Endocrine disruptors

The endocrine system is comprised of a network of hormone-producing glands. These glands include the pituitary, thyroid, adrenal, thymus, pancreas, ovaries, and testes. The hormones produced are released in carefully 

The World Health Organization defines endocrine-disrupting compounds (EDCs) as exogenous substances that alter function(s) or the endocrine system and consequently cause adverse health effects in an intact organism, or its progeny or (sub)-populations. I13l Endocrine disrup-tors can act in any of four different waysJ14 These are 

Mimicking the effects of endogenous hormones by attaching themselves to hormone receptor sites and thus increasing hormone levels in the body. 

Antagonizing the effects of endogenous hormones, thus depriving the body of needed hormones. 

Disrupting the synthesis and metabolism of endogenous hormones, either by excessively promoting these reactions or retarding them. 

The Endocrine Society defines an endocrine disrupting substance as a compound either natural or synthetic, which, through environmental or inappropriate developmental exposures, alters the hormonal and homeostatic systems that enable the organism to communicate with and respond to its environment. Effects may include developmental, reproductive, neurological, and immune system defects. The field is a controversial one most of the data come from wildlife studies, and the dose/response effect is problematic. In laboratory studies, many anthropogenic compounds 

PCBs that do not have substituents at the ort/zo-positions are described as coplanar PCBs and are the most toxic of the PCBs. Given what we learned about the geometry of biphenyl in 

Biphenyl itself is not planar in its ground state but has an angle of approx. 44 ° between the rings. It thus seems unlikely that the ground state of more substituted biphenyls is planar either. What should be said is that the barrier to rotation about the interring bond in non-ort/zo-substituted biphenyls is low, 6-8 kj moH, so the molecule is able to become planar for the purpose of interaction with the aryl hydrocarbon receptor. 

Some of the endocrine disrupters in the aquatic environment are human hormones, from incomplete processing of human waste. Progestins and estrogens are derived from the contraceptive pill, and other materials are derived from treatments for hormone-responsive cancers (such as tamoxifen, an anti-estrogen). It seems that these cause feminization effects in fish, and there have been claims that the incidence of human prostate cancer is higher in countries where the use of the contraceptive pill is higher (correlation, not proven causation). 

Environmental estrogens are part of a group of chemicals known as endocrine disruptors that can affect hormone action in an animal or person. This group of chemicals first gained attention in the 1980s when several environmental studies indicated that sex ratios of some reptiles and amphibians in specific areas were abnormal. Entire populations were composed primarily of females, and the males 

A wide variety of chemicals have been shown to have endocrine disruption effects, including various types of pesticides, surfactants amd detergents, plasticizers and resins, metals, PCBs, dioxins, PAHs, and pharmaceuticals (see table 11.1). Also, several natural chemicals have been shown to have estrogenic effects, as well as those manufactured for specific reproductive use by humans (e.g., birth control and anabolic steroids). The following types of effects have been linked to endocrine disrupters in animals and/or humans  

Reproductive (feminization, demasculination, embryo death, failure to reproduce) 

Neurological (courtship behavior disruption, altered metabolic rate, abnormal sexual differentiation in the brain, impaired/delayed intelligence, teratogenicity of the central nervous system) 

Immunological (autoimmune syndromes, altered functions, reduced immune 

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European Commission, European Workshop on the Impact of Endocrine Disruptors on Human Health and Wildlife, Weybridge, 2—4 Dec. 1996, Environment and Climate Researeh Programme, European Commission, DG XII, Brussels, Report EUR 17549. 

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. ... 

Table 1 Chemicals which can be considered as potential endocrine disruptors in fish"...

Recently, attention has focused on the potential hazardous effects of certain chemicals on the endocrine system because of the abihty of these chemicals to mimic or block endogenous hormones, or otherwise interfere with the normal function of the endocrine system. Chemicals with this type of activity are most commonly referred to as endocrine disruptors. Some scientists believe that chemicals with the ability to disrupt the endocrine system are a potential threat to the health of humans, aquatic animals, and wildlife. Others believe that endocrine disrupting chemicals do not pose a significant health risk, particularly in light of the fact that hormone mimics exist in the natural environment. Examples of natural hormone mimics are the isoflavinoid phytoestrogens (Adlercreutz 1995 Livingston 1978 Mayr et al. 1992). 

NMR Studies on Lipid Bilayer Interfaces Coupled with Anesthetics and Endocrine Disruptors... 

FIG. 1 Molecular structures of the drugs examined in the delivery study the general anesthetics, alkanols (I), halothane (II), enflurane (III), isoflurane (IV), halogenated cyclobutane (V) the local anesthetics, dibucaine hydrochloride (VI), procaine hydrochloride (VII), tetracaine hydrochloride (VIII), lidocaine hydrochloride (IX), benzyl alcohol (X) the endocrine disruptor, bisphenol A (XI), and alkylbenzenes, benzene (XII), toluene (XIII), ethylbenzene (XIV), and propylbenzene (XV). 

In this section, we focus on how to determine DD sites by NMR. The specification of the DD sites in bilayers can be done by utilizing the NMR signals of both drugs and membrane lipids. An example of the delivery site determination is given for the case of two benzene derivatives, propylbenezene (PrBe) and benzyl alcohol (BzOH) in egg phosphatidylcholine (EPC) bilayers [46]. Alkylbenzenes are suspected to be endocrine disruptors, and BzOH is one of the local anesthetics. 

V. LIPID BILAYER INTERFACES COUPLED WITH ENDOCRINE DISRUPTORS, BISPHENOL A, AND ALKYLBENZENES... 

As an example of suspected endocrine disruptors (EDs), studies of the estrogenic action of bisphenol A (BPA) have been in progress in medical, physiological, and biological fields. In this situation, physicochemical approaches are required to get the structural information of BPA trapped in biomembranes. Most recently, we have determined the site and the orientation of BPA trapped in phospholipid vesicles by NMR, using the HCS rule [47]. In particular, we have succeeded in monitoring the NMR spectral changes of phospholipid vesicles, which are induced by the BPA delivery. 

In recent years the interest of environmental analytical chemistry was turned to the so-called emerging contaminants or new unregulated contaminants including pharmaceuticals, endocrine disruptors, detergents, personal care products, plasticizers, flame retardants, gasoline additives, etc. These compounds are released continuously to the environment and can be found in water, sediments, soils, etc. In most of the cases they are found at trace level concentration (ng/L) therefore, powerful analytical capabilities are required for their determination. 

Convention on Control of Transboundary Movements of Hazardous Wastes and their Disposal and 69 ratified the ban on all kinds of hazardous waste export from wealthy OECD-countries to non-OECD countries, large amounts of waste electrical and electronic equipment (WEEE) are shipped overseas for recycling, the majority to China as reported by Brigden et al. [2] and Puckett et al. [3], lesser quantities to India and Western Africa reported by Kuper and Hojsik [4]. WEEE contains a variety of harmful substances like endocrine disruptors and persistent organic pollutants (POPs). Additionally, hazardous substances may be formed during informal recycling. This often practised informal treatment without proper equipment for metal extraction and labour safety heavily affects the environment and human health of workers and the inhabitants of whole stretches of land. 

Langdon KA, Wame MS, Smemik RJ, Shareef A, Kookana RS (2011) Selected personal care products and endocrine disruptors in biosolids an Australia-wide survey. Sci Total Environ 409 1075-1081... 

Bioanalytical and Chemical Methods for Endocrine Disruptors Volume Editors D. Barcelo and P.-D. Hansen Vol. 5/J, 2009... 

Kasprzyk-Hordern B, Dinsdale RM, Guwy AJ (2008) The occurrence of pharmaceuticals, personal care products, endocrine disruptors and illicit drugs in surface water in South Wales, UK. Water Res 42 3498-3518... 

Porte C, Janer G, Lorusso LC, Ortiz-Zarragoitia M, Cajaraville MP, Fossi MC, Canesi L (2006) Endocrine disruptors in marine organisms approaches and perspectives. Comp Bio-chem Physiol C 143 303-315... 

The chemical structure of the substances capable of interacting with a determinate nuclear receptor is tremendously varied. For now no pattern exists that permits one to assure that a particular substance is going to interact with the receptor to produce an agonist or antagonist effect. In recent years the concept of endocrine disruptors has been introduced to describe the substances that are capable of modifying the endocrine equilibrium. Some of them act by binding with nuclear hormone receptors, while others interfere with the processes of regulation of hormone secretion (Lathers 2002 Melnick et al. 2002 Nakata 2002 Powles 2002 Brown et al. 2002 Sonnenschein et al. 1998). 

Endocrine disruptors apparently affect all nuclear receptors. Thus, a notable increment in impotence, alterations of the libido and of oligospermia in workers exposed to pesticides has been described. These alterations are due to the action of some compounds with estrogen-mimetic action and to their interaction with the androgen receptor. Additionally, alterations of thyroid function have been detected in rats exposed to dioxin and other toxic agents,... 

Lathers CM (2002) Endocrine disruptors a new scientific role for clinical pharmacologists Impact on human health, wildlife, and the environment. J Clin Pharmacol 2 7... 

Melnick R, Lucier G, Wolfe M, Hall R, Stancel G, Prins G, Gallo M, Reuhl K, Ho SM, Brown T, Moore J, Leakey J, Haseman J, Kohn M (2002) Summary of the National Toxicology Program s report of the endocrine disruptors low-dose peer review. Environ Health Perspect 110 427... 

Nakata K (2002) Theoretical approach to endocrine disruptors. Front Biosci 7 c68... 

Veldhoen, N., and Helbing, C.C., Detection of environmental endocrine-disruptor effects on gene expression in live Rana catesbeiana tadpoles using a tail fin biopsy technique, Environ. Toxicol. Chem., 20, 2704, 2001. 

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. 

Endocrine disruptors are nowadays considered among the most important emerging pollutants in wastewater, but they are not actually monitored on-line. A recent study [48] described the implementation of a broad-spectrum analytical scheme for the screening of more than 200 compounds (endocrine disruptors, pharmaceutical compounds,...) in urban wastewater. For other specific organic compounds, a study concerning the improvement of immunoassays with a solid-phase extraction (SPE) membrane was reported for the on-site detection in soils and water of energetic materials (i.e. explosives) [49], but unfortunately it was not really tested for wastewater. 

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