Part I: General Toxicology

1. Nonclinical Development of Combination Drugs

Alberto Lodola

2. Juvenile Non-Clinical Safety Studies in Support of Pediatric Drug Development

Paul C. Barrow and Georg Schmitt

Part II: Pathology

3. Procedures of Necropsy and Tissue Sampling

Laurence Fiette, Mohamed Slaoui, and Anne-Laure Bauchet

4. Tissue Sampling and Processing for Histopathology Evaluation

Mohamed Slaoui, Anne-Laure Bauchet, and Laurence Fiette

5. Principles and Methods of Immunohistochemistry

José A. Ramos-Vara

6. Applications of Mass Spectrometry Imaging for Safety Evaluation

David Bonnel and Jonathan Stauber

Part III Genetic Toxicology

7. In vivo rat T-lymphocyte Pig-a assay: detection and expansion of cells deficient in the GPI-anchored CD48 surface marker for analysis of mutation in the endogenous Pig-a gene

Vasily N Dobrovolsky, Javier Revollo, Dayton M Petibone, and Robert H Heflich

8. Detection of In Vivo Mutation in the Pig-a Gene of Mouse Bone Marrow Erythroids

Takafumi Kimoto and Daishiro Miura

9. The Use of Bacterial Repair Endonucleases in the Comet Assay

Andrew R. Collins

Part IV Safety Pharmacology

10. Automated Patch-Clamp methods for the hERG Cardiac Potassium Channel

Sylvie Houtmann, Brigitte Schombert, Camille Sanson, Michel Partiseti, and G. Andrees Bohme

11. Impedance Measurement in Induced Pluripotent Stem Cell Derived Cardiomyocytes

Emma-Jane Poulton

Part V Investigative Toxicology

12. Target Safety Assessment: Strategies and Resources

Richard J. Brennan

13. NMR and MS Methods for Metabolomics

Alexander Amberg, Björn Riefke, Götz Schlotterbeck, Alfred Ross, Hans Senn, Frank Dieterle, and Matthias Keck

14. Protocols and Applications of Cellular Metabolomics in Safety Studies Using

Precision-Cut Tissue Slices and Carbon 13 NMR

Gabriel Baverel, Maha El Hage, and Guy Martin

Richard Khan-Malek and Ying Wang

Jean-Pierre Marchandeau and Gilles Labbe

Part VI Screening Assays for Developmental Toxicity

17. FETAX Assay for Evaluation of Developmental Toxicity

Isabelle Mouche, Laure Malésic, and Olivier Gillardeaux

18. Evaluation of Embryotoxicity Using