Environmental Estrogens and Human Health

Estrogens have many functions in the body. Their principal function is to cause cellular proliferation and growth of the sex organs and other tissues related to reproduction. However, they affect bone growth and strength, protein deposition, general metabolism, fat deposition, hair distribution, skin texture and water retention. They act by stimulating special estrogen receptors within cells. There are, however, other chemicals which through direct activation of the estrogen receptor, or through other methods are able to either mimic the effects of estrogen or disrupt its function. These chemicals are known as environmental estrogens (EE). EEs are compounds which are either intentional or unintentional byproducts of chemical manufacturing which have come to be present in our air, food and water supplies. Some studies have correlated exposure to them with a higher risk of breast cancer, while other studies have found no such correlation. Studies have also examined their potential role in stimulating endometriosis and endometrial cancer. Still others blame them for male reproductive problems such as worldwide decreasing sperm counts and significant rises in incidence of testicular cancer and cryptorchidism (undescended testes).

One major group of chemicals displaying estrogenic (estrogen mimicking) effects are the organochlorines. Their largest uses are in the production of polyvinyl chloride (PVC) plastics and pesticide production, but they are also used in bleaching, disinfection, dry cleaning, fire prevention, and refrigeration. The estrogenic pesticides/herbicides include DDT, lindane and atrazine, and alachlor (one of the most widely used herbicides in the U.S). DDT is now banned in the U.S., but the other compounds are still in use. They are very persistent in the environment and tend to bioaccumulate up the food chain because they are stored in the fat of animals exposed to them, as do all of the chemicals discussed here. Atrazine is known to induce breast cancer in exposed subjects. More then 4.3 million Americans (most in the midwest) are exposed to atrazine concentrations exceeding the acceptable cancer risk level established by the Safe Drinking Water Act, which is still 30 times what is considered safe in Europe.

By far, the most infamous of these compounds is the pesticide DDT. DDT use in the U.S. peaked at 61 million pounds in 1963 and then gradually declined until its ban in 1972. However, manufacture continued in the U.S. for sale to other countries into the 1980’s. Mexico and Brazil both put about 1,000 metric tons a year into the environment to this day. Other places were DDT is still widely used include India, China and Indonesia. It reaches the U.S. today by means of imported food products and air and ocean currents. Once in the environment, or in the body, DDT slowly breaks down into many metabolites. It was found that DDT and its estrogenic metabolites could trigger estrogen receptors, and that these compounds were found to do this at concentrations commonly found in human tissues.

Polychlorinated biphenyls (PCBs), of which dioxin (the primary toxic ingredient in Agent Orange) is one, are also estrogenic compounds. Their production is now banned, but they are still produced as byproducts during incineration, paper manufacture and bleaching and in the production of some other herbicides and pesticides. For the most part, they themselves are not estrogenic. However, when the body attempts to break them down, it produces metabolites which are effective at mimicking estrogen. Dioxins are known to be toxic and carcinogenic. A 1994 report by the U.S. EPA concluded that there appeared to be no safe level of exposure to dioxin. The report also confirmed that dioxin can cause severe reproductive and developmental problems at levels already present in the average American. A 1989 EPA investigation found that no hazardous waste incineration plant in the country met the EPAs requirement of near total destruction of dioxin. It is fat soluble and bioaccumulates up the food chain with the highest levels found in our beef, cheese, milk, chicken, pork, fish and egg products in that order.

Another major class of environmental estrogens are the phthalates. Phthalate esters have been used since the 1930s as plasticizers in the production of many plastics including PVC. They are found in inks used to print on plastic, board and foil food wrappers, baby formula, cheese, margarine, chips, vinyl flooring and emulsion paint. Due to their persistence in the environment, they are also commonly found in rivers, groundwater and drinking water. A survey of fatty foods in 1993 found significant phthalate levels in every sample tested including various meats, fish, eggs, milk and milk products. Very little is known about the overall estrogenic effects of phthalates or at what levels they become harmful to people. However, in levels of baby milk formula taken in the UK, babies were found to be receiving a dose of phthalates just 4 times lower then the dose required to produce toxicity in rats. Usually, the dose considered safe for humans is 100 times lower then that determined in animal models.

Alkyphenol ethoxylate surfactants first entered wide use in the 1940s for a wide range of detergent and surfactant uses. Today, we are highly exposed to these compounds in a variety of ways. They are in industrial and domestic detergents (*In the UK, and most of the rest of Western Europe, these compounds have been banned in domestic detergents since 1976, but they are still used in the U.S.), some shampoos, shaving foams and other cosmetics, detergent containing gasoline (which enters the environment via road run-off), the spermicidal lubricant nonoxynol-9 (this is especially troubling considering that this substance has the strong potential to come into direct contact with estrogen sensitive tissues) and a variety of pesticides. One of the largest sources of environmental contamination, though, is through industrial effluent released into the world’s waterways. It is well documented that these compounds, in rats, stimulate estrogen dependent uterine growth and disrupt reproductive development in offspring of exposed mothers. There is no data to indicate at what level of exposure these effects would occur in humans.

The final major estrogenic toxin is bisphenol A. Bisphenol A is used in the production of epoxy resins and polycarbonate plastics. These particular plastics are used to coat the insides of food and beverage metal cans, bottle tops and water supply pipes. They are also present in high quantities in dental polymers and resins. This toxin was first shown to be estrogenic in 1938. In 1993 it was shown to stimulate human breast cancer cell cultures. Bisphenol A leaches into the fluid inside a can during autoclaving, and all canned foods are autoclaved. Liquor from canned vegetables purchased in the U.S. was shown to be estrogenic to a human breast cancer cell assay, and the most contaminated product, peas, produced 58% of the response of an equal amount of estrogen(!). Not all canned products contain bisphenol A, but it is impossible to know which ones do and which do not. In 1996, the newest analytical methods estimated our dietary exposure at about.1microgram/ kg/day, or 5 times the supposed safe amount determined in animal studies. In addition, bisphenol A has been measured in significant quantities in human saliva up to two years after epoxy dental fillings were placed. This would imply that dental fillings continually leach bisphenol A for years after placement.

The fact that we have been and continue to be exposed to many compounds capable of estrogenic activity is not of question. One hundred seventy seven different organochlorines have been detected in human tissue. It is unknown how many of them are capable of producing estrogenic effects. The next step in understanding the environmental estrogen story is to examine the mechanism of action of these compounds once they enter the body. It is known that despite their structural differences, many environmental compounds displaying estrogenic effect can bind directly to the estrogen receptor and initiate both appropriate and inappropriate responses. They are also able to: influence the body to produce more “bad” estrogen, disrupt the body’s ability to break down estrogen, cause the body to produce more estrogen, disrupt immune function, cause neurotoxicity, and even bind directly to our DNA. It is apparent that these chemicals interact with our bodies in a myriad of ways, most of which are yet to be understood.

Research to this point is divided over whether these compounds contribute to breast cancer or not. Most of the studies that found no link looked at blood levels of these compounds. As mentioned above, these compounds reside primarily in the fat. Studies looking at fat levels, especially breast fat levels, have found a consistent relationship between these compounds and the incidence of breast cancer. A piece of circumstantial evidence comes from a Scientific American article entitled “Deaths Caused by Breast Cancer, by County” accompanied by a map of the U.S. The author states that the controversial notion that environmental chemicals promote breast cancer is supported: the distribution of toxic waste dump sites parallels fairly closely the sites of highest breast cancer mortality. A study looking at the same topic found that counties home to a hazardous waste site were 6.5 times more likely to have elevated breast cancer rates.

The case for endometriosis not as investigated, though. Endometriosis is on the rise. Chillingly, there were only 21 reported cases of it in the US seventy years ago, now there are 5 million. Unfortunately, there is still no known etiology and only guesses at possible risk factors. Some believe environmental estrogens to be strongly involved in the incidence of this disease. In a study done on rhesus monkeys, the animals were exposed to dioxin chronically for 4 years. Ten years after that, the presence and severity of endometriosis was assessed. It was found that moderate to severe endometriosis was present in three of seven animals exposed to 5 parts/per/trillion dioxin and in five of seven animals exposed to 25 ppt. No endometriosis of these types were detected in controls. These are levels that a human living in an industrialized country could be exposed to in the highest exposure areas. A 1992 study in Germany found a positive correlation between serum PCB levels and the incidence of endometriosis in humans. Although this data seems to be implicating environmental estrogens in the incidence of endometriosis in humans, there is not yet enough epidemiological evidence to say for sure. Hopefully, more attention will be paid to this disease in the future and more research will be done.