Theo Colborn Speaking at 20th Anniversary Meeting of NCAP 

Portland OR   11oct97

I am truly pleased to have been invited to speak to you today and to celebrate your 20th anniversary. I have followed your work for years and admired what you have accomplished. You have been successful because you have used sound science to make your case - and avoided hype and sensationalism. Keep up the good work.

With this in mind - let's start with the definition of--

ENDOCRINE SYSTEM - So what is the endocrine system?

It regulates those processes that keep you alive through a group of chemicals called hormones. Hormones are signaling chemicals released by the brain and the endocrine glands ... such as the pituitary, thyroid, and adrenal glands; the ovaries, uterus, and breasts in females; and the testes and adrenals in males.

ENDOCRINE SYSTEM DEFINITION

Hormones move to other sites in the body where they exert their effect. Starting in the womb in mammals and in the egg in birds, fish and reptiles; they control how the brain and behavior develop. They influence the development of the immune system. They regulate responses to stress. Throughout life, they coordinate metabolism among muscle, liver, and fat, and coordinate function over time, such as the changes required for normal sexual development and reproductive ability. This is the system that assures the integrity and survival of the species.

My discussion today about endocrine disruptors covers two aspects that in my opinion are the least understood: (1) the extent of exposure by humans and wildlife to synthetic or man-made chemicals and (2) the implications of exposure to these chemicals for the integrity and stability of populations of humans and wildlife.

And as we look at the pervasiveness and implications of exposure to man-made chemicals that can disrupt the endocrine system, there are three messages that I want you to keep in mind.

STICK PERSON

First, endocrine disruption goes well beyond sex hormones and "estrogens in the environment". A growing body of evidence makes it imperative that more attention be devoted to the potential for interference with the thyroid system ... with resultant damage to the developing brain, nervous system, and intelligence and thyroid hormone control of the reproductive system and sperm production. Actually, at several recent expert meetings on endocrine disruption, it was conceded that the problem extends to all internally produced chemical messengers that control development of all the parts of the body before birth and later control how an individual functions throughout life.

QUESTION MARKS

Second, cur-rent risk assessment based on extrapolation from high-dose testing using one chemical at a time does not adequately determine the safety of synthetic chemicals. Now, after 14 years, we realize that risk assessment has not worked for cancer...certainly, we cannot expect the same approach to work for synthetic chemicals that might interfere with your genetic program that determines the development of your child throughout all stages of development ... from conception to birth through adulthood ... and, as a result, have endless endpoints of concern ... effects that can interfere with how one functions, rather than causing obvious birth defects or clinical diseases. If risk assessment had been adequate these chemicals would not be in your bodies or in the products you use or are exposed to today.

Third, and most important current background body burdens of persistent organochlorine chemicals and co-contaminants are at or above concentrations where effects are being reported in laboratory animals and children.

For example, let's start by looking at several human studies undertaken in the industrialized world:

JACOBSON

Infants born between 1980 and 1981 of mothers who ate 2 to 3 meals per month of Lake Michigan fish at least six years prior to their pregnancies, were behind at birth in neuromuscular maturity when compared with controls. This deficit was also associated with levels of PCBs in the unborn baby's blood which the mother shared with her baby. At age four, again based on elevated PCB concentrations in the unborn baby's blood, these children had difficulty with short term memory ... they processed information more slowly, they had reduced auditory verbal skills, and lower quantitative and visual discrimination memory. At age 11, the most highly exposed children during gestation had an average 6.2 IQ deficit, and some were more than a year behind their peers in word and reading comprehension. Those in the highest group were more than 2 years behind their peers.

When assaying the blood of these children at age 11, none of the children's PCB concentrations were associated with their achievement measures or IQ scores. This is an extremely important consideration for researchers and health professionals to keep in mind when seeking causal links with synthetic chemicals. Millions of dollars are being poured into cancer studies to look at the concentration of contaminants in diseased tissue, such as in cancerous breast tissue, seeking a causal link with chemicals ... unfortunately, if the study finds no association, it is easy to immediately jump to the conclusion that chemicals are not involved. But, what if the breast cancers were associated with synthetic chemicals that the women were exposed to before birth? Chemicals that were in their mothers? Chemicals that sensitized them for cancer before they were born?

Also important is the finding in this study that when PCBs in mothers' fat approached 1.25 ppm the intellectual decrements among the children became significant. As the authors of the Lake Michigan study point out - one does not have to eat fish to accumulate this amount of PCBs ... PCBs are found in meat, dairy products, and other food products and in electrical and building material. And, most important, average PCB fat levels hover around I ppm in the industrialized world suggesting that a sizeable proportion of the general population is being affected.

DAILY

In another mother/infant study that commenced 12 years later than the Lake Michigan study, between 1992-1995, infants of mothers who ate again - approximately 2 -3 meals/month of Lake Ontario fish over their lifetime prior to their pregnancies, when compared with controls, also displayed the same neuromotor decrements at birth as the Lake Michigan infants and when tested with an additional set of tasks were found to be hyperreactive, similar to the effects reported in rats fed Lake Ontario fish. Using new testing protocols, these babies were found to smile and laugh less, expressed more fear, and were more difficult to soothe or calm down than the control babies in the study. As in the first study, the effects reported in the babies were associated with the mother's lifetime fish consumption not just what she ate during gestation. These findings suggest that PCB concentrations in Lake Ontario are still not low enough to protect human health.

It is important to keep in mind that chemists have spent a great deal of time developing the technology to quantify the PCBs and as a result, our research has been directed toward this suite of compounds ... but, the PCBs are never found alone in human and animal tissue ... they keep bad company with other chemicals .... like dioxins, PCBs, and pesticides .... and there are a host of other organochlorine chemicals and non-chlorinated compounds in our tissues that have not been identified yet. PCBs in these human studies may only be an indicator chemical for other contaminants - just like E. coli that is used to alert us to other possible pathogens in water.

NETHERLANDS

In the Netherlands, another large healthy mother/infant study was undertaken across the general population from an urban through an industrialized area not necessarily looking at fish eaters. Those infants of mothers with highest PCB/dioxin levels exhibited psychomotor deficits at 3 months. A different battery of neurological developmental tests were used in this study, making comparisons difficult. This reveals the need for coordination in some of these large, expensive, long term studies. for comparison purposes. Other biochemical measurements were added to the testing protocol in this study. For example, thyroid hormone levels in the infants decreased as PCBs/dioxins increased. Remember thyroid hormone plays a critical role in brain development. Today there are increasing reports about the impacts of PCBs, dioxins, and pesticides on the thyroid system, the brain, and behavioral development. In addition, the infants' immune systems were different and varied in a dose response manner with the PCBs and dioxins. What this means in the long-term is yet to be determined. And again a sizable proportion of the population was affected.

It is important to note that in each of the human studies I just mentioned even though the decrements among the children were statistically significant at the population level, their loss would not have been recognized by the infants' parents or doctors. It took skilled psychologists and technicians to quantify the changes in the children. These children are not obviously sick. Physicians and public health officials would miss this - These children are not retarded or obviously ,different, nevertheless they are not developing to their fullest potential and certainly the quality of their lives and their parents' lives will be reduced.

ERICE STATEMENT

The economic and social costs of this loss at the population level have not been calculated to date. Economists are now considering the lifetime earnings lost for each IQ point reduction per year class of children. From the experience with lead, this could mean billions of dollars in lifetime earnings per year class of children born in the US. And as a group of experts who met to look at the impacts of endocrine disruptors on the developing brain and behavior reported recently: they were certain that "-widespread loss of this nature can change the character of human societies and destabilize wildlife populations."

It is impossible to avoid exposure to these chemicals. The Eastern Canadian Inuit mothers who depend upon country foods for survival share about 7 ppm PCBs in their breast milk fat with their babies (7 times higher than mothers share with their babies at our latitude) and their youngsters have 20 times more middle ear infections than the children on the lower Continent. Researchers discovered not long ago that the Western Greenland natives share 14 times more PCB with their babies than we do.

Let's jump here to a simple model to better understand how subtle, but permanent changes in function at the individual level can affect populations.

INTRAUTERINE POSITION

Scientists at the University of MO, do Caesarean sections in mice on the last day of gestation and mark the mice according to their position in the womb. They discovered that males that developed between two females had smaller testes, larger prostates, shorter anal urethral distance, and feminized behavior and more aggressive. These males were influenced by the hormonal environment generated by their sisters.

This is not a pathological condition....this variation occurs within the normal range of a mouse population. These differences are critical in assuring that rodent populations can survive under all conditions. Under normal conditions the top males and females do better. They are ideal parents and waste little energy on aggression. But under conditions of predation, water, or food shortage, the bottom animals do better, thus assuring continuation of the mouse gene pool. But what if every animal in the population were so exposed because of synthetic chemical exposure by the mother? What happens to the social structure in that population? What about those individuals that are on the tails of the normal curve and are already skewed in one direction for other reasons?

The Missouri scientists found that just a shift of less than 1/10th of a trillion of a gram free E2 (a female hormone) led to the changes in the males. This system operates in the range of 1/10th trillionth of a gram or less. Working with the University of Missouri Medical School the scientists discovered that the human embryo also develops within a similar range of free estradiol.

Are there chemicals that can interfere with this delicately tuned process of embryonic development? Scientists fed one extremely low dose of dioxin to pregnant rats on a critical day .... in this case, one meal on day 15 of gestation, the day that sexual differentiation commences in the rat. In the human fetus, this is day 56.

The male rat pups developed like the mouse pups that developed between the two sisters in the womb. They were demasculinized and feminized.

SEXUAL DIFFERENTIATION

Up until this time in the womb, there is no visible difference between male and female tissue. In other words, the same tissue is present in both males and females. This is the beginning of the critical stage where the male and female anatomy and orientation are determined. This signaled that only one hit at the right time with a man-made chemical ... in a critical stage of development .... can produce irreversible changes in the behavior, physical characteristics, and the role of that individual in a population. Bioaccumulation may not be required to initiate a long-term effect. Timing of exposure was the key here. No treatment could reverse this outcome ... There is no going back and undoing or rewiring what happened during the early stages of development.

OFFSPRING URINE MARKING

The Missouri team became fascinated by what the Wisconsin team had discovered and decided to look at some other chemical that might interfere with development ... chemicals that are known to act like the natural female hormone ... Here they fed pregnant mice equivalent doses of DES, DDT, and methoxychlor ...Urine marking is a signal of aggressive behavior in male mice ... Note here as the dose was increased beyond a certain point, their aggressiveness subsided ... This is characteristic of the endocrine system that shuts down under high exposure .... Here you can see that the current high dose testing protocol used to test chemicals for their safety would not have predicted this effect. These results challenge the standard approach to test with high doses (to be sure not to miss an effect). Results cannot be extrapolate to a low dose from the effects reported at high doses. The effects in the most cases will be different.

PROSTATE SIZE

The Missouri team also looked at the developing prostates in their mice. Using a wide range of exposure with DES you can see that prostate weight plotted in an obvious inverted U curve. Prostates were heavier because of an increase in hormonally sensitive tissue in the prostate ... more receptors ... that later proved promiscuous by responding to P, T, and E which sensitized the prostate as they matured. Note that the doses where these effects were seen are at least 6 to 9 orders of magnitude lower than those used in traditional DES testing. These studies are opening the door for cancer researchers ... the role of estrogens and estrogen-like compounds that upload receptors during development may lead to long term delayed effects. I am glad to say that increase in interest is being directed toward the presence of receptors in malignant tissue.

In this study the dose of BPA used was 25,000 times lower than the FDA's reference or allowable dose for daily human consumption.

BPA is a commonly encountered plastic monomer. It is the building block for polycarbonates. It is used to line food cans, to make dental sealants, is being used with the blessing of the American Dental Association to coat children's teeth to prevent cavities, to make the 5 gallon demijohns that hold water, and will be used to make 4 billion Compact Discs in the year 2000 ... high impact glass, and high impact sporting equipment, etc.

I was surprised to discover how often the methoxychlor metabolites are found in human tissue now that chemists are broadening their testing protocols. The doses used in these mice are well within the range of ambient exposure.

IN YOUR HANDOUT -
THE LIST

The majority of the chemicals on this list are pesticides ... insecticides, herbicides, fungicides ... many are already regulated in one country or another ... but in most cases none have been banned fully. PCBs are no longer produced but are still used in closed systems.

Newcomers on the list are plastics and plastics additives ... fire retardants, antioxidants, ingredients to impart flexibility ... have a 1/2 life of centuries ... in landfills and sediments, constantly accumulating in and leaching into the environment. It is impossible to find a water sample that does not contain phthallates. A new paper from Australia reported that the very fine granules in soft scrub cleansers are made of plastic and are found in coastal areas at the air-water interface and the sediments ... so light in weight .... Also, phthallates as well as bpa and phenolics are used as inert ingredients in pesticides.

And only 4 years ago, 55 years after DDT was first commercially produced in 1938.. was it discovered that DDE is an anti-androgen. This DDT metabolite, is commonly found in human and wildlife tissue around the world.

In this new role it was discovered that DDE is only 1/10th less potent as the prescription drug, flutamide as an androgen or testerone blocker. Flutamide is a pharmaceutical used for chemical castration rather than surgical castration in men with prostate cancer. And metabolite of vinclozin, a commonly used fungicide on soft fruits and vegetables and found in snap beans is equally as potent as flutamide. It might be considered protective in adulthood against prostate cancer, but obviously dangerous during development and throughout puberty.

EARL GRAY'S RAT DDE EFFECT

The scientist working in the EPA lab asked me to show these pictures as evidence. Son of DDE fed rat. Shortened anal urethal distance.

EARL GRAY'S RATS VINCLOZIN EFFECT

Son of Vinclozolin exposed rat. Undescended testicle vaginal sac no penis he had nipples.

It is important to keep in mind the vast amounts of synthetic chemicals in production.

Industry's own research laboratory recently found that di-n-butyl phthalate blocks normal male development as well. This is a widely used plasticizer in vinyl tiles and other commonly encountered household products. A number of other phthalates have been found to be estrogen-like.

PLASTIC PRODUCTION

85 billion lbs plastics produced in US last year - 330 lb/person
270 billion lbs globally - 38 lb/person
6-12% per year increase ... expect a 40% increase

PLASTICS PRODUCTION BAR GRAPH

The plastics industry has been growing at 6 to .12% a year since the mid 1940s. In the developing world, it is estimated that this industry will grow as much as 40% a year in the near future.

SATELLITE GULFSTREAM MAP

The bulk of the water that came down the Mississippi River in the flood of 1994 was followed by aerial surveillance and six weeks later the slug was mapped off the coast of New Foundland heading toward the North Sea and Svalbard, riding on the Gulf stream. Last year's flood on the Hudson River released vast amounts of PCBs along the river banks. Concentrations of PCBs have spiralled upward in the system and fish are heavily contaminated.

SPOT TAILED SHINER

You will hear over and over again that concentrations of persistent chemicals have come down in the environment and we therefore do not have to worry anymore. There was a significant decline in the late 1970s as the result of regulatory action on some chemicals like DDT and dieldrin and PCBs. However, there has been no decline over the past 10 years since 1985 in Great Lakes fish and there is some indication that several contaminants are increasing again ... PCBs, DDT, mirex, according to Wisconsin DNR and Canadian wildlife researchers. The same pattern of reduction in Europe ... was reported at a recent toxicology meeting in Amsterdam. And there is accompanying evidence that the wildlife around the Great Lakes are no better off than they were in the 1960s when their numbers were obviously low. This raises such questions as ... are the current levels of contaminants low enough to protect wildlife and human health ... or are there other factors involved? Are there new chemicals in the system or are there other chemicals out there that we thought were safe, and they are not?

FISH THYROID

For example, for years now wildlife biologists have not been able to find a salmonoid fish in the Great Lakes that has not had an enlarged thyroid and in the past 5 years as the eutrophication problem in Lake Erie has been reduced, the thyroids have been getting larger and actually bursting. Beautification of the Lake in this case certainly did not lead to purification. Lots of shoreline and harbor restoration has gone on around the world ... but are contaminant loadings improving?

GIESY

Recently, biologists found that although some nuisance birds had made a remarkable comeback after DDT concentrations were reduced and egg shell thinning abated in the Great Lakes but the other bird populations, including bald eagles and terns had not. Using the same biochemical assays and chemistry as the infant/mother Dutch study team ... they found toxic effects at both the biochemical and population level in a number of bird species.

NORTH PACIFIC MAP

We now know that the black footed albatrosses that feed only on the surface of the North Pacific Ocean 100s of miles from shore are as biochemically affected ... as the birds in the troubled spots around the Great Lakes and exhibiting the same developmental problems.

ALBATROSS

These are the same chemical agents similar to those measured in the mother/infant studies in the Netherlands, and the Great Lakes. The Pacific birds are also carrying unexpectedly high concentrations of fresh DDT in their bodies and exhibiting changes in their shell structure.

JAR

4 birds gallon jar

These and other studies provide evidence that segments of both wildlife and human populations are currently exposed to a class of contaminants, organochlorine compounds and their co-contaminants, that interfere with the endocrine system at or above the threshold where their health is affected. A major challenge, now, will be to separate the effects of persistent background contamination from that of chronic daily exposure to less persistent chemicals. Chemicals that have come upon the scene in the more recent past but are endocrine disruptors as well. As a society we have some tough choices to make because many of the new chemicals are an important part of our current life style, our convenience, and our economy ... they are a part of the world's commerce and trade. And, as a result of improved research protocols leading to new findings, today the concern moves now beyond disrupted hormones ... but to disruption of all internally produced natural chemical messengers that control the development of our children and how they function.

What should be done? First, we already know enough about a number of synthetic chemicals many of which are pesticides that it is time to move forward and phase them out ... quickly and completely on a global scale. NCAP should endorse this and educate your members and legislators about the issue. No one with any conscience would produce these chemicals today and most important you do not want them contaminating the products you are using and the food you are eating.

For example - Market Basket Survey - Here you can see that a Big Mae, a 6" anchovy pizza, and 3 pieces of KFC are equally as contaminated as freshwater fish.

There are no institutions capable of dealing with the problem at the global level. Consequently we need an independent or ad hoc international research and regulatory effort to understand better and solve the problem. We need an effort that can respond to the urgency of the problem much like the World War 11, Manhattan Proect, but instead of developing a weapon of destruction, in this case undo much that has evolved as the result of the technology that came out of WWII.

The corporate world will have to take the lead to fund the effort with governments falling in line. The process from the beginning must be above reproach. This includes the process of framing the research, evaluating the results, and sharing the information. Everything will hinge on the ability to separate the industry and government monies supporting the effort from the research design stage through to the communication of the results.

Unfortunately, the public has lost faith in the research industry does when it comes to health issues. Many industrialists agree that even if industry were to do good science, the public would not believe it. It is to their advantage to have the research done independently. In no way should the shame of "cigarette science" taint this effort.

A research agenda such as this will require cooperation among industry, regulatory, academia, and nongovernmental organizations and will require a long-term commitment for funding for at least 10 years.

It must be broad, for with hindsight, we know we must address the fact that these chemicals are moving poleward on oceanic and atmospheric currents and accumulating in wildlife and human tissue in the Northern Hemisphere at dangerously high levels.

And with foresight we must take into consideration those nations that are still in the early stages of development, suffering from economic hardship, over-population, and in dire need of clean water and sufficient food. It is imperative that through our research efforts we seek answers to how these countries can meet their needs for food and insect disease vector control ... and at the same time not allow them to perpetuate the mistakes we made nor become our accomplices to the problem. We can do this by letting your elected officials and administration know that you support Persistent Organic Pollutants Convention (POPS) for which there is already an international convention signed by 104 nations to phase out the production and use of 12 chemicals - most of which are organochlorine pesticides. But to do so, the research must assist in developing alternative strategies to control insect born disease to assure the phasing out of DDT that is mentioned in the POPs convention. We must develop alternatives for insect vector control. All 12 chemicals listed in the POPs agreement ... are endocrine disruptors...

MOST IMPORTANT from your perspective so that you can be assured that the products you purchase and the food you eat are safe, there must be a crash program to develop a battery of screens and assays, both short- and long-term tests, to determine the biological activity of current use and new or alternative chemicals, as well as the common everyday products and mixtures that contain these chemicals.

The agenda must also support international studies to address questions about prenatal exposure in the role of hormonally driven cancers; to support a multinational study to investigate the incidence of reduced and semen quality in certain populations. Certainly, the effort should support extending and replicating the research on reduced intelligence, behavioral, and immune changes in children. And of course there must be more research about the role of transgenerational exposure in the viability and stability of wildlife populations that include the status of ocean fishes stocks and declines of amphibians on a global scale that equates to a threat to survival of all species.

THANK YOU!

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