What is NIEHS research telling us about endocrine disruptors?
NIEHS has been a pioneer in conducting research on the health effects of endocrine disruptors for more than three decades, starting with the endocrine-disrupting effects of the pharmaceutical, diethylstilbestrol (DES).
From the 1940s–1970s, DES was used to treat women with high-risk pregnancies, with the mistaken belief that it prevented miscarriage. In 1972, prenatal exposure to DES was linked to the development of a rare form of vaginal cancer in daughters whose mother received DES, and with numerous noncancerous changes in both sons and daughters. NIEHS researchers developed animal models of DES exposure that successfully replicated and predicted human health problems, and have been useful in studying the mechanisms involved in DES toxic effects. NIEHS researchers also showed that the effects of DES and other endocrine disruptors involved the estrogen receptor.
In addition to the fact that we now know that endocrine disruptors are widely dispersed in our environment, some other key points about exposure to endocrine disruptors have emerged.
Exposure at low levels count.
The body’s own normal endocrine signaling involves very small changes in hormone levels, yet we know these changes can have significant biological effects. This leads scientists to think that chemical exposures, even at low doses, can disrupt the body’s delicate endocrine system and lead to disease.
In 2000, an independent panel of experts convened by NIEHS and NTP found that there was “credible evidence” that some hormone-like chemicals can affect test animals’ bodily functions at very low levels — well below the “no effect” levels determined by traditional testing.
Endocrine disrupting chemicals may impact a broad range of health effects.
Although there is limited evidence to prove that low-dose exposures are causing adverse human health effects, there is a large body of research in experimental animals and wildlife suggesting that endocrine disruptors may cause:
- Reductions in male fertility and declines in the numbers of males born.
- Abnormalities in male reproductive organs.
- Female reproductive health issues, including fertility problems, early puberty, and early reproductive senescence.
- Increases in mammary, ovarian, and prostate cancers.
- Increases in immune and autoimmune diseases, and some neurodegenerative diseases.
There are data showing that exposure to BPA, as well as other endocrine disrupting chemicals with estrogenic activity, may have effects on obesity and diabetes. These data, while preliminary and only in animals, indicate the potential for endocrine disrupting agents to have effects on other endocrine systems not yet fully examined.
Effects of endocrine disruptors may begin early and be persistent.
Research shows that endocrine disruptors may pose the greatest risk during prenatal and early postnatal development when organ and neural systems are developing. In animals, adverse consequences, such as subfertility, premature reproductive senescence, and cancer, are linked to early exposure, but they may not be apparent until much later in life.
Research from NIEHS investigators have shown that the adverse effects of DES in mice can be passed to subsequent generations even though they were not directly exposed. The increased susceptibility for tumors was seen in both the granddaughters and grandsons of mice who were developmentally exposed to DES. Mechanisms involved in the transmission of disease were shown to involve epigenetic events — that is altering gene function without altering DNA sequence.
New research funded by NIEHS also found that endocrine disruptors may affect not just the offspring of mothers exposed during pregnancy, but future offspring as well. The researchers found that several endocrine disrupting chemicals caused fertility defects in male rats that were passed down to nearly every male in subsequent generations. This study suggests that the compounds may have caused changes in the developing male germ cells, and that endocrine disruptors may be able to reprogram or change the expression of genes without mutating DNA. The role of environmental endocrine disrupting chemicals in the transmission of disease from one generation to another is of great research interest to NIEHS.
What are some current areas of Research NIEHS is pursuing?
Researchers are playing a lead role in uncovering the mechanisms of action of endocrine disruptors. Today, scientists are:
- Developing new models and tools to better understand how endocrine disruptors work.
- Developing high throughput assays to determine which chemicals have endocrine disrupting activity.
- Examining the long-term effects of exposure to various endocrine disrupting compounds during development and on diseases later in life.
- Conducting epidemiological studies in human populations.
- Developing new assessments and biomarkers to determine exposure and toxicity levels — especially how mixtures of chemicals impact individuals.
- Developing intervention and prevention strategies
For basic information on endocrine disruptors, please see our Endocrine Disruptors Health Topic webpage.