Maria Marino
Published: 2007-01-01
Total Pages: 179
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In recent years, it has become evident that many chemicals present in the environment can mimic, antagonize or alter the physiological actions of endogenous hormones. These compounds have been termed endocrine disrupters (EDs) and defined as exogenous substances that cause adverse health effects in an intact organism or in its progeny, consequent to changes in endocrine function [1]. EDs, even when present in minute amounts (part per trillion), could interfere with the synthesis, secretion, transport, metabolism, binding, action, or elimination of natural hormones responsible for homeostasis maintenance, reproduction, and developmental processes [2]. Currently more than 100 chemicals have been identified as EDs. Within this heterogeneous group of molecules we find: (a) synthetic chemicals used in industry, agriculture, and consumer products; (b) synthetic chemicals used as pharmaceutical drugs; and (c) natural chemicals found in human and animal food. About half of these compounds are substituted with halogen groups, mostly chlorine and bromine, and include dioxins, polychlorinated biphenyls, organochlorine pesticides, methoxychlor, dieldrin, and hexachlorocyclohexane. EDs have long environmental half-life resulting in a continue increase of their global concentration in the environment and can be detected and may concentrate at great distances from where they are produced, used or released. EDs have very low water solubility and extremely high lipid solubility, leading to their bioaccumulation in adipose tissue. Exposure to EDs can occur from a number of different sources: humans and animals can be exposed involuntarily by drinking contaminated polluted water, breathing contaminated air, ingesting food, contacting contaminated soil or even in the workplace. Although endocrine disruption has only received high-profile attention for just over a decade [2], the phenomenon does have a longer historical background. In the early 1900s, pig farmers in the USA complained of fertility problems in swine herds fed on moldy grain [3], and concern was stimulated in the 1940s by reports of infertility in sheep grazing on certain clovers in Western Australia [4]. Over the following two decades, estrogenic actions were evidenced in birds [5] and in mammals [6] owing to the dissemination of the agrochemical orto-dichlorodiphenyltrichloroethane (DDT), at the same time masculinization of bivalves and gastropods[7], with concomitant declines in population, was found in the 1970s with the introduction of tributyltin into antifouling paints for the boats, while feminization of fishes was observed in UK rivers in the presence of estrogenic components in sewage effluent [8]. Also the occurrence of genital abnormalities in both male and female alligators in Lake Apopka (FL, USA) were observed as effect of a spill of the pesticide difocol in 1980. After these first observations the scientific community increased the awareness of the consequences of exposure to chemicals which can interfere with reproductive functions [9]. Endocrine disruption in wildlife is now acknowledged to be a widespread problem, much resulting from environmental pollution, and, in the case of aquatic forms of wildlife, from the continuous exposure to these chemicals in the water. Extrapolation of the results of these researches on wildlife resulted in concern that the same compounds could interfere with hormone action in humans. Handling hazardous substances and the risk of exposure to chemicals are a painful part of modern life, as technology and science progress. Moreover, exposure to chemicals present in foods, at home, and at work is an important risk factor for human health, especially since our scientific knowledge is still not sufficient to ensure proper prevention. Nowadays there is justifiable concern that endocrine disruption could be the underlying cause of increasing female and male reproductive problems, thus endocrine disruption is one of the topics receiving much attention throughout all sectors of the society, and the debate between pharmaceutical companies and public health organisms is increasing. Both parts will call for urgent need of more research. The scientific challenge for the future is to identify the relevant real-life sources of exposure of the human population to endocrine-disrupting compounds and to find the appropriate remediation actions. This can be done: (a) by assessing the impact on human health of long-term, low-dose exposure to such chemicals; (b) by understanding the synergistic effects of the copious number of chemicals to which humans and animals are exposed; (c) by defining the variety of underlying mechanisms at molecular, cellular and physiological level, (d) by exploiting new technologies addressed to the remediation of the environment polluted by the presence of EDs, and (e) by designing and developing new sensors or biosensors capable of determining their concentration in traces. The review presented in this book has been written under the sponsorship of the Interuniversitary Consortium National Institute of Biostructures and Biosystems (INBB) , constituted by 26 Public Italian Universities. INBB is stimulating the research on endocrine disruptors, by encouraging and coordinating joint research projects between its members and those of other Italian public scientific institutions. This book represents one of the results of the meeting The biological and clinical research on endocrine disruptors: current status and perspectives , held in Rome during 2005 from October 27 to 28 and organized by INBB and ISPESL (Istituto Superiore Prevenzione e Sicurezza del Lavoro). The first three chapters of this book review the EDs effects on natural population living in aquatic ecosystems where EDs, due to their lipophilicity, tend to concentrate in sediments and in food webs. The edible mussel Mytilus (Chapter 1), a marine bivalve that can accumulate large amounts of organic contaminants, represents a species of economical, ecological and public health-related interest. Amphibians (Chapter 2) are favourite models for studying various aspects of reproduction, development of the central nervous system and metamorphosis. Moreover, there is great concern about the EDs and the dramatic decline of wild amphibian populations. In Chapter 3 different species of fishes are considered as experimental models to analyze, by both genomic and proteomic approaches, the expression of key molecules involved in reproduction and in detoxification processes. The following two chapters focus on the EDs effects on thyroid functions and on the development of central mechanisms controlling reproduction. Wildlife observations in polluted areas clearly demonstrate a significant incidence of thyroid imbalance in several species. Several EDs are now known or suspected to be thyroid disruptors altering thyroid economy at multiple levels. These compounds may interfere with thyroid homeostasis through many mechanisms of action, at receptor level, in binding to transport proteins, in cellular uptake mechanisms or in modifying the metabolism of thyroid hormones. Chapter 4 offers a focus on endocrine disrupting activity of chemical compounds on thyroid function. The dimorphic control of reproductive functions depends on the ability of the central nervous system, particularly the hypothalamus, to respond properly to circulating reproductive hormones. This ability is acquired during a perinatal critical period, when the presence of different levels of sex steroid hormones in male and female fetuses/neonates induces a sex-specific morpho-functional development of the neuronal networks controlling reproduction. The perinatal stage is thus particularly sensitive to endogenous or exogenous substances that interfere with the activities of sex steroid hormones. Chapter 5 summarizes the current knowledge on the neuro-endocrine disrupting potential of the perinatal exposure to the major classes of EDs focusing the attention on animal studies aimed to identify the EDs action mechanisms and the resulting impairment of the reproductive behavior. Flavonoids are defined as naturally occurring molecules of plant origin, capable of acting as hormone mimetics or antagonists, but also as endocrine disruptors. Many of them have been marketed as dietary supplements or nutraceuticals with health claims, thus leading to significant increase in flavonoid consumption levels in the Western population. Even though several reports suggest for these compounds health-promoting effects in preventing age-related diseases such as atherosclerosis, hormone-dependent cancers, and osteoporosis, the mechanistic aspects of their activity have not been fully clarified and a wide consensus of the pros and cons of their use in humans has not been reached by the scientific community. Chapter 6 presents an overview of the state of the art of the knowledge on the molecular mechanisms underlying flavonoids estrogen-like activity. Feed additives represent a major issue for the safety of foods of animal origin, as they constitute the bulk of chemicals used in animal production. Feeds can also be a major vehicle for human dietary intake of persistent EDs (Chapter 7). Farm animals ingest these substances with food and drinking water and it is likely that the range of ingestion will increase in the future as growing amounts of sewage sludges are recycled onto agricultural land with an overall increase of environmental contamination exerting adverse effects on human health. Research on how the exposure to EDs affects human health in the work environment (Chapter 8) attracts increasing attention among international scientists. Certain workplaces pose particular problems as regards the potential risk connected to processes involving the use, manufacture and handling of these chemicals, and the type of job that puts workers at greatest risk of contact with them. Some EDCs represent occupational risk factors credibly capable of inducing hormone-dependent tumors. Occupational exposure to EDs is a highly complicated question: risk factors in the workplace must be identified; how they penetrate the body has to be established; confounding factors in everyday environments are numerous, and it is hard to make a definite diagnosis of their effects on human health. Owing to the harmful health effects of EDs, the attention of many scientists has been attracted towards the remediation of environment polluted by their presence and the design and development of sensors or biosensors capable of determining their concentration in traces. In Chapter 9 the experimental results concerning the enzymatic remediation of waters polluted by Bisphenol A (BPA), taken as a model of endocrine disruptors, is discussed in view of the potential application of the technology of non-isothermal bioreactors to the treatment of polluted waters. Also the functioning of a tyrosinase-based sensor able to measure the BPA concentration in traces is presented in the same chapter. These reviews emphasize that many environmental chemicals possess endocrine-disrupting properties, and that exposure to such chemicals can have adverse effects on health and reproduction even at very low concentrations. Great care should be used when attempting to apply these data to other species or real life situations. Indeed only a paucity of information is available on the metabolism and tissue distribution of these chemicals which may vary according to species physiology as well as to levels and duration of exposure. Furthermore, the possible interactions between single contaminants of the complex mixtures present in the environment may induce completely unpredictable effects, due to synergies or reciprocal inhibition effects, suggesting great caution in drawing conclusions. It is hoped that these reviews will serve to stimulate further research on EDs and human health. References 1.Report of the proceedings of the European workshop on the impact of endocrine disrupters on human health and wildlife. 1996, Weybridge, UK, report EUR17549 of the environment and climate change research programme of DGXII of the European commission. 2.Colborn T, vom Saal FS & Soto AM. Environ Health Perspectiv 1993, 101, 378 384. 3.McNutt SH, Purwin P & Murray C. J Amer Veterinary Medical Ass 1928, 73, 484. 4.Bennets H, Underwood EJ & Shier FL. Australian Veterinary Journal 1946, 22, 2 12. 5.Burlington H & Linderman VF. Proceedings of the Society for Experimental Biology and Medicine 1950, 74, 48 51. 6.Bitman J, Cecil HC, Harris SJ & Fries GF. Science 1968, 162, 371 372. 7.Matthiessen P. Pure and Applied Chemistry 2003, 75, 2197 2206. 8.Jobling S, Nolan M, Tyler CR et al. Environmental Science and Technology 1998, 32, 2498 2506. 9.Guillette Jr. LJ & Gunderson MP. Reproduction 2001, 122, 857 864.
