Toxicokinetics and Risk Assessment

by John C. Lipscomb (Editor), Edward V. Ohanian (Editor)

Overview

Toxicokinetics in Risk Assessment discusses the noncancer risk assessment process and its reliance on uncertainty factors in order to facilitate the continued study and refinement of the scientific basis for health risk assessment. This text clearly demonstrates the application of physiologically-based pharmacokinetic (PBPK) modeling in human healt

Product Details

ISBN-13:	9781000612134
Publisher:	CRC Press
Publication date:	04/19/2016
Sold by:	Barnes & Noble
Format:	eBook
Pages:	361
File size:	10 MB

About the Author

John C. Lipscomb is a Toxicologist for the U.S. Environmental Protection Agency (EPA), Office of Research and Development, at the National Center for Environmental Assessment in Cincinnati, Ohio. There, Dr. Lipscomb serves as co-leader of a technical panel for the EPA's Risk Assessment Forum, responsible for drafting guidance on the replacement of default uncertainty factors with data-derived uncertainty factors. Prior to joining the EPA, Dr. Lipscomb was a Captain in the United States Air Force and served as chief of the metabolism section in the toxicology division of Armstrong Laboratory, USAF, Wright-Patterson Air Force Base, Ohio. He serves on the Board of Directors of the American Board of Toxicology and has held and continues to act in leadership positions for specialty groups and regional chapters of the Society of Toxicology and the Society for Risk Analysis. Dr. Lipscomb received the B.S. and M.S. degrees from the University of Central Arkansas, Conway, in 1984 and 1986, respectively, and the Ph.D. degree in interdisciplinary toxicology from the University of Arkansas for Medical Sciences, Little Rock, in 1991. He became a Diplomate of the American Board of Toxicology in 1995., Edward V. Ohanian is the Director of the Health and Ecological Criteria Division, Office of Science and Technology, Office of Water at the U.S. Environmental Protection Agency (EPA) in Washington, D.C. He serves as Chairman of the EPA's Risk Assessment Forum, Chairman of the Health Advisory Board for the not-for-profit organization NSF International in Ann Arbor, Michigan, and Co-chairman of the EPA Federal-State Toxicology and Risk Analysis Committee. He is Adjunct Associate Professor of Medicine and Health Care Sciences at the School of Medicine and Health Sciences and the School of Public Health and Health Services, The George Washington University, Washington, D.C., as well as Adjunct Associate Professor of Environmental Health Sciences at the Tulane University Medical Center's School of Public Health and Tropical Medicine in New Orleans, Louisiana. Dr. Ohanian received the B.S. degree in biological sciences from Columbia University, New York, New York in 1969, the M.S. degree in physiology from New York Medical College, Valhalla in 1974, and the Ph.D. degree in biomedical sciences from the Mount Sinai School of Medicine, New York, New York in 1976.

Table of Contents

Overview of the Approach to Noncancer Risk Assessment o Guidance for the Development of Chemical Specific Adjustment Factors: Integration with Mode of Action Frameworks o Derivation and Modeling of Mechanistic Data for Use in Risk Assessment o Empirically Observed Distributions of Pharmacokinetic and Pharmacodynamic Variability in Humans-Implications for the Derivation of Single Point Component Uncertainty Factors Providing Equivalent Protection as Existing RFDs o Use of Classical Pharmacokinetic Evaluations in Drug Development and Safety Assessment o Considerations for Applying Physiologically Based Pharmacokinetic Models in Risk Assessment o Considerations of Design and Data when Developing Physiologically Based Pharmacokinetic Models o In Silico Predictions of Partition Coefficients for Physiologically Based Pharmacokinetic Models o In Vitro to In Vivo Extrapolation of Metabolic Rate Constants for Physiologically Based Pharmacokinetic Models o Use of Physiologically Based Pharmacokinetic Modeling to Evaluate Implications of Human Variability o Developmental Aspects of Children's Pharmacokinetics o Sensitive Populations and Risk Assessment o Statistical Issues in Physiologically Based Pharmacokinetic Modeling o Drug Development and the Use of Pharmacokinetics/Toxicokinetics in Selecting the First Dose of Systemically Administered Drugs in Humans-A Nonclinical Perspective o Pharmacokinetic/PBPK Models in IRIS Assessments

Editorial Reviews

Reviewer: Dave Stone, PhD, MS (Oregon State University)
Description: This book is designed to acquaint readers with methods to integrate toxicokinetic data in the risk assessment framework. Authors address uncertainty factors, PBPK modeling, statistical issues, and considerations in animal to human data and provide examples of how toxicokinetics are used in risk assessment.
Purpose: The purpose is to heighten the awareness and capacity of scientists who plan, conduct, and review risk assessments on the use of toxicokinetic information to improve quantitative estimates of risk, as well as to highlight the complexity of toxicokinetic data. These are worthy objectives since substitution of default uncertainty factors for physiological and pharmacological information should provide a better estimate of risk. The authors have met the objectives.
Audience: According to the authors, this book is intended for risk assessors, organizations that develop studies of chemical metabolism and tissue dosimetry for risk assessment, and those who make decisions about which areas of risk science to advance. The authors adequately target these audiences. They use credible sources for the information, although with perhaps too much reliance on contributions from U.S. EPA scientists.
Features: The book begins with an overview of the noncancer risk assessment process. The chapters that follow provide a detailed examination and examples of how toxicokinetic information can be used to improve risk assessments, including design of PBPK models, evaluation of human variability and sensitive populations, statistical issues in PBPK modeling, and incorporation in the Integrated Risk Information System. A particularly noteworthy chapter is developmental aspects of children's pharmacokinetics. Most chapters provide appropriate illustrations or examples of data. A limiting factor of this book is the amount of redundant information in the introductory sections of several chapters and the absence of a chapter on exposure assessment.
Assessment: This is well written and useful for the intended audiences. The focus is narrow, but the book incorporates the necessary disciplines to provide a comprehensive review of how toxicokinetics can improve the risk assessment process. Given the rapid advance of toxicokinetics and related fields, future editions are appropriate.

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