Abstract
Temperature and Toxicology: An Integrative, Comparative, and Environmental Approach is a unique textbook in the fields of thermoregulation and toxicology. It provides a platform for understanding toxicology research in the context of temperature regulation. Author Dr. Christopher Gordon is a scientist at the U.S. Environmental Protection Agency located in Research Triangle Park (North Carolina) and is a world-renowned expert and contributor in both fields of research.
Temperature is among the most pervasive, nonspecific, and universally influential parameters known to affect biophysical and biochemical processes, including the action of toxicants. In fact, on the one hand, xenobiotics and natural toxic agents substantially affect regulation of body temperature in animals, and, on the other hand, temperature itself feeds back on their metabolic regulation. These complex interactions are often overlooked in designing the experiments and interpreting the data, both in in vivo and in vitro settings. In the book, Dr. Gordon makes an attempt to define these problems by combining a wealth of carefully selected data into a text that provides a clear cut message: toxicologists, and perhaps all researchers in the field of biomedicine, should be concerned with the regulation of temperature while studying processes at the level of whole organism.
The text is divided into 10 well-presented, sufficiently illustrated, and easy to read chapters. A list of over 500 references cited is assembled at the end of the book, followed by an alphabetical index.
Chapter 1 provides introductory information on the unique nature of thermoregulation as a hallmark of homeostasis, justifying a question of “why should toxicologists study temperature?” The chapter concludes with an excellent preview of the whole book, defining three approaches to studying temperature and toxicology: an integrative, comparative, and environmental approach. An integrative approach is paramount in temperature regulation because this system can only be studied in the intact organism.
Chapter 2, one of the pivotal chapters of this contribution, deals with principals of the temperature regulation. It defines thermoregulation in sufficient detail that scientists who have little training in thermal physiology can easily understand this phenomenon. The author emphasized the thermoregulatory responses of rodents, which is justified considering that much of the toxicological data presented in the book focuses on these laboratory species. The introduction of radio telemetry in monitoring a variety of physiological measures such as temperature, motor activity, heart rate, and blood pressure, among others, in freely moving and unstressed laboratory animals has thus far revolutionized the exploration and data acquisition procedures in biomedical research. The technique provides new approaches also in toxicological research. Investigation in toxicology and temperature regulation may create a basis for novel terminology in defining aspects of thermal biology. Accordingly, in this chapter Dr. Gordon introduces novel terms such as regulated hyperthermia and forced hyperthermia, as well as regulated hypothermia and forced hypothermia to describe behavior of the rodents in the context of the effects of toxicants on body temperature. These terms are somewhat debatable and may be confusing, since they have not yet been defined in the literature and a glossary of the IUPS Thermal Commission. The author applied this terminology in addition to more commonly used and well-defined terms such as anapyrexia ascribed to as regulated decrease of body temperature (i.e., reverse to fever) as well as hyperthermia and hypothermia, which are defined, respectively, as nonregulated increases and decreases of body temperature. It indicates that, in general, the thermoregulation as a discipline is active and rapidly expanding with the help of toxicology studies.
Chapters 3 through 5 emerge as a logical result and consequence of Chapter 2. Chapter 3 describes aspects of the acute effects of toxicants on regulation of body temperature. It is the largest chapter in the book. It covers the thermoregulatory effects of a large variety of factors. Studies revealed hypothermic effects, i.e., inducing a drop of body temperature, of agents, such as organophosphate and carbamate pesticides, possessing anti-cholinesterase activities, chlordecone, which is a chlorinated hydrocarbon insecticide, airborne toxicants such as ozone, carbon monoxide, and oil fly ash. Similar effects have been detected in studies using metals, alcohols, and organic solvents. Relatively few toxicants elicit a hyperthermic response. Among them are DDT and agents possessing the ability to uncouple an oxidative phosphorylation, e.g., 2,4-dinitrophenol. This chapter discusses in great detail the mechanisms of these effects.
Chapter 4 addresses a question of the effect of body temperature on toxicity of agents, i.e., how the body thermal state may affect the toxic activity of toxicants, whereas Chapter 5 provides arguments for conclusion that regulated hypothermia constitutes an adaptive response to the toxic insult.
Chapter 6 presents data on the hyperthermic and febrile effects of toxicants, including author’s own research on the effect of cholinesterase-inhibiting (anti-ChE) insecticides on changes in body temperature. Rather than a response to the xenobiotic toxicants, fever is generally ascribed to as a nonspecific defense response to infectious agents, i.e., involving immunologic factors, such as cytokines, complement, eicosanoids, and acute phase reactants, among others. Dr. Gordon provides evidence that elevation of body temperature following the exposure to antiChE agents may be regarded as fever. It has recently been shown that enzyme systems such as heme oxygenase and cytochrome P450 may be involved in fever induced by infectious agents, constituting, therefore, a metabolic link between the immune elements and the systems that may directly be affected by toxicants.
Chapter 7 explains an impact of environmental stress on metabolic effects of toxicants. The physiological response to a toxicant is determined by three factors: nature of the toxic agent and its dosage, the subject, and the exposure situation. Many natural as well as artificial physical factors alter a physiological response. Dr. Gordon focuses on the thermal stress provoked by exposure to various thermal conditions, exercise and work activity, psychological stress including a stress of handling and restraint. These factors in combination with toxicants may generate an environment, which seriously affect a human well-being. Among them is Gulf War syndrome which is also discussed in the Chapter 7.
Chapter 8 describes ecotoxicology and importance of a comparative approach in toxicology. Studies using insects, fish, amphibians, as well as unicellular organisms in addition to endothermic homeotherms such as mammals and birds are critical in understanding the global effects of xenobiotics. Comparative studies are particularly helpful in unraveling the physiological mechanisms underlying adaptive behavioral and thermal responses to pollutants and stressful conditions, such as low oxygen supply.
The influence of genetic variability on the thermoregulatory response to toxic insults is depicted in Chapter 9. Genetic variation within a strain, selective breeding, and quantitative trait loci were used as tools in number of toxicology studies identifying genetic and molecular markers involved in behavioral and thermal reactions to toxicants. One of them is expression of heat shock proteins, a factor initially discovered in Drosophila melanogaster exposed to heat, which rendered the fly tolerant to subsequent heat shock episodes. The implications of heat shock protein responses in human health and toxicology are enormous.
The book concludes with Chapter 10 describing the effects of natural toxins and venoms on thermoregulation. Many of these toxins have a profound economic impact on key agricultural species and represent a significant human health hazard. Among them are fungal toxins found in grain and grass used for grazing. These toxins may cause a pathological condition known as fescue toxicosis often associated with a sharp increase of core body temperature resulting in a thermal stress of grazing animals. Elevated environmental temperature is a key facet in the manifestation of the thermoregulatory stress in fescue toxicosis. The neurochemical mechanisms of fungal (endophyte) toxins on temperature regulation are not sufficiently understood. It is interesting that hyperthermic effects of these toxins under heat stress are similar to actions of amphetamine-like compounds on thermoregulation.
In summary, this book is well-written and is a significant contribution to the field of thermoregulation and toxicology. It explains a complexity of the interactions between toxicants and temperature at the level of intact organism in a clear concise fashion. The book was written by a distinguished expert in the field and is supported by solid literature research and selection. It is a “must read” by students and researchers dealing with various disciplines of biomedicine.