EDITOR'S NOTE: This disturbing and thought-provoking article was published in the May 1995 issue of National Wildlife, the journal of the National Wildlife Federation. Our thanks go to NWF for permission to reprint in OUR ENVIRONMENT.

THE ALARMING LANGUAGE OF POLLUTION

By Daniel Glick

In California's Channel Islands in the mid-1970s, an ecologist found an abnormally high ratio of female gulls to male gulls. In Florida in the early 1990s, a team of endocrinologists discovered abnormally small penises in alligators near a former Superfund site. And in Great Britain, biochemists have noticed in the last few years that something in wastewater effluent appears to be creating hermaphroditic fish.

Sound like bizarre episodes of Wild Kingdom? Actually, these observations are all clues to a far-flung scientific sleuthing saga. Over the last few years, experts from a dozen disciplines have been piecing together field and laboratory evidence that environmental pollutants may be doing far more damage to wildlife and humans than previously suspected, in ways no one had imagined possible. For starters, by sending various false signals to endocrine (or hormonal) systems in the body, pollutants could be harming vertebrate reproduction worldwide. All of this evidence could comprise one of the most alarming messages wildlife has ever sent our way. "If we don't believe that animals in the wild are sentinels for us humans, we're burying our heads in the sand," says Linda Bimbaum, director of the environmental toxics division of the Environmental Protection Agency (EPA)

Endocrine-disrupting chemicals are associated with problems ranging from developmental deficiencies in children, to smaller penises in pubescent boys, to infertility. "Every day, I get more concerned," says John McLachlan, chief of the laboratory of reproductive and developmental toxicology at the National Institute of Environmental Health and Science (NIEHS).

Implicated are huge numbers of products-including some pesticides, industrial solvents, adhesives and plastics. A very few, such as PCBs and the pesticide DDT, have been banned or are more heavily regulated in this country than in the past- though they persist in the environment. But thousands have never been regulated. Much of the stuff is deposited worldwide by the atmosphere and has been found in both the Arctic and Antarctica.

Until the last few years, the biggest question for regulators has been: Does a given chemical causecancer, and if so, at what exposure level? (And very few chemicals have even been tested for carcinogenicity.) Now some researchers are also asking: Does a chemical harm reproduction, immunity, behavior or growth?

Also, regulators have long assumed each chemical to be innocent until proven guilty. But researchers are growing increasingly concerned at evidence that related chemicals may be able to harm the body in similar ways. For example, DDT and dioxins (often commonly referred to in the singular) are members of a group of similar chemicals called organochlorines. They are not to be con-fused with the chlorine we safely use to disinfect swimming-pool water and bleach our clothes. While DDT is a deliberate product, dioxins are unwanted byproducts of industrial high-temperature use of chlorine.

A 1994 National Wildlife Federation report, Fertility on the Brink: The Legacy of the Chemical Age, concluded that there is enough evidence to warrant phaseouts, at the very least, of certain chemicals released into the environment. The list includes dioxins, some pesticides and hexachlorobenzene. Federation counsel Elise Hoerath argues that the problem has become "a significant public health threat."

Others warn that hormonal activity is so complicated and poorly understood that costly action to ban certain chemicals is uncalled for until we know more. "As a citizen, I would like to see some Of these chemicals banned," says Carlos Sonneschein, professor of cellular biology at Tufts University School of Medi-cine. "As a scientist, I would like to have more data."

Still, the data have been steadily adding up, thanks largely to the work of zoologist Theo Colbom, a senior scientist at the World Wildlife Fund and director of its wfldlife and contaminants program. In late 1987, Colborn began sifting through studies of declining wildlife populations in the Great Lakes region. On the left side of a piece of paper, she listed species with steep population drops: bald eagle, Forster's tem, double crested cormorant, mink and river otter, among others. On the right, she listed their health problems, including organ damage, eggshell thinning, hormonal changes and low birth survival rates.

Each of the animals depended on a fish diet. Fish in the notoriously polluted Great Lakes were known to contain high concentrations of various synthetic chemicals, especially in fatty tissue, and Colborn wondered if the pollutants were causing the disorders. Were toxics tinkering with the immunity, behavior, growth or behavior of fish eaters? Colbom began searching the scientific literature. "I was really concerned," she recalls. "It was very obvious that these chemicals were developmental toxicants." Yet for the most part, testing had only looked for cancer. "We've been blinded," she says. "We never tested for developmental effects."

Even so, some studies did find those effects. Researchers had found in the mid- 1970s that exposure to DDT seemed to be correlated with an abnormally low number of males in a Califomia gull population. In the late 1970s, toxicologist Michael Fry of the University of California at Davis was able to cause "feminization" of male gull embryos (they developed abnormal testes containing ovarian tissue) in his lab by injecting uncontaminated eggs with DDT

Still, the data have been steadily adding up, thanks largely to the work of zoologist Theo Colbom, a senior scientist at the World Wildlife Fund and director of its wfldlife and contaminants program. In late 1987, Colborn began sifting through studies of declining wildlife populations in the Great Lakes region. On the left side of a piece of paper, she listed species with steep population drops: bald eagle, Forster's tem, double crested cormorant, mink and river otter, among others. On the right, she listed their health problems, including organ damage, eggshell thinning, hon-nonal changes and low birth survival rates.

Each of the animals depended on a fish diet. Fish in the notoriously polluted Great Lakes were known to contain high concentrations of various synthetic chemicals, especially in fatty tissue, and Colborn wondered if the pollutants were causing the disorders. Were toxics tinkering with the immunity, behavior, growth or behavior of fish eaters? Colbom began searching the scientific literature. "I was really concerned," she recalls. "It was very obvious that these chemicals were developmental toxicants." Yet for the most part, testing had only looked for cancer. "We've been blinded," she says. "We never tested for developmental effects. "

Even so, some studies did find those effects. Researchers had found in the mid- 1970s that exposure to DDT seemed to be correlated with an abnormally low number of males in a Califomia gull population. In the late 1970s, toxicologist Michael Fry of the University of California at Davis was able to cause "feminization" of male gull embryos (they developed abnormal testes containing ovarian tissue) in his lab by injecting uncontaminated eggs with DDT.

Many years later, in the early 1990s, University of Florida comparative endociinologist Louis Guillette started finding similar problems in alligators at Florida's Lake Apopka. The area was a fon-ner Superfund site that had been contaminated in 1980 with the chemical dicofol, an organochlorine that also contained some DDT. The lake also contained a mix of agricultural chemicals from farm runoff.

Working with colleague Timothy Gross and other researchers, Guillette found that alligator eggs were barely hatching, teenage males had abnon-nally small penises and the level of the male hormone testosterone was far below normal. Later, Guillette conferred with a researcher who had produced remarkably similar results in lab rats by exposing them to a compound similar to DDE, a breakdown product of DDT. "Oh my God," Guillette said after seeing the data. "I think we have a major problem here."

As Colborn compiled evidence from wildlife biologists, toxicologists and the medical literature, she realized that other scientists were asking some of the same questions. So, in 1991, she helped bring a group of them together to compare notes for the first time. After another meeting last year in Washington, D.C., 23 wildlife biologists agreed that "populations of many long-lived species are declining .... Some of these declines are related to exposure to man-made chemicals and their effects on the development of embryos.">

Their reasoning is based on the knowledge that sex differentiation is determined by tiny amounts of male and female hormones interacting in the developiiig fetus. Contrary to what we've all been taught in introductory biology classes, animals do not exhibit male or female traits simply because they possess or lack, a Y chromosome. If a hormone imposter shows up during fetal development, sexual function can go akimbo. "Very, very low levels of contaminants can have an effect on developing embryos," says the University of Florida's Guillette. "A dose that wouldn't bother an adult can be catasti- ophic to an embryo."

Soon after Fry's discovery that DDT injections could "feminize" gull eggs, biologist David Crews of the University of Texas discovered in 1984 that he could control the gender of slider turtles with minute quantities of the female hormone estradiol. For many turtles, the temperature of the eggs' environment determines gender. Heat produces a female; cold yields a male. But in the lab, Crews could coax embryos incubating at a male-producing temperature to become female with just a drop of estradiol on the eggs.

Estradiol is an estrogen, and Crews' study fits a scary pattem. A number of synthetic substances are so-called "environmental estrogens," acting like the hormone Crews used to bend the turtlesgender. In recent work, he and colleagues have found they can create sexually mixed-up turtles with "cocktail" mixtures of certain PCB compounds. Some of the turtles have testes and oviducts. Others have ovaries but no oviduct. Most alarming, these effects occurred at extremely low doses. Somehow, the combination of several PCBs is far more disrupting than one PCB compound alone.

Of course, not all estrogens are bad; when they occur naturally, they play critical roles in the body. Deliberate therapeutic doses even help women through and beyond menopause, in part by protecting bone density and cardiac health. Environmental estrogens, however, are a different story. NIEHS researcher McLachlan, who calls estrogen the "Earth Mother of hormones," has shown that certain chemicals can bind to or block estrogen receptors, which may in turn cause developmental deviations.

Think of the estrogen receptor as a lock on a cell, and natural estrogen as a perfect key. Scientists believe that literally hundreds of compounds have a chemical structure that also fits the lock-and which could produce similar responses. But then, these chemicals may "fit" into estrogen receptors without producing the cascade of cellular events that follow exposure to actual estrogen-and no harm may be done. Still, even if that's so, when the imposter key is in the lock, the real key may not be able to enter.

Since the number of chemicals that fit into the estrogen lock, or receptor, are so numerous, no one can clarify all the effects of these multiple exposures. "If there are so many estrogens out there, how can anybody figure out which one is doing what?' asks Thomas Goldsworthy of the Chemical Industries Institute of Toxicology. 'Some of the mechanisms aren't clear yet."

Some of the effects, however, are becoming clearer. Toxicologists Earl Gray and Bill Kelce of the EPA reported last year that the common fungicide vinclozolin, used on many fruits and vegetables, can block receptors for the male hormone androgen and cause sexual damage in male rats. At certain doses, rats exposed to vinclozolin do not develop normal male traits even though they do produce testosterone. At high exposures, male rats develop severely abnormal genitalia. Gray thinks fruit treated with the fungicide does not contain enough residue to harm humans, but he is looking into the question. And he is sure of one thing: "There are clearly other environmental anti-androgens we haven't discovered yet," he says.

The findings of field work like Guillette's and laboratory analysis like Gray's have been bolstered by studies of inadvertent human exposures to endocrinedisrupting compounds. In 1979, women in Taiwan who ate rice oil contaminated with polychlorinated biphenyls (PCBS) and polychlorinated dibenzofurans (PCDSs) offered an ideal if tragic laboratory to track long-term effects in humans. Researchers followed 118 children of the women of the women and an identically sized control group. Members of the exposed group have suffered developmental delays, growth retardation and slightly lower 10s. Many of the boys, who are now reaching puberty have abnormally small penises.

Between the 1940s and 1970s diesthulstilbestrol, or DES, was given to an estimated two million to six million women during pregnancy to help prevent miscarriage. In children of DES mothers, the drug caused a range of developmental an dhelath problems, some of which only surfaced in the process of creating the next generation. Among males researchres have noted abnormalities in scrotums, an unusually high prevalence of undescended testicles and decreased sperm counts. Among DES daughters, clinical problems include organ dysfunction, reduction in fertility, immune-system disorders and other difficulties.

The DES example leads to an alarming hypothesis: If some endocrine- disrupting pollutants act like DES, which had effects long fter birth, perhaps we won't see the consequences until exposed offspring themselves begin trying to have kids. And that raises the question: What actual harm to humans have scinetists found from exposure to the sea of chemicals released into the environment over the past 50 years?

Enter Niels Skakkebaek, a Danish researcher in Copenhagen. In 1991, he published a meta-analysis of many smaller studies of global human sperm counts over the past half century and found that the counts declined by half between 1940 and 1990. Other, more recent European studies sought to disprove Skakkebaek's results, but ended up corroborating them. If sperm counts heve indeed dropped, one clue to the reason may come from lab tests in which estrogen-mimicking compounds have affected the Sertoli cell, which is related to sperm production.

Research has also implicated environmental toxics in the rise of endometriosis, testicular cancer and possibly other cancers as well in recent decades. In one study that went on for 15 years, 79 percent of a rhesus monkey colony exposed to dioxin developed endometriosis (the development of endometrial tissue in females in places it is not normally present. Dioxin is not thought to imitate estrogen, but is clearly an endocrine disruptor in at least some animals. In the monkeys, the endometriosis increased in severity inproportion to the amount of dioxin exposure.

What should the rest of society do while the researchers compare notes? "The tough call isn't for the scientists now," says Devra Lee Davis, a top scientific advisor at the U.S. Department of Health and Human Services. "It's for the regulators." There are signs that the federal government is beginning to pay heed. In the EPA draft dioxin reassessment report, now under review, dioxin is characterized as a potent toxic "producing a wide range of effects at very low levels when compared to other environmental contaminants."

The International Joint Commission, a bilateral organization that advises on environmental issues along the U.S.-Canada border, has repeatedly called for virtual elimination of toxic substances in the Great Lakes region. And a little-noticed ,amendment to the Clean Water Act proposed by the Clinton administration (the reauthotization died in the last Congress) would have required regulators to look at "impairments to reproductive, endocrine and immune systems as a result of water pollution." Even skeptic Goldsworthy of the Chemical Industries Institute of Toxicology says, "We are changing our environment. There's no question about that. "

The World Wildlife Fund's Colborn says she welcomes scientific skepticism and even has days when she hopes she is imagining the whole thing. "We admit there are weaknesses, because we are never going to be able to show simple cause-and-effect relationships," she says of the complicated theory. Still, she adds, "The research has reached a point where you can't ignore it any more, and new evidence is coming in every week." For visitors to her Washington, D.C., office, Colborn lets a pesticide manufacturer have the last word: On the wall hangs a 1950s label from a one- pound package of a substance called DuraDust, 50 percent of which was pure DDT The label promises, "Its killing power endures."

WHAT CAN the nation do to reduce the health threats posed by endocrine-disrupting pollutants ? Last year, as part of its efforts to find answers to that question, the National Wildlife Federation released a detailed study: Fertility on Brink: Legacy of the Chemical Age.

"The fact that some chemicals persist and bioaccumulate in the food chain has been known for some time, " reads the NWF report. "What is new is the understanding that some of these chemicals interfere with operations of the body's endocrine system."

The Federation has made a number of recommendations to the Environmental Protection Agency, including these:

The agency should require the phaseout of dioxins and other chemicals scientifically linked to these health effects. The NWF report identifies 48 such chemicals

The agency should establish national standards for fish monitoring.

EPA should ensure that all chemicals are screened for endocrine- disrupting effects.

A copy of Fertility on the Brink can be ordered by calling NWF at 1-800-432-6564.

Frequent National Wildlife contributor Daniel Glick recently relocated from Washington, D.C., to Lafayette, Pennsylvania.

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