Washington Toxics Coalition

Human Evidence

Limits on Human Evidence

http://www.watoxics.org/Poisons/poisons3.htm

There are enormous barriers to obtaining human evidence linking pollutants to health problems. Unless huge numbers of people are examined in a study, it is hard to prove significance of their health problems in a statistical sense. And because we are each exposed to hundreds of different pollutants from conception onward, it is hard for scientists to sort out what is causing what, especially since mixtures of pollutants can be more deadly than pollutants acting alone. In fact, given the extent of global contamination, there are no longer any uncontaminated groups of people to serve as comparison groups in studies. Moreover, since many of the worst impacts of pollutants may be apparent only in offspring when those offspring reach reproductive age or later, there may be huge delays between exposure and effect, making definitive proof even more elusive.

Politics and funding also limit human data. As public funding of research comes under increasing attack, a large percentage of the studies that are done are those that large corporations are willing to fund. The biggest limit on human data is that it is considered unethical in most circumstances to conduct controlled experiments exposing people to toxic chemicals in order to see what happens to them. Yet a massive uncontrolled experiment is underway due to the global contamination which has occurred. And despite the limits on human data which could obscure serious problems, some human data are available.

These data are backed by findings from the laboratory. Here are some examples. Cancer Incidences


Cancers

Many studies have found connections between specific toxic exposures and higher cancer rates. For example, children whose families use pesticides in and around the home were found to have higher cancer rates in two studies.  (23, 60) As another example, soft-tissue sarcoma and respiratory cancer death rates were significantly increased for workers in 12 plants in the United States that produced chemicals contaminated with dioxin, if they worked there for more than a year and there had been at least 20 years for the cancer to develop, according to another study.  (31) A variety of studies find elevated cancer rates at various other workplaces. (53, 75)

Cancer incidence in the U.S. increased by 31.7% between 1950 and 1990, after adjusting for changes in age distribution in the population and excluding lung cancer increases.  (64) Men born in the 1940s had more than twice as much cancer not linked to smoking as those born in 1888 through 1897; women born in the 1940s had 30% greater rates of these cancers compared to those born in 1888 through 1897.(20) Cancer types that increased in incidence between 1950 and 1990 include, among others, non-Hodgkin's lymphoma, leukemia and cancers of the testicles, breast, bladder, ovaries, thyroid, liver pancreas and brain.

Better diagnosis may explain part of the increased incidence, but cannot account for all of it.  (21) Noting that "(we) are just beginning to understand the full range of health effects resulting from the exposure to occupational and environmental agents and factors," the National Cancer Advisory Board now says that "(t)he elimination or reduction of exposure to carcinogenic agents is a priority in the prevention of cancer.  "(12)

Many of the increasing types of cancers involve reproductive tissues like the breast, ovary, and testicles. Researchers have shown that there is a relationship between the level and duration of hormone exposure and tumor development in these hormonally sensitive tissues.  (12) Wildlife and laboratory evidence that pollutants act like hormones is very important in the struggle to understand and prevent these cancers.

Breast cancer is good example. In 1961 a woman's lifetime risk of getting this disease was 1 in 20; now it is 1 in 8. Many of the known risk factors for this cancer relate to a woman's lifetime exposure to estrogen's. Earlier onset of the first menstrual period, later age at menopause, and later age at first birth all correlate to both increased lifetime estrogen exposure and higher breast cancer risk. These and other known risk factors for breast cancer only account for 30% of the breast cancer cases while 70% remain unexplained. Some believe that estrogen-mimicking pollutants may be the cause of some of these breast cancer cases.  (22)

This hypothesis is supported by laboratory studies in which pesticides and other pollutants have behaved like estrogen's causing human breast cancer cells to proliferate. In two instances, the estrogen-mimicking characteristics of pollutants were discovered by chance by breast cancer researchers whose experiments went awry. At Tufts University, for example, Dr. Ana Soto was doing experiments in which she added estrogen's to human breast cancer cells and measured rates of resulting cell proliferation. One day she returned to petri dishes of breast cancer cells to which she had not yet added estrogen's to find that the cells had proliferated. Over and over again, breast cancer cells in dishes without added estrogen proliferated. Eventually, Dr. Soto and her colleagues discovered that nonylphenol - a new supposedly inert ingredients in the plastic dishes themselves - was leaching and causing the cell proliferation. Nonylphenol is one of the categories of chemicals found in English rivers believed to be causing male fish to produce female egg proteins as noted above. It is used widely in plastics, detergents, personal care products, and other products.

The findings of Soto and others have been made all the more frightening by evidence that combinations of chemicals can cause more harm than single chemicals. (3)

Some studies have found that women with breast cancer have higher levels of pesticides in their breast tissues and blood (25, 86), although at least one study did not. (83) Other studies have found higher rates of breast cancer in women exposed to high pollution levels at the job or in their neighborhoods. (79)

Testicular cancer is another example of a hormonally-influenced cancer which is increasing, apparently worldwide. (9, 10, 35, 81) In Denmark, incidence rates increased 3-4 fold from the 1940s to the 1980s. In the United States, rates of increase for men under 45 have been labeled "epidemic.  "(10) Worldwide, the incidence of this cancer has increased about 2 to 4 % per year in men under 50 years of age over the past 40 years. While this cancer is still rare compared to cancers prevalent in old age, it is now the most common malignancy of young men, at least in the Western World. (36) These increases are unlikely to be due to improved diagnosis. (9)

Sperm Loss and Other Reproductive Problems.

Various studies have linked workplace exposures to specific toxic chemicals with lowered sperm counts in workers. (7, 28, 41, 63) A recent study of chemical production workers linked workplace exposures to dioxins to lowered testosterone in the blood of male workers.  (27)

In 1992 Elisabeth Carlsen and other Danish researchers published a study which looked at data from 61 studies on sperm counts in men without histories of infertility from many western countries, including the United States.  (14) Their analysis showed a 42 % decrease in average sperm count since 1940, from 113 million sperm per milliliter of semen to 66 million per milliliter. It also showed a decline in average volume of semen, bringing the total sperm decline to 53% since 1940.

Some believe that the downward trend in Carlsen's analysis is not real due to limitations in methodology in the different studies it reviews and other factors. (67) Two recent studies found no declines in populations in three U.S. locations for the last 20 to 25 years.  (32, 68) But at least three studies published since the Carlsen study have found dramatic declines in other locations using data and methods that address the criticisms levied against the Carlsen analysis (6, 47, 84)

Pierre Jouannet and other French researchers, for example, were skeptical of Carlsen's findings and set out to prove them wrong by analyzing data from men who had donated sperm to a Parisian sperm bank between 1973 and 1992. To their amazement they found that average sperm count declined at a rate of 2.1 percent per year, from 89 million per cubic centimeter of semen to 60 million. During the same period of time, the percentage of motile sperm (able to swim) declined at a rate of 0.6 percent per year, and the percentage of normal (as opposed to misshapen) sperm dropped by 0.5 percent per year. The Parisian man born in 1962 had exactly half as much sperm as the man born in 1945. If the decline were to continue at the same rate, Jouannet warns, "it will take seventy or eighty years before it goes to zero."  (87)

The power of seemingly tiny chemical exposures to hurt offspring is demonstrated by laboratory experiments on rats. In one study, pregnant rats were given a single low oral dose of dioxin on day 15 of gestation. A dose of only 1 ug/kg resulted in a 43% sperm decrease as measured on day 49. Even at the lowest dose levels (0.064 ug/kg) there were significant decreases.  (61) In a similar study, researchers found a 10 to 21% decline in mean daily sperm production in male offspring when mother rats were exposed to minute concentrations of certain phthalates and alkylphenols, common pollutants associated with plastics, cleaning products and other products. (Alkylphenols include nonylphenols, the substance that leached from plastic lab dishes causing proliferation of human breast cancer cells in Dr. Soto's laboratory as mentioned above. They are implicated in the production of vitellogenin in male fish in English rivers as discussed above.) These effects were observed at exposures hundreds of times lower than the level identified for regulatory purposes as the No-Observed Effect Level. (NOEL).  (76) The toxic exposures in these laboratory experiments did not result in obvious injury to the mothers during the course of the experiment.

These laboratory studies also found that the low toxic exposures led to other genital and reproductive problems including delayed descent of testis, reduced anogenital distance and decreased weight of sex organs, and demasculinized/feminized behavior.

There is evidence that some of these same sorts of problems may be increasing in humans. Cryptorchidism, a failure of the testes to descend into the scrotum, and hypospadias, a condition in which the urinary duct does not extend to the end of the penis, may be increasing. Anecdotal evidence and preliminary studies indicate that incidence of these conditions may have doubled over the past several decades.  (1, 15, 35, 36, 54, 56)

Boys with undescended testicles have a greater chance than boys with normal testicles of getting testicular cancer (33), a disease which is undoubtedly swiftly increasing in incidence, as noted earlier. Because testicular cancer, hypospadias, cryptorchidism, and lessened sperm-producing capacity may all be linked to problems during fetal development, they all may share a common cause. Scientists theorize that hormone-disrupting pollutants may be involved in apparent increases in all of these problems.  (13, 36, 77)

Studies of boys whose mothers were exposed to high levels of hormone-disrupting substances provide strong evidence that humans are not immune from reproductive problems in children that are seen in laboratory animals. Boys in Taiwan whose mothers ate rice oil contaminated with PCBs and furans in 1979 suffer an array of problems, including significantly shorter penises, for example. (44) As another example, some large studies have found that sons of women given synthetic estrogen (DES) during pregnancy had higher rates of underdeveloped testes, stunted penises, undescended testicles, and abnormal sperm, though other studies haven't confirmed all of these findings. (17)

DES daughters have been studied much more than the sons and suffer higher rates of clear-cell cancer of the vagina, major structural deformities of the uterus and other reproductive disorders, more infertility and problems with pregnancies, and other problems due to DES exposure prior to birth. (38)

Recent studies and media attention have focused on problems in males potentially linked to pollution, but as the DES data makes clear, women and girls are no less susceptible to reproductive troubles linked to pollutants. One female reproductive problem that seems to be increasing is endometriosis, an often painful condition in which cells from the uterus move to other locations in the abdomen, often interfering with the ability to have children. (57) The condition was once fairly unusual. Now an estimated ten percent of U.S. women of child-bearing age - approximately 5.5 million women - may have this disease.  (45) Research with rhesus monkeys provides an interesting clue about possible causes of this disease. There is a correlation between dioxin exposures and endometriosis in the monkeys. Both occurrence and severity of the disease parallels levels of exposure to dioxin. (71)

Other Birth Defects and Problems in Children

According to the Centers for Disease Control, of 38 types of birth defects analyzed comparing information from 1979-80 through 1986-87, a seven year period, 29 increased in incidence, 2 decreased, and 7 changed less than 2% per year. (26) Some of the increases can be attributed to better diagnosis and similar factors. But others cannot be. Doctors and parents years ago would be as likely to notice missing eyeballs and other severe eye deformities as they are now. Yet rates have increased.

Could toxic exposures play a role as they seem to do in wildlife where birth defects have been observed?

Learning and Behavioral Problems in Children

Other birth defects and impacts on offspring are more subtle, but potentially equally devastating. Several human studies provide evidence that low concentrations of pollutants can cause behavioral and learning problems in children.

In one group of studies, psychologists Joseph and Sandra Jacobson and their colleagues examined the effects of organochlorine pollution on the children of women who ate Lake Michigan fish as compared to those who did not.  (30, 48-52) The Jacobsons obtained information on pollution concentrations in the fish and measured concentrations entering children via the umbilical cords and breast milk.

Learning impairments and other problems in children of women who eat fish correlate to pollution levels in the fish.

Babies from the contaminated group had lower birth weights and smaller head sizes, weaker reflexes, impaired responsiveness, reduced motor coordination and reduced muscle tone as compared to the other children. At seven months old, the contaminated children had decreased visual recognition ability. At 4 years old, they had slower reactions to visual stimuli, took longer to solve problems on memory tests, and made more mistakes on the tests. Lack of ability to maintain attention may have been involved in the children's poorer performance.

There was a dose-response relationship between these effects and the level of toxic exposure. The children who were hit with more pollution in the womb, had more severe effects.

A new study by psychologist Helen Daly and others involving mothers who ate Lake Ontario fish has also concluded that toxic exposures associated with eating contaminated fish correlates to cognitive impairments in children. (59) And researchers in North Carolina found that weaker reflexes, poorer muscle tone, and poorer psychomotor skills in children correlated to their PCB exposures as measured by PCB levels in their mothers' milk, which is an indicator of prenatal exposures as well as postnatal ones.  (37, 73)

While it is impossible to say whether the contaminated children's' poorer performances in the U.S. studies will translate into visible problems later in life, some of the functions tested are fundamental to learning. The subtle loss of ability to retain information and to process it quickly, as well as other problems, may limit the affected children as they grow older.

"Every pregnant woman in the world has endocrine disruptors in her body that are transferred to the fetus."

(Consensus statement signed by scientists from around the world)

Dr. Daly has also done laboratory research in which rats fed Lake Ontario fish had significant behavioral and learning deficits compared to rats that ate fish that was less contaminated. Other studies have found that monkeys whose mothers were exposed to low levels of dioxins and PCBs exhibited behavioral and learning problems as compared to control groups. (8, 80)

Hyperactivity is noted as a problem of more highly exposed animals in both the rat, mice and monkey studies. The Jacobsons did not use data from 17 children who refused to cooperate with testers. These children were those most highly exposed. Some have hypothesized that these children may have exhibited hyperactive behavior.  b(66) while Daly has speculated that they were hyper-reactive to the mildly frustrating nature of some of the tests, just as the more highly exposed rats in her study were more easily put off by frustrating events. In addition in explaining the poorer performance of more highly exposed children on memory tests, the Jacobsons note that lack of ability to sustain attention may have been a factor.  (48) Attention problems are often linked to hyperactivity.

Chemical accidents provide additional human evidence of the power of pollutants to hurt children's' ability to learn and develop properly. In 1979, for example, cooking oil in Taiwan became contaminated with PCBs.  (72) Many people ate the contaminated oil before the problem was discovered and the oil removed from the market. Children of women who ate the oil have been delayed in reaching developmental milestones, have done more poorly than other children on various tests, and have behavioral abnormalities. They also have been shorter and lighter than other children and have suffered various physical abnormalities of the skin, nails, teeth and lungs more frequently than other children.

The Taiwan disaster and other situations like it involved very high contamination levels, but the learning and behavioral problems observed are of the same sort as those seen in the U.S. studies.

Mothers in the Jacobson study ate only two to three fish meals per month (11.8 kg or 26 pounds total) in the six years before becoming pregnant. The threshold for the high fish consumption group in the Daly study was only 40 pounds of fish over their lifetimes prior to pregnancy. The North Carolina mothers were from the general population and were not selected on the basis of having eaten significant quantities of fish. Thus, it appears that children can suffer subtle yet potentially serious problems as the result of common exposures experienced by a large percentage of the population.

Some Native Americans, Asian Americans, low-income individuals, and other groups eat far more fish than other people, thereby potentially suffering much higher exposures. (See for example, (18) This is one of the many ways in which pollution is an environmental justice problem with impacts falling disproportionately on some.

The topic of neurological and behavioral problems linked to pollution is receiving growing attention. In November of 1995, prominent scientists from around the world met in Erice, Sicily primarily to discuss the impact of hormone disruptors on brain development and behavior. Based on the studies mentioned here and many others, they issued a powerful consensus statement.  (20) "We are certain....endocrine-disrupting chemicals can undermine neurological and behavioral development and subsequent potential of individuals exposed in the womb, or in fish, amphibians, reptiles, and birds, the egg," the scientists say. "It may be expressed as reduced intellectual capacity and social adaptability, as impaired responsiveness to environmental demands, or in a variety of other functional guises. Widespread loss of this in nature can change the character of human societies and destabilize wildlife populations."

Air Pollution on reproductive health

Every pregnant woman "has measurable concentrations of endocrine disruptors in her milk that are transferred to her infant."

(Consensus statement signed by scientists from around the world) "The timing of exposure is crucial during early developmental stages, particularly during fetal development when a fixed sequence of structural change is occurring and before protective mechanisms have developed," the consensus statement notes. "A variety of chemical challenges in humans and animals early in life can lead to profound and irreversible abnormalities in brain development at exposure levels that do not produce permanent effects in adults."

The scientists "estimate with confidence that: Every pregnant woman in the world has endocrine disruptors in her body that are transferred to the fetus. She also has measurable concentrations of endocrine disruptors in her milk that are transferred to the infant." These facts could obscure the true impact of pollution on the learning and behavior in children because with no child free from contamination, no pollution-free comparison groups exist.

Other Problems

There are a broad range of other problems that humans experience as a result of toxic exposures which are beyond the scope of this paper. For example, a growing number of people suffer a range of neurological and immunological problems linked to chemical exposures. In recent years, the phenomenon of "sick building syndrome" has been observed in many different office buildings and schools where new carpets and other toxic chemical-laden materials "offgas" causing many people in the buildings to suffer symptoms like dizziness, nausea, inability to concentrate, and other problems. Contact the Toxics Coalition for materials on these topics, including videos from recent conferences.



http://www.monitor.net/rachel/r432.html

TWO MORE STUDIES SHOW HUMAN SPERM LOSS


Two new studies have found that sperm count in men has declined precipitously over the past 20 years.  [1] Sperm count is the number of sperm in each cubic centimeter of semen. The NEW ENGLAND JOURNAL OF MEDICINE reported last month that sperm count has declined 33% during the past 20 years among a study-population of 1351 healthy, fertile men in Paris, France. A briefer report in the BRITISH MEDICAL JOURNAL last summer found that, comparing men of similar ages, sperm count in 3729 Scottish men had declined 41% among those born in 1969 compared to those born in 1941.

In 1992, a historical analysis of 62 separate sperm-count studies, by Elisabeth Carlsen, concluded that sperm count among men throughout the industrialized world has declined by about 50% during the past 50 years.  [2] In 1994 this finding was challenged by researchers who said that it might have been caused by Carlsen's erroneous choice of statistical methods, not by an actual decline in sperm count.  [3] The two new studies appear to confirm the conclusion than an actual decline in sperm count has occurred and is occurring.

No one knows what is causing the apparent decline in sperm count among men. It is still possible that the decline is not real, that it results from some unknown hidden bias in the 64 studies that have been conducted so far. For example, these 64 studies may have examined men who are not typical of the general population. And various factors that influence sperm count may not have been fully accounted for.  [4] On the other hand, it is entirely possible that the decline IS real. As Carlsen and her co-workers said in 1994, defending their 1992 conclusion, "The most cautious conclusion that can be drawn from the existing data is that semen quality has declined significantly between 1940 and 1990." Even if the decline is real, no one knows for sure what might be causing it. Various hypotheses have been suggested.

The hypothesis getting the most attention is this one: something--perhaps hormone-mimicking chemicals in the mother's blood --is affecting male children before they are born. This hypothesis suggests that male children are being born with fewer Sertoli cells --the cells which, after puberty, cause the production of sperm. Reduced numbers of Sertoli cells (and reduced sperm count) have been observed in the male offspring of estrogen-exposed pregnant rats. [5]


| Environment |

ENVIRONMENTAL POLLUTANTS & REPRODUCTIVE HEALTH

What Primary Care Physicians Should Know

Reproductive disorders, hormonally related cancers, and infertility appear to be on the rise. During the past 50 years, the rate of testicular cancer in industrialized countries has increased by a factor of two to four. Breast cancer mortality in the United States has been rising by

about one percent per year since the 1940s. There is some evidence that sperm counts and semen volume may have declined substantially (Carlsen et al. Br. Med. J. 1992;304:609-613). There are also signs that abnormal sexual development in infants may be increasing. A doubling of the incidence of undescended testes in male infants since 1960 has been reported in the United Kingdom (Group JRHCS, Br.

Med. J. 1986;293:1401-1404).


Today's increased prevalence of these reproductive problems is puzzling. Although some increases in cancer rates have occurred in the elderly, younger populations have also displayed conditions such as abnormal sexual development in infants and testicular cancer and

infertility in young adults. Improved diagnosis may account for some of the increase, but it probably is not the only explanation. To be sure, large quantities of man-made chemicals have been discharged into the environment over the past 50 years, and very few were tested for their reproductive or developmental toxicity. Indeed, it has been discovered that many pesticides and industrial chemicals mimic or interfere with hormones and that some are biologically active in minuscule quantities. Could these compounds, now so common in the environment, be causing adverse reproductive and developmental effects in humans?

Medical researchers are seriously considering this possibility. It is clear that some chemical pollutants have had a profound impact on the reproductive systems of wildlife. Now, 40 years after Great Lakes birds and fish first showed signs of endocrine problems, the lakes are

considered much cleaner, but animals are still suffering the effects many generations later. For example, Lake Michigan Forster's terns exposed to PCBs and dioxin often fail to reproduce and abandon their nests (Kubiak et al. Arch. Environ. Contam. Toxicol.

1989;18:706-727). Lake Superior white sucker fish exposed to dioxins have smaller gonads and lower fecundity, and the males are often demasculinized (Munkittrick et al. Can. J. Fish. Aquat. Sci. 1991;48:1-10). Bald eagles carrying elevated levels of pesticides, such as DDT, have difficulties reproducing (Anthony et al. J. Wildl. Manage. 1993;57:10-19).

A cadre of researchers are now investigating whether hormone-like compounds in the environment could be causing adverse health effects in people. These chemicals potentially could trigger a variety of reproductive disorders in humans by influencing the endocrine system of both males and females (Sharpe and Skakkebaek, Lancet 1993;341:1392-1395; Colborn et al. Environ. Health Perspect.

1993;101:378-384). A growing concern has already led the U.S. Environmental Protection Agency (EPA) to reevaluate its regulation of chemical releases: in addition to carcinogenicity, the agency will now consider a chemical's effects on reproductive and developmental health when drawing up federal safety guidelines. Also, the International Joint Commission has called for a ban on the release into the Great Lakes of chlorinated compounds, many of which mimic or interfere with hormones.

Public awareness has been raised as well by the spate of articles in the popular press on environmental estrogen's and their potential impact on male fertility. Your patients are likely to ask questions about a possible connection between their exposure to chemicals in the environment and their health. As a primary care physician, it is important that you keep abreast of research that will shed light on this subject. The possibility that environmental pollutants with endocrine activity are influencing human reproductive potential is sure to receive continued attention the story is still far from complete. The purpose of this booklet is to provide you with the latest information on what is known and what is still unknown about the toxicity of hormone-like chemicals in the environment and to offer help in communicating this knowledge to patients.

What do we know about chemicals in the environment and their effects on the endocrine system?

A wide variety of common chemicals potentially could influence endocrine function in humans.

ENVIRONMENTAL ESTROGENS: By definition, an environmental estrogen is a chemical that acts like endogenous estradiol. To test for estrogenicity, researchers add the chemical in question to cultured human breast cancer cells (or other estrogen-responsive cells) and evaluate its ability to spur cell proliferation. In laboratory animals, they assess the chemical's ability to trigger enlargement of uterine and breast tissues. Often these compounds have a molecular shape that allows them to fit like a key into the binding sites of the body's estrogen receptors. Once bound, the chemical can unlock or provoke the same physiological changes induced by endogenous estradiol. Pollutants with estrogenic activity bind to the receptor more weakly than does estradiol, so larger doses are needed to elicit the usual physiological responses.

A variety of common chemicals have been found to be estrogenic in cell cultures and/or animal studies. They include the insecticides DDT, kepone, dieldrin, toxaphene, and chlordane. Certain PCBs, once used as electrical insulators, are also on the list of environmental estrogen's. So are compounds in plastics: bis-phenol A, a chemical shed from polycarbonate plastics; and nonylphenol, a strengthener used in polystyrene and in PVC products and also a breakdown product of surfactants in detergents and toiletries. Most recently, endosulfan, one of the most commonly used pesticides in the United States today, was found to be estrogenic (Soto et al. Environ.

Health Perspect. 1994;102:380-383).

OTHER ENDOCRINE DISRUPTORS: Not all chemicals of concern mimic estrogen. Some can influence the endocrine system through other mechanisms -- for instance, an antagonist may bind to a receptor and prevent the endogenous hormone from gaining access.

Other compounds may alter the synthesis and metabolism of natural hormones or alter hormone receptor levels in tissues. Dozens of common chemicals have shown endocrine activity: they include dioxins and dibenzofurans (by-products of bleaching and the manufacture and incineration of chlorinated compounds); the herbicides atrazine, 2,4-D, and 2,4,5-T; and the heavy metals lead and mercury.

Impact of the enviorment on reproductive health


| Environment |

ENVIRONMENTAL POLLUTANTS & REPRODUCTIVE HEALTH

What Primary Care Physicians Should Know

Reproductive disorders, hormonally related cancers, and infertility appear to be on the rise. During the past 50 years, the rate of testicular cancer in industrialized countries has increased by a factor of two to four. Breast cancer mortality in the United States has been rising by

about one percent per year since the 1940s. There is some evidence that sperm counts and semen volume may have declined substantially (Carlsen et al. Br. Med. J. 1992;304:609-613). There are also signs that abnormal sexual development in infants may be increasing. A doubling of the incidence of undescended testes in male infants since 1960 has been reported in the United Kingdom (Group JRHCS, Br.

Med. J. 1986;293:1401-1404).

Today's increased prevalence of these reproductive problems is puzzling. Although some increases in cancer rates have occurred in the elderly, younger populations have also displayed conditions such as abnormal sexual development in infants and testicular cancer and

infertility in young adults. Improved diagnosis may account for some of the increase, but it probably is not the only explanation. To be sure, large quantities of man-made chemicals have been discharged into the environment over the past 50 years, and very few were tested for their reproductive or developmental toxicity. Indeed, it has been discovered that many pesticides and industrial chemicals mimic or interfere with hormones and that some are biologically active in minuscule quantities. Could these compounds, now so common in the environment, be causing adverse reproductive and developmental effects in humans?

Medical researchers are seriously considering this possibility. It is clear that some chemical pollutants have had a profound impact on the reproductive systems of wildlife. Now, 40 years after Great Lakes birds and fish first showed signs of endocrine problems, the lakes are

considered much cleaner, but animals are still suffering the effects many generations later. For example, Lake Michigan Forster's terns exposed to PCBs and dioxin often fail to reproduce and abandon their nests (Kubiak et al. Arch. Environ. Contam. Toxicol.

1989;18:706-727). Lake Superior white sucker fish exposed to dioxins have smaller gonads and lower fecundity, and the males are often demasculinized (Munkittrick et al. Can. J. Fish. Aquat. Sci. 1991;48:1-10). Bald eagles carrying elevated levels of pesticides, such as DDT, have difficulties reproducing (Anthony et al. J. Wildl. Manage. 1993;57:10-19).

A cadre of researchers are now investigating whether hormone-like compounds in the environment could be causing adverse health effects in people. These chemicals potentially could trigger a variety of reproductive disorders in humans by influencing the endocrine system of both males and females (Sharpe and Skakkebaek, Lancet 1993;341:1392-1395; Colborn et al. Environ. Health Perspect.

1993;101:378-384). A growing concern has already led the U.S. Environmental Protection Agency (EPA) to reevaluate its regulation of chemical releases: in addition to carcinogenicity, the agency will now consider a chemical's effects on reproductive and developmental health when drawing up federal safety guidelines. Also, the International Joint Commission has called for a ban on the release into the Great Lakes of chlorinated compounds, many of which mimic or interfere with hormones.

Public awareness has been raised as well by the spate of articles in the popular press on environmental estrogen's and their potential impact on male fertility. Your patients are likely to ask questions about a possible connection between their exposure to chemicals in the environment and their health. As a primary care physician, it is important that you keep abreast of research that will shed light on this subject. The possibility that environmental pollutants with endocrine activity are influencing human reproductive potential is sure to receive continued attention the story is still far from complete. The purpose of this booklet is to provide you with the latest information on what is known and what is still unknown about the toxicity of hormone-like chemicals in the environment and to offer help in communicating this knowledge to patients.

What do we know about chemicals in the environment and their effects on the endocrine system?

A wide variety of common chemicals potentially could influence endocrine function in humans.

ENVIRONMENTAL ESTROGENS: By definition, an environmental estrogen is a chemical that acts like endogenous estradiol. To test for estrogenicity, researchers add the chemical in question to cultured human breast cancer cells (or other estrogen-responsive cells) and evaluate its ability to spur cell proliferation. In laboratory animals, they assess the chemical's ability to trigger enlargement of uterine and breast tissues. Often these compounds have a molecular shape that allows them to fit like a key into the binding sites of the body's estrogen receptors. Once bound, the chemical can unlock or provoke the same physiological changes induced by endogenous estradiol. Pollutants with estrogenic activity bind to the receptor more weakly than does estradiol, so larger doses are needed to elicit the usual physiological responses.

A variety of common chemicals have been found to be estrogenic in cell cultures and/or animal studies. They include the insecticides DDT, kepone, dieldrin, toxaphene, and chlordane. Certain PCBs, once used as electrical insulators, are also on the list of environmental estrogen's. So are compounds in plastics: bis-phenol A, a chemical shed from polycarbonate plastics; and nonylphenol, a strengthener used in polystyrene and in PVC products and also a breakdown product of surfactants in detergents and toiletries. Most recently, endosulfan, one of the most commonly used pesticides in the United States today, was found to be estrogenic (Soto et al. Environ.

Health Perspect. 1994;102:380-383).
 

OTHER ENDOCRINE DISRUPTORS: Not all chemicals of concern mimic estrogen. Some can influence the endocrine system through other mechanisms -- for instance, an antagonist may bind to a receptor and prevent the endogenous hormone from gaining access.

Other compounds may alter the synthesis and metabolism of natural hormones or alter hormone receptor levels in tissues. Dozens of common chemicals have shown endocrine activity: they include dioxins and dibenzofurans (by-products of bleaching and the manufacture and incineration of chlorinated compounds); the herbicides atrazine, 2,4-D, and 2,4,5-T; and the heavy metals lead and mercury.
 

Agents Associated with Adverse Female Reproductive Capacity or Developmental Effects and Male Reproductive Dysfunction

Benzo(a)pyrene None NA* Birth defects 1
Chloroprene None NA Birth defects 2,3
Dibromochloro- Decreased sperm count, azoospermia, hormonal changes 2
propane (DBCP) Testicular damage 2
Estrogen Decreased sperm count 2 Decreased sperm count 2
Ethylene dibromide (EDB)
Abnormal sperm motility 1 Testicular damage 2,3
Inorganic mercury**
Menstrual disorders, spontaneous abortion
1 Fetal loss, Birth defects 1
Lead** Spontaneous abortion prematurely, neuralgic
dysfunction in child 2 Birth defects, Fetal loss 2
Lead Decreased sperm count 2 Testicular damage, decreased 2 sperm count, Decreased sperm motility, abnormal morphology
Organic mercury CNS malformation, 2 Birth defects, fetal loss 2
Cerebral palsy
Polybrominated None NA Fetal loss 2
biphenyls (PBBs)
Polybrominated None NA Testicular damage 1
biphenyls (PBBs)
Polychlorinated Neonatal PCB syndrome (low birth weight,
biphenyls (PCBs) hyperpigmentation, eye abnormalities)
2 Low birth weight, Fetal loss 2
Polychlorinated biphenyls None NA Testicular damage 1
(PCBs)
2,4-Dichloro Skeletal defects 4 Birth defects 1
phenoxyacetic
acid (2,4-D)
2,4,5-Trichloro- Skeletal defects 4 Birth defects 1
phenoxyacetic
acid (2,4,5-T)

Male related results are in italics. *=Not applicable because no adverse outcomes were observed. **=Agent that may have male-mediated effects.

1=limited positive data. 2=strong positive data. 3=limited negative data. 4=strong negative data.

Chemicals that potentially could influence the endocrine system are ubiquitous.


Although most organochlorine pesticides, such as DDT, have been banned in the United States, many are still used in other countries. The manufacture of products with PCBs ceased in this country in 1977, but products made previously are still in use and being discarded. These chemicals continue to circulate widely and, indeed, they can be found in air, water, soil, plants, animals, and people around the globe even far from the original sources. With their propensity to settle in fatty tissues, persistent organochlorines continue to migrate into wildlife and people and, once in the body, they resist metabolic breakdown. In industrialized countries, DDE (the metabolite of DDT), PCBs, and dioxins can be detected in human tissues, including breast milk, blood serum, and even follicular fluid (Trapp et al. Fertil. Steril. 1984;42:146-148).

Perturbation of normal hormonal balance in people could cause adverse health effects in both males and females.
 

When adult men are exposed to compounds with endocrine activity, they may suffer reduced fertility. For instance, male pesticide workers exposed to the nematocide DBCP showed decreased testosterone and elevated FSH levels, low sperm counts, azoospermia (absence of living spermatozoa in the semen), and long-term sterility (Whorton et al. J. Occup. Med. 1979;21:161-166). In women, a lifetime of high exposure to estrogen's, affected by age of menarche and childbearing history, among other things increases the risk of developing cancers of the uterus, endometrium, ovary, and, possibly, breast. A recent study in rhesus monkeys found that endometriosis could be linked to chronic exposure to relatively high levels of dioxin and that the severity of the disease correlated with dose

(Rier et al. Fundam. Appl. Toxicol. 1993; 21:433-441).


Low-level exposures to hormone-like chemicals potentially could cause subtle health problems.
 

Like hormones, some man-made chemicals are biologically active at very low concentrations and thus may cause health effects at low doses. Moreover, since many of these chemicals resist metabolic breakdown, small amounts ingested chronically can accumulate, leading to greater body burdens with age. A significant association has been found between higher blood levels of DDE and increased risk of breast cancer in Caucasian women (Wolff et al. J. Natl. Cancer Inst. 1993; 85:648- 652). Another study found no association overall, but when Asian American women were excluded, Caucasian and African American women with the highest blood levels of DDE showed rates of breast cancer two to three times higher than those with the lowest exposures

(Krieger et al. J. Natl. Cancer Inst. 1994; 86:589-599 and correspondence 86:1094-1096).


Developing embryos and fetuses are the most sensitive to chemicals that influence hormonal balance.

Sex hormones direct the embryonic and fetal development of the reproductive system and greatly influence the emerging immune and nervous systems. An embryo or fetus exposed to abnormal levels of sex hormones could suffer permanent deficits in any or all of these systems. The proper balance of hormones in the womb is very finely regulated. The precise impact of endocrine-disrupting chemicals on development would depend on the fetus' sex and the dose and timing of the exposure.


The effects of in utero exposure to endocrine-disrupting chemicals may not appear for decades.


The groundwork for adult reproductive function is laid during embryonic and fetal development. Exposure to estrogenic chemicals in the womb could derail normal male development and cause an array of reproductive disorders, presumably by altering the normal multiplication of Sertoli cells in the testes. Indeed, the more subtle consequences of in utero exposures may not become apparent until puberty or adulthood. This was first demonstrated when a high percentage of women exposed in utero to diethyl stilbestrol (DES) -- a potent estrogenic drug prescribed to prevent miscarriage -- developed clear cell adenocarcinoma (CCAC) of the vagina and cervix during their late teens and twenties. The appearance of this rare cancer in young women can be directly linked to in utero exposure to DES. The sons of women who took DES, in addition to showing increased rates of cryptorchidism and hypospadias at birth, are more likely to suffer during adulthood from low sperm counts and decreased semen volume

(Stillman et al. Am. J. Obstet. Gynecol. 1982;142:905-921).


High-dose exposures to endocrine-disrupting chemicals cause adverse development in humans.


As the DES tragedy has revealed, exposure to high doses of estrogenic compounds in utero can have subtle, yet serious health consequences. An accident in Taiwan provides evidence of more immediate adverse effects caused by in utero exposure to high doses of chemicals with endocrine activity. For several months in 1979 some Taiwanese women consumed rice oil contaminated with PCBs and dibenzofurans (chemicals with dioxin-like toxicity). They gave birth over the following six years to children with ectodermal defects, including abnormal skin and nails, developmental delay, mildly disordered behavior, and increased activity level (Chen et al. Am. J. Public Health 1994;84:415-421). The boys now reaching puberty have shortened penises (Guo et al. Sexual Developments and Biological

Findings in Yu-cheng Children, abstract Dioxin; 1993 conference).


One study suggests that low-dose exposures in the womb to PCBs may affect the neurological development of children. The researchers studied Michigan mothers who ate the equivalent of two to three Great Lakes salmon or trout meals per month for at least six years before pregnancy. These mother's infants had a lower birth weight, smaller skull circumference, and cognitive, motor, and developmental deficits at birth compared to babies of mothers who ate no fish. The infants of mothers who ate fish did not perform as well on a visual recognition memory test -- an effect that persisted when the children were reassessed at age four (Jacobsen et al. J. Pediatr.

1990;116:38-45). The offspring of female rats fed Lake Ontario fish during pregnancy exhibit hyperreactivity to stress (Daly, HB. In: "The Vulnerable Brain," vol. I. Plenum Press, 1992;151-171).

What still needs to be learned about endocrine-disrupting chemicals in the environment?

What is the public's exposure to these chemicals?

Estimating human exposure to chemicals in the environment is very difficult. To accurately assess the total dose a person is receiving, researchers must consider exposure to all chemicals with similar toxicities for example, all estrogenic compounds. Detailed assessments of public exposure to environmental estrogen's and other endocrine-disrupting chemicals are still in the early stages. Declining measurements of these compounds in water, air, and soil may be misleading. Although many banned pesticides are no longer detectable in some places, the chemicals may now be residing exclusively in the food chain. Furthermore, primarily because of their diets, some populations receive higher than average exposures. For instance, a study in Quebec found that Inuit women of the north, who consume a lot of fish and marine mammals, had concentrations of PCBs in their breast milk five times greater than the concentrations found in women from the south (Dewailly et al. Chemosphere 1992;25:1245-1249).

How does the human body respond to low doses of chemicals with weak endocrine activity?

While the evidence is clear that high doses of chemicals with endocrine activity cause adverse health effects, researchers cannot yet be certain that low-dose exposures from the environment are harmful. Moreover, most of the man-made hormone mimics are less potent than endogenous hormones. However, there is still reason for concern because the body does not metabolize and regulate these foreign compounds in the same way as it does endogenous hormones. Many of these foreign compounds have half-lives of years or decades. The health effects, if any, of constant exposure to these compounds in some tissues is poorly understood. It is also possible that some individuals may be genetically inclined to respond with exquisite sensitivity to certain hormone-like chemicals in the environment.


What effects might result from exposure to a mixture of endocrine-disrupting chemicals? Different chemicals with endocrine activity may be able to act synergistically to enhance their individual toxicities. Alternatively, some chemicals might have opposing effects that reduce their individual toxicities. Researchers are still far from understanding the toxic consequences of chemical mixtures. However, a recent study found that a mixture of 10 estrogenic compounds, each at one-tenth the dose needed to individually cause an effect, acted in concert to cause an estrogenic effect (Soto et al. Environ. Health Perspect. 1994;102:380-383).


Could increased rates of reproductive health problems be caused by exposure to endocrine-disrupting chemicals in the environment?


It will be very difficult to show a cause-and-effect relationship, if one exists, between the release of large quantities of man-made chemicals and a rise in reproductive health problems. However, a clear picture may begin to emerge from accumulation of a wide variety of cellular, animal, and epidemiological data. Researchers are just now beginning to investigate the toxicity of endocrine-disrupting chemicals in the environment. The National Cancer Institute will be conducting a major epidemiological study to see if exposure to pesticides correlates with high rates of breast cancer on Long Island, NY. The Center for Disease Control Agency for Toxic Substances and Disease Registry has awarded grants to 10 researchers who are examining the health effects of consuming Great Lakes sport fish. The National Research Council/National Academy of Sciences is about to launch a 26-month study of the health effects of hormone-like chemicals in the environment.


Patient Q&A :

Answers to Eight Commonly Asked Questions


Q: Is it safe to eat fish from the Great Lakes?


A: Fish is nutritious food choice, but more than half of the fish in inland lakes and rivers in the United States contain detectable levels of toxic chemicals. To minimize your exposure to these pollutants, avoid frequent consumption of fatty fish and follow these recommendations taken from a National Academy of Science report on Seafood Safety:

  1. Don't eat fish more than three times a week.
  2. Alternate between freshwater and saltwater fish. In general, ocean fish and seafood are less contaminated.
  3. Before cooking, remove all visible fat including the skin, since toxic chemicals generally accumulate there.
  4. Select smaller fish; they've spent less time in polluted waters and thus have picked up fewer contaminants.

If you're an avid angler, call your state department of natural resources and find out if your favorite fishing hole has been listed in any bans or restrictions. Pay attention to fish advisories. Limit your consumption of large game fish, such as Great Lakes salmon and trout.

Q: If I eat Great Lakes fish, should I breast feed my baby?


A: In addition to the nutrient value of breast milk, nursing gives infants other benefits, such as factors that boost immunity and emotional closeness to the mother. In general, these benefits outweigh the risk that contaminants in your milk will harm your baby. However, if you have consumed large quantities of Great Lakes fish in the past, you may carry higher than usual amounts of contaminants in your milk. Little is known about the effects that high levels of contaminants in breast milk might have on infants. If this worries you, consider bottle feeding, reducing the time that you nurse your baby, or expressing and discarding some of your milk.
 

Q: How can I reduce my own -- and my family's exposure to potentially harmful chemicals in the

environment?


A: The food you eat is the most important source of exposure to pesticides and other compounds that tend to bioaccumulate. That's why carefully controlling your diet is the most effective way to limit your exposure. Most importantly, follow the recommended fish consumption guidelines (above) and eat fatty animal products sparingly. The chemicals of most concern, PCBs, DDT, and dioxin, tend to accumulate in animal fats. Steer clear of rich cheeses, cream, whole milk, butter, pork, and beef and remove the skin from fish and chicken. By keeping your own percentage of body fat low, you will minimize your body burden of these chemicals. In addition, you should eat plenty of vegetables, grains, beans, and fruit. Women, in particular, may be able to counter some of the effects of estrogenic chemicals with a diet rich in fiber, which appears to reduce the amount of endogenous estrogen's that are reabsorbed by the intestine.


Q: Should I have tests done to find out if I have high levels of DDT, PCBs, and dioxin in my body?


A: Testing to estimate your body burden of chemical contaminants is not recommended. The tests are very expensive, and few clinical laboratories are capable of accurately performing such analyses. Moreover, no treatments are available for reducing high body burdens.

Most importantly, you should follow the prevention guidelines for minimizing exposure.


Q: Could my infertility be caused by exposure to chemicals in the environment?


A: Infertility can be caused by many things, including infection by a sexually transmitted disease, ingestion of certain drugs, inherited physical abnormalities, exposure to relatively high doses of certain toxic chemicals on the job, and perhaps even stress-related hormonal

imbalances. Infertility can result from a combination of these factors affecting both partners, and it's often difficult to determine the precise cause. As for pollution, many chemicals in the environment are known to have hormonal properties that potentially could influence fertility.

Reproductive problems have been widely observed in exposed wildlife. A study in rhesus monkeys did find a link between chronic exposure to dioxin and endometriosis, a common disorder in women that can lead to infertility. However, it's still unclear whether low-level exposure to environmental pollution contributes either to endometriosis or to infertility in humans.


Q: Could exposure to environmental pollutants raise my risk of cancer?


A: Many factors contribute to cancer. They include genetics, exposure to viruses, and personal habits, such as diet, alcohol consumption, and cigarette smoking. Exposure to chemicals in the environment also plays a role, although the relationship is much more difficult to sort out. Scientists know that a number of common pollutants, including some plasticizers, fuels, drugs, and pesticides, potentially could disrupt normal hormonal function in the body -- for example, by mimicking estrogen -- and that some cancers, particularly of the reproductive tract, are affected by hormones.


Q: Could my child's behavioral problem (or birth defect) be related to my eating Great Lakes fish during pregnancy?


A: The causes of most birth defects and behavioral disorders are multiple and not well-understood. We do know that in addition to genetics, environmental factors play a role --- that is, chemical exposures can affect a baby's development. One study found that if a woman ate two or three meals of Great Lakes fish per month for six years before pregnancy, her child was more likely to show slight memory deficits and mild hyperactivity. Several states have issued advisories warning women and men who wish to have children to avoid eating Great Lakes fish.


Q: Is my tap water safe to drink?


A: Water from municipal systems is tested for a variety of chemicals and is generally safe to drink. Drinking plenty of water is important for good health, and in most cases the benefits outweigh the risk. However, some water supplies may contain chemical and/or microbial

contaminants at levels that pose a health risk. Areas where substantial agricultural, municipal, or industrial discharges enter the water supply are at elevated risk of such contamination. Drinking water drawn from surface water, from shallow wells or from wells in an area with extremely sandy soils is most susceptible to contamination. If you have concerns about your local water supply, the water utility, the state environmental agency, or the regional office of the U.S. EPA may be able to tell you about contaminants in your water. If your water is contaminated, the problem is best addressed by municipal water treatment facilities. Indeed, skin contact and inhalation of chemicals in water may be more important sources of exposure than ingestion. That s why home drinking water treatment and bottled water (frequently drawn from municipal supplies) should be solutions of last resort.


Resources


For more information on the effects of environmental pollution on health, contact your state's department of public health or:
National Institute of Environmental Health Sciences (NIEHS)
P.O. Box 12233
Research Triangle Park, NC 27709
919-541-3345 <
REPROTOX (a computer database on reproductive and developmental hazards)
Reproductive Toxicology Center
Columbia Hospital for Women Medical Center
2425 L Street, NW
Washington, DC 20037
202-293-5137
EnviroHealth,
an information clearinghouse
1-800-643-4794
International Joint Commission (Great Lakes Regional Office)
100 Ouelette Avenue, 8th Floor
Windsor, Ontario N9A 6T3
519-257-6700

or
P.O. Box 32869
Detroit, MI 48232-2869
313-226-2170


http://www.georgiastrait.org/xenofacts.html

What are Xeno-Estrogens?

More than 50 years ago it was revealed that chemicals in the environment were having a profound affect on reproduction in many species. Despite this warning, humanity continued to embrace the quick fixes offered by the chemical industry.

Chlorine, widely used as a chemical weapon during World War I, was combined with other toxic chemicals to make PCBs, pesticides and plastic. We added chlorine to our drinking water and used it to bleach our paper and clothes. We bought disposable paper and plastic products, threw them out and then burned the waste, unaware that burning chlorine-contaminated waste created dioxins -- one of the most toxic chemicals ever identified.

We've used heavy metals such as cadmium, mercury and lead, in a huge array of products. And, while some countries got the lead out of gasoline, cars and trucks still spew out a cocktail of toxics, including aromatic hydrocarbons.

Since the explosive, post-World War II expansion of the chemical industry, thousands of long-lasting toxic chemicals, which bioaccumulate in the tissues of animals, have been discharged into our environment.  A second warning was sounded in Rachel Carson's award-winning 1960 book, "Silent Spring", which detailed the dangers of pesticide use, including the impacts on the reproductive abilities of birds.

This book played a pivotal role in the banning of DDT as an agricultural pesticide. (DDT is still extensively used to control malaria in developing countries -- a short-term gain for a long-term loss.)  Some of these chemicals have now been identified as xenoestrogens -- substances which cross the placenta and disrupt the hormone-regulating endocrine system by mimicking the female hormone estrogen.

MIXED MESSAGES

Hormones are essential for the regulation of many biological processes in the body. Hormones act as messengers, relaying information to cells about how and when to grow, produce bodily substances, divide and die. To exert their powerful effects, hormones must first bind with specifically tailored cell proteins called receptors. Hormones and receptors have an intricate and precise, lock-and-key fit. This hormone-receptor complex then binds to DNA in a cell's nucleus to activate specific genes.

There are two ways xenoestrogens disrupt the function of the endocrine system. They can mimic natural hormones and "turn on" cell activity at the wrong time or they can "block" normal biological response by occupying the receptor site and preventing hormones from fitting.

The result is not genetic damage but inappropriate activation of genes, including incorrect timing or too much or too little cellular activity.

Interference with hormone function is particularly dangerous to the developing embryo and newborn. At this stage, alteration of sexual, physical or cognitive development is irreversible and potentially life threatening.

Damage from fetal exposure to xenoestrogens may be apparent at birth, but will probably not emerge until later in life when sexual maturity is reached. While exposed mothers may show not ill effects, their offspring may have trouble reproducing.
Even one small dose of a xenoestrogen at the point when a fetus is developing can cause permanent damage. For example, on day 56 of gestation, the human fetus begins the process of male/female differentiation and sexual organ development.

Information about the full range of threats to human and wildlife health is provide in "Listening to the Canaries" and "Why Women/Men/Parents Should Be Xenoestrogenphobic".

COMBINED EFFECTS

KNOWN XENOESTROGENS

The following chemicals are considered to have serious reproductive and endocrinal disruptive effects:

PESTICIDES (Commercial and/or domestic)

2,4,5-T, 2,4-D, alachlor, aldicarb, amitrole, atrazine,

benomyl, lindane, carbaryl, chlordane, cypermethrin, DBCP, DDT, dicofol, dieldrin, endosulfan, esfenvalerate, ethyl parathion, fenvalerate, heptachlor, hexachlorobenzene, malathion, mancozeb, maneb, methomyl, methoxychlor, metiram, metribuzin, mirex, nitrofen, oxychlordane, permethrin and other synthetic pyrethroids, toxaphen, transnonachlor, tributyltin oxide, trifluralin, vinclozolin, zineb, ziram.

HEAVY METALS

CADMIUM - Used in nickel/cadmium batteries, coatings, pigments, stabilizers in plastics and synthetic products and alloys, fossil fuels.

LEAD - Used in lead batteries, paints, pipes, leaded gasoline.

MERCURY - Used in nickel/cadmium batteries, fluorescent lighting ballasts, seed dressings, chlorine production, dental amalgams, fossil fuels.

ORGANOCHLORINES

DIOXIN - (2,3,7,8-TCDD) a byproduct of other organochlorine production, use and disposal (not intentionally produced). include incinerator emissions, metal smelting,

PVC (vinyl) plastic production, chlorine-bleached pulping.

PBBs & PCBs - Production now banned, but PCBs still used in electrical transformers. PCBs still reside in landfills, toxic waste dumps and sediments.

PENTACHLOROPHENOL Wood preservative, used in textile industry.

PLASTIC INGREDIENTS & SURFACTANTS

BISPHENOL A - Breakdown product of polycarbonate

PHTHALATES - POLYCARBONS - Used to make plastic soft

STYRENES - ALKYL/NONYL PHENOL ETHOXYLATES - Used in detergents, pulp & paper and textile industry, some plastic products, paints, pesticides.

AROMATIC HYDROCARBONS

PAHs - Present is crude oil and most fossil fuels, product of combustion of these fuels.

-- Source: Eagle's Eye, World Wildlife Fund,

1995

To Toxic Chemicals,

Your Health & the Environment


XENO-ESTROGEN EFFECTS

Why Women Should be Xeno-Estrogenophobic

Nobody knows exactly why hundreds of thousands of North American women develop breast cancer every year. The disease does have some established risk factors: early commencement of menstruation, never breast feeding a child, late onset of menopause and inheritance of the long-researched "breast cancer gene", BRCA1. These risks apply to approximately 30% of breast cancer cases, leaving the vast majority unexplained. Or are they?

Some scientists are beginning to look at xenoestrogens (foreign estrogen's) as a probable culprit. Xenoestrogens, contaminants introduced into the body from the environment, mimic the action of estrogen produced in cells or alter hormonal activity.  Some naturally occurring and easily degraded xenoestrogens, such as those found in soy products, broccoli and cauliflower, can reduce estrogen's effects. Others, usually synthetic and difficult for the body to break down, can amplify the effects of estrogen. The latter xenoestrogens -- found in certain pesticides, plastics, fuels and drugs -- have proliferated since World War Two.

Evidence is steadily growing that xenoestrogens and other hormone mimicking substances are implicated in a wide range of human and wildlife health problems, including breast cancer.

CONNECTING THE RISKS

Breast cancer develops when a cell escapes the usual restraints on replication and multiplies out of control. This escape is probably due to a build up of mutations in genes which regulate cell division and ensure accurate replication of DNA, although hormones and other substances around the cell may also prompt abnormal growth. In attempting to explain the unexplained, scientists began to re-examine what was known. Linking most established risk factors is the fact that they promote breast cancer by elevating total lifetime exposure to the biologically active estrogen estradiol.

They began to hypothesize: If too much natural estrogen was dangerous, could prolonged exposure to xenoestrogens also be harmful? Not only might this theory explain breast cancer cases in women with no known risk factors, it made sense for another reason -- breast cancer has been on the rise worldwide ever since the explosive growth of the chemical industry in the 1940s. Natural estradiol can cause epithelial cells in breast tissue to multiply. It influences cell growth by binding to an estrogen receptor.

Complexes of hormone and receptor can bind to DNA in the nucleus and activate genes which direct cell divisions, speeding the rate of DNA replication and so increasing the likelihood of a possibly carcinogenic mutation arising and going undetected.  At some point after it is formed, estradiol metabolizes into other forms of estrogen. Like "good" and "bad" cholesterol, the "good" estrogen (2-hydroxyestrone) activates the estrogen receptor only weakly. The "bad" estrogen (16-alpha-hydroxyestrone) strongly increases interaction of the receptor with growth-promoting genes, enhances breast cell proliferation and possibly damages DNA.

Studies have already linked this "bad" estrogen to breast cancer.

Some xenoestrogens may promote cancer by enhancing production of "bad" estrogen. Others may act by binding to an estrogen receptor and inducing it to issue unneeded proliferation signals.Chemicals with these properties may encourage the development of cancer in other ways. Some xenoestrogens seem to help cells generate the new blood needed for tumor growth and spread, others appear to damage DNA.

HOW ARE WE EXPOSED?

Xenoestrogens accumulate in fatty tissue, so food from animals at the top of the food chain are likely to deliver the largest doses -- meat from animals which eat smaller animals or contaminated food or water would, for example, probably yield more exposure than a plate of vegetables carrying residues of estrogenic pesticides.

Corn oil and related polyunsaturated fats seem to have estrogenic effects and can also be a source of exposure.
People who live in areas where air or water is highly polluted by industry or by the dumping or burning of wastes might take in xenoestrogens simply by breathing the air or drinking the water.

Occupational exposures can also occur.  Evidence that synthetic chemicals could exert harmful estrogenic effects first emerged 50 years ago, when researchers reported that chemicals in the environment seemed to affect reproduction profoundly in many species.

Later research confirmed that DDT and other chlorinated organic pesticides could indeed disrupt the endocrine system. Injections of DDT have been found to accelerate the growth of existing mammary tumors in male mice. Growth of such tumors is a sign that a chemical is unusually carcinogenic, as male rodents are generally resistant to breast cancer. Injection into male rats of atrazine, a popular weed killer often found in groundwater, also increases the incidence of breast cancer.

In the past 15 years, studies have shown several compounds to be estrogenic and to cause mammary tumors in animals. These include certain aromatic hydrocarbons in fuels and some PCBs. PCBs are long-lived chlorinated organics, once used as electrical insulators. Although their manufacture has been banned in Canada and the US, they can still be found in old transformers and have been detected in soil, water, animals and human tissue.

Recent examinations of various pesticides support the idea that certain xenoestrogens promote breast cancer by shifting the balance of estradiol's by products towards the "bad" estrogen. Natural plant xenoestrogens produce the opposite effect -- broccoli, cabbage, brussel sprouts, cauliflower and soy products encourage the production of "good" estrogen. [1]

* * * THE PLASTIC CONNECTION * * *

Evidence that plastics can also be estrogenic has emerged only in the past five years.  The first culprit to be exposed was the chemical bisphenol A, a breakdown product of polycarbonate, widely used in many plastics, including the lining in food cans and juice packages. Bisphenol A escapes when polycarbonate is subjected to high temperatures.

The estrogenic effects of bisphenol A became clear when men working in the plastics industry developed breasts after chronically inhaling the chemical in dust.

Another link between plastics and breast cancer was uncovered by Drs. Ana Soto and Carlos Sonnenschein in 1992. While working on research unconnected with xenoestrogens, they found cultures from breast cancer cells multiplying more rapidly than expected. Further research revealed that a chemical used to make plastic more flexible -- nonylphenol
[2] -- was the culprit. This estrogen mimicking chemical had escaped from the laboratory's plastic ware. Related substances can be found in polystyrene containers, intravenous tubing and some detergents and household cleaners.
-- Excerpted from "Can Environmental Estrogen's Cause Breast Cancer?" by Drs. Devra Lee Davis and Leon Bradlow, with permission. This article appeared in Scientific American, October 1995.

OTHER CONCERNS

While breast cancer is unquestionably the most serious threat to women's health linked with exposure to xenoestrogens, it is by no means the only problem.  Studies have also tied hormone mimicking chemicals with increases in vaginal and cervical cancers. In addition, xenoestrogens have been implicated in the rising incidences  of endometriosis, a painful condition which occurs when cells from the womb lining grow outside the uterus. Infertility can result.  Studies of rhesus monkeys show exposure to dioxin or PCBs increases risk of developing endometriosis, even at levels 7-8 times lower than the "safe" level proposed by the World Health Organization.  [1] US studies have revealed that white and African-American women with high levels of DDE (a breakdown product of DDT) and PCBs in their blood are two to three times more likely to develop breast cancer than those with lower levels. Asian women, who eat diets rich in soy products, cabbage, broccoli and other vegetables, seem to have no increased risk from higher blood levels of these contaminants.

[2] When Drs. Soto and Sonnenschein identified plastic ware in their laboratory as the cause of cell multiplication, the manufacturer refused to provide them with a list of ingredients, as this was a "trade secret".  They broke the plastic down themselves to isolate the culprit, nonylphenol.


Reuters Thursday, May 31, 2001

Greenpeace: Ban Testicle-Restricting Burners

LONDON (Reuters) - Environmental pressure group Greenpeace called on the British government on Tuesday to ban large rubbish incinerators after a recent study linked them to delays in the sexual development of adolescents. Greenpeace spokesman Mark Strutt told Reuters: "The study found that teenagers living near the incinerators had smaller sexual organs than those in rural areas. "The boys had significantly smaller testicles than their rural counterparts and the girls were developing later."

There are 12 rubbish incinerators in Britain, mostly in large cities. Two are located in London.  Bodies of teenagers living close to similar burners in the Netherlands during the study were found to contain high levels of toxic chemicals thought to interfere with sexual development and already linked to cancer, heart disease and breathing illnesses.
 

Burned by Flame Retardents?  Science News Vol 160 #15   www.sciencenews.org

Two years ago unnerving news from researchers in Stockholm hit the Eurpean press.  An analysis of samples of women's breast milk since 1972 showed dramatic increases in a class of relatively unknown chemicals that toxicologists liken to the notorious pollutants polychlorinated biphenyls (PCB's).

The lesser-lnown chemicals, polybromo diphenyl eithers (PBDE's), had been noted a year earlier in the Swedish food supply.  Soon, researchers in North America also documented an accumulation of women's milk.
They obsevered Paces in fat, too, where the chemicals lodge.  Furthermore, PBDEs have been reported in human tissue in Japan, Israel, and Spain.