Krishnan / Andersen Quantitative Modeling in Toxicology

1. Auflage 2010
ISBN: 978-0-470-68670-6
Verlag: John Wiley & Sons
Format: PDF
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, 504 Seiten, E-Book

Governments around the world are passing laws requiring industry toassess the toxicity of the chemicals and products they produce, butto do so while reducing, refining, or even replacing testing onanimals. To meet these requirements, experimental toxicologists andrisk assessors are adopting quantitative approaches and computersimulations to study the biological fate and effects of chemicalsand drugs.
In Quantitative Modeling in Toxicology leading expertsoutline the current state of knowledge on the modeling of dose,tissue interactions and tissue responses. Each chapterdescribes the mathematical foundation, parameter estimation,challenges and perspectives for development, along with thepresentation of a modeling template. Additionally, tools andapproaches for conducting uncertainty, sensitivity and variabilityanalyses in these models are described. Topics coveredinclude:
* the quantitative models of pharmacokinetics of individualchemicals and mixtures
* models for toxicant-target tissue interaction.
* models for cellular, organ, and organism responses.
* approaches, tools and challenges for model application andevaluation
A website containing computer codes accompanies the book to helpthe reader reconstruct the models described and discussed in thevarious chapters.
Quantitative Modeling in Toxicology serves as anessential reference source and tool box for risk assessors andresearchers and students in toxicology, public health,pharmacology, and human toxicology interested in developingquantitative models for a better understanding of dose-responserelationships.

Autoren/Hrsg.

Krishnan, Kannan

Andersen, Melvin E.

Inhaltsverzeichnis

About the Editors.
About the Book.
List of Contributors.
SECTION 1 INTRODUCTION.
1 Quantitative Modeling in Toxicology: An Introduction(Melvin E. Andersen and Kannan Krishnan).
SECTION 2 PHYSIOLOGICALLY-BASED TOXICOKINETIC ANDPHARMACOKINETIC (PBPK) MODELING.
2 PBPK Modeling: A Primer (Kannan Krishnan, George D. Loizou,Martin Spendiff, John C. Lipscomb and Melvin E. Andersen).
3 Pharmacokinetic Modeling of Manganese - An EssentialElement (Andy Nong, Michael D. Taylor, Miyoung Yoon, and MelvinE. Andersen).
4 Physiologically Based Modeling of Pharmacokinetic Interactionsin Chemical Mixtures (Sami Haddad, Robert Tardif, Jonathan Boyd,and Kannan Krishnan).
5 Physiological Parameters and Databases for PBPK Modeling(Douglas O. Johns, Elizabeth Oesterling Owens, Chad M. Thompson,Babasaheb Sonawane, Dale Hattis and Kannan Krishnan).
SECTION 3 MODELING TOXICANT-TARGET INTERACTIONS.
6 Modeling Cholinesterase Inhibition (Charles Timchalk, PaulM. Hinderliter, and Torka S. Poet).
7 Modeling of Protein Induction and Dose-Dependent HepaticSequestration (Andy Nong and Melvin E. Andersen).
8 Bistable Signaling Motifs and Cell Fate Decisions (SudinBhattacharya, Qiang Zhang, and Melvin E. Andersen).
9 Ultrasensitive Response Motifs in Biochemical Networks(Qiang Zhang, Sudin Bhattacharya, Courtney G. Woods, and MelvinE. Andersen).
10 Gene and Protein Expression - Modeling Nested Motifs inCellular and Tissue Response Networks (Melvin E. Andersen, QiangZhang, and Sudin Bhattacharya).
11 Modeling Liver and Kidney Cytotoxicity (Kai H. Liao, YeiM. Tan, Harvey J. Clewell III, and Melvin E. Andersen).
SECTION 4 MODELING TISSUE AND ORGANISM RESPONSES.
12 Computational Model for Iodide Economy and the HPT Axis inthe Adult Rat (Jeffrey W. Fisher and Eva D. McLanahan).
13 Two-Stage Clonal Growth Modeling of Cancer (Rory B.Conolly and Melvin E. Andersen).
14 Statistical and Physiological Modeling of the Toxicity ofChemicals in Mixtures (Hisham A. El-Masri, Michael A. Lyons, andRaymond S.H. Yang).
15 (Q)SAR Models of Adverse Responses: Acute Systemic Toxicity(Mark T.D. Cronin, Yana K. Koleva, and Judith C.Madden).
SECTION 5 MODEL APPLICATION AND EVALUATION.
16 Modeling Exposures to Chemicals From Multiple Sources andRoutes (Panos G. Georgopoulos, Sastry S. Isukapalli, and KannanKrishnan).
17 Probabilistic Reverse Dosimetry Modeling for InterpretingBiomonitoring Data (Yu-Mei Tan and Harvey J. ClewellIII).
18 Quantitative Modeling in Noncancer Risk Assessment (Q. JayZhao, Lynne Haber, Melissa Kohrman-Vincent, Patricia Nance, andMichael Dourson).
19 Application of Physiologically Based Pharmacokinetic Modelingin Health Risk Assessment (Harvey J. Clewell III).
20 Uncertainty, Variability, and Sensitivity Analyses inSimulation Models (Sastry S. Isukapalli, Martin Spendiff, PanosG. Georgopoulos and Kannan Krishnan).
21 Evaluation of Quantitative Models in Toxicology: Progress andChallenges (Kannan Krishnan and Melvin E. Andersen).
Index.

Über Autor(innen)

Dr. Kannan Krishnan, Director of Human Toxicology Research Group (TOXHUM), Université de Montréal, Canada
An expert in pharmacokinetics/toxicokinetics, toxicology of chemical mixtures, computational toxicology, and health risk assessment methods, Dr. Krishnan has been the leader of the risk assessment methodologies theme team of the Canadian Network of Toxicology Centers, member of the U.S. National Academy of Sciences' Sub-committee on Acute Exposure Guideline Levels, President of the Risk Assessment Specialty Section of the Society of Toxicology, and advisor for the International Programme on Chemical Safety (IPCS) of WHO. He is a member of the editorial boards of Toxicological Sciences, International Journal of Toxicology, Journal of Applied Toxicology and Journal of Child Health.

Dr. Melvin E. Andersen, CIIT Centers for Health Research, Research Triangle Park, NC
Dr. Andersen is (1) the Director, Computational Biology Division, (2) Director, LRI-ACC Research Program and (3) Science Advisor, Center for Human Health Assessment at CIIT Centers for Health Research, Research Triangle Park, NC. Between 1971 and 1994, he held positions in toxicology research and research management in the federal government (DoD and US EPA) and in private industry (Chemical Industry Institute of Toxicology). He is recognized for developing short-courses and computer demonstrations in pharmacokinetic and pharmacodynamic modeling. He has received several awards for professional contributions, is a Fellow of the Academy of Toxicological Sciences and is recognized as a 'highly cited' scientist by the Institute for Scientific Information.