Abstract
Developmental and reproductive toxicology is a complex and important subset of the science of toxicology. The consequences of even some minor missteps during the reproductive process and/or the biology of the developing gamete/fetus can have devastating consequences to the very survival of that organism. Although much progress has been made in the field, our true understanding of the mechanics and etiology of abnormal development is limited at best. As with many subdivisions of toxicology, this discipline covers a host of different scientific areas of study, such as molecular genetics, animal reproduction, environmental contaminants, teratology, xenobiotics, toxicokinetics, and in vitro methods, that are rarely found collectively under the rubric of reproductive and developmental toxicology. Given the vast expanse of the reproductive and developmental biology, there simply have not been many, if any, publications that have successfully attempted to bring together in one place the many disciplines that constitute this field of study. With the publication of Developmental and Reproductive Toxicology—A Practical Approach, Ronald Hood and his collaborators have created a critical reference work that is a wealth of information with respect to developmental and reproductive toxicological testing, methodology, data interpretation, reproductive mechanisms, as well as regulatory considerations in the United States and abroad. This book is the best attempt to date to assemble all of the many facets of reproductive and developmental biology into one relatively complete volume. The publication has been significantly updated from the first edition entitled Handbook of Developmental Toxicology, published in 1996, to include cutting edge topics such as genomics, proteomics, toxicokinetics, xenobiotic metabolism, and neonatal and nonclinical juvenile testing. In addition, there are inclusions of the Environmental Protection Agency (EPA)’s endocrine disruptor program as well as the Food and Drug Administration (FDA) and EPA guidance and considerations in the review of data obtained in current reproductive and developmental testing protocols. Many international regulatory guidelines are also presented along with applications of these guidelines to real world interpretations of the meaning of these reproductive and developmental data. Hood is to be commended for assembling a stellar group of scientists with many years of practical laboratory experience, coupled with presenting in-depth evaluation and interpretation of these data and the latest research applications of the science in one volume. The book is a major step forward in this field and will become a hallmark as a reference guide in years to come.
Developmental and Reproductive Toxicology: A Practical Approach is divided into two sections: Section 1: Principles and Mechanisms, and Section 2: Hazard and Risk Assessment and Regulatory Guidance. The first section is further divided into six chapters. The first chapter provides a foundation for the reader to understand how the science has developed over the years and, interestingly, how, because of funding pressure, many of the recent study programs have focused almost singularly on cellular and molecular bases of reproductive toxicology while providing limited experience with the results of such abnormal development and the biological consequences in the whole animal. Chapter 2 describes the mechanisms of developmental toxicants whereas Chapter 3 provides the reader with the pathogenesis of adverse results. Primarily, the chapters in Section 1 concentrate on providing the reader with background information about the general mechanisms of abnormal development—from paternal (Chapter 5) and maternal origins (Chapter 4) as well as in the developing embryo itself (Chapter 3). Chapter 6 provides the reader with a vast amount of comparative embryological milestones on the rat, mouse, rabbit, hamster, guinea pig, rhesus monkey, chicken, and human. The chapters in this section are well written and clear in their descriptions and explanations of what is known and what is not known. Although there is considerable depth in this section, one can easily locate specific areas of concern from the extensive chapter outlines, references and indexing provided.
The second section is comprised of 16 chapters. Chapter 7 provides important details of study design, implementation, data collection, relevant compliance issues with government agencies, and review of reports and records to be maintained. Chapter 8 provides historical and scientific perspective on pediatric safety assessment. This chapter provides background on neonatal and nonclinical juvenile toxicity study design, model selection, parameters for evaluation, and statistical considerations. Chapters 9 and 10 describe the classical study designs in considerable depth from their beginnings in the 1970s through the most current protocols. The reviews are excellent and the evaluations provide deep insights of data interpretation in lucid, refreshing formats, which are most helpful for both the novice and seasoned reproductive toxicologist. Chapter 11 provides a timely update on the US EPA’s endocrine disruptor screening program and how those data are being evaluated for consideration into the final Tier I and II Screening Batteries. The chapter also provides some background on how these tests can add to the spectrum of reproductive knowledge. Chapters 12, 14, and 16 provide important discussions on the molecular and cellular components of reproduction and developmental toxicology, whereas Chapter 13 delves into the use of toxicokinetics in experimental design, data interpretation, and risk assessment. Chapter 15 provides the reader with background and theoretical perspective on the application of proteomics and genomics in determining the etiology of reproductive toxicants. Chapters 17 and 18 discuss the management of data statistics and quality control as they relate specifically to reproduction and developmental studies. Chapters 19 and 22 provide the reader with various comparisons, analyses, and perspectives of the regulators’ views and rationale for International Conference on Harmonisation (ICH), Organization for Economic Cooperation (OECD), FDA, and EPA data interpretation and testing guidelines. Chapter 20 addresses the analysis of human data. Each applicable epidemiological technique is clearly identified along with the confidence levels and confounding factors. Chapter 21 provides a thorough update from the first edition of reproductive toxicity risk evaluation for environmental agents. The chapters in section are also well written and clear in their descriptions and explanations of what is known and what is not known. With the extensive chapter outlines, location of specifics within each chapter is relatively easy.
Lastly, Hood has included over 200 pages of appendices that extensively cover the following topics:
Appendix A: Terminology of Anatomical Defects. This is an extensive glossary of developmental effects and includes a critical consensus manuscript that addresses this very topic in considerable detail.
Appendix B: Books Related to Developmental and Reproductive Toxicology.
Appendix C: Postnatal Developmental Milestones. This includes eight recent seminal manuscripts comparing human developmental milestones in various species with respect to (1) bone growth; (2) renal development; (3) lung development; (4) male reproductive system development; (5) female reproductive system development; (6) heart development; (7) and immune system development; and (8) functional central nervous system (CNS) development measurements.
The book provides these seminal manuscripts in their original publication form so that readers can access original information without having to further research critical papers in interpretation of reproduction and developmental data.
Hood and his collaborators have provided a compendium of important manuscripts along with an in-depth book that presents both practical approaches and theoretical concepts on reproductive and developmental toxicology. It is unparalleled in its thorough handling of huge amounts of diverse data covering many disciplines comprising the science/art of reproductive and developmental toxicity.
In summary, this book makes a substantial contribution to our understanding of reproductive and developmental toxicology. The field is rapidly expanding and, no doubt, further editions of this reference book will be forthcoming as the science proceeds forward. As of this date, however, it is one of the most comprehensive and definitive publications in the field and should be a mandatory addition to the libraries of students, researchers, and regulators alike in the field of reproductive and developmental toxicology.