Abstract
“Fundamental Neuropathology for Pathologists and Toxicologists: Principles and Techniques,” edited by Brad Bolon and Mark T. Butt, 590 pages, published by John Wiley & Sons, Inc, was released on October 4, 2011. The volume has a retail price of $149.95. It has 35 chapters and divided into sections entitled: Fundamentals of Neurobiology, Toxicologic Neuropathology: Methodology, Toxicological Neuropathology: General Practices, and Applied Toxicological Neuropathology. Each chapter has different authors. There are 55 authors and coauthors, mostly from the United States, including 10 international scientists. The authors are generally employed in university settings, with additional authors employed in private research laboratories, the US Environmental Protection Agency, the National Institute of Environmental Health Sciences, and the National Center for Toxicological Research.
The editors, graduates of veterinary colleges, who have spent many years focusing on toxicological neuropathology, have designed a text for the general toxicological pathologist desiring more familiarity with neuropathology. As stated by the authors in their preface, the goal of this work was to provide a complete reference on the design and interpretation of studies involving toxicological neuropathology. In addition to pathologists, the book is aimed to assist toxicologists and other scientists involved in the investigation of neurotoxicity. Based on my review, I believe that the editors have achieved their goal.
The authors emphasize that the nervous system is a complex system that requires “more than a lifetime” to understand. To that end, this text addresses neuropathological approaches to understanding toxic effects, primarily effects on morphology. They gather a wide array of neuropathology resources to provide both introductory and advanced information needed to understand a wide array of neuropathological methods applied to toxicology.
In chapter 1, the authors point out that between 2000 and 5000 chemical products in the United States are estimated to be neurotoxic to some degree and that yearly more than 1 000 000 pounds of high production volume chemicals have never been tested sufficiently for neurotoxic potential. According to the authors, “regulators place more emphasis on morphological data than on behavioral or biochemical alterations to determine reference doses for assessing neurotoxic risk”, emphasizing the importance of neuropathology. Because neurotoxicity can have such devastating outcomes, and incurs an inordinate cost with regard to treatment and continuing care, neurobehavioral end points, including morphology, are highly significant for assessing risk. Emphasizing the importance of toxicological neuropathology, the authors eloquently assert that the correct identification of neurotoxic substances in laboratory animals is preferred to retrospectively discovering neurotoxicity after epidemics in humans.
Chapter 29 reviews the toxicological neuropathology in medical practice. This chapter will be helpful for the clinical neurotoxicologist when reviewing neuropathological data with regard to clinical cases. Chapter 34 is a regulatory guide to the histological assessment of neurotoxicity studies. Review of this chapter by the clinical neurotoxicologist can provide further insights regarding the development of regulatory standards. There are also 9 appendices that provide neurobiology information, including neural cell markers of potential utility for toxicological neuropathology applications. Again, this would be a helpful reference material as the clinical neurotoxicologist reviews cases.
One of the vexing problems affecting the ability to regulate chemicals is the sensitivity of the human nervous system and the variety of potential outcomes. For example, human executive dysfunction is a common outcome of neurotoxicity, as well as emotional disorders such as depression, anxiety disorders, and so on. These types of pathology are difficult to measure in nonhuman species. A rat or mouse may be able to adapt to relatively small impacts to their executive function and to their emotional function, so that behaviorally, the deterioration may be unnoticed by the laboratory personnel. However, a relatively small decrement in these functions could have a significant impact on a contemporary man or woman, especially as we become increasingly programmed in our daily lives from technological advances of modern society. In addition, psychological variables such as stress have been found to augment the effects of neurotoxicity. Such factors, as well as the possibility of simultaneous exposures to multiple neurotoxic substances, with the possibility of synergistic effects, hamper the regulator’s ability to determine safe exposure levels to single substances with regard to higher levels of human nervous system function.
The authors address these issues to a limited extent in chapter 7, “Cognitive Assessments in Nonhuman Primates.” The authors point out that “remarkably few animal models have been validated thoroughly in terms of their relevance to the human condition. This is one potential reason that many drugs, developed and tested in animal models, fail during clinical trials in humans. For a variety of obvious and not-so-obvious reasons that will not be detailed here . . . the monkey is the laboratory animal that most often best mimics humans . . . presuming then that the monkey is probably the best animal model.” The authors describe the use of standardized computer-based testing for cognitive assessments in nonhuman primates and its cross-relevance to human function. Of course, nonhuman primate testing is expensive, prohibitively so with regard to the large number of chemicals and drugs that need to be tested for neurotoxicity. In addition, such testing entails more effort in salving public relations, due to the closer similarity of nonhuman primates to humans.
Per the book index, less than 1 page in this text is devoted to discussion of hormones, and on that page, the authors note gender-specific hormones with regional differences in the quantities and circadian cycling of hormones and neurotransmitters. However, hormone disruption can be an important effect of neurotoxic substances.
In summary, the work can assist the clinical and translational neurotoxicologist, and toxicologist in general, in performing clinical tasks. The work offers the general toxicology pathologist an overview of the general field of neuropathology. The editors met their goal of providing a comprehensive reference on the principles and techniques of toxicological neuropathology. They compiled introductory and advanced information into a single reference source, to assist various scientists in understanding neuropathology as applied to toxicology.
Note to Readers
Publishers who wish to submit books to be reviewed should send their request for review along with the books directly to book review editor. Occasionally, books and monographs are published and reach the scientific community before publishers send courtesy copies to IJT for consideration as a text to be reviewed. If a reader would like a book or monograph re]viewed or would like to submit a review to be considered for publication in IJT, please submit your book, suggestion or manuscript to: