Endocrine also system

Generally, it appears that effects of xenobiotics on organs or endpoints may be similar in children and adults, e.g., liver necrosis observed in adults will also be observed in children. As regards toxicodynamics, age-dependent differences are primarily related to the specific and unique effects that substances may have on the development of the embryo, fetus, and child in that the physiological development of the nervous, immune, and endocrine/reproductive systems continues until adolescence (12 to 18 years). Furthermore, receptors and other molecular targets for various xenobiotics are continuously developing during the embryonic, fetal, and infant periods. This may cause age-dependent differences in the outcome of receptor-xenobiotic interactions and even result in opposite effects of xenobiotics in infants and adults. The available data are insufficient to evaluate... 

Although it is the dominant organ of the neural system, the brain also has an endocrine function, enabling the all-important overlap between neural and endocrine control systems. The most obvious and classically recognized hormonal function of the brain arises from the peptide hormones of the hypothalamus. The hypothalamus is intimately connected with the pituitary, producing the hypothalamic-pituitary axis. The hypothalamus is part of the brain the pituitary, although located within the skull, is not part of the brain but is part of the endocrine system. Peptide hormones from the hypothalamus influence pituitary function and thus endocrine function throughout the body. 

Plants not only evolved allelochemicals with broad activities (see Section 1.3.1) but also some that can interfere vdth a particular target [3,6,17-19,25]. Targets that are present in animals but not in plants are nerve cells, neuronal signal transduction, and the endocrinal hormone system. Compounds that interfere with these targets are usually not toxic for the plants producing them. Plants have had to develop special precautions (compartmentation resin ducts, trichomes, laticifers) in order to store the allelochemicals with broad activities that could also harm the producer. 

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. ... 

The liver plays an important role in the endocrine system. The concentrations of hormones in plasma, and the activity of the glands which secrete them, are determined by the rate at which they are deactivated by the liver. The liver also has a major function in female reproduction since it is the target tissue of ovarian estrogen, to which it responds by producing the yolk protein vitellogenin. " Xenobiotics that affect either of these functions can therefore be considered to be potential endocrine disrupters. 

Some biomarkers only provide a measure of exposure others also provide a measure of toxic effect. Biomarkers of the latter kind are of particular interest and importance and will be referred to as mechanistic biomarkers in the present text. Some mechanistic biomarker assays directly measure effects at the site of action as described in Section 2.4 (see Chapter 4, Table 4.2, for examples). Inhibition of acetylcholinesterase is one example. Others measure secondary effects on the operation of nerves or the endocrine system (examples given in Table 4.2 and Chapters 15 and 16). 

Apart from the wide range of neurotoxic and behavioral effects caused by OPs, many of which can be related to inhibition of AChE, other symptoms of toxicity have been reported. These include effects on the immune system of rodents (Galloway and Handy 2003), and effects on fish reproduction (Cook et al. 2005 Sebire et al. 2008). In these examples, the site of action of the chemicals is not identified. Indirect effects on the immune system or on reproduction following initial interaction with AChE of the nervous system cannot be ruled out. It is also possible that OPs act directly on the endocrine system or the reproductive system, and phosphorylate other targets in these locations (Galloway and Handy 2003). 

As onr knowledge of the pathways of effects for EDCs has evolved, the number of chemicals classified as EDCs has increased, and a more extensive list of these chemicals is detailed later in this chapter. The terminology used to describe chemicals that affect the endocrine system has also changed over time. Some now refer to EDCs as endocrine-active or endocrine-modulating, rather than endocrine-disrupting chemicals, as they do not necessarily always have deleterious effects. 

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