Endocrine disruptor
Endocrine disruptors, sometimes also referred to as hormonally active agents, endocrine disrupting chemicals, or endocrine disrupting compounds are chemicals that can interfere with endocrine systems. These disruptions can cause numerous adverse human health outcomes, including alterations in sperm quality and fertility; abnormalities in sex organs‚ endometriosis‚ early puberty‚ altered nervous system or immune function; certain cancers; respiratory problems; metabolic issues; diabetes, obesity, or cardiovascular problems; growth, neurological and learning disabilities, and more. Found in many household and industrial products, endocrine disruptors "interfere with the synthesis, secretion, transport, binding, action, or elimination of natural hormones in the body that are responsible for development, behavior, fertility, and maintenance of homeostasis."
Any system in the body controlled by hormones can be derailed by hormone disruptors. Specifically, endocrine disruptors may be associated with the development of learning disabilities, severe attention deficit disorder, and cognitive and brain development problems.
There has been controversy over endocrine disruptors, with some groups calling for swift action by regulators to remove them from the market, and regulators and other scientists calling for further study. Some endocrine disruptors have been identified and removed from the market, but it is uncertain whether some endocrine disruptors on the market actually harm humans and wildlife at the doses to which wildlife and humans are exposed. The World Health Organization published a 2012 report stating that low-level exposures may cause adverse effects in humans.
History
The term endocrine disruptor was coined in 1991 at the Wingspread Conference Center in Wisconsin. One of the early papers on the phenomenon was by Theo Colborn et al. in 1993. It stated that environmental chemicals disrupt the development of the endocrine system, and that effects of exposure during development are often permanent.Although the endocrine disruption has been disputed by some, work sessions from 1992 to 1999 have generated consensus statements from scientists regarding the hazard from endocrine disruptors, particularly in wildlife and also in humans.
The Endocrine Society released a scientific statement outlining mechanisms and effects of endocrine disruptors on "male and female reproduction, breast development and cancer, prostate cancer, neuroendocrinology, thyroid, metabolism and obesity, and cardiovascular endocrinology," and showing how experimental and epidemiological studies converge with human clinical observations "to implicate endocrine disruptive chemicals as a significant concern to public health." The statement noted that it is difficult to show that endocrine disruptors cause human diseases, and it recommended that the precautionary principle should be followed. A concurrent statement expresses policy concerns.
Endocrine disrupting compounds encompass a variety of chemical classes, including drugs, pesticides, compounds used in the plastics industry and in consumer products, industrial by-products and pollutants, heavy metals and even some naturally produced botanical chemicals. Industrial chemicals such as parabens, phenols and phthalates are also considered potent endocrine disruptors. Some are pervasive and widely dispersed in the environment and may bioaccumulate. Some are persistent organic pollutants, and can be transported long distances across national boundaries and have been found in virtually all regions of the world, and may even concentrate near the North Pole, due to weather patterns and cold conditions. Others are rapidly degraded in the environment or human body or may be present for only short periods of time. Health effects attributed to endocrine disrupting compounds include a range of reproductive problems ; changes in hormone levels; early puberty; brain and behavior problems; impaired immune functions; and various cancers.
One example of the consequences of the exposure of developing animals, including humans, to hormonally active agents is the case of the drug diethylstilbestrol, a nonsteroidal 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.
Aquatic life subjected to endocrine disruptors in an urban effluent have experienced decreased levels of serotonin and increased feminization.
In 2013 the WHO and the United Nations Environment Programme released a study, the most comprehensive report on EDCs to date, calling for more research to fully understand the associations between EDCs and the risks to health of human and animal life. The team pointed to wide gaps in knowledge and called for more research to obtain a fuller picture of the health and environmental impacts of endocrine disruptors. To improve global knowledge the team has recommended:
- Testing: known EDCs are only the 'tip of the iceberg' and more comprehensive testing methods are required to identify other possible endocrine disruptors, their sources, and routes of exposure.
- Research: more scientific evidence is needed to identify the effects of mixtures of EDCs on humans and wildlife to which humans and wildlife are increasingly exposed.
- Reporting: many sources of EDCs are not known because of insufficient reporting and information on chemicals in products, materials and goods.
- Collaboration: more data sharing between scientists and between countries can fill gaps in data, primarily in developing countries and emerging economies.
Endocrine system
Hormones travel throughout the body via the bloodstream 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. 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. Sex steroids such as estrogens and androgens, as well as thyroid hormones, are subject to feedback regulation, which tends to limit the sensitivity of these glands.
Hormones work at very small doses. Endocrine disruption can thereby also occur from low-dose exposure to exogenous hormones or hormonally active chemicals such as bisphenol A. These chemicals can bind to receptors for other hormonally mediated processes. Furthermore, since endogenous hormones are already present in the body in biologically active concentrations, additional 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 can elicit adverse effects at much lower doses than a toxicity, acting through a different mechanism.
The timing of exposure is also critical. Most critical stages of development occur in utero, where the fertilized egg divides, rapidly developing every structure of a fully formed baby, including much of the wiring in the brain. Interfering with the hormonal communication in utero can have profound effects both structurally and toward brain development. 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. 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. Disruption of thyroid function early in development may be the cause of abnormal sexual development in both males and females early motor development impairment, and learning disabilities.
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." While compounds that produce estrogenic, androgenic, antiandrogenic, and antithyroid actions have been studied, less is known about interactions with other hormones.
The interrelationships 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 develop overt or subtle lifelong health or reproductive abnormalities. Prebirth exposure, in some cases, can lead to permanent alterations and adult diseases.
Some in the scientific community are concerned that exposure to endocrine disruptors in the womb or early in life may be associated with neurodevelopmental disorders including reduced IQ, ADHD, and autism. Certain cancers and uterine abnormalities in women are associated with exposure to diethylstilbestrol in the womb due to DES used as a medical treatment.
In a 2005 publication, phthalates in pregnant women's urine was linked to subtle, but specific, genital changes in their male infants—a shorter, more female-like anogenital distance and associated incomplete descent of testes and a smaller scrotum and penis. The science behind this study was questioned by phthalate industry consultants, and back in 2008, there were only five studies of anogenital distance in humans, with one researcher stating, "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 epidemiological studies." Today, it is well-established that AGD is an indicator of fetal androgen exposure, and several studies have found a correlation between AGD and the incidence of prostate cancer.