Abstract
The 3rd edition of Ramesh Gupta’s “Reproductive and Developmental Toxicology” is the current update of the 2nd edition by the same title which was released in mid-2017. Dr. Gupta – Chair of the Toxicology Department at Murray State University in Kentucky – edited this comprehensive volume that contains 1556 pages. It includes 173 worldwide experts (9 more contributors than the previous edition). Over 50% of the contributors are from the United States. The 91 USA contributors are followed by Canada with 13 contributors; Spain and India with 11 contributors each; Russia has 6 contributors, while Brazil and Turkey each had 5 contributors. There were also contributors from the United Kingdom, Portugal, Switzerland, Denmark, Italy, China, Finland, Japan, Taiwan, Iraq, the Netherlands, and Germany. Dr. Gupta has once again assembled a stellar group of world-renowned experts in the field of reproductive and developmental toxicity in an updated and authoritative publication covering the most current literature and latest methodologies, as well as updated data on the effects of nanoparticles, radiation, gases and solvents, smoking, alcohol and drugs of abuse, and metals. In this compendium, the complexity of reproductive and developmental toxicology is examined in light of the effects on the parents, the placenta and the fetus. It examines the continuity as well as the myriad of changes noted amongst these three spheres as they affect reproductive outcome. The book is divided into 15 sections. The first Section (General) consists of 4 chapters (72 pages) that examine the basics, including anatomy and physiology, pharmacokinetics and adverse pathways found in reproductive and developmental toxicological studies. This provides the reader with rigorous reviews of the special concepts in the field, what constitutes normal reproduction, factors that affect the pharmacokinetics of pregnancy, PBPK modeling, and an in depth discussion of adverse outcomes seen in reproductive and developmental toxicology. Section II is entitled “Toxicity testing models, safety evaluation, and regulatory aspect.” This section contains 11 chapters (210 pages) which cover the details of the types of testing available, such as the OECD tests and purposes, what alternative methods are available, the use of in silico tools in reproductive toxicology, the use of in vitro biomarkers, juvenile testing, reproductive safety evaluation in drug development, the use of various organisms for screening large numbers of compounds such as the worm Caenorhabditis elegans in predicting abnormal development in mammals and providing a bridge between in vitro and in vivo reproductive toxicity studies. This section concludes with a thorough historical review of the USFDA’s involvement in drug development as well as continuation of their post marketing surveillance and regulatory considerations, whether the drug in question is for human or animal consumption and if it is a vaccine. The FDA must maintain a razor-thin edge to allow new development/out-of-the-box thinking and yet protect the public from unnecessary or harmful exposures. Section III contains 2 chapters (54 pages) which are devoted to nanoparticles (NP) and radiation and their effects on reproduction. The recent engineering of nanoparticles has added a new complexity to reproductive health because of the ease of transferability of NP across the placenta. In addition, there is evidence that some indirect effects may also occur with NP. The challenge is for researchers to adequately design the studies to identify as many potential adverse effects as possible. Radiation effects on reproduction are well known. There is an excellent review of the history of radiation and the resulting potential health effects, which include cancer as well as fetal effects going back to World War II. The controversy over the linear non-threshold response model continues along with the cloud of suspicion around the peaceful use of nuclear energy. Section IV is entitled “Gases and solvents” with one chapter (20 pages) that focuses on reproductive effects noted with common solvents and gases, such as carbon tetrachloride, tetrachloroethylene, toluene, benzene and gasoline. There is considerable exposure to industrial workers, as well as general populations, and each of the aforementioned substances can severely affect reproductive and/or developmental activities in mammals given the critical exposure period. Section V consists of 3 chapters (64 pages) and is entitled “Drugs of abuse and addiction, smoking, and alcohol.” This covers the complexities of drug abuse and the mechanisms involved, as well as animal models and details various types of addictive drugs. There is also an exhaustive review of fetal alcohol syndrome and what is known about the mechanisms. Lastly, this section provides an extensive review of the reproductive effects of tobacco and e-cigarette use. Section VI is “Pharmaceuticals, nutraceuticals, and food additives” and is divided into 6 separate chapters (108 pages) covering historical information such as thalidomide, as well as effects of retinoids, cannabis, CBD and hemp, caffeine, melamines and ionophores. Section VII covers metals and is divided into 5 separate chapters (86 pages): boron, arsenic/cadmium/lead, mercury, manganese and selenium. Section VIII is entitled “Pesticides, industrial and other environmental contaminants” and is presented in 13 chapters (294 pages) covering organophosphates, chlorinated hydrocarbons, herbicides, fungicides, flame retardants, dioxins, polychlorinated biphenyls, polycyclic aromatic hydrocarbons, bisphenol A, ethylene glycol, PFCs, environmental pollution from automobiles, personal care products and sunscreens, so this is a fairly comprehensive section. Section IX is entitled “Phytotoxicants and mycotoxins” and includes 4 chapters (86 pages) including toxic plants, fumonisins, aflatoxins and the mycotoxins trichothecenes and zearalenone. Section X is entitled “Special topics” and its seven chapters (144 pages) cover topics as varied as stem cells, drugs, nonmedicinal substances, and xenobiotics in breast milk, epigenetics in reproduction studies, the role of mitochondria in reproduction, cell signaling and neuroinflammation in developmental neurotoxicity, the effects of stress and general endocrine disruption. Section XI is entitled “Endocrine disruption” and is covered in 2 chapters (34 pages) and addresses this multidisciplinary area of research which involved both toxicology and endocrinology of chemicals affecting life processes and the effects of endocrine disruption in male infertility by COVID-19. Section XII is entitled “Infertility and teratogenicity” which is divided into 3 chapters (92 pages) which cover infertility, environmental effects on neural tube development, and an thorough overview of teratogenicity. Section XIII is entitled “Toxicologic pathology” which discusses the great number of threats to reproduction in an industrialized setting and how one can characterize the effects (36 pages). Section XIV is entitled “Placental toxicity.” It has 5 chapters (98 pages) which provide a review of exactly what is known about the placenta and its function in placental transfer and how that can affect the developing fetus; another chapter in this section discusses various aspects of hemochorial placentation where maternal blood contacts the fetal chorion. Another chapter reviews the significance of ABC transporters in the human placenta when exposed to xenobiotics; placental toxicity and pathology are also presented. Lastly, Section XV is entitled “Domestic and wildlife species” and contains 3 chapters (64 pages) that cover endocrine disruption and teratogenicity in wildlife, teratogenic plants, minerals that can cause severe issues in domestic animals, as well as effects seen in avian species. Lastly, the publication has a comprehensive 46 page – triple-columned index, and the e-book version that I had a very workable search function. The cross referencing was adequate and the links to all the references were helpful. The complexity of the subject is underscored by the breadth and depth of this third edition. Dr. Gupta has successfully overseen the updating and integration of the latest methodologies that even discuss effects of COVID-19, with well over 1000 new references since the second edition was published in 2017. There is new text on predictive modeling and adverse pathways, as well as air pollution relative to neurotoxicity. It also contains critical current discussions of the issues of reproductive interference and infertility associated with nutraceuticals, pharmaceuticals, plastics, hemp/cannabis and CBD, and sun screening chemicals. The hallmark of the book is that is amasses an extraordinary amount of information in a logical format dealing with the mother, the placenta and the fetus and how these interact to create life and present possible adverse effects. The format is easy to use and the logic of the organization of the material is spot on. One would need a massive library to accumulate the breadth of knowledge and publications referenced in this third edition of Reproductive and Developmental Toxicology. This volume is a clearly the most updated source of reproductive data available in this format. I highly recommend this book to students and/or practicing toxicologists alike without hesitation. Truly an enlightened resource for reproductive toxicology.
Book Review Editor
Robert W. Kapp, Jr