Toxicity Assessment Alternatives: Methods, Issues, Opportunities / Edition 1

by Harry Salem, Sidney A. Katz

Overview

Toxicity Assessment Alternatives: Methods, Issues, Opportunities contains a broad array of critical surveys, contributed by active and respected investigators, describing their research and offering updates on toxicity assessment alternatives, directions determined by current and future grant programs, opportunities for mechanistically based test methods to detect endocrine disruptor activity, the use of alternatives in the Department of Defense hazard assessment initiatives, and the issues and opportunities for validation and regulatory acceptance. Several of these advances make use oftransgenic models that reduce the time and cost of carcinogenicity testing. Others use tissue cultures for the assessment of endocrine disrupting chemicals. Cultures of human epidermal keratinocytes are applicable as models for sulfur mustard lesions, and in vitro protein denaturation is used as a chemical test for assessing the ocular and dermal irritation potential of cosmetic prod­ ucts. Molecular modeling is applied to explaining chemical toxicity. Commercially developed assay systems have undergone extensive evaluation by their manufacturers. Some of these await external valida­ tion, and others await acceptance by North American and European regulatory agencies. Toxicity Assessment Alternatives: Methods, Issues, Opportunities provides information from members of the scientific and regulatory communities on what has been achieved and what has been accepted in alternatives to animal testing.

Product Details

ISBN-13:	9780896037878
Publisher:	Springer-Verlag New York, LLC
Publication date:	07/02/1999
Edition description:	1999
Pages:	262
Product dimensions:	5.83(w) x 8.70(h) x 0.03(d)

About the Author

Salem, Harry, PhD (U.S. Army Soldier and Biological Chemical Command); Katz, Sidney A., PhD (Rutgers Univ)

Table of Contents

I. Recent Developments on Alternatives.- 1 Tissue Engineering: An Important Technology for Assessment of Toxicity.- 2 Tissue Engineering: Technology Applications and FDA Initiatives.- 3 Electrical Resistance Method for Measuring Volume Changes in Astrocytes.- 4 Cytotoxicity Profiles for a Series of Investigational Compounds Using Liver Slice Technology and Human-Derived Cell Cultures.- 5 Antagonistic Interaction of Sodium Arsenite and Lead Sulfate with UV Light on Sister Chromatid Exchanges in Human Peripheral Lymphocytes.- 6 The Role of Upper Airway Heat and Water Vapor Exchange in Hygroscopic Aerosol Deposition in the Human Airway: A Deposition Model.- 7 Moving Average Interpolation for Malathion LC50 Estimation on Dugesia tigrina: Comparison with Probit and “One-Point” Methods.- 8 Physiological Modeling of Benzo(a)pyrene Pharmacokinetics in the Rat.- II. Current Trends and Future Directions.- 9 Resources for Biomedical Research: Opportunities for Alternatives.- III. Mechanistically Based Test Methods as Alternatives.- 10 Endocrine Disruption in Wildlife: Scientific Processes and Principles for Evaluating Effects.- 11 Mechanistic Animal-Replacement Approaches for Predicting Pharmacokinetics of Organic Chemicals.- IV. Use of Alternatives in Hazard Assessment Initiatives.- 12 Validation of the CytosensorTM Microphysiometer for In Vitro Cytotoxicity Testing.- 13 Sulfur Mustard Effects on Cell Yield Alter Viability Assessment in Normal Human Epidermal Keratinocytes.- 14 Development of Human Keratinocyte Colonies for Confocal Microscopy and for Study of Calcium Effects on Growth Differentiation and Sulfur Mustard Lesions: A Model.- 15 Phosgene-Induced Calcium Changes in Pulmonary Artery Endothelial Cells.- 16 Enhanced Proteolytic Activity and Fc Receptor Expression inHuman Epithelial Cells Following Exposure to Sulfur Mustard.- 17 Altered Expression of lntracellular and Surface Antigens by Cultured Human Epidermal Keratinocytes Exposed to Sulfur Mustard.- 18 Effect of Sulfur Mustard Exposure on Human Epidermal Keratinocyte Viability and Protein Content.- 19 The Use of In Vitro Systems to Define Therapeutic Approaches to Cutaneous Injury by Sulfur Mustard.- 20 Effects of Poly (ADP-Ribose) Polymerase Inhibitors on the Sulfur Mustard-Induced Disruption of the Higher-Order Nuclear Structure of Human Lymphocytes.- 21 DNA Repair Enzymatic Response in Cultured Human Epidermal Keratinocytes Following Sulfur Mustard Exposure.- 22 Human Hepaytes: A Novel Animal Alternative.- V. Validation, Regulatory Acceptance, and Animal Protection Perspectives.- 23 An Animal Protection Perspective.- 24 Federal Interagency Activities Toward Validation and Regulatory Acceptance of Alternative Tests.

Editorial Reviews

Reviewer: Tim K. Takaro, MD, MPH, MS. (University of Washington)
Description: This book is a compilation of studies utilizing novel short-term assays to assess toxicologic risk. While attempting to cover a broad range of in vitro systems, the major focus is on cell culture of human keratinocytes to elucidate mechanisms involved in the response to sulfur mustard.
Purpose: The purpose is to describe the development and use of short-term toxicological assays that can be applied to risk management. The primary value of these methods is that they can provide alternatives to more expensive and politically sensitive animal testing. In light of the large number of untested materials that can reach the marketplace such alternatives are clearly needed. This book partially meets these objectives with an in-depth evaluation of the complex dermatologic response to sulfur mustard utilizing the in-vitro human keratinocyte system. However, little attention is paid to other novel systems such as assays of mutagenesis and gene expression.
Audience: This book will be of particular interest to risk assessors and regulators and perhaps entrepreneurs interested in marketing new modalities for testing the adverse effects of their products. It is highly readable for those accustomed to reading scientific studies, many of which are presented in a pithy style. There is essentially no overall summary, and the editors do not attempt to focus the contributions except in the complex dermatologic response to sulfur mustard utilizing the in-vitro human keratinocyte system. In this area there is comprehensive coverage of a number of novel markers that will clearly be of value for risk assessors and investigators of dermatologic toxicants.
Features: Alternative risk assessment methods are framed with a description of the National Institute of Standards and Technology's advanced technology program as it relates to the improvement of toxicologic assays. The conclusion is, appropriately, a discussion of the regulatory framework in which such assays can be applied and what criteria are used for validation. The first section on recent developments in alternative assays is the most diverse, with descriptions of models of electrical resistance in astrocytes, in vitro hepatic function, moving average interpolation for toxicologic endpoints, and an interesting use of sister chromatid exchange to study combined effects of UV light and chemical exposure.
Assessment: By focusing on the human keratinocyte cell system, the complex response to sulfur mustard provides an excellent case example of the value of these alternative methods, and in this, this book is unique in the field. It would clearly benefit from a broader treatment of short-term assay methods, particularly ones utilizing florescent-based mutation and gene expression. As noted in the beginning of the book, the Human Genome Project and related progress in molecular biology provide nearly endless opportunities for such approaches.

Doody's Review Service

"The value of these methods is that they can provide alternatives to more expensive and politically sensitive animal testing methods. . .By focusing on the human keratinocyte cell system, the complex response to sulfur mustard provides an excellent case example of the value of these alternative methods, and in this, this book is unique in the field. "-Doody's Health Sciences Book Review Journal

"This book is an up-to-date description of what has been accomplished thus far in developing acceptable alternatives to classical animal toxicity assessment methods. It includes not only reviews about alternatives for animal testing as such (e.g., tissue cultures for dermal toxicity and endocrine disruptor assessment, in vitro protein denaturation to assess ocular and dermal irritation potential of chemicals, and validation of alternative tests), it also reports on increasing testing efficiency (e.g., trans-genic models that reduce time and cost of carcinogenicity testing), and it presents tools for a better understanding of the toxic process (e.g., molecular modeling to explain chemical toxicity)....it presents a handsome and conveniently arranged overview of the topics and perspectives regarding the state-of-the-art of alternative toxicity testing."-EUROTOX European Societies of Toxicology

From the Publisher

3 Stars from Doody

This book is a compilation of studies utilizing novel short-term assays to assess toxicologic risk. While attempting to cover a broad range of in vitro systems, the major focus is on cell culture of human keratinocytes to elucidate mechanisms involved in the response to sulfur mustard. The purpose is to describe the development and use of short-term toxicological assays that can be applied to risk management. The primary value of these methods is that they can provide alternatives to more expensive and politically sensitive animal testing. In light of the large number of untested materials that can reach the marketplace such alternatives are clearly needed. This book partially meets these objectives with an in-depth evaluation of the complex dermatologic response to sulfur mustard utilizing the in-vitro human keratinocyte system. However, little attention is paid to other novel systems such as assays of mutagenesis and gene expression. This book will be of particular interest to risk assessors and regulators and perhaps entrepreneurs interested in marketing new modalities for testing the adverse effects of their products. It is highly readable for those accustomed to reading scientific studies, many of which are presented in a pithy style. There is essentially no overall summary, and the editors do not attempt to focus the contributions except in the complex dermatologic response to sulfur mustard utilizing the in-vitro human keratinocyte system. In this area there is comprehensive coverage of a number of novel markers that will clearly be of value for risk assessors and investigators of dermatologic toxicants. Alternative risk assessment methods are framed with a description ofthe National Institute of Standards and Technology's advanced technology program as it relates to the improvement of toxicologic assays. The conclusion is, appropriately, a discussion of the regulatory framework in which such assays can be applied and what criteria are used for validation. The first section on recent developments in alternative assays is the most diverse, with descriptions of models of electrical resistance in astrocytes, in vitro hepatic function, moving average interpolation for toxicologic endpoints, and an interesting use of sister chromatid exchange to study combined effects of UV light and chemical exposure. By focusing on the human keratinocyte cell system, the complex response to sulfur mustard provides an excellent case example of the value of these alternative methods, and in this, this book is unique in the field. It would clearly benefit from a broader treatment of short-term assay methods, particularly ones utilizing florescent-based mutation and gene expression. As noted in the beginning of the book, the Human Genome Project and related progress in molecular biology provide nearly endless opportunities for such approaches.

Tim K. Takaro

Twenty-four contributions from members of the scientific and regulatory communities describe what has been achieved and what has been accepted in alternatives to animal testing. Several advances make use of transgenic models that reduce the cost and time of carcinogenicity testing; others use tissue cultures for the assessment of endocrine disrupting chemicals. Still others discuss the use of human epidermal keratinocytes as models for sulfur mustard lesions, and in vitro protein denaturation as a chemical test for assessing the ocular and dermal irritation potential of cosmetic products. The methods described with help toxicologists, cosmetic chemists, and pharmacologists greatly reduce, refine, or even possibly replace the use of laboratory animals in their work. Annotation c. Book News, Inc., Portland, OR (booknews.com)

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