Mammals endocrine disruption

Development of toxic responses to a number of drugs/ small molecules comparable to mammals (endocrine disruption, reproductive and developmental toxicity, behavioral defects, carcinogenesis, cardiotoxicity, hepatotoxicity, neurotoxicity, and ototoxicity, to name a few). 

Female sexual development and behaviour in mammals occurs by default and requires no ovarian secretion, and it is only in genetic males that the testis can secrete hormones which destroy this female pattern and superimpose that of the male. Sexual differentiation is not so well defined in fish, and larval exposure to both synthetic estrogens and androgens is widely used in aquaculture to produce monosex cultures. Endocrine disruption of sexual differentiation in fish may therefore reflect both the complexity and diversity of such processes between different species. Some care is required in use of the terms hermaphrodite and sex-reversal since a true hermaphrodite has both functional testes and ovaries and a sex-reversed fish is fully functional as its final sex—both produce the appropriate viable gametes. Such functional sex-reversal is not possible in mammals, but in some species of fish it is the normal developmental pattern. In most of the cases of hermaphroditism or sex-reversal reported in the non-scientific press, there is evidence only for a few ovarian follicles within a functional testis. This may be considered as feminisation or a form of intersex, and is very clearly endocrine disruption, but it is certainly neither sex-reversal nor hermaphroditism. In some cases the terms have even been used to infer induction of a single female characteristic such as production of yolk-protein by males. 

In addition to reproductive effects, fish exposed to endocrine disrupters may have a decreased response to stress or decreased growth and metabolism which can affect their ability to survive, or to defend themselves against predators. All of these factors can affect the ability of the species to survive and to reproduce itself in sufficient numbers to maintain the stocks on which our commercial and sport fisheries are based. Not all fish species will be equally susceptible to the effects of endocrine disrupters. Selective sensitivity to such effects, especially those affecting reproduction, may well lead to major changes in the flora and fauna of some of our major aquatic ecosystems as the balance between fish, mammals, invertebrates and plants, and between predators and prey, is destabilised... 

Fish have many advantages as experimental models in the study of endocrine disruption, and although they do have some significant differences in their endocrine system to that of mammals, the underlying basis is very similar. Chemicals which are shown to be either actual or potential endocrine disrupters... 

Exposure to estrogenic compounds through diet will differ for herbivores and carnivores, the latter being most likely to encounter endogenous steroids in their prey. Efficient uptake of steroids in mammals is illustrated by the use of the contraceptive pill, but routes of absorption in invertebrates remain to be determined. The relationship between endocrine disruption and metabolic toxicity, with reduced reproductive viability a secondary consequence of metabolic disturbance, also merits further study in invertebrate species. 

Endocrine Disruption in Mammals, Birds, Reptiles and Amphibiians... 

A number of other chemicals suspected of having endocrine disrupting potential also occur at high levels in the tissues of marine mammals. For example, tribiityltin compounds are present in the tissues of the Steller sea lion (Eumetopias juhatus) from Hokaido, Japan, and in stranded bottlenose dolphins (Tursiops truncatus) found along the US Atlantic and Gulf coasts.Additional chemicals detected include PAHs, toxaphene and chlordane. ... 

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. 

Tanabe, S., 2002. Contamination and toxic effects of persistent endocrine disrupters in marine mammals and birds. Mar. Pollut. Bull. 45, 69-77. 

For the purposes of this chapter, the term reproduction will be used primarily in reference to vertebrate species of animals (especially mammals) and will be inclusive of development (Figure 36.1), which is sometimes treated as a separate topic in toxicology texts. This particular chapter emphasizes what is currently known about the adverse effects of known chemical warfare agents and selected environmental contaminants on male and female reproductive function, as well as xenobiotic-induced effects on the growth, maturation, and sexual differentiation of the embryo and fetus. Endocrine disruption is an extremely common mechanism of action for xenobiotics associated with impaired reproductive function and will be discussed along... 

Fig. 15. Predicted metabolites of some tetrachlorobenzyltoluene (TCBT) isomers with supposed estrogenic and/or other endocrine-disrupting effects in fish and mammals including human...

---