Endocrine also disruptor

It is also clear that it is difficult to relate cause and effect to any specific chemical since, with the exception of point source effluents, many waterways contain a multitude of chemicals, of which the active endocrine disruptor may not be that which has been measured in the water or tissue. For such reasons, many studies have used in vitro experiments in which isolated tissue, either from a control animal or one captured in a polluted water system, is exposed to a single pollutant in the laboratory. Such experiments have shown significant disruption to testicular activity by a wide range of xenobiotics, including cadmium, lindane, DDT, cythion, hexadrin and PCBs. ... 

But if we take into account the emerging pollutants and compounds, the choice of which is guided by environmental considerations (mainly risks for health), then surfactants, endocrine disruptors, pesticides, other industrial organics (PAH, aromatic amines,...) or inorganics (sulphides, arsenic,...) and microbiological indicators (pathogens) must also be considered. 

Successful reproduction (and sex) involves many complex chemical processes that can be disrupted at various points to reduce fertility and conception. Part of this process is under control of the endocrine system, and chemicals that affect the endocrine system are termed endocrine disruptors. In the 1950s, understanding of the endocrine system led to the development of birth control pills as a way to reduce fertility in humans. This is a desirable and planned use of endocrine disruptors. Subsequently, it was discovered that a number of chemicals released into the environment could disrupt the endocrine system and reduce fertility of wildlife. Some are concerned that exposure to these chemicals, such as DDT and dioxin (TCDD), may also affect human fertility (Table 17.1). Approximately 15% of couples of reproductive age are infertile. Endocrine disruptors may also affect fetal development, causing demasculization and feminization of the offspring, which in turn cause reduced fertility in the next generation. 

Depending upon the circumstance and desired effects, endocrine-disrupting chemicals can be either good or bad. The endocrine system is a finely balanced system responsible for fertility and many of the feminine and masculine traits we are all familiar with. Endocrine disruptors are used by millions of women in the form of the pill to control fertility. Chemicals in birth control pills subtly manipulate the endocrine system to reduce fertility. Unfortunately, we now know that many chemicals are capable of influencing the endocrine systems. When these chemicals, such as DDT and TCDD, are released into the environment, they reduce the fertility of wildlife. Exposure to endocrine disruptors is linked to decreased fertility in shellfish, fish, birds, and mammals. Endocrine disruptors such as nonylphenol have been shown to feminize male fish, interfering with reproduction. Some studies have also linked exposure to endocrine disruptors to decreases in human male sperm count. Ironically, urinary metabolites of the birth control pill as well as the female hormone estrogen pass through waste treatment plants and are released into the aquatic environment, where even small concentrations cause feminization of male fish. 

The government has been measuring PCB, HCB, DDT, chlordane, heptachlor epoxide and dieldrin since 1998 to identify their effects on wildlife as part of the Environmental Survey on Endocrine Disruptors. The specimens taken include land animals such as raccoons, bears, monkeys and frog, and marine mammals such as seals and whales, in addition to domestic birds and birds of prey. A relatively high concentration of POPs was seen in birds of prey and Phalacrocorax carbo. Eggs of mountain hawk eagles were also found to have a higher concentration of PCB, DDT, heptachlor epoxide, chlordane and dieldrin than other wildlife specimens... 

Prominent among toxicants that adversely affect both male and female reproductive systems are endocrine disruptors (see Section 9.7). Toxicants that mimic the actions of sex hormones are agonists, and those that prevent hormonal action or bind competitively to hormone receptor sites are antagonists,12 Male patients treated with cimetidine for peptic ulcers have exhibited low sperm counts and abnormal breast enlargement, a condition called gynecomastia. Gynecomastia has also been caused in men working in oral contraceptive production. Ketoconozole inhibits the enzymes required to produce hormones involved in sperm production and can immobilize sperm in seminal fluid. 

Administration of 2,3,7,8-TCDD to animals results in a wide range of endocrine responses which are not only species-dependent, but also exhibit variability within species. Endocrine effects observed in humans have not been limited to thyroid effects and diabetes alterations in levels of reproductive hormones, as summarized in the sections on reproductive effects have also been observed. The wide array of endocrine effects induced by CDDs and structurally-related chemicals has triggered increased interest within the scientific community and the term endocrine disruptors is currently being used to describe some members of this class of chemicals. The available information suggests that CDDs may cause adverse endocrine effects in humans. 

An overview of the literature shows that in the majority of cases, CA did yield accurate predictions of combination effects, even with mixtures composed of chemicals that operate by diverse modes of action. The studies available were dealing with mixtures of chemicals having an unspecific mode of action (membrane disturbance or narcosis) or with pesticides, mycotoxins, or endocrine disruptors. In ecotoxicol-ogy, CA usually produced more conservative predictions than IA. There are indications that this is true also for mammalian toxicology, but more data are needed to come to more definitive conclusions. The validity of CA or IA was confirmed for individual-based endpoints like growth or reproduction, but also for effects at the cellular or subcellular level and for community-based endpoints. 

Wastewater from pharmaceutical industries producing these therapeutics may allow introduction of these endocrine disruptors into the ecosystem if proper filtration is not employed. Moreover, the conjugated products excreted in urine and feces from individuals receiving these pharmaceuticals also can be introduced into the wastewater supply. There are few published results regarding bioaccumulation and biotransformation of estrogen-like pharmaceutics released into the ecosystem. 

From an analysis of the published financial research on the chemical industry, the sustainability issues of concern in the mainstream investment world revolve first around exposure to hot-button issues such as asbestos and genetic modification. There are some indications that this concern may extend to issues that have not yet fully blossomed, such as endocrine disruptors. There is also lingering concern about the potential for European Union rules that, if adopted, would essentially shift the burden of proof from showing that a chemical caused harm to having to demonstrate the safety of a number of chemicals in current use. Among those analyzing the sustainability of the chemical industry, the primary task appears to be to evaluate the companies ability to deal with complex issues of safety, emission reductions, community relations, and so on. 

The effects of EDCs were first discovered in wildlife in the 1970s. It was found that extremely low concentration levels of these can have powerful deleterious effects on the reproduction of wildlife. Human effects were not studied until much later because most EDCs are neither mutagenic nor acutely toxic at the ambient concentrations found to have endocrine disruption effects on wildlife. It was also believed that effects on birds and turtles were not necessarily indicators of human toxicity. This, however, turned out to be exactly the case. Though toxic effects of chemicals are not always similar for different species of animals, they are just that for endocrine disruptors. The effects of EDCs on birds and amphibians are exactly analogous to those on humans. 

Amphibian endocrine disruption is of special interest to humans. The estrogen found in the painted turtle is identical to that found circulating in the human bloodstream and the endocrine disruptors that threaten wildlife populations have also been shown to be jeopardizing human reproductionAccordingly, animal studies on endocrine disrupting properties of toxic chemicals are relevant to understanding human responses to these chemicals. Pesticide mixtures have been shown to be powerful endocrine disruptors in numerous other animal studiesJ16 Illustrative examples follow. 

One study that overcomes some of the shortcomings of those just cited reported adverse neurodevelopment outcomes following maternal exposures to 19 organic solvents and mixtures of these. 13 In this study, the women were occupationally exposed to the chemicals listed in Table 24.3. Also included in this table are the K, values and whether or not the specific chemical is a known teratogen or a known endocrine disruptor. 5 It is interesting to note that only three of the chemicals in the study—ethanol, trichloroethylene, and mineral spirits (a mixture of hydrocarbon solvents)—are endocrine disruptors. This shows that teratogenic effects can be induced by chemicals and mixtures that are independent of the endocrine system. 

The ability to predict drug-drug interactions and likely endocrine disruptors remains a major goal of toxicity studies. In the last decade many of the NHRs have been solved by X-ray crystallography, and this has added greatly to our understanding of their modes of action (see also Chapter 12). 

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