**5. Impact of natural and xenoestrogenic compounds in human health**

Estimating with certainty the contribution of aquatic environmental pollution — namely by the above mentioned EDCs — to the burden of disease in humans is extremely difficult and consequently quite polemic [10, 128]. This fact comes from the difficulty to measure and link exposures with the health disorders that may occur in humans, as these are not in regular contact with "oestrogenic waters" as aquatic animals. However, the consumption of contami‐ nated drinking water and/or seafood together with some other sporadic contact between humans and contaminated waters, e.g., during recreational activities either in sea or fluvial beaches [60, 64], may change some preconception about this issue. In fact, and despite the confounding variables, recent studies have linked the presence of environmental natural oestrogens, phytoestrogens and xenoestrogens with the development of a range of disorders that go from immune deficiencies, birth defects, chronic endocrine diseases to cancer (Table 8).

During the last decade researchers devoted to both environmental health and human oncology have shown an increasing interest in the environmental impacts of EDCs over human health as the chemical structures of some of these chemicals, namely those refereed in this work, resemble that of E2 which is a molecule that evolution maintained conserved amongst different species [10]. This means that, alike fishes and other aquatic animals, the distribution of oestrogen receptors in mammalian/human tissues is so wide that the presence of these EDCs are able to interfere with the orchestration of an important number of pathways, some of which, are close related with the development of cancer [129-132]. Besides, in both fish and mammals high levels of oestrogens induce the production of reactive oxygen species causing hypome‐ thylation and microsatellite instability [133, 134]; these phenomena, which is an early step in the process of carcinogenesis, cause DNA adducts and other genetic damages, seen, e.g., by the emergence of micronuclei, a fact that was observed by our group in fish caught in areas described here as having high estrogenic loads [135].

Estrogenic Compounds in Estuarine and Coastal Water Environments of the Iberian Western Atlantic Coast… http://dx.doi.org/10.5772/59885 177


**Table 8.** Examples of some disorders promoted by the EDCs focused in this Chapter.

Some epidemiologic studies also support the correlation between oestrogenic EDCs and cancer as, it was found that in Europe childhood cancer incidence is having an annual increase of 1% [137]. This worrying result it is also associated with a rising trend of other cancer types such as the soft tissue sarcoma, brain tumours, germ-cell tumours, lymphomas, renal cancers, leukaemia, breast cancer and lung cancer in women [10, 151, 152]. These occurrences are much preoccupant and alert all society to the possible risk that these compounds can pose for public health.

## **6. Conclusion and perspectives**

Portugal) [126]. As this task was considered essential for the implementation of various articles defined in the WFD, including the Article 8 that aims the implementation of standards for water monitoring, Portugal together with others (Spain, Greece and Luxembourg) were condemned by the Court of Justice of the European Community. Besides this occurrence, in 2013 the WFD published a list of other, most common, defaults recorded in many states [127]: (*i*) existence of severe gaps in the levels of chemical pollutants from anthropogenic origins in surface waters; (*ii*) 60% of groundwater resources in cities were over-exploitation; (*iii*) 25% of the groundwater was polluted; (*iv*) 47% of the surface waters showed bad ecological status; and (*v*) 50% of the wetlands showed extinction risks of indigenous species. Considering the first item of this list, it is demonstrated the need of implement chemical monitoring programs for all states involved in the implementation of the WFD. As a corollary, we do emphasize herein the relevance of the regular chemical monitoring and the implementation of strategies

**5. Impact of natural and xenoestrogenic compounds in human health**

Estimating with certainty the contribution of aquatic environmental pollution — namely by the above mentioned EDCs — to the burden of disease in humans is extremely difficult and consequently quite polemic [10, 128]. This fact comes from the difficulty to measure and link exposures with the health disorders that may occur in humans, as these are not in regular contact with "oestrogenic waters" as aquatic animals. However, the consumption of contami‐ nated drinking water and/or seafood together with some other sporadic contact between humans and contaminated waters, e.g., during recreational activities either in sea or fluvial beaches [60, 64], may change some preconception about this issue. In fact, and despite the confounding variables, recent studies have linked the presence of environmental natural oestrogens, phytoestrogens and xenoestrogens with the development of a range of disorders that go from immune deficiencies, birth defects, chronic endocrine diseases to cancer (Table 8).

During the last decade researchers devoted to both environmental health and human oncology have shown an increasing interest in the environmental impacts of EDCs over human health as the chemical structures of some of these chemicals, namely those refereed in this work, resemble that of E2 which is a molecule that evolution maintained conserved amongst different species [10]. This means that, alike fishes and other aquatic animals, the distribution of oestrogen receptors in mammalian/human tissues is so wide that the presence of these EDCs are able to interfere with the orchestration of an important number of pathways, some of which, are close related with the development of cancer [129-132]. Besides, in both fish and mammals high levels of oestrogens induce the production of reactive oxygen species causing hypome‐ thylation and microsatellite instability [133, 134]; these phenomena, which is an early step in the process of carcinogenesis, cause DNA adducts and other genetic damages, seen, e.g., by the emergence of micronuclei, a fact that was observed by our group in fish caught in areas

for reducing the levels of the EDCs referred in this Chapter.

176 Toxicology Studies - Cells, Drugs and Environment

described here as having high estrogenic loads [135].

As demonstrated in this Chapter, with regard to the xenobiotics that can act as oestrogens there is still much to do in both Portugal and other countries in order to reduce this type of chemical pollution in the surface waters from rivers, estuaries and coastal areas. Thus it would be very useful to conceive national monitoring plans, coordinated in time and space (location of the areas under evaluation), using not only chemical methods but also biological tools (e.g., via the usage of biomarkers). This type of plans, involving and networking public and private agents, would make it possible to assess risks and if measures of prevention and remediation that are being promoted on the ground produce, the desired effects, namely as required by the implementation of the WFD. With regard to research activities done in the west Iberian Peninsula, we seek to continue developing projects that allow the diagnosis of the aquatic systems, not only focusing the attention in the type of EDCs discussed here but also in others judged relevant, such as emerging pharmaceutical compounds, PAHs, PCBs and pesticides some data are already published concerning these compounds [153-159]. Introduction of passive sampling methods should be pursued too, to get time-integrated characterizations. In parallel, we also view as utterly important to contribute with knowledge about the mechanisms of action that underlie the disruptive effects in aquatic organisms, as illustrated in works we co-authored [160-169]. At last, it is very relevant to reinforce the efforts to investigate causeeffect associations related with potential long term risks of drinking (inc. tape) waters conta‐ minated with estrogenic compounds, both by monitoring the types and quantities of compounds [170] and by epidemiological approaches [171].
