Chemicals with the Endocrine System

The term endocrine disruptor emerged from a seminal workshop sponsored by the World Wildlife Fund held in 1991 at the Wingspread Conference Center in Racine, WI [1]. The workshop focused on reviewing a wide range of experimental data and environmental observations that pointed to adverse effects that might 

Handbook of Green Chemistry Volume 9 Designing Safer Chemicals, First Edition. Edited by Robert Boethling and Adelina Voutchkova. 

An exogenous substance that changes endocrine function and causes adverse effects at the level of the organism, its progeny, and/or (sub)populations of organisms.1  

Another useful definition came from the European Workshop on the Impact of Endocrine Disruptors on Human Health and Wildlife held in 1996. Known as the Weybridge definition after the location the UK where the meeting took place, an important distinction was made between an endocrine disruptor and a potential endocrine disruptor [3]. 

A potential endocrine disruptor is a substance that might be expected to lead to endocrine disruption in an intact organism. 

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Most of the knowledge that we have regarding the interaction of chemicals with the endocrine system comes from in vitro receptor binding data. These receptor interaction data form the basis for many of the structure-activity relationships that have been derived for potential endocrine disruptors. It is important to note that potency measured in in vitro studies may or may not be relevant to the in vivo situation. The relative binding affinity (RBA) and potency of binding vary significantly within a given class of substances. For example, Branham et al. [11] reported... 

There are many possible mechanisms by which chemicals may interact with the endocrine system, some of which are discussed below. 

Recently, attention has focused on the potential hazardous effects of certain chemicals on the endocrine system because of the abihty of these chemicals to mimic or block endogenous hormones, or otherwise interfere with the normal function of the endocrine system. Chemicals with this type of activity are most commonly referred to as endocrine disruptors. Some scientists believe that chemicals with the ability to disrupt the endocrine system are a potential threat to the health of humans, aquatic animals, and wildlife. Others believe that endocrine disrupting chemicals do not pose a significant health risk, particularly in light of the fact that hormone mimics exist in the natural environment. Examples of natural hormone mimics are the isoflavinoid phytoestrogens (Adlercreutz 1995 Livingston 1978 Mayr et al. 1992). 

UBA (2001). Chemicals in the Environment which I nterfere with the Endocrine Systems of Humans and Wildlife- Pollution, Effects, Control Strategies... 

Global concerns have been raised in recent years over the potential adverse effects that may result from exposure to chemicals that have the potential to interfere with the endocrine system. WUdlife and human health effects of endocrine dismpting chemicals (EDCs) were first proclaimed by Rachel Carson in 1962, and based on a growing body of knowledge those concerns have increased. This concern regarding EDCs is directed at both humans and wildlife (WHO/IPCS 2002). 

The nervous system has several properties in common with the endocrine system, which is the other major system for control of body function. These include high-level integration in the brain, the ability to influence processes in distant regions of the body, and extensive use of negative feedback. Both systems use chemicals for the transmission of information. In the nervous system, chemical transmission occurs between nerve cells and between nerve cells and their effector cells. Chemical transmission takes place through the release of small amounts of transmitter substances from the nerve terminals into the synaptic cleft. The transmitter crosses the cleft by diffusion and activates or inhibits the postsynaptic cell by binding to a specialized receptor molecule. In a few cases, retrograde transmission may occur from the postsynaptic cell to the presynaptic neuron terminal. 

Substances with the ability to modulate the endocrine system do not necessary pose any health risk for humans and other organisms. In fact, humans and animals are constantly exposed to substances in food and other environmental media that interact with the endocrine system. In general, due to precise yet adaptable control mechanisms, and the intertwined nature of the hormonal balance, moderate amounts of chemical effects on hormones seldom compromise normal physiological functions. Fluctuations of hormone concentration and receptor activities, by design, absorb environmental and physiological challenges in order to maintain functional equilibrium in the body. Only when the equilibrium control mechanisms are overwhelmed do deleterious effects occur. 

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