Endocrine disruptors activity

The metabolite DDE acts as an antiandrogen. Similarly, endocrine disruptor activity is well established for DDT, DDE, and related species. In particular, they are implicated in many types of cancers. Meanwhile, mosquitoes have developed resistance to these species. 

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. ... 

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). 

Mindless personal attacks by individuals whom you do not know are disappointing, particularly in light of results of continuing studies that have not identified linkages between exposure to endocrine disruptors and human disease. I have always acknowledged the adverse impact of environmental endocrine-active compounds on fish and wildlife populations in some areas, but have questioned their impact on human health. Scientific studies published in the past six to eight years have addressed many of the critical issues associated with endocrine disruptors and human health, and extensive references to these papers have been intentionally included in this chapter. Results of the more recent studies indicate that initial concerns regarding hypothesized endocrine disruptor-induced human problems may not be justified. 

Most of the knowledge that we have regarding the interaction of chemicals with the endocrine system comes from in vitro receptor binding data. These receptor interaction data form the basis for many of the structure-activity relationships that have been derived for potential endocrine disruptors. It is important to note that potency measured in in vitro studies may or may not be relevant to the in vivo situation. The relative binding affinity (RBA) and potency of binding vary significantly within a given class of substances. For example, Branham et al. [11] reported... 

The MultiCASE system has been used to identify a common 6-A unit biophore on a range of hormonally active chemicals with estrogenic activity that act as endocrine disruptors. This structural feature is a spacer biophore that is thought to be involved in the molecules binding to the estrogen receptor and is found on the standard estrogenic chemical, 17-beta-estradiol (see Combes, 2000). Other examples of molecules possessing this biophore include 4-hydroxytamoxifen, 2-chloro-4-hydroxybiphenyl, 3,4-dihydroxyfluorene, and 2,2-(fcE-4-hydroxyphenyl-1,1,1 -trichloroethane). 

Perkins, R., Anson, J., Blair, R., Branham, W.S., Dial, S., Fang, H., Hass, B.S., Moland, C., Shi, L., Tong, W., Welsh, W., Walker, J.D., and Sheehan, D.M., The endocrine disruptor knowledge base (EDKB), a prototype toxicological knowledge base for endocrine disrupting chemicals, in Handbook on Quantitative Structure Activity Relationships (QSARs) for Predicting Chemical Endocrine Disruption Potentials, Walker, J.D., Ed., SETAC Press, Pensacola, FL, 2003 (in press). 

Tong, W.D., Perkins, R., Fang, H., Hong, H., Xie, Q., Branham, W., Sheehan, D., and Anson, J., Development of quantitative structure-activity relationships (QSARs) and their use for priority setting in testing strategy of endocrine disruptors, Regul. Res. Perspect., 1, 1-16, 2002. 

Experimental evaluations of combination effects at the cellular or subcellular level from suspected endocrine disruptors or mycotoxins have demonstrated the usefulness of CA (Speijers and Speijers 2004 Kortenkamp 2007). However, on the grounds of theoretical considerations, this may not be surprising. For biological responses at the molecular level, for example, enzyme activities or receptor interactions, the dilution principle that is at the heart of CA can be readily interpreted in terms of molecular interactions. For this reason, other than concentration-additive effects may be difficult to envisage, and there is little scope for IA or substantial... 

Political and scientific attention has recently turned towards investigating substances that possess hormonal activity or alter patterns of hormone effects. Not only does detecting such changes in organisms prove to be extremely complicated, these endocrine disruptors can be active at very low doses. Considerable work for the standardisation of endocrine disruptor test methods has been undertaken at EU and international levels, but there is currently little agreement on how to test for such effects [123]. 

The term endocrine disruptors was first used by Theo Colborn and Peter Thomas in 1992. In 1996, the US Environmental Protection Agency (EPA) convened a panel called the Endocrine Disruptors Screening and Testing Advisory Committee to make recommendations to EPA concerning endocrine disruptors. The term endocrine disruptors has been used interchangeably with hormonally active agents and endocrine modulators. As the term is used now, endocrine disruptors include any substance that affects the synthesis, secretion, transport, binding, action, inactivation, or elimination of natural hormones in the body. 

Endocrine disruption is a newly discovered mode of action and has encouraged a great deal of research. Compared to some of the other mechanisms described in this chapter, endocrine disruption is more subtle with alterations in reproductive physiology and morphology often being the effects, instead of death. Because of the hormone-like activity, these compounds can have identifiable effects at very low concentrations. It is not yet clear what the overall importance of endocrine disruptors are in creating environmental impacts compared to other modes of action. 

Recently, the hazardous effects of endocrine disruptors (environmental hormones) such as bisphenol A and nonylphenol on the human body have been reported, and led to the initiation of many studies concerning the detection and structural determination of these compounds present in tiny amounts [57]. As one of the QSAR analyses of environmental hormones, the relationship between their biological activity and chemical hardness has been reported [16]. By applying these analytical methods, the molecular toxicity and estrogen-like activity of environmental hormones have been found... 

Finally, it should be noted that smoking, both active and passive, has been associated with breast cancer risk. I87 Tobacco smoke contains cadmium, a known endocrine disruptor, as well as numerous carcinogens. No mechanism has yet been proposed for the association between smoking and breast cancer. 

NICEATM. NICEATM pre-screen evaluation of the in vitro endocrine disruptor assay (Robotic MCF-7 cell proliferation assay of estrogenic activity), chttp // iccvamniehsnihgov/methods/endodocs/CCiPrescreenEvalpdf>. Accessed November 1, 2006. 

Metcalfe C.D., Metcalfe T.L., Kiparissis Y., et al., 2001. Environ. Toxicol. Chem., 20, 297. Murk A.J., Legler J., Van Lipzig M.M.H., et al., 2002. Environ. Toxicol. Chem., 21, 16. NICEATM, 2002. Background Review Document Current Status of Test Methods for Detecting Endocrine Disruptors In vitro Estrogen Receptor Transcriptional Activation Assays. 

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