxicology in Vitro 13, 639­643.

Pfiefer, A.M.A., Cole, K.E., Smoot, D.T., Weston, A., Groopman, J.D., Shields, P.G., Vignaud, J-M., Juillerat, M., Lipsky, M.M., Trump, B., Lechner, J.F. & Harris, C.C. (1993). Simian virus 40 large tumor antigen-immortalized normal human liver epithelial cells express hepatocyte characteristics and metabolise chemical carcinogens. Proceedings of the National Academy of Sciences of the USA 90, 5123­5127.

Wiebel, F.J., Andersson, T.B., Casciano, D.A., Dickins, M., Fischer, V., Glatt, H., Horbach, J., Langenbach, R.J., Luyten, W., Turchi, G. & Vandewalle, A. (1997). Genetically engineered cell lines: characterisation and applications in toxicity testing. ATLA 25, 625­639.

Doehmer, J., Krebsfänger, N., Schober, W., Luch, A., Buters, J.T.M., Jacob, J., Seidel, A., Mürdter, T., Zanger, U.M. & Eichelbaum, M. (2000). Building a biotechnology platform for metabolism studies in pharmacology and toxicology. In Progress in the Reduction, Refinement and Replacement of Animal Experimentation (ed. M. Balls, A-M. van Zeller & M.E. Halder), pp. 139­146. Amsterdam, The Netherlands: Elsevier.

Macé, K., Offord, E.A. & Pfeifer, A.M.A. (1997). Drug metabolism and carcinogen activation studies with human genetically engineered cells. In In Vitro Methods in Pharmaceutical Research (ed. J.V. Castell & M.J. Gómez-Lechón), pp. 433­456. London, UK: Academic Press.

Gasser, R., Funk, C., Matzinger, P., Klemisch, W. & Viger-Chougnet, A. (1999). Use of transgenic cell lines in mechanistic studies of drug metabolism. Toxicology in Vitro 13, 625­632.

Crespi, C. (1995). Use of genetically engineered cells for genotoxicity testing. In Environmental Mutagenesis (ed. D.H. Phillips & S. Venitt), pp. 233­260. Oxford, UK: Bios Scientific Publishers. Crespi, C. & Penman, B. (1997). Use of cDNAexpressed human cytochrome P450 enzymes to study potential drug­drug interactions. Advances in Pharmacology 43, 171­188.

Crespi, C. & Penman, B. (1998). Use of human engineered cells in toxicology. Human and Experimental Toxicology 17, 485.

Crespi, C., Miller, V. & Penman, B. (1997). Microtiter plate assays for inhibition of human, drugmetabolising cytochromes P450. Analytical Biochemistry 248, 188­190.

Coecke, S., Catalini, P., Bull, S., Langezaal, I., Bogni, A., Bremer, S. & Balls, M. (2000). The integrated use of a genetically engineered cell line panel harbouring drug metabolizing enzymes to detect metabolism related problem compounds. In Progress in the Reduction, Refinement and Replacement of Animal Experimentation (ed. M. Balls, A-M. van Zeller & M.E. Halder), pp. 147­157. Amsterdam, The Netherlands: Elsevier.

Yoshitomi, S., Ikemoto, K., Takahashi, J., Miki, H., Namba, M. & Asahi, S. (2001). Establishment of the transformants expressing human cytochrome P450 subtypes in HepG2, and their applications on drug metabolism and toxicology. Toxicology in Vitro 15, 245­256.

Jover, R., Bort, R., Gómez-Lechón, M.J. & Castell, J.V. (1998). Re-expression of C/EBP induces CYP26, CYP2C9 and CYP2D6 genes in HepG2 cells. FEBS Letters 431, 227­230.

Bull, S., Langezaal, I., Clothier, R. & Coecke, S. (2001). A genetically engineered cell-based system for detecting metabolism-mediated toxicity. ATLA 29, 703­716. Gülden, M. & Seibert, H. (1997). Influence of protein binding and lipophilicity on the distribution of chemical compounds in in vitro systems. Toxicology in Vitro 11, 479­483.

Gómez-Lechón, M.J., Donato, T., Ponsoda, X. & Castell, J.V. (2003). Human hepatic cell cultures: in vitro and in vivo drug metabolism. ATLA 31, 257­266.

Yueh, M-F., Kawahara, M. & Raucy, J. (2005). Cellbased high-throughput bioassays to assess induction and inhibition of CYP1A enzymes. Toxicology in Vitro 19, 275­287.

Abourashad, E.A., Clark, A.M. & Hufford, C.D. (1999). Microbial models of mammalian metabolism of xenobiotics: an updated review. Current Medicinal Chemistry 6, 359­374. Cha, C-J., Doerge, D.R. & Cerniglia, C.E. (2001). Biotransformation of malachite green by the fungus Cunninghamella elegans. Applied Environmental Microbiology 67, 4358­4360.

Parry, J. (1985). A summary of the effects of benzidine, 4,4´-diaminoterphenyl, 4-dimethylaminoazobenzene and 4-cyanodimethylaniline as observed by the yeast group in the Second UKEMS Collaborative Study. In Comparative Genetic Toxicology -- the Second UKEMS Collaborative Trial (ed. J.M. Parry & C.F. Arlett.), pp. 267­277. Basingstoke, UK: Macmillan.

Masimirembwa, C.M., Otter, C., Berg, M., Jonsson, M., Leidvik, B., Jonsson, E., Johansson, T., Backman, A., Edlund, A. & Andersson, T.B. (1999). Heterologous expression and kinetic characterization of human cytochromes P-450: validation of a pharmaceutical tool for drug metabolism research. Drug Metabolism Disposition 27, 1117­1122.

Combes, R., Barratt, M. & Balls, M. (2003). An overall strategy for the testing of chemicals for human hazard and risk assessment under the EU REACH system. ATLA 31, 7­19.

Payne, M.P. (2004). Computer-Based Methods for the Prediction of Chemical Metabolism and Biotrnasformation Within Biological Organisms. In Predicting Toxicity and Fate (eds M.T.D. Cronin & D.J. Livingstone) pp. 205­227. Boca Raton, FL, USA: CRC Press.

Soffers, A.E.M.F., Boersma, M.G., Vaes, W.H.J., Vervoort, J., Tyrakowska, B., Hermens, J.L.M. & Rietjens, I.M.C.M. (2001). Computer-modelingbased QSARs for analyzing experimental data on biotransformation and toxicity. Toxicology in Vitro 15, 539­551.

Pelkonen, O., Turpeinen., M., Uusitalo, J., Rautio, A. & Raunio, H. (2005). Prediction of drug metabolism and interactions on the basis of in vitro investigations. Basic and Clinical Pharmacology & Toxicology 96, 167­175.

Raunio, H., Taavitsainen, P., Honkakoksi, P., Juvonen, R. & Pelkonene, O. (2004). In vitro methods in the prediction of kinetics of drugs: focus on drug metabolism. ATLA 32, 425­430.

De Graaf, C., Vermeulen, N.P.E. & Feenstra, K.A. (2005). Cytochrome P450 in silico: an integrative modeling approach. Journal of Medicinal Chemistry 48, 2725­2755.

Vedani, A. (2005). Computer-based quantification of (adverse) effects triggered by drugs and chemicals. 3R-Info-Bulletin 29, 2pp.

Lewis, D.F.V., Lake, B.G., Dickins, M. & Goldfarb, P.S. (2003). Homology modelling of CYP2A6 based on the CYP2C5 crystallographic template: enzyme­ substrate interactions and QSARs for binding affinity and inhibition. Toxicology in Vitro 17, 179­190.

Lewis, D.F.V., Lake, B.G. & Bird, M.G. (2005). Molecular modelling of human microsomal epoxide hydrolase (EH) by homology with a fungal (Aspergillus niger) EH crystal structure of 1.8 Å resolution: structure-activity relationships in epoxides inhibiting EH activity. Toxicology in Vitro 18, 517­522.

Lewis, D.F.V. (2004). Quantitative structure-activity relationships (QSARs) for substrates of human cytochromes P450 CYP2 family enzymes. Toxicology in Vitro 18, 89­97.

Dearden, J.C., Barratt, M.D., Benigni, R., Bristol, D.W., Combes, R.D., Cronin, M.T.D., Judson, P.M., Payne, M.P., Richard, A.M., Tichy, M., Worth, A.P. & Yourick, J.J. (1997). The development and validation of expert systems for predicting toxicity. The report and recommendations of an ECVAM/ECB workshop (ECVAM workshop 24). ATLA 25, 223­252.

Combes, R.D. & Rodford, R. (2003). The use of expert systems for toxicity prediction -- illustrated with reference to the DEREK program. In Predicting Chemical Toxicity and Fate (ed. M.T.D. Cronin & D. Livingstone), pp. 193­204. Boca Raton, FL, USA: CRC Press.

Testa, B., Balmat, A-L. & Long, A. (2004). Predicting drug metabolism: concepts and challenges. Pure and Applied Chemistry 76, 907­914.

Mekenyan, O.G., Sabchop, D.D., Pavlov, T.S. & Veith, G.D. (2004). A systematic approach to simulating metabolism in computational toxicology. 1. The TIMES heuristic modelling framework. Current Pharmaceutical Design 10, 1273­1293.

Jaworska, J., Dimitrov, S., Nikolova, N. & Mekenyan, O. (2002). Probabilistic assessment of biodegradability based on metabolic pathways: CATABOL System. SAR and QSAR in Environmental Research 13, 307­323.

Button, W.G., Judson, P.N., Long, A. & Vessey, J.D. (2003). Using absolute and relative reasoning in the prediction of the potential metabolism of xenobiotics. Journal of Chemical Information and Computer Sciences 43, 1371­1377.

Mekenyan, O., Dimitrov, S., Schmeider, P. & Veith, G. (2003). In silico modelling of hazard endpoints: current problems and perspectives. SAR and QSAR in Environmental Research 14, 361­371.

Boobis, A., Gudert-Remy, U., Kremers, P., Macheras, P. & Pelkonen, O. (2002). In silico prediction of ADME and pharmacokinetics: report of an expert meeting organised by COST B 15. Journal of Pharmaceutical Sciences 17, 183­193.

Combes, R.D. & Balls, M. (2005). Intelligent testing strategies for chemicals testing -- a case of more haste, less speed? ATLA 33, 289­297.

Goryanin, I., Hodgman, T.C. & Selkov, E. (1999). Mathematical simulation and analysis of cellular metabolism and regulation. Bioinformatics 15, 749­758.

DeJongh, J., Forsby, A., Houston, J.B., Beckman, M., Combes, R. & Blaauboer, B.J. (1999). An integrated approach to the prediction of systemic toxicity using computer-based biokinetic models and biological in vitro test methods: overview of a prevalidation study based on the ECITTS project. Toxicology in Vitro 13, 549­554.

Blaauboer, B.J., Barratt, M.D. & Houston, J.B. (1999). The integrated use of alternative methods in toxicological risk evaluation. ECVAM integrated testing stategies task force report 1. ATLA 27, 229­237.

Gubbels-van Hal, W.M.L.G., Blaauboer, B.J., Barentsen, H.M., Hoitink, M.A., Meerts, I.A.T.M. & van der Hoeven, J.C.M. (2005). An alternative approach for the safety evaluation of new and existing chemicals, an exercise in integrated testing. Regulatory Toxicology and Pharmacology 42, 284­295.

Ponsoda, X., Donato, M.T., Perez-Cataldo, G., Gomez-Lechon, M.J. & Castell, J.V. (2004). Drug metabolism by cultured human hepatocytes: how far are we from the in vivo reality? ATLA 32, 101­110.

Chauret, N., Gauthier, A. & Nicoll-Griffith, D.A. (1998). Effect of common organic solvents on in vitro cytochrome P450-mediated metabolic activities in human liver microsomes. Drug Metabolism and Disposition 26, 1­4.

Waring, J.F., Ciurlionis, R., Jolly, R.A., Heindel, M., Gagne, G., Fagerland, J.A. & Ulrich, R.G. (2003). Isolated human hepatocytes in culture display markedly different gene expression patterns depending on attachment status. Toxicology in Vitro 17, 693­701.

Combes, R.D. (2004). The use of human cells in biomedical research and testing. ATLA 32, Suppl. 1, 43­49.

Serralta, A., Donato, M.T., Orbis, F., Castell, J.V., Mir, J. & Gómez-Lechón, M.J. (2003). Functionality of cultured human hepatocytes from elective samples, cadaveric grafts and hepatectomies. Toxicology in Vitro 17, 769­774.

Bjornsson, T.D., Callaghan, J.T., Einolf, H.J., Volker, F., Gan, L., Grimm, S., Kao, J., King, S.P., Miwa, G., Ni, L., Kumar, G., McLeod, J., Obach, R.S., Roberts, S., Roe, A., Shah, A., Snikeris, F., Sullivan, J.T., Tweedie, D., Vega, J.M., Walsh, J. & Wrighton, S.A. (2003). The conduct of in vitro and in vivo drug­drug interaction studies: A pharmaceutical research and manufacturers of America (PhRMA) perspective. Drug Metabolism and Disposition 31, 815­832.

Benoit, J., Cormier, M. & Wepierre, J. (1987). Effect of proteins on the assessment of surfactant cytotoxicity by an in vitro test: possible correlations with in vivo data. Toxicology in Vitro 1, 91­96.

Deglmann, C.J., Ebner, T., Ludwig, E., Happich, S., Schildberg, F.W. & Koebe, H.G. (2004). Protein binding capacity in vitro changes metabolism of substrates and influences the predictability of metabolic pathways in vivo. Toxicology in Vitro 18, 835­840.

Papeleu, P., Vanhaecke, T., Elaut, G., Vinken, M., Henkens, T., Snykers, S. & Rogiers, V. (2005). Differential effects of histone deacetylase inhibitors in tumor and normal cells -- what is the toxicological relevance? Critical Reviews in Toxicology 35, 363­378.

Maurel, P., Duret, C., Gerbal-Chaloin, S. & DaujatChavanieu, M. (2006). Differentiation of hepatocyte-like cells from human embryonic stem cells and adult liver progenitors. Proceedings of the Fifth World Congress on Alternatives and Animal Use in the Life Science, Berlin, August, 2005. ALTEX (in press).

Engl, T., Boost, K.A., Leckel, K., Beecken, W-D., Jonas, D., Oppermann, E., Auth, M.K.H., Schaudt, A., Bechstein, W-O. & Blaheta, R.A. (2004). Phosphorylation of hepatocyte growth factor receptor and epidermal growth factor receptor of human hepatocytes can be maintained in a (3D) collagen gel sandwich culture system. Toxicology in Vitro 18, 527­532.

Chen, H-L., Wu, H-L., Fon, C-C., Chen, P-J., Lai, MY. & Chen, D-S. (1998). Long-term culture of hepatocytes from human adults. Journal of Biomedical Sciences 5, 435­440.

Yuan, J., Liu, L., Shimada, M., Wand, A., Ruhnke, M., Heeckt, P., Muller, A.R., Nussler, N.C., Neuhaus, P. & Nussler, A. (2004). Induction, expression and maintenance of cytochrome P450 isoforms in long-term cultures of primary human hepatocytes. ALTEX 21, 3­11.

Combes, R.D. (1989). Cytochrome P-450, mixed function oxidases and formation of genotoxic metabolites by the intestinal tract. Progress in Pharmacology 7, 119­145.

Eling, T.E., Thompson, D.C., Foureman, G.L., Curtis, J.F. & Hughes, M.F. (1990). Prostaglandin synthase and xenobiotic oxidation. Annual Reviews of Pharmacology and Toxicology 30, 1­45.

Dimova, S., Brewster, M.E., Noppe, M., Jorissen, M. & Augustijns, P. (2004). The use of human nasal in vitro cell systems during drug discovery and development. Toxicology in Vitro 19, 107­122.

Genschow, E., Spielmann, H., Scholz, G., Seiler, A., Brown, N., Piersma, A., Brady, M., Clemann, N., Huuskonen, H., Paillard, F., Bremer, S. & Becker, K. (2002). The ECVAM International Validation Study on In Vitro Embryotoxicity Tests: results of the definitive phase and evaluation of prediction models. ATLA 30, 151­176.

Bremer, S. & Hartung, T. (2004). The use of embryonic stem cells for regulatory developmental toxicity testing in vitro -- the current status of test development. Current Pharmaceutical Design 10, 2733­2747.

Hakkola, J., Pelkonen, O., Pasanen, M. & Raunio, H. (1998). Xenobiotic-metabolizing cytochrome P450 enzymes in the human feto-placental unit: role in intrauterine toxicity. Critical Reviews in Toxicology 28, 35­72.

Parsons, J.F., Rockley, J. & Richold, M. (1990). In vitro micromass teratogen test: interpretation of results from a blind trial of 25 compounds using three separate criteria. Toxicology in Vitro 4, 609­611.

Genschow, E., Spielmann, H., Scholz, G., Pohl, I., Seiler, A., Clemann, N., Bremer, S. & Becker, K. (2004). Validation of the embryonic stem cell test in the International ECVAM validation study on three in vitro embryotoxicity tests. ATLA 32, 209­244.

Gonzalez, R.J. & Tarloff, J.B. (2004). Expression and activities of several drug-metabolizing enzymes in LLC-PK1 cells. Toxicology in Vitro 18, 887­894.

Morohoshi, K., Yamamato, H., Kamata, R., Shiraishi, F., Koda, T. & Morita, M. (2005). Estrogenic activity of 37 components of commercial sunscreeen lotions evaluated by in vitro assays. Toxicology in Vitro 19, 457­469.

Combes, R.D. (2000). The use of structure-activity relationships and markers of cell toxicity to detect non-genotoxic carcinogens. Toxicology in Vitro 14, 387­399.

Ekwall, B. (1999). Overview of the final MEIC results: II. The in vitro­in vivo evaluation of a practical battery of cell tests for prediction of acute lethal block concentrations in humans. Toxicology in Vitro 13, 665­673.

Halle, W. (2003). The registry of cytotoxicity: toxicity testing in cell cultures to predict acute toxicity (LD50) and to reduce testing in animals. ATLA 31, 89­198.

Clemedson, C., Nordin-Andersson, M., Bjerregaard, H.F., Clausen, J., Forsby, A., Gustafsson, H., Hansson, U., Isomaa, B., Jorgensen, C., Kolman, A., Kotova, N., Krause, G., Kristen, U., Kurppa, K., Romert, L. & Scheers, E. (2002). Development of an in vitro test battery for the estimation of acute human systemic toxicity: An outline of the EDIT project. Evaluation-guided Development of New In Vitro Test Batteries. ATLA 30, 313­322.

MacGregor, J.T., Collins, J.M., Sugiyama, Y., Tyson, C.A., Dean, J., Smith, L., Andersen, M., Curren, R.D., Houston, J.B., Kadlubar, F.F., Kedderis, G.L., Krishnan, D., Li, A.P., Parchment, R.E., Thummel, K., Tomaszewski, J.E., Ulrich, R., Vickers, A.E.M. & Wrighton, S.A. (2001). In vitro human tissue models in risk assessment: report of a consensus-building workshop. Toxicological Sciences 59, 17­36.

Combes, R., Balls, M., Curren, R., Fischbach, M., Fusenig, N., Kirkland, D., Lasne, C., Landolph, J., LeBoeuf, R., Marquardt, H., McCormick, J., Müller, L., Rivedal, E., Sabbioni, E., Tanaka, N., Vasseur, P. & Yamasaki, H. (1999). Cell transformation assays as predictors of human carcinogenicity. ATLA 27, 745­767.

Mitchell, I. de G. & Combes, R.D. (1997). In vitro genotoxicity and cell transformation assessment. In In vitro Methods in Pharmaceutical Research, (eds J.V. Castell & M.J. Gómez-Lechón), pp. 318­352. San Diego, CA, USA: Academic Press.

LeBoeuf, R.A., Kerckaert, K.A., Aardema, M.J. & Isfort, R.J. (1999). Use of Syrian hamster embryo and Balb/c 3T3 cell transformation for assessing the carcinogenicity potential of chemicals. In The Use of Short- and Medium-term tests for Carcinogenic Hazard Evaluation. (ed. D.B. McGregor, J.M. Rice & S. Venitt) pp. 409­425. Lyon, France: IRAC Scientific Publications.

Sasaki, K., Mizusawa, H., Ishidate, M. & Tanaka, N. (1990). Transformation of ras transfected BALB 3T3 clone (Bhas 42) by promoters: Application for screening and specificity of promoters. Toxicology in Vitro 4, 657­659.

Stuard, S.B., Kerckaert, G.A. & Lehman-McKeeman, L.D. (1999). Characterisation of the metabolic capacity of Syrian Hamster Embryo (SHE) Cells. Toxicological Sciences 48, 366.

Coecke, S., Blaauboer, B.J., Elaut, G., Freeman, S., Freidig, A., Gensmantel, N., Hoet, P., Kapoulas, V.M., Ladstetter, B., Langley, G., Leahy, D., Mannens, G., Meneguz, A., Monshouwer, M., Nemery, B., Pelkonen, O., Pfaller, W., Prieto, P., Proctor, N., Rogiers, V., Rostami-Hodjegan, A., Sabbioni, E., Steiling, A. & van de Sandt, J.J.M. (2005). Toxicokinetics and metabolism. ATLA 33, Suppl. 1, 147­175.