Overview of Alternative Methodologies in Toxicology

Laura Gribaldo1

1 European Centre for Validation of Alternative Methods (ECVAM), Joint Research Centre (JRC), Ispra, Italy
Publication Name:  Current Protocols in Toxicology
Unit Number:  Unit 20.1
DOI:  10.1002/0471140856.tx2001s34
Online Posting Date:  November, 2007
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In vitro toxicology generally refers to the study of toxicological phenomena in non‐whole‐animal models. This broader connotation includes studies utilizing isolated organs, tissue slices, explants cultures, and isolated primary cells, as well as cell lines and subcellular fractions (e.g., microsomes). These model systems have made major contributions to toxicological sciences, particularly in our understanding of the mechanisms of toxicity, xenobiotic metabolism, and species differences in expressions of toxicity. This unit reviews the use of in vitro models and their value in toxicology testing. Curr. Protoc. Toxicol. 34:20.1.1‐20.1.6. © 2007 by John Wiley & Sons, Inc.

Keywords: alternative methodologies; in vitro assays

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Table of Contents

  • Introduction
  • The Concept of Validation
  • Overview of Methods
  • Literature Cited
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Literature Cited

Literature Cited
   Balls, M. and Karcher, W. 1995. The validation of alternative methods. Altern. Lab. Anim. 23:884‐886.
   Balls, M., Blaauboer, B., Brusick, D., Frazier, J., Lamb, D., Pemberton, M., Reinhardt, C., Roberfroid, M., Rosenkranz, H., Schmid, B., Spielmann, H., Stammati, A.‐L., and Walum, E. 1990. Report and recommendations of the CAAT/ERGATT workshop on the validation of toxicity test procedures. Altern. Lab. Anim. 18:313‐337.
   Balls, M., Blaauboer, B.J., Fentem, J.H., Bruner, L., Combes, R.D., Ekwall, B., Fielder, R.J., Guillouzo, A., Lewis, R.W., Lovell, D.P., Reinhardt, C.A., Repetto, G., Sladowski, D., Spielmann, H., and Zucco, F. 1995. Practical aspects of the validation of toxicity test procedures. The report and recommendations of ECVAM workshop 5. Altern. Lab. Anim. 23:129‐147.
   Balls, M., Amcoff, P., Bremer, S., Casati, S., Coecke, S., Clothier, R., Combes, R., Corvi, R., Curren, R., Eskes, C., Fentem, J., Gribaldo, L., Halder, M., Hartung, T., Hoffmann, S., Schechtman, L., Scott, L., Spielmann, H., Stokes, W., Tice, R., Wagner, D., and Zuang, V. 2006. The principles of weight of evidence validation of test methods and testing strategies. Altern. Lab. Anim. 34:603‐620.
   Curren, R.D., Southee, J.A., Spielmann, H., Liebsch, M., Fentem, J.H., and Balls, M. 1995. The role of prevalidation in the development, validation and acceptance of alternative methods. Altern. Lab. Anim. 23:211‐217.
   Frazier, J.M. 1990. Scientific criteria for validation of in vitro toxicity testing. OECD Publishing Office, Paris.
   Hartung, T., Bremer, S., Casati, S., Coecke, S., Corvi, R., Fortaner, S., Gribaldo, L., Halder, M., Janusch Roi, A., Prieto, P., Sabbioni, E., Worth, A., and Zuang, V. 2003. ECVAM's response to the changing political environment for alternatives: Consequences of the European Union chemicals and cosmetics policies. Altern. Lab. Anim. 31:473‐481.
   Pessina, A., Malerba, I., and Gribaldo, L. 2005. Hematotoxicity testing by cell clonogenic assay in drug development and preclinical trials. Curr. Pharm. Des. 11:1055‐1065.
   Schindler, S., Spreitzer, I., Löschner, B., Hoffmann, S., Hennes, K., Halder, M., Brügger, P., Frey, E., Hartung, T., and Montag, T. 2006. International validation of pyrogen tests based on cryopreserved human primary blood cells. J. Immunol. Methods 316:42‐51.
   Swierenga, S.H.H. and Yamasaki, H. 1992. Performance of tests for cell transformation and gap junctional intercellular communication for detecting non‐genotoxic carcinogenic activity. In Mechanisms of Carcinogenesis in Risk Identification. IARC Scientific Publications No. 116 (H. Vainio, P.N. McGee, D.B. McGregor, and A.J. McMichael, eds.) pp. 165‐193. IARC. Lyon, France.
   Worth, A.P. and Balls, M. 2001. The role of ECVAM in promoting the regulatory acceptance of alternative methods in the European Union. Altern. Lab. Anim. 29:525‐535.
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