Endocrine-disrupting activity

It was agreed at the workshop that endocrine disrupting activity could only be adequately defined in terms of effects in intact animals, be they juvenile or adult, or in the offspring of exposed parents. For many chemicals, evidence of endocrine disrupting activity has been obtained only by the use of in vitro models, such as hormone binding assays. It was accepted, therefore, that chemicals active in such models should be considered only as potential EDs and should be distinguished from those established as active in vivo. For such chemicals, an alternative definition was recommended ... 

The list of chemicals with endocrine-disrupting activity has increased considerably with the systematic screening of chemicals employing some of the methods described in the previons section. Here we expand on the list of known EDCs to illustrate the diversity of chemicals of concern, but the list is by no means exhaustive. 

ZEA resembles the human 17P-oestradiol hormone produced by theovaries. Although almost non-toxic, in very small doses it has oestrogenic effects that can disrupt the human endocrine system (Benbrook, 2005). It is important to note that transformation products of ZEA can have three to four times higher endocrine disrupting activity than ZEA. 

An example of a TIE approach is that described by Desbrow et al. [7]. In this work, the endocrine disrupting activity detected in effluents of seven UK WWTPs by means of a yeast-based screening assay [52] was mainly attributed to the presence of estradiol, estrone, and ethynylestradiol. However, to assess the estrogenic activity different bioassays may be used, e.g., the yeast-based recombinant estrogen receptor-reporter assay (YES), the MCF-7 cell proliferation (E-screen), and the estrogen receptor-mediated chemically activated... 

The designation potential endocrine disrupter has been proposed for chemical products with an endocrine-disruption ability that is demonstrated in an in vitro assay but not confirmed in an in vivo animal model. To date, most of the available information on chemical products with endocrine disrupter activity has been generated by in vitro experiments [10]. Various existing tests and bioassays of very different types have been proposed by distinct international bodies to identify hormonal... 

Novic, M. and Vracko, M. (2010) QSAR models for reproductive toxicity and endocrine disruption activity. Molecules, 15 (3), 1987-1999. 

The investigation provided evidence of limited migration of both TPA and IPA. The UK Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment (COT) advised that the levels of TPA and IPA found in foods in this survey were not of concern for public health based on available information. Nevertheless, they recommended that further studies be carried out for TPA and IPA to see if they have endocrine disrupter activity. 

Table 11. Assays for detecting endocrine disrupting activity in juvenile or young animals (examples)...

An important question in this area relates to the widespread use of exposure biomarker responses for monitoring effluents and receiving waters for endocrine disrupter activity. In oviparous species, vitellogenin is the major example of such a... 

Mechanistic assays Various systems, e.g. cell lines, cell-free extracts, mitochondria, nuclear extracts GAP junction inhibition, oxidative stress measure, protein-binding activity, endocrine-disrupting activity, oxygen consumption, metabolite levels, etc. Mechanistic studies Non-genotoxic carcinogenicity, weight of evidence... 

In agriculture, several hundreds of different pesticides have been used worldwide over the last few decades. Owing to their widespread appHcations and persistence in the environment, pesticides are acciunulating in media such as soil and ground water. Many pesticides exhibit endocrine-disrupting activity, which poses a threat to public health and local ecosystems, and are therefore regulated. In the European Union, the maximiun allowable concentrations in... 

Polychlorinated biphenyls (PCB) - currently banned compounds - were formerly used in hydraulic fluids, plasticizers, adhesives, fire retardants, and pesticide extenders. These contaminants are persistent in the environment and are present in sediments at the bottom of lakes, rivers, and seas. As they exhibit carcinogenic and endocrine-disrupting activity, they are subject to regulation. For instance, in the United States, the maximum allowed concentration of PCBs in drinking water is 0.5 ng mL [21]. 

Dioxins are released in the environment in emissions from the incineration of mimicipal refuse and certain chemical wastes and in exhaust from automobiles powered by leaded gasohne. Dioxins are highly persistent and accumulate in the environment. They are highly toxic and exhibit endocrine-disrupting activity. Therefore, they are regulated by authorities, e.g., in the United States for the most toxic 2,3,7,8-TCDD the maximum allowed concentration in drinking water is 10 ngmL [21]. 

However, investigations of incidents involving misuse of OP and CM pesticides have revealed virtually no endocrine-disrupting activity of these chemicals (Flickinger et ai, 1984), The putative endocrine-disrupting effect of OPs and CMs in wildlife is largely a prediction based on data obtained from laboratory animals. The influence of these pesticides on human health i.s also discussed here, based on observed endocrine-disrupting actions of OPs and CMs ill vitro and in laboratory animals in vivo. 

Cespedes, R. Petrovic, M. Raldua, D. Saura, U. Pina, P. Lacorte, S. Viana, P. Barceld, D. Integrated procedure for determination of endocrine-disrupting activity in surface waters and sediments by use of the biological technique recombinant yeast assay and chemical analysis by LC ESI MS. Anal. Bioanal. Chem. 2004, 378, 697-708. 

Human exposure to certain plasticizers has been debated because di-(2-ethylhexyl) phthalate (DOP), used in medical plastics, has been found at detectable levels in the blood supply and potential health risks may arise from its chronic exposure. A further issue is the use of phthalates in baby-care products and toys. Since yovmg children often put their plastic toys in the mouth, the plasticizers are prone to be leached out and can be swallowed (2). Research with animals revealed a possible endocrine-disruption activity (13). 

---