Endocrine disruptors

“Endocrine disruptors are exogenous substances that act like hormones in the endocrine system and disrupt the physiologic function of endogenous hormones. They are sometimes also referred to as hormonally active agents[1] or endocrine disrupting chemicals[2]/compounds[3] (EDC). Studies have linked endocrine disruptors to adverse biological effects in animals, giving rise to concerns that low-level exposure might cause similar effects in human beings.[4]

Background

Since the publication of Rachel Carson’s Silent Spring, there has been concern that chemicals in the environment might exert profound and deleterious effects on wildlife populations, and that human health is inextricably linked to the health of the environment.

Although researchers had studied the endocrine effects of chemicals in the past, the term endocrine disruptor was coined in 1991 at a conference at the Wingspread Conference Center in Racine, Wisconsin. This conference was chaired by Theo Colborn, then with the World Wildlife Fund and the W. Alton Jones Foundation. The term was introduced into the scientific literature with her 1993 paper.[5] In this paper, she stated that environmental chemicals disrupt the development of the endocrine system, and that effects of exposure during development are permanent.

Endocrine disrupting compounds encompass a variety of chemical classes, including hormones, plant constituents, pesticides, compounds used in the plastics industry and in consumer products, and other industrial by-products and pollutants. Some are pervasive and widely dispersed in the environment. Some are persistent organic pollutants (POP’s), and can be transported long distances across national boundaries and have been found in virtually all regions of the world. Others are rapidly degraded in the environment or human body or may be present for only short periods of time.[6] Health effects attributed to endocrine disrupting compounds include a range of reproductive problems (reduced fertility, male and female reproductive tract abnormalities, and skewed male/female sex ratios, loss of fetus, menstrual problems[7]); changes in hormone levels; early puberty; brain and behavior problems; impaired immune functions; and various cancers.[8]

One example of the consequences of the exposure of developing animals, including humans, to hormonally active agents is the case of the drug diethylstilbestrol (DES), a non-steroidal estrogen and not an environmental pollutant. Prior to its ban in the early 1970s, doctors prescribed DES to as many as five million pregnant women to block spontaneous abortion, an Off-label use of this medication prior to 1947. It was discovered after the children went through puberty that DES affected the development of the reproductive system and caused vaginal cancer. The relevance of the DES saga to the risks of exposure to endocrine disruptors is questionable, as the doses involved are much higher in these individuals than in those due to environmental exposures.[9]

Endocrine system
Main article: Endocrine system

Endocrine systems are found in most varieties of animal life. The endocrine system is made up of glands which secrete hormones, and receptors which detect and react to the hormones.

Hormones travel throughout the body and act as chemical messengers. Hormones interface with cells that contain matching receptors in or on their surfaces. The hormone binds with the receptor, much like a key would fit into a lock.

Sex steroids such as estrogens and androgens, as well as thyroid hormones, are subject to feedback regulation, which tends to limit the effects of environmental chemicals.

Theory of endocrine disruption

All communication within the human body is facilitated either by the nervous system or the endocrine system. The nervous system transmits sensory messages to the brain and enables quick responses to sudden environmental events. Typically, these responses involve physical adjustments to avoid something harmful, such as intense heat. The endocrine system regulates adjustments through slower internal processes, using hormones as messengers. The endocrine system secretes hormones in response to environmental stimuli and to orchestrate developmental and reproductive changes. The adjustments brought on by the endocrine system are biochemical, changing the cell’s internal and external chemistry to bring about a long term change in the body. These systems work together to maintain the proper functioning of the body through its entire life cycle.

The theory of endocrine disruption posits that low-dose exposure to chemicals that interact with hormone receptors can interfere with reproduction, development, and other hormonally mediated processes. Furthermore, since endogenous hormones are typically present in the body in relatively tiny concentrations, the theory holds that exposure to relatively small amounts of exogenous hormonally active substances can disrupt the proper functioning of the body’s endocrine system. Thus, an endocrine disruptor might be able to elicit adverse effects at a much lower doses than a toxicant acting through a different mechanism.

The timing of exposure is also presumed to be critical, since different hormone pathways are active during different stages of development. Particularly with younger individuals that are growing rapidly, interfering with the hormonal communication processes these systems provide can have profound effects on the body. Depending on the stage of reproductive development, interference with hormonal signaling can result in irreversible effects not seen in adults exposed to the same dose for the same length of time.[10][11][12] Experiments with animals have identified critical developmental time points in utero and days after birth when exposure to chemicals that interfere with or mimic hormones have adverse effects that persist into adulthood.[11][13][14][15] Disruption of thyroid function early in development may be the cause of abnormal sexual development in both males[16] and females[17] early motor development impairment,[18] and learning disabilities.[19]

There are studies of cell cultures, laboratory animals, wildlife, and accidentally exposed humans that show that environmental chemicals cause a wide range of reproductive, developmental, growth, and behavior effects, and so while “endocrine disruption in humans by pollutant chemicals remains largely undemonstrated, the underlying science is sound and the potential for such effects is real.”[20] While compounds that produce estrogenic, androgenic, antiandrogenic, and antithyroid actions have been studied, less is known about interactions with other hormones.

The interrelationship between exposures to chemicals and health effects are rather complex. It is hard to definitively link a particular chemical with a specific health effect, and exposed adults may not show any ill effects. But, fetuses and embryos, whose growth and development are highly controlled by the endocrine system, are more vulnerable to exposure and may suffer overt or subtle lifelong health and/or reproductive abnormalities.[21] Prebirth exposure, in some cases, can lead to permanent alterations and adult diseases.[22]

There is concern by some in the scientific community that exposure to endocrine disruptors in the womb or early in life may be associated with neurodevelopmental disorders including reduced IQ, ADHD, and autism.[23] Certain cancers and uterine abnormalities in women are associated with exposure to DES in the womb due to DES used a medical treatment.

In another case, phthalates in pregnant women’s urine was linked to subtle, but specific, genital changes in their male infants – a shorter, more female-like anal-genital distance and associated incomplete descent of testes and a smaller scrotum and penis.[24] The science behind this study has been questioned by phthalate industry consultants.[25] As of June 2008, there are only five studies of anogenital distance in humans,[26] and one researcher has stated “Whether AGD measures in humans relate to clinically important outcomes, however, remains to be determined, as does its utility as a measure of androgen action in epidemiologic studies.”[27]

Dose-response controversy

One major objection to the theory of endocrine disruptors is the dosage effect. There is a large gap between high exposures seen in a some laboratory experiment versus the relatively low levels found in the environment.[28][29] Critics argue that dose-response relationship data suggest that the amounts of the chemicals actually in the environment are too low to cause an effect. A consensus statement by the Learning and Development Disabilities Initiative rebuts this criticism arguing that “The very low-dose effects of endocrine disruptors can not be predicted from high-dose studies, which contradicts the standard ‘dose makes the poison’ rule of toxicology. Nontraditional dose-response curves are referred to as nonmonotonic dose response curves.”[23] Furthermore, endocrine disrupting effects have been noted in animals exposed to environmentally relevant levels of some chemicals. For example, researchers have found that a common flame retardant, PBDE-47, affects the reproductive system and thyroid gland of female rats in doses of the order of those to which humans are exposed.[30]

The dosage objection could also be overcome if low concentrations of different endocrine disruptors were synergistic, which was asserted in a paper by Arnold.[31] This paper was published in Science in June 1996, and was one reason for the passage of the Food Quality Protection Act of 1996.[32] The results could not be confirmed with the same and alternative methodologies,[33] and the original paper was retracted,[34] and Arnold was found to have committed scientific misconduct by the United States Office of Research Integrity.[35] Subsequent papers by other authors demonstrated that low concentrations of endocrine disruptors can have synergistic effects in amphibians, but it is not clear that this is an effect mediated through the endocrine system.[36]

The conventional relationship (more exposure equals higher risk) has been challenged by some studying endocrine disruptors. For example, it has been claimed that Tamoxifen and some phthalates have fundamentally different (and harmful) effects on the body at low doses than at high doses.[37]

Routes of exposure

Food is a major source of pollutant exposure. Diet is thought to account for up to 90% of a person’s PCB and DDT body burden.[38] In a study of 32 different common food products from three grocery stores in Dallas, fish and other animal products were found to be contaminated with PBDE.[39] Since these compounds are fat soluble, it is likely they are accumulating from the environment in the fatty tissue of animals we eat. Some suspect fish consumption is a major source of many environmental contaminates. Indeed, both wild and farmed salmon from all over the world have been shown to contain a variety of man-made organic compounds.[40]

With the increase in household products containing pollutants and the decrease in the quality of building ventilation, indoor air has become a significant source of pollutant exposure.[41]

Residents living in homes with wood floors treated in the 1960s with PCB-based wood finish have a much higher body burden than the general population.[42] A study of indoor house dust and dryer lint of 16 homes found high levels of all 22 different PBDE congeners tested for in all samples.[43] Recent studies suggest that contaminated house dust, not food, may be the major source of PBDE in our bodies.[44][45] One study estimated that ingestion of house dust accounts for up to 82% of our PBDE body burden.[46]

Research conducted by the Environmental Working Group found that 19 out of 20 children tested had levels of PBDE in their blood 3.5 times higher than the amount in their mothers’ blood.[47] It has been shown that contaminated housedust is a primary source of lead in young children’s bodies.[48] It may be that babies and toddlers ingest more contaminated housedust than the adults they live with, and therefore have much higher levels of pollutants in their systems.

Types of endocrine disruptors

All people are exposed to chemicals with estrogenic effects in their everyday life, because endocrine disrupting chemicals are found in low doses in literally thousands of products. Chemicals commonly detected in people include DDT, Polychlorinated biphenyls (PCB’s), Bisphenol A, Polybrominated diphenyl ethers (PBDE’s), and a variety of Phthalates.[49] There is a some dispute in the scientific community surrounding the claim that these chemicals actually disrupt the endocrine system. Many believe that there is little evidence that the degree of exposure in humans is enough to warrant concern,[20][29] while many others believe there is evidence that these chemicals pose some risk to human health.[50][51][52]

Some researchers are investigating the health risks to children of endocrine disrupting chemicals. Bisphenol A has come under a great deal of scrutiny as it is a common component of plastic baby bottles. In March 2007, a class action lawsuit was filed in California charging that manufacturers and retailers of plastic baby bottles failed to warn consumers that their products contained Bisphenol A, a chemical that they allege poses developmental and health risks to infants and children.[53]”

Continue reading on: http://en.wikipedia.org/wiki/Endocrine_disruptor

Related links:
http://www.niehs.nih.gov/health/topics/agents/endocrine/index.cfm
http://www.niehs.nih.gov/health/docs/endocrine-disruptors.pdf

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