ABSTRACT
Introduction .................................................................................................................................... 150 Ethical Considerations ................................................................................................................... 150 Choice of Animal Species ............................................................................................................. 151 Physiology and Experimental Conditions, Including Microbiological Status and Diet and Feeding Conditions ........................................................................................................................ 152 Animal Models in Pharmacology .................................................................................................. 153
Animal Models in Pharmacodynamic Primary Effect ............................................................. 154 Drugs to Treat Infections...................................................................................................... 154 Drugs to Treat Mental Disorders .......................................................................................... 154 Drugs to Treat Neurodegenerative Diseases ........................................................................ 156 Drugs to Treat Endocrine Diseases ...................................................................................... 157 Drugs to Treat Neurogenic In–ammation (Rheumatoid Arthritis) ...................................... 157 Drugs to Treat Pain .............................................................................................................. 157
Animal Models in Pharmacodynamic Secondary Effect ......................................................... 158 Animal Models in Pharmacokinetics ............................................................................................ 158 Animal Models in Toxicology ....................................................................................................... 159 Extrapolation .................................................................................................................................. 160 Toxicity Tests ................................................................................................................................. 161
Tests for Acute Toxicity ............................................................................................................ 162 Eye Irritation ............................................................................................................................. 163 Skin Irritation ............................................................................................................................ 164 Skin Sensitization ...................................................................................................................... 164 Repeated-Dose Toxicity: 28 Days, 90 Days (Subchronic), and 1 Year (Chronic) ..................... 165 Carcinogenicity Studies ............................................................................................................ 167 Reproductive Toxicity Tests ...................................................................................................... 168 One-, Two-, and Multi-generation Studies ................................................................................ 169 The Prenatal Developmental Toxicity Study ............................................................................ 171 Developmental Neurotoxicity Studies ....................................................................................... 172 Screening Tests for Reproductive and Developmental Toxicity ............................................... 174 Special Studies for Testing and Assessment of Endocrine-Disrupting Chemicals .................. 175 Neurotoxicity Study .................................................................................................................. 176 Genetic Toxicology Testing ....................................................................................................... 177 Future Trends in the Use of Laboratory Animals in Regulatory Toxicology ........................... 178
References ...................................................................................................................................... 178 Recommended Reading ................................................................................................................. 181
INTRODUCTION
Current knowledge in the disciplines of pharmacology and toxicology has been achieved largely by using experimental animals. In recent years, new knowledge in pharmacology has accumulated from strong interfaces among molecular pharmacology, receptor pharmacology, and in vivo pharmacology, including experimental studies in laboratory animals and humans. A similar strong interface can be seen between in vitro and in vivo toxicology. Over the years, the animal models in pharmacology and toxicology have become increasingly sophisticated because of continuous changes in end points. Many relatively simple animal models that were very important in the past have become redundant and have been replaced by nonanimal methodologies with the same, or an even more speci—c, end point.
