Endocrine disruption mechanism

Endocrine disruption is a relatively new concept in risk assessment, and there are currently no test methods available, which specifically detect all effects that have been finked to the endocrine disruption mechanism(s) and mode(s) of action. 

With few exceptions (c.g., DES), a causal relationship between exposure to a specific environmental agent and an adverse effect on human health operating via an endocrine disruption mechanism has not been established. Short-term screening studies could be developed and validated in an effort to elucidate the mechanism. Through controlled dose-response studies, it appears that these compounds (e.g., alkyl phenol ethylates and their degradation products, chlorinated dibenzodioxins and difurans, and polychlorinated biphenyls) can induce irreversible induction of male sex characteristics on females (impo-sex), which can lead to sterility and reduced reproductive performance. 

Castaneda OL, Kraak GVD, Canul RR (2007) Endocrine disruption mechanism of o, p -DDT in mature male tilapia (Oreochromis niloticus). Toxicol Appl Pharm 221 158-167... 

Table 1 Examples of chemicals suspected of causing endocrine disruption listed according to suspected mechanism of action...

A proper assessment of the ability of chemicals, or mixtures of chemicals, to act as endocrine disrupters requires a multi-tiered approach which is able to identify mechanisms, give early warning of adverse effects and identify which of these effects is likely to be ecologically relevant. A strategy has been proposed by Depledge and Billinghurst " and is outlined below. 

Mechanistic studies to identify how endocrine disrupting chemicals interact with hormone systems are required. Although population effects coupled with biomarkers of exposure are strongly suggestive of endocrine disruption, the effect could be secondary to metabolic toxicity. Establishing mechanisms may avoid the need to make decisions on a weight of evidence approach alone. 

In addition to the foregoing, three further examples in this list (numbers 5-7) deserve consideration. These are (5) interaction of endocrine disrupters with the estrogen receptor, (6) the action of uncouplers of oxidative phosphorylation, and (7) mechanisms of oxidative stress. Until now only the first is well represented by biomarker assays that have been employed in ecotoxicology. 

A general overview of endocrine disrupters and estrogens mechanism(s)... 

Few epidemiologic studies of pesticide use in general, or specific pesticides, in relation to any autoimmune disease. Mechanistic research primarily for hexachlorobenzene and malathion. Mechanisms other than endocrine-disruption should be considered, even for pesticides with endocrine-disrupting properties. 

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