Abstract
The book begins with an attempt to define the scope of this multifocused work, describing each of the chapters, their authors, and the basic content of each of the chapters. The topics undertaken under this cover clearly have a common thread but seem beyond the capability of 1 volume. I note that this book is about the same size as the first Edition of “Dioxins and Health” and, considering the multiple additional topics addressed here, one wonders what information about dioxins is being eliminated in order to accommodate the additional topics including other persistent organic pollutants (POPs), flame retardants, and endocrine disruptors. The introductory comments are followed by a listing of tables and figures which I find to be a refreshing approach for the person seeking hard data such as toxicity equivalence factors (TEFs) without having to resort to the index. However, the compilation of data tables gives one pause because of the apparent random way in which the work is organized, mixing the various subjects in almost a random fashion.
The first chapter on POPs outlines how this loose class of materials are defined via the commonality of their persistence in the body due to their lipophilicity and their resulting toxicity. Chemical structures are presented and residues in human tissue are shown in a table. This led to a discussion of how some of these materials are similar to dioxins, that is, dioxin-like compounds (DLCs). This is a very important part of the integration of POPs into dioxin toxicity and carcinogenicity. The chapter goes on to address nondioxin-like polychlorinated biphenyls (PCBs), brominated biphenyls, and diphenylethers and effects on the thyroid and central nervous system. Hexabromocyclodecane and a number of fluorinated long-chained carboxylic and sulfonic acids are then addressed in some detail and differences from the highly lipophilic chlorinated and brominated compounds are addressed, and the effects of differences in chemical structure on potential health effects are noted. In short, this chapter lays the groundwork for addressing in more detail each of the different classes of chemicals addressed in this work and the common thread that holds them together and allows their discussion in the ongoing chapters. Chapter 2 describes the latest values for the TEFs for dioxins and related compounds, but it also describes the logic and foundation for calculating these values for polychlorinated dioxins and dibenzofurans as well as the uncertainties involved in using the TEF methodology. Also addressed are the compounds that are not addressed by the TEF methodology, including brominated dioxins and dibenzofurans, among others. Also mentioned is the future direction of assessing risk from not just a single DLC but multiple chemicals that may interact to produce an additive or synergistic effect.
The next chapter addresses the issue of POPs in foodstuffs. This ties in where the last chapter left off in which it describes the numerous substances to which humans are exposed in their diet. Whereas it has been known for some time that traces of PCBs and dioxins have been found in our food supply, now a whole host of other POPs has been identified. This chapter goes into extreme detail about the extent of this contamination, including detailed tables which contain extensive quantitative data on the subject. Data are included from various countries and from various food sources including fish, meat, poultry, eggs, dairy products, cereals, fruits, vegetables, and other foodstuffs. It is basically a compilation of data from North America, Europe, Asia, and Australia and would be very useful for someone seeking this reference material.
Chapter 4 focuses on flame retardants, including the polybrominated diphenyl ethers (PBDEs) as well as their chlorinated and brominated replacements. Chemical structures are presented, distinguishing the various classes of chemicals as well as a timeline of awareness and action relating to specific flame retardants. Exposure scenarios are then discussed, including diet and sources of contamination of indoor air. Effects on children are only marginally addressed here as is the toxicology of PDBEs. The amount of detail presented under the different subchapters is somewhat disappointing compared to the previous chapter.
Chapter 5 brings us back to dioxins with a discussion of the pharmacokinetics, including a detailed table showing individual dioxin and PCB congeners and the gastrointestinal absorption of each in humans of various ages. This is followed by a brief discussion of dermal absorption and an even more limited discussion of inhalation exposures. Tissue distribution in animals and humans is discussed in some detail including the dynamics related to various dioxin and dibenzofuran congeners in the liver and adipose tissue. Metabolism and excretion mechanisms are addressed and the toxicity of metabolites for dioxins and PCBs are also discussed. One of the tables in this chapter looks at half-lives of specific congeners from individuals. The table is quite extensive and has allowed for some indication of the effects of age, body fat, smoking status, dosing level, and breastfeeding on the rate of elimination from the body. Pharmacokinetic models are then addressed in normal and special populations, including prenatal and postnatal exposures. Overall, the chapter delivers as promised in the title.
Chapter 6 addresses the effects of POPs on the immune system but initially provides a tutorial on the immune system and the potential adverse effects that may occur under the influence to immune toxicants. A discussion of the immunosuppressive effects of dioxins and PCBs in humans and animals follows. Mechanisms are then addressed, followed by effects of other POPs, including an even more detailed discussion of the immunomodulatory effects of perfluorinated compounds, chlorinated pesticides, and tributyltin (TBT) compounds. It is not clear how TBT fits into this chapter or this book, other than the fact that it does modulate the immune system as shown in in vitro studies and in animals. The authors do not provide any foundation as to why TBT and TBT oxide should be included here and why it should be considered as a POP.
Developmental neurotoxicity of dioxins is addressed in chapter 7 of this book. The focus here is on dioxins and PCBs and their devastating effects on the developing nervous system through in utero and neonatal exposures. Detail is presented on Identified mechanism and tutorials on factors that regulate neurodevelopment, neuronal apoptosis, and neurogenesis, after which a further discussion of the involvement of the aryl hydrocarbon receptor as it is involved in dioxin neurotoxicity. Experimental studies investigating molecular and cellular effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in model systems are described. This is followed by several detailed experimental studies in animals. This chapter contains information critical to understanding the risks of exposure to dioxins particularly at an early age. It is well organized and pertinent to the overall mission of the work.
Chapter 8 launches into perfluorooctanoic acid (PFOA), an industrial chemical that is highly stable as a result of very strong carbon–fluorine bonding. Unlike the long half-lives of elimination of the more heavily chlorinated dioxins and PCBs, the half-life here is measured within a few years, and yet it is apparently still considered as a POP. Discussions follow related to information suggesting an effect of PFOA on cholesterol and uric acid levels. This is followed by epidemiological data addressing its effects on cardiovascular disease, cerebrovascular disease, diabetes, and cancer. Then the effects on immune, thyroid, liver, and kidney function are discussed in detail as well as the effects of PFOA on sex hormones, development, and function. Particular emphasis was placed on male and female reproductive systems via epidemiological studies. The authors conclude by acknowledging the limited available information on PFOA but clearly raising a red flag. The chapter was done well but the appropriateness of including PFOA as a POP is questioned.
Chapter 9 is devoted to the brominated dioxins and dibenzofurans. After displaying chemical structures, the authors proceed to look at physical properties of congener grouping bases on degree of chlorination, including partition coefficients. It would have been useful to include dioxins and dibenzofurans as reference points in this table. Sources of polybrominated dibenzodioxins (PBDDs) and furans are noted to be formed by the combustion of brominated flame retardant mixtures. A detailed scheme showing their formation from thermolysis of various brominated flame retardants and a table presents the results of several thermolysis studies. Most of this chapter addresses the various sources of PBDDs and PBDFs including their presence in flame-retarded plastics, their formation in industrial processes, municipal waste incinerators, motor vehicle exhaust, textiles, and recycling operation. A discussion of the analytical methodology follows, using high-resolution gas chromatography and mass spectroscopy and the problems related to decomposition in the injection port of the gas chromatograph. Environmental distribution follows with numerous examples in tabular form of measured contamination. Indoor dust, soil, sludge, sediment, and biota contamination are discussed followed by findings in humans. This is followed by a discussion of congener profiles in various media from a variety of sources. Finally, the toxicity of PBDDs and PBDFs are discussed with most of the emphasis on chronic toxicity in animals and a large table of findings using an in vitro assay (DR-CALUX), indicating relative potency of various congeners in that assay. This is followed by brief sections on neurotoxicity, endocrine effects, pharmacokinetics, and bioaccumulation. Brief discussions of mechanism and TEFs bring this section to a conclusion. The section contains what I would estimate to be an up-to-date account of PBDDs and PBDFs.
Throughout the chapters, acronyms are used freely and are defined in the text but they should also be defined when used as subchapter headers. This is clearly a problem for those not totally immersed in the subject matter at hand.
Chapter 10 addresses cancer epidemiological issues related to dioxins and provides a fine summary of the current knowledge related to human exposures to dioxins and the consequences thereof. The authors, however, have reserved some specific incidents for later chapters in the book. Once again, headers of chapters use acronyms. Various studies from the United States and elsewhere are summarized in a concise manner and offer the reader a quick look at a mass of data with appropriate references for follow-up. Issues involving 2,4-dichlorophenoxyacetic acid and 2,4,5-trichlorophenoxyacetic acid and their potential contamination by dioxins are included here, and the studies that are summarized are categorized by the diseases with which they are associated, that is, soft tissue sarcomas, malignant lymphomas including non-Hodgkin lymphoma, multiple myeloma, leukemia, nasopharyngeal cancer, and other cancers. This is followed by various cohort studies describing the incidence of disease in various industries dealing with herbicides, Vietnam veterans, tannery workers, and farmers. Additional information about the Seveso and Yusho/Yucheng studies as well as paper mill workers and other human exposure situations are described in fine summaries; then other chlorinated compounds, including PCBs, are addressed, culminating in general conclusions that include the positions of various regulatory bodies relating to these compounds. This is a long chapter but it provides the reader with a capsule of the health issues related to dioxins and related compounds.
How appropriate that chapter 11 should also address epidemiology but relating to the very important issue of reproductive and developmental epidemiology of dioxins. The chapter begins by defining dioxin such as TCDD, the most potent of the dioxin congeners. A brief discussion of biomarkers follows. Then, the literature is reviewed with a discussion of various incidents which involved more than dioxin as initially defined and also PCBs and chlorinated dibenzofurans. Various developmental and reproductive parameters are addressed in response to dioxin and related compounds including neonatal growth patterns, breast development in females, congenital abnormalities, stillbirths, and neonatal deaths among exposed populations. Both maternal exposures and paternal exposures and the consequences of both are discussed. Once again the Seveso disaster is addressed and reproductive/developmental consequences described. The chapter concludes with a section recommending specific areas of future research. Once again, this is a useful chapter giving the reader a capsule of the issues and some insight into the overview of what is known.
In the middle of all of the information about dioxins and similar compounds chapter 12 is entitled “Bisphenol A”. It just does not seem appropriate here, and if one were searching for information on bisphenol A (BPA) would one look in a book entitled “Dioxins and Health”? The introduction provides no segue into the topic at hand but launches directly into a section on physical properties and where BPA is found in our environment. Then, we progress to its endocrine disrupting properties, human exposures, and biomonitoring, which basically is the analytical chemistry of BPA. Toxicokinetics follows and then effects in humans are addressed. It is clear that BPA is not persistent, having a short half-life of elimination, but it is an endocrine disruptor. The chapter goes on to discuss possible carcinogenic responses or lack of reproductive, metabolic, and developmental outcomes, growth. and neurodevelopmental effects of BPA and points out the paucity of data which exists on the human effects of BPA. This sets the stage for a discussion of various animal studies describing effects on prostate, reproduction, mammary development, and behavior in various animal models. The chapter concludes with regulatory concerns and suggestions for future research. I am not certain that BPA issues are addressed fully here but the chapter again provides an overview of current thinking and knowledge of BPA.
Another intrusion into the continuity of the book is the next chapter on phthalates. It might have been best to include this and the previous chapter as the final 2 chapters in the book, but this would have looked like they were added as an afterthought. Phthalates are described here as another class of endocrine disrupting compounds (EDCs). Initially, the chapter describes how phthalates disrupt various systems and why they are called EDCs. This is followed by a description of human exposure to phthalates and why we are concerned about phthalates in our personal environment. Numerous phthalates are described chemically and various human health effects are described in a table, including developmental effects and pregnancy outcome. Neurological development in neonates exposed in utero is described based on a few limited studies. Asthma and allergy in children is briefly mentioned as there are limited data related to this effect. Phthalates are also described as having effects on adults, including sperm quality, respiratory and allergy effects, metabolic and thyroid problems, but limited data are available.
Chapter 14 describes the July 1976 Seveso Accident resulting from a run-away reaction in the manufacture of 2,4,5-trichlorphenol. Potentially, more than 200 000 persons were exposed. This is a fine account of the details of the incident, the demeanor of the people at the time, the extent of human exposure and dose, and finally the health effects that included chloracne, reproductive problems in men and women, semen quality, and reproductive hormones. Various female health problems were summarized in tabular form and ranged from reproductive problems to thyroid disruption while another table describes cancer mortality from 1976 to 2001 and another table looking at cancer incidence from 1977 to 1996. Other noncancer effects are described. This chapter represents an insider's view of what happened in Seveso and describes the results of the human experiment which ensued.
Continuing with the main focus of the book, chapter 15 describes the “Agent Orange” health issue in Vietnam, Cambodia, and Laos, with emphasis on the exposed native population as well as the US military force who were also exposed. “Agent Orange” is the herbicide that was sprayed during the Vietnam War in order to defoliate the forest and expose the enemy population. It was largely 2,3,5-trichlorophenoxyacetic acid but much of it contained dioxin (TCDD). After being introduced to the situation, the chapter goes on to describe the history of using herbicides in the military and the quantities used in Vietnam, including the acreage sprayed as well as the populations that were exposed and the areas that were sprayed most heavily. As the chapter progresses so does the account of the state of developing knowledge and those involved including Dr Schecter, coauthor of the chapter. Identification of hot spots and efforts made to mitigate situations found in various military facilities follows. The discussion then expands to Cambodia, Laos as well as Vietnam. Descriptions of various health studies in US veterans of the war, including those involved in the “Ranch Hand” study follows, with US Congressional action related to dioxins, including those health conditions identified as being related to Agent Orange exposure, including birth defects. Then the chapter progresses to studies of the health effects on Vietnamese people. The chapter concludes with a notation that the base of knowledge about dioxins is still expanding. This fine account of the “Agent Orange” issue is replete with personal insights by the coauthor of the chapter and is supported by many references related to the science and to the other publications that describe the details of the contamination and efforts to remediate same.
Chapter 16 addresses the Yusho and Yucheng rice oil poisoning incidents. Again, while Dr Schecter is well familiar with the incident and its consequences, he coauthors the chapter in order to bring additional detail and local perspective to the table. While these are PCB food contamination incidents they clearly indicate polychlorinated dibenzofurans and other polychlorinated polyaromatics are involved. The chapter details the extent of contamination in rice oil and lists many of the toxic agents found in blood and even provides extensive epidemiological information showing ranges of blood and organ contamination as well as some of the physiological effects. The latter includes symptomatology and long-term effects as well as one of the classical signs of exposure to these materials, chloracne. The chapter goes on to delve further into effects on adults and children including the incidence of cancer. The chapter is very well written and is a welcome addition to the knowledge base on PCBs, dioxins, dibenzofurans, and other similar compounds.
Chapter 17 describes an incident in Binghamton, New York related to a transformer fire in the basement of a large office building which eventually required its evacuation and discarding of much of its content. Dr Schecter was living in Binghamton at the time and was involved in the incident from the beginning. The transformer in question contained about 60% of PCBs and about 40% tri- and tetrachlorobenzenes which, when burned, were converted to dioxins and dibenzofurans. The chapter describes sampling and toxicology studies that were carried out as well as contamination limits for remediation activities at a time when little or no data for acceptable daily intake were available. The story is well presented with personal insights that add to its utility.
The Yushchenko dioxin poisoning incident is addressed in chapter 18. Of particular interest are the before and after photos of Victor Yushchenko. The sequence of events involving his poisoning with TCDD are presented in tabular form as well as his symptomatology and treatment, thereby providing the reader with a summary of most aspects of this incident.
The final chapter of the book relates to POPs, encompassing a broader scope of chemicals that show some similarity to the dioxins and PCBs and, in some cases, include brominated structural analogs to these compounds. Many pesticides that have been widely used in the past are discussed, including DDT, dieldrin, mjirex, and so on. The Stockholm Convention identified and participants agreed to reduce the use of many of these persistent compounds. Risk assessments have been carried out on many of these compounds and the results from various agencies are presented in tabular form. Discussions of the various classes of POPs, including supporting references from the scientific literature are included. Even though this chapter goes far beyond the dioxin question, it seems to be appropriate as the final chapter to set the stage for creating an awareness of the risks associated with materials that persist in the environment and in the body.
In sum, the book is well written and certainly, no one will dispute Dr Schecter’s knowledge and personal insights into the risks of exposure to DLCs. He begins with a discussion of POPs and concludes on the same note. Many of the chapters presented are devoted to POPs and the book might be better entitled something other than “Dioxins and Health” since a good part of the book addresses other issues. Although I could see it including POPs since the issues presented are similar to those of dioxins, but including “Endocrine Disruptors” in this work seems inappropriate. However, the “Endocrine Disruptors” chapter is well written and informative; however, it just does not flow with the main theme of the book. I did not find that the chapters on phthalates and on BPA were particularly appropriate for inclusion in this work. I found the accounts of incidences of gross contamination presented in chapters 14 to 18 to be of particular interest with the personal insights being much appreciated.
This book is certain worthy of a place on your bookshelf if you are interested in environmental contamination or POPs in general.
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