Endocrine Disruption

Human Effects

  1. What’s the fuss?
  2. Biomonitoring: They’re in Us, Too
  3. General Effects
  4. High Dose Exposures: Known Human Effects
  5. Other Exposures: Some Examples
  6. Concern is Warranted
  7. References

earth chemicalsThousands of chemicals first made to improve our lives have spread unchecked to every corner of the world, polluting oceans, mountains, polar regions, tropics, wildlife, and people. Moved about by wind, water, and animals, the chemicals, and sometimes their more harmful breakdown products, contaminate soil, water, plants, people, and animals on every continent.

CAPTION: Synthetic chemicals pollute every part of our planet, including this coastal redwood forest. CREDIT: Wikimedia

Some of these ubiquitous chemicals, along with natural plant compounds called phytochemicals, can interact with the endocrine system, especially during critical developmental stages. These endocrine disrupting chemicals (EDCs) interfere by mimicking, blocking, or altering hormones and their signaling systems. Hormones work with the immune and nervous systems to regulate growth, reproduction, metabolism, immunity, cognition, and behavior.

What's the fuss?

Altering hormone signals can change how the body works and may lead to health problems. Some people speculate that EDCs may be linked to many health concerns, such as cancer, diabetes, obesity, learning disabilities and behavior changes. Solid evidence linking EDCs with these kinds of effects is lacking, but increasing anecdotal evidence suggests there might be something to the claims.

However, studies of cell cultures, laboratory animals, wildlife, and accidentally exposed humans do show EDCs can cause a wide range of reproductive, developmental, growth, and behavior problems. The most attention has been given to those compounds that produce estrogenic, androgenic, antiandrogenic, and antithyroid actions. Less is known about interactions with other hormones and possible effects on immunity (infections), metabolism, (obesity), the brain (intelligence, behavior), the heart, the lungs, and multiple generations.

But effects vary. Distinct health effects can occur in different organs and at different life stages. Exposed adults may not show 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 (Bern 1992). Prebirth exposure, in some cases, can lead to permanent alterations and adult diseases.

For example, testicular cancer in young men takes root before birth during fetal development. Certain cancers and uterine abnormalities in women are associated with exposure to DES in the womb. In another case, phthalates in pregnant women’s urine was liked 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 (Swan et al. 2005). The ubiquitous compounds, found in plastics and cosmetics, are known to block the androgens that control development of the normally longer male anal-genital distance.

Biomonitoring: They’re in Us, Too

We all carry a heavy mix of hormonally active compounds within us. Synthetic contaminants are passed to us by our parents and picked up at home, at work, in the car, and outside via skin, while breathing, and through food and drink. We accumulate the longer-lasting chemicals (the PCBs, dioxins, and organochlorine pesticides) just by living, store them in fat, and often pass them on to our children through the womb and breast milk. Our exposure to other widely used but less persistent toxic chemicals - such as phthalates, phytochemicals, hormonal drugs, and additives like bisphenol A - is also widespread and occurs throughout life.

family pictureAccording to the Centers for Disease Control’s (CDC) 2005 National Report on Human Exposure to Environmental Chemicals, Americans harbor dozens of chemicals from pesticides, consumer products, and cigarette smoke in their blood and tissue. In its third report, the agency checked 2,400 people for 148 chemicals and found more than 90 percent have a mix of pesticides. And although almost everyone is contaminated with phthalates, children carry a bigger load of the plasticizer and of pesticide ingredients than adults (CDC 2005a).

CAPTION: We all carry a heavy mix of compounds in our bodies, but kids have a bigger share.

Although the CDC’s and other recent biomonitoring projects carried out by interest groups confirm people’s chemical body burdens, it is not clear if the contaminants in us pose health threats. While certain individuals or populations in specific regions of the world could face higher risks, no one is sure exactly how or to what extent EDCs affect human health.

As with any risk, factors such as length of exposure, dose, age, genetics, lifestyle, and other individual differences will influence the kinds and severity of associated health problems. That is, one person may experience many problems while another may experience none.

General Effects

But, some evidence does point to human impacts. Because experimenting on people is illegal and unethical, pinpointing troubles or establishing cause and effect in humans is darned near impossible. Researchers rely on accidental exposures, job-related exposures, and epidemiology studies (using surveys and health clinic data) to obtain evidence of EDCs effects in people.

In general, health effects associated with EDCs 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); changes in hormone levels; early puberty; brain and behavior problems; impaired immune functions; and various cancers.

More specifically, women could face higher risks of breast and reproductive organ tissue cancers, fibrocystic disease of the breast, polycystic ovarian syndrome, endometriosis, uterine fibroids, and pelvic inflammatory diseases.

For men, most of the health effects fall under what is called testicular dysgenisis syndrome. This term describes a range of effects that are tied to disrupted gonadal development during fetal life, possibly caused by exposure to hormone-like compounds (Sharpe and Skakkeback 1993). Human health trends in some countries loosely support trends of decreased sperm quality and increased cancer. Animals studies, however, have confirmed the links between chemical exposure during critical development times and the associated problems. The male effects, then, include: poor semen quality (low sperm counts, low ejaculate volume, high number of abnormal sperm, low number of motile sperm), increases in testicular cancer, malformed reproductive tissue (undescended testes, small penis size, hypospadias), prostate disease, and other recognized abnormalities of male reproductive tissues.

High Dose Exposures: Known Human Effects

Two examples where people were exposed to very high doses illustrate that EDCs can affect humans health: the drug diethylstilbestrol (DES) and the accidental exposure of the population of Seveso, Italy to dioxin (TCDD or tetrachloro-dibenzo-p-dioxin).

DES, a strong synthetic estrogen banned since the 1970s, was given to pregnant women for about 40 years to prevent miscarriages. It was not until the daughters were grown that the negative side effects became known. Daughters of mothers who took the synthetic estrogen during pregnancy have higher rates of reproductive problems, reproductive cancer (vagina, cervix) and malformed reproductive organs (uterus, cervix) (Noller et al. 1990). Sons may also face higher rates of malformed or small penises, undescended testicles and abnormal sperm (Gill et al. 1976). However, there is no evidence of reduced fertility in DES sons. Mice studies confirmed that DES caused the reproductive problems and certain cancers (including the rare rete-testicular cancer in males). More recent animal studies show multigenerational effects and find granddaughters and sons may also be affected (CDC 2005b).

DES is not only a potent estrogen, similar in strength to the natural estrogen estradiol, but it also has the unique ability to concentrate in target tissues, such as the reproductive tracts of birds, reptiles and other animals, during development and cause abnormalities. This drug serves as an example of what potent estrogenic compounds can do and may illustrate the health effects that other environmental estrogens can produce.

The Seveso, Italy, dioxin event, though not the only known case, is probably the most studied population following a chemical disaster in the world. On a quiet July day in 1976, a cloud of industrial chemicals rose in the air from the Industrie Chimiche Meda Societa Azionaria chemical plant and engulfed the unsuspecting town and region. The chemicals, a mix of herbicide ingredients, contained about 30 kilograms (66 pounds) of dioxin, a long-lived, hormonally active, cancer causing poison. It took hours for the first burns to appear on children, days for animals to die, months before the classic dioxin-associated skin disease chloracne developed, and years before the more insipid effects were found. Decades later, people’s health is still affected. Residents have been poked, prodded, and studied since the explosion and continue to be part of research to determine the long-range effects from a heavy dose of a strong pollutant. Studies evaluating cancers, endometriosis, reproduction, immune function, menopause, miscarriages, and other parameters are numerous. Some effects have not correlated with the dioxin. Other effects have taken years to manifest. For example, a significant increase in breast cancer risk with higher dioxin exposures was found more than 10 years after initial exposure (Warner 2002) and life-long immune system problems continue with lowered ability to resist disease.

Other Exposures: Some Examples

Human health is affected by direct exposure to large doses of EDCs. Less clear are effects from everyday exposures to complicated mixes of pollutants. Circumstantial evidence suggests there might be reason to be worried. Below are some examples of less cut and dried cases of possible human health effects from various sources and unclear doses of exposure.

Plant compounds can interact with hormone receptors and produce mainly estrogen-like effects. The results of these disruptions are not always agreed upon. For example, phytoestrogens, such as genistein, in soybeans and soy products has been shown to provide benefits – cancer prevention, heart protection - as well as risks - mainly cancers and reproductive troubles. Most concern surrounds effects on infants fed only soy-based formula.

Sperm Counts
Considerable controversy surrounds a study that found that sperm counts in men were falling worldwide, that rates of testicular cancer were increasing and that environmental estrogens may be responsible for these trends (Sharpe and Skakkebaek 1993). Other studies did not support all of these findings and suggested that lower fertility and high cancer rates may only occur in certain human populations. (Fisch and Goluboff 1996) The 1992 study evaluated human sperm quality using 40 years of data gathered from clinics around the world. Researchers found a statistically significant trend towards lower sperm quality (lower volume, numbers and motility) that could be linked to environmental estrogens (Carlsen et al. 1992; Sharpe and Skakkenbaek 1993). In response, other scientists published contrary clinical data studies directly challenging the idea that declining sperm quality is pervasive in the modern world (Safe 1995). Further studies definitely confirmed significant declines in human sperm quality in Europe and North America but not in other world regions (Swan et al. 1997, 2000, 2003a). International efforts to track human sperm quality and to investigate potential causes of significant declines revealed that environmental exposure to some chemicals is strongly associated with low sperm quality (Duty et al. 2003; Hauser et al. 2003; Swan et al. 2003b).

Sex Ratios
Normally, more boys are born than girls resulting in a global birth ratio of about 51 to 54 boys born to every 50 girls born. Some countries, including Canada, the US, and the Netherlands, have reported small but significant changes to these numbers, especially in certain populations. Occupational and accidental exposures to chemicals are also reported to slightly skew the affected populations toward more girls. In Canada, the Aamjiwnaang First Nation community, which is located near many chemical factories in a heavily polluted part of Ontario, reported a sharp and significant drop in boy-girl birth ratios starting in 1993. Ratios changed from about normal prior to 1993 to 41.2 boys and 58.8 girls in the period between 1993 and 2003 (Mackenzie et al. 2005). Another First Nation community had no change and remained similar to Canada’s normal range. Although the reason for the dramatic sex ratio change is not known, some wonder if environmental pollution is involved. Chemical exposure of fathers could play a role. Researchers studying the dioxin release in Seveso, Italy (see above), determined the higher dioxin exposure a father had, the less likely he was to father a boy (Macorelli et al. 2000).

Brain, behavior, intelligence
Certain chemicals - namely pesticides, PCBs, and dioxins - may affect human memory, intelligence, attention, and play behavior, and growing evidence shows similar effects in animals (Clotfelter et al. 2004; Zala and Penn 2004). The evidence is pronounced in children. Mexican 4- and 5-year-old children living in valleys surrounded by modern chemical-laden agriculture had lower age appropriate drawing, memory, and physical coordination skills than their mountain dwelling counterparts living in farming communities that use traditional, nonchemical farming practices (Guillette 1998).

Chemicals, some of them known EDCs, contaminate native Inuit populations living in Canada’s frozen Arctic Circle. Ongoing studies of these traditional people – who eat mainly seal, whale, and other meat heavily laden with synthetic, persistent chemicals – paint a picture of altered health, increased cancers, and immune problems. One example shows infants exposed prenatally to the hormone-active compounds p,p´-DDE and hexachlorobenzene were more likely to suffer ear infections in their first year than those with lower exposure (Dewailly et al. 2000). No differences were found between breast fed and bottle fed babies suggesting a role for prebirth exposure.

Bisphenol A has gained a reputation for producing effects at low-doses. It is also linked to miscarriages. A 2005 study found higher levels of the estrogenic compound and evidence of genetic abnormalities (called aneuploidy, too many chromosomes) in the fetuses (Sugiura-Ogasawara 2005). Similar conclusion were drawn from previous rodent studies conducted by Patricia Hunt (Hunt 2003).

Concern is Warranted

Although large exposures produce known effects, impacts from long term, low level adult exposure is less clear and more controversial. It’s the kids, though, that cause the most concern. Because, even more unknown is the prospect that developing embryos, fetuses, infants, and children, whose growth and development is highly controlled by endocrine signals, may be more vulnerable to exposure at certain times and may suffer lifelong effects from those encounters. Although the 1993 global assessment found insufficient data to reach concrete conclusions about impacts to human health, it concluded there is sufficient evidence to warrant concern (IPCS 2002).

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