Modelling survival under chemical stress
Modelling survival under chemical stress
A comprehensive guide to the GUTS framework
About the Book
Stressors, such as toxicants, can cause mortality among organisms. Interestingly, not all individuals will die at the same time in the same exposure treatment, and the number of deaths will change with exposure time. The pattern of mortality will also depend on the exposure profile (e.g., constant versus pulsed exposure), and can be modified by the addition of other stresses (e.g., mixture toxicity). Making sense of these complex issues requires mechanism-based models, known as toxicokinetic-toxicodynamic (TKTD) models. For mortality, almost all published TKTD models can now be viewed as members of an over-arching framework, that we have christened GUTS: the General Unified Threshold model of Survival. GUTS has been published in the scientific literature in 2011, but a publication is obviously not the place to provide a detailed description of the model or to provide guidance on how to apply the model in practical situations. As the GUTS framework is now gaining broader interest in the scientific, regulatory and industry communities, it is time for a more in-depth treatise.
This book presents the background and history of GUTS, the concepts applied and the underlying assumptions, as well as the mathematical details (in a separate chapter). Furthermore, two worked out case studies are provided, demonstrating how the model can be used in practice. Further chapters deal with potential applications in a regulatory context, ring testing of various software implementations, and more (see the table of contents). We expect to provide regular updates of the book to include novel developments in this field (and to correct errors).
The supporting web page for this book is at http://www.debtox.info/book_guts.html. There, you can also find a log file with version information and known errors. The first version of this book was released on 18 January 2018.
About the Authors
Table of Contents
Preface
- Introduction
- Description of GUTS
- Mathematical treatment
- Case study: dieldrin in guppies
- Case study: propiconazole in amphipods
- Use cases
- Model evaluation
- Outlook
Bibliography
Glossary
Appendix A: Ring test
Appendix B: Model extensions
Appendix C: Typical identifiability problems and limit cases
Appendix D: Sampling from parameter space
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