The Latest Hormone Science
Rachel's Environment & Health News (parts 1-4) 22aug02-3oct02
Part 1, n.750 22aug02
Last week the NEW YORK TIMES took a slap at one of my favorite organizations, the Science and Environmental Health Network or SEHN (http://www.sehn.org). The TIMES accused SEHN of harboring beliefs far outside the mainstream of science: "[SEHN] gives much more weight than do most industry scientists and government regulators to theories that chemicals in the environment are disrupting the human endocrine system and contributing to a wide range of ailments." (NY TIMES Aug. 19, pg. C5.)
As president of the board of SEHN, I thought I should take this accusation seriously. It is true that SEHN supports the view that industrial chemicals in the environment can disrupt hormones and by this means are probably contributing to a wide range of human ailments. Is this view not generally held by the mainstream scientific community?
SEHN's position has been stated best by science director, Ted Schettler, a physician. Before he joined SEHN, Schettler, along with several co-authors published GENERATIONS AT RISK: REPRODUCTIVE HEALTH AND THE ENVIRONMENT (MIT Press, 1999) -- a 230-page review of medical and scientific data showing that some industrial chemicals in the environment (such as lead, mercury, cadmium, arsenic, manganese, chlorinated solvents, some pesticides, PCBs and dioxins) can and probably do interfere with the hormone systems of humans (and non-human animals), causing or exacerbating disease in some who are exposed.[1]
In 2000, Schettler and SEHN board member David Wallinga (also a physician) and other co-authors published a shorter book titled, IN HARM'S WAY: TOXIC THREATS TO CHILD DEVELOPMENT. That book concluded that "Neurodevelopmental disabilities are widespread, and chemical exposures are important and preventable contributors to these conditions."[2, pg. 117; and see RACHEL'S #712.] Is this conclusion warranted by the facts? It certainly seems so. Scientific studies of a single toxic element, lead, spanning the last 100 years provide ample justification for such a statement. (Notably, the hormone-disrupting characteristics of lead and about 75 other environmental chemicals are described in three recent technical books.[3])
Do "most industry scientists and government regulators" disagree with Ted Schettler and SEHN? Neither we nor the NEW YORK TIMES has any reliable information about what "most" scientists and regulators think about hormone-disruptors. I suspect the TIMES simply manufactured its conclusion out of thin air. (Unfortunately, it wouldn't be the first time the TIMES had done such a thing to belittle health dangers from industrial chemicals. See, for example, RACHEL'S #346 and #486.)
Still, the accusation against SEHN warrants a fresh look. I decided to investigate the current scientific status of the idea that chemicals can interfere with hormones. To do so, I chose one hefty scientific journal that often carries articles about the effects of environmental chemicals on wildlife and humans. Then I spent a grueling week reading every chemicals-and-health study in the last 24 monthly issues. The journal I chose is ENVIRONMENTAL HEALTH PERSPECTIVES (EHP), which is published by the federal government's National Institute of Environmental Health Sciences, a division of the National Institutes of Health. The editorial board of EHP is composed mainly of academic scientists but it also includes representatives from Dow Chemical Company, the Schering Plough pharmaceutical company, and the Chemical Industry Institute of Toxicology (CIIT). You can think of CIIT as the research arm of the American chemical industry.
Of course I didn't start off completely ignorant. I had been reporting on environmental hormone disruptors since 1991 (see RACHEL'S #263). But I have to tell you, I wasn't prepared for what I found. I'm going to summarize recent studies of hormone-disrupters published in EHP, but first some background on this problem:
In 1991, about two dozen scientists from half a dozen countries published a consensus document that became known as The Wingspread Statement. (See RACHEL'S #263.) It said in part,
"We are certain of the following:
"A large number of man-made chemicals that have been released into the environment, as well as a few natural ones, have the potential to disrupt the endocrine [hormone] system of animals, including humans. Among these are the persistent, bioaccumulative, organohalogen compounds that include some pesticides (fungicides, herbicides, and insecticides) and industrial chemicals, other synthetic products, and some metals.
"Many wildlife populations are already affected by these compounds. The impacts include thyroid dysfunction [impaired or abnormal functioning] in birds and fish; decreased fertility in birds, fish, shellfish, and mammals; decreased hatching success in birds, fish and turtles; gross birth deformities in birds, fish and turtles; metabolic abnormalities [impaired or abnormal use of energy, manufacture of tissue, or handling of resulting wastes] in birds, fish, and mammals; behavioral abnormalities in birds; demasculinization and feminization in male fish, birds, and mammals; defeminization and masculinization of female fish and birds; and compromised [impaired] immune systems in birds and mammals.
"The patterns of effects vary among species and among compounds. Four general points can nonetheless be made: (1) the chemicals of concern may have entirely different effects on the embryo, fetus, or perinatal [meaning "near the time of birth," from the 28th week of pregnancy through the first week of life, in humans] organism than on the adult; (2) the effects are most often manifested in offspring, not in the exposed parent; (3) the timing of exposure in the developing organism is crucial in determining its character and future potential; and (4) although critical exposure occurs during embryonic development [from conception through the end of the second month of pregnancy], obvious manifestations [effects] may not occur until maturity.
"Laboratory studies corroborate the abnormal sexual development observed in the field and provide biological mechanisms to explain the observations in wildlife.
"Humans have been affected by compounds of this nature, too. The effects of DES (diethylstilbestrol), a synthetic therapeutic agent, like many of the compounds mentioned are estrogenic [meaning they act like estrogen, female sex hormone]. Daughters born to mothers who took DES now suffer increased rates of clear cell adenocarcinoma [cancer], various genital tract abnormalities, abnormal pregnancies, and some changes in immune responses. Both sons and daughters exposed in utero [while in the uterus] experience congenital anomalies of their reproductive system and reduced fertility. The effects seen in in utero DES-exposed humans parallel those found in contaminated wildlife and laboratory animals, suggesting that humans may be at risk to those same environmental hazards as wildlife." The Wingspread Statement continued on, but those were the key points.
The main message of the Wingspread Statement -- that industrial chemicals can interfere with hormones and thus harm animals and humans -- wasn't totally new in 1991. Researchers in 1950 had demonstrated that the pesticide DDT could dramatically shrink the testicles of roosters, obviously interfering with their normal testosterone (male sex hormone).[4] In the early 1970s, researchers discovered to their horror that "occupational exposures to pesticides could diminish or destroy the fertility of workers." [EHP Vol. 108, No. 9 (September, 2000), pgs. 803-813.] In 1980, the term "environmental estrogens" was invented to describe industrial chemicals found in the environment that behaved like the female sex hormone, estrogen.[5]
What the 1991 Wingspread Statement did was shine a spotlight on an unrecognized world-wide pattern of harm from endocrine-disrupting chemicals, mainly in wildlife, but also plausibly in humans. The following year Theo Colborn, who had convened the original Wingspread meeting, published a volume of scientific evidence supporting the Wingspread conclusions.[6] As time passed, these findings electrified the scientific community, persuading thousands of researchers to look for similar effects in wildlife, laboratory animals, and humans all over the world.
In 1995 Theo Colborn, J.P Myers and Dianne Dumanoski published OUR STOLEN FUTURE, a scientific treatise on hormones written like a mystery story to reach a wide audience. OUR STOLEN FUTURE awoke the environmental community and focused enormous media attention on this emerging problem. The web site http://www.ourstolenfuture.org is still the best single place to learn about the latest hormone-disruptor studies. Because it was scientifically solid yet easily readable by the general public, OUR STOLEN FUTURE drove the chemical industry into a frenzy of denial and retribution. They hired PR attack dogs aiming to destroy the reputations of Colborn, Myers and Dumanoski, and NY TIMES science writer Gina Kolata began barking and snarling with the best of them (see RACHEL'S #486).
Now, 11 years after the Wingspread Statement, are these ideas ridiculed, held in disrepute, or simply ignored by the scientists who publish in EHP? Has the scientific community moved beyond "endocrine disruptors" or is this problem still being taken seriously? By way of answers to these questions, here are a few general statements from EHP:
"Endocrine-disrupting chemicals are among the most complex environmental health threats known today. By mimicking natural hormones such as estrogen and testosterone, these chemicals can interact with the body's endocrine system and exert toxic effects that may lead to reproductive and developmental abnormalities or cancer." [EHP Vol. 109, No. 9 (September 2001), pg. A420.]
"The developing organism is exquisitely sensitive to alterations in hormone function. In the early embryonic state, the gonads of human males and females are morphologically [physically] identical. Sexual differentiation [turning a fetus into a boy or a girl] begins under hormonal influence during the fifth and sixth weeks of fetal development, and thus alteration of hormone function during this highly sensitive period can have profound, often debilitating, consequences. The balance of estrogens and androgens [male hormones] is critical for normal development, growth, and functioning of the reproductive system. Although it is especially important during development, this balance is important throughout life for preservation of normal feminine or masculine traits.
"A number of environmental chemicals have actions that mimic or alter the normal sex steroid hormones. The fetus is especially vulnerable because this is the period of time when organs develop. If the normal balance between estrogens and androgens is disrupted, the result may be feminization of males, masculinization of females, birth defects of the reproductive organs, reduced fertility, and alteration of the expression of normal feminine or masculine personality traits, probably including sexual preference."[7]
To be continued.
[1] Ted Schettler, Gina Solomon, Maria Valenti, and Annette Huddle, GENERATIONS AT RISK: REPRODUCTIVE HEALTH AND THE ENVIRONMENT (Cambridge, Mass.: MIT Press, 1999). ISBN 0-262-19413-9.
[2] Ted Schettler, Jill Stein, Fay Reich, Maria Valenti, and David Wallinga, IN HARM'S WAY: TOXIC THREATS TO CHILD DEVELOPMENT (Cambridge, Mass.: Greater Boston Physicians for Social Responsibility [GBPSR], May 2000). Available on the web at http://www.igc.org/psr/ihwrept/ihwcomplete.pdf or as a paper copy from GBPSR in Cambridge, Mass.; telephone 617-497-7440.
[3] See, for example, Lawrence H. Keith, editor, ENVIRONMENTAL ENDOCRINE DISRUPTORS: A HANDBOOK OF PROPERTY DATA (New York: Wiley, 1997; ISBN 0471191264). See also M. Metzler, editor, ENDOCRINE DISRUPTORS; THE HANDBOOK OF ENVIRONMENTAL CHEMISTRY VOL. 3 (New York: Springer-Verlag, 2002; ISBN 3540422803); and Louis Guillette, Jr. and D. Andrew Crain, ENVIRONMENTAL ENDOCRINE DISRUPTERS; AN EVOLUTIONARY PERSPECTIVE (New York: Taylor & Francis, 2000; ISBN 1560325712).
[4] H. Burlington and V.F. Lindeman, "Effect of DDT on testes and secondary sex characteristics of white leghorn cockerels," PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE Vol. 74 (1950), pgs. 48-51.
[5] Sheldon Krimsky, "An Epistemological Inquiry into the Endocrine Disruptor Thesis," ANNALS OF THE NEW YORK ACADEMY OF SCIENCES Vol. 948 (Dec., 2001), pgs. 130-142.
[6] Theo Colborn and Coralie Clement, editors, CHEMICALLY-INDUCED ALTERATIONS IN SEXUAL AND FUNCTIONAL DEVELOPMENT: THE WILDLIFE/HUMAN CONNECTION [Advances in Modern Environmental Toxicology Vol. XXI] (Princeton, N.J.: Princeton Scientific Publishing Co., 1992).
[ continued]
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Part 2, n.751 5sep02
In this series we are exploring whether mainstream scientists take seriously the idea that some industrial chemicals can interfere with hormones (the "endocrine system") in living things and thus cause health problems. The NEW YORK TIMES says they don't. See RACHEL'S #750. Hormones are naturally-occurring chemicals that circulate at very low levels in the blood stream of all vertebrate animals including reptiles, amphibians, fish, birds and mammals.[1] (Vertebrates are animals with a backbone.) In all vertebrate species, hormones act as chemical messengers and as switches, turning on and off bodily systems that control growth, development, learning and behavior. Hormones start affecting every animal shortly after it begins life as a fertilized egg. Hormones control growth and development prior to birth or hatching, and they continue to influence behavior throughout life. Hormones determine when bears will hibernate, when salmon will return to their spawning grounds, and when women will menstruate. Hormones profoundly affect the nervous system, the reproductive system, and the immune system. Naturally-occurring hormones are also implicated in some forms of cancer, such as female breast cancer which is widely believed to be linked to a woman's lifetime exposure to estradiol (estrogen), the main female sex hormone.
The question is, do some hormonally-active industrial chemicals interfere with naturally-occurring hormones and give rise to disease (certain cancers or autoimmune disorders such as diabetes, for example), or hinder growth, development, behavior, intelligence, learning, or immunity? Three years ago, in 1999, the National Academy of Sciences studied this question and concluded that the answer is a qualified Yes:
Here are some quotations from the Academy's 1999 report:
"Adverse reproductive and developmental effects have been observed in human populations, wildlife, and laboratory animals as a consequence of exposure to HAAs [hormonally active agents]."[2,pg.3]
"Studies with laboratory animals have shown that prenatal exposure to some HAAs, such as methoxychlor [a pesticide], TCDD [dioxin], and octylphenol and bisphenol A can reduce sperm production."[2,pg.131]
"Taken together, the results of animal and human studies indicate that prenatal exposure to PCBs can affect neurologic development."[2,pg.175] [PCBs are highly-toxic, persistent industrial chemicals released into the environment for 40 years by Monsanto and now found in food, water and soil world-wide.]
"In the Michigan/Maternal Infant Cohort Study, Fein et al. (1984) evaluated the birth size and gestational age of 242 infants and found that maternal consumption of fish and concentrations of PCBs in cord serum [in blood in the umbilical cord] were correlated with lowered birth weight, shortened gestation [time in the womb], and smaller head circumference. Lower weight was also observed in children from this cohort at 4 yr [years] in a dose-dependent fashion (Jacobson et al. 1990). Children with cord serum PCB levels of 5.0 ng/mL [nanograms per milliliter] or more weighed 1.8 kg [4 pounds] less on average than the lowest exposed children. Prenatal exposure was also associated with deficits in neurologic development in followup studies of these children at up to 11 yr [years]."[2,pg.125]
"It has been well documented that HAHs [halogenated aromatic hydrocarbons] such as TCDD [dioxin], polychlorinated dibenzofurans (PCDFs), and PCBs, affect immune response, and they appear to affect all functional arms of the immune system (innate immunity and host resistance, cell-mediated immunity, and humoral immunity)."[2,pg.178]
"There have only been a few studies of the effects of HAAs [hormonally active agents] in humans, but the results of laboratory and wildlife studies suggest that HAAs have the potential to affect human immune functions."[2,pg.194]
With this background, let's review the last two years' worth of studies appearing in ENVIRONMENTAL HEALTH PERSPECTIVES (EHP), a peer-reviewed journal published by the federal National Institutes of Health. This will tell us whether scientists have recently rejected or abandoned the idea that industrial chemicals can interfere with hormones.
The first thing that struck me as I read through the past 24 monthly issues of EHP is that there is much more human data now than there was 5 years ago. Most studies still involve laboratory animals or wildlife, but humans figure prominently in many recent findings. Here is a sampling:
** Women exposed to dioxin by living near the scene of an industrial accident in Seveso, Italy in 1976 are now showing an excess of breast cancer, even though they are still relatively young (average age 40.8 years). Scientists within U.S. Environmental protection Agency (EPA) have been referring to dioxin as an "environmental hormone" since 1992. (See RACHEL'S #269.) [EHP Vol. 110, No. 7 (July 2002), pgs. 625-628.]
** Forest pesticide applicators who spray the popular herbicide known as 2,4-D have altered levels of male sex hormone in their blood. [EHP Vol. 109, No. 5 [May 2001], pgs. 495-500.] Thus 2,4-D joins the growing list of common chemicals known to disrupt hormones. 2,4-D is the herbicide used more than any other on lawns to kill dandelions and crab grass. It is sold under many names, including my personal favorite, Hormotox. It is also known as Demise, Weed-B-Gone, Weedone, Lawn-Keep, Raid Weed Killer, Plantgard, and Ded-Weed, among other trademarked names. Earlier studies showed that pet dogs die of cancer at twice the normal rate if they live in a family that uses 2,4-D on its lawn. (See RACHEL'S #250.)
A recent study shows that children's exposure to 2,4-D inside homes increases 10-fold after lawns are treated with 2,4-D. The family dog and humans' shoes are the main vehicles transporting 2,4-D into homes, exposing children living there. [EHP Vol. 109, No. 11 (November 2001), pgs. 1185-1191.]
** A study of 100 adolescents who grew up near waste incinerators or a metal smelter shows developmental delays in sexual maturity, compared to a control group living in an uncontaminated rural area. Adolescents in Flanders (Belgium) living in moderately polluted urban neighborhoods have "relatively low" levels of PCBs and dioxin-like polychlorinated aromatic hydrocarbons (PCAHs) in their blood. Even these low levels correlated with delayed sexual maturation in both girls and boys, the study concludes. In 1997 the Flemish government had reported a higher percentage of conceptions requiring medical assistance near incinerators, compared to the rest of Flanders.
The authors conclude, "Through endocrine disruption, environmental exposure to PCAHs may interfere with sexual maturation and in the long-run adversely affect human reproduction." [EHP Vol. 110, No. 8 (August 2002), pgs. 771-776.]
** Premature breast development (known as thelarche, pronounced thee-larkey) is the growth of breasts in girls younger than 8 with no other signs of puberty. Puerto Rico has the highest incidence of thelarche ever reported. The problem there has been studied for years, to no avail. Now a study of 41 girls in Puerto Rico with thelarche and 35 girls without thelarche has found that 68% of the thelarche girls had high levels of several phthalates (pronounced tha-lates) in their blood. Only one of the non-thelarche girls had measureable levels of one phthalate in her blood. The phthalates found in the thelarche group are known to have estrogenic and anti-androgenic effects. (Anti-androgenic means "interferes with male hormone." Humans of both genders always have a mix of male and female hormones in their blood stream, the balance between them being important.) [EHP Vol. 108, No. 9 (September 2000), pgs. 895-900.]
Phthalates are common industrial chemicals used in building materials, food packaging and food wrap, toys and other children's products, medical devices, garden hose, shoes, shoe soles, automobile undercoating, wires and cables, carpet backing, carpet tile, vinyl tile, pool liners, artificial leather, canvas tarps, notebook covers, tool handles, dishwasher baskets, flea collars, insect repellents, skin emollients, hair sprays, nail polish, and perfumes, among other uses.
In October, 2000, a study reported in EHP measured the metabolic byproducts of 7 phthalates in the urine of adults and concluded that exposure to phthalates "is both higher and more common than previously suspected." The highest levels (1 to 16 parts per million in urine) were phthalates known as MEP, MBP, and MBzP and they occurred at the highest levels in women of child-bearing age. MBP and MBzP have previously been shown to cause reproductive and developmental toxicity in animals. [EHP Vol, 108, No. 10 (October 2000), pgs. 979-982.]
** A study of 63 female Air Force personnel with exposure to jet fuel (JP-8) and solvents showed that the most exposed women had the lowest levels of four reproductive hormones in their urine. The hormones were studied because they indicate likelihood of success or failure in conception. Thus the components of jet fuel, and/or solvents, are likely hormone disruptors in human females. [EHP Vol. 110, No. 8 (August, 2002), pgs. 805-811.]
** Two new studies indicate that Monsanto's herbicide, Roundup, is a hormone-disruptor and is associated with birth defects in humans.
Farm families that applied pesticides to their crops in Minnesota were studied to see if their elevated exposure to pesticides caused birth defects in their children. The study found that two kinds of pesticides -- fungicides and the herbicide Roundup -- were linked to statistically significant increases in birth defects. Roundup was linked to a 3-fold increase in neurodevelopmental (attention deficit) disorders. [EHP Supplement 3, Vol. 110 (June 2002), pgs. 441-449.]
A recent test tube study reveals that Roundup can severely reduce the ability of mouse cells to produce hormones. Roundup interferes with a fundamental protein called StAR (steroidogenic acute regulatory protein). The StAR protein is key to the production of testosterone in men (thus controlling male characteristics, including sperm production) but also the production of adrenal hormone (essential for brain development), carbohydrate metabolism (leading to loss or gain of weight), and immune system function. The authors point out that "a disruption of the StAR protein may underlie many of the toxic effects of environmental pollutants." [EHP Vol. 108, No. 8 (August 2000), pgs. 769-776.]
Monsanto, the St. Louis chemical giant and creator of Roundup as well as PCBs, is now a leader in genetically engineered crops. Monsanto sells "Roundup ready" seeds for corn, soybeans, and cotton; wheat and lawn grasses will be next. These are seeds engineered to withstand a thorough dousing with Roundup, which kills weeds without killing the Roundup-ready crops. To make Monsanto's "Roundup ready" seeds legal, U.S. Environmental Protection Agency (EPA) had to triple the amount of Roundup residues that it allows on crops. For years, Roundup has been Monsanto's most profitable product, and genetic engineering has now allowed the firm to sell much more of it. See RACHEL'S #637, #639, #660, #686, #726.
For example, a 1999 study of soybean farming in the U.S. Midwest found that farmers planting Roundup Ready soybeans used 2 to 5 times as many pounds of herbicide per acre as farmers using conventional systems, and ten times as much herbicide as farmers using Integrated Weed Management systems, which are intended to reduce the need for chemical herbicides.[3,pg.2]
More chemical dangers probably lie ahead as new products of genetic engineering come to market. According to the NEW YORK TIMES, Scotts Company is collaborating with Monsanto to develop Roundup Ready grass for lawns.[4] Children and pregnant women, beware.
[continued]
[1] H. Maurice Goodman, BASIC MEDICAL ENDOCRINOLOGY [Second Edition] (New York: Raven Press, 1994).
[2] Ernst Knobil and others, HORMONALLY ACTIVE AGENTS IN THE ENVIRONMENT (Washington, D.C.: National Academy Press, July 1999). ISBN 0-309-06419-8.
[3] Charles Benbrook, "Evidence of the Magnitude and Consequences of the Roundup Ready Soybean Yield Drag from University-Based Varietal Trials in 1998," AgBioTech InfoNet Technical Paper #1, July 13, 1999. Available at http://www.biotech-info.net/RR_yield_drag_98.pdf.
[4] David Barboza, "Suburban Genetics: Scientists Searching for a Perfect Lawn," NEW YORK TIMES July 9, 2000, pg. A1.
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Part 3, n.752 19sep02
In this series we are asking whether mainstream scientists still believe that industrial chemicals released into the environment can interfere with hormones in wildlife and humans, causing widespread harm. The NEW YORK TIMES in August said most scientists don't. (See RACHEL'S #750, #751.) We have tried to answer the question by examining the most recent 24 monthly issues of ENVIRONMENTAL HEALTH PERSPECTIVES (EHP), a peer-reviewed journal published by the federal National Institutes of Health.
In RACHEL'S #751 we reported on seven studies linking hormone-disrupting chemicals to human illnesses. This week, we continue reporting on human studies, then turn to animal studies (wildlife and laboratory animals).
** Background (meaning "normal" or everyday) exposure of healthy Dutch pre-school children to PCBs and dioxins (potent hormone-disrupting chemicals) via breast feeding is related to a diminished number of immune system cells and increased middle ear infections, coughing, and chest congestion, persisting at least to the age of 42 months. Previously, immune system damage had been observed in laboratory animals exposed to PCBs and dioxins in their diet (see RACHEL'S #414).
(Dioxins are extremely toxic chemicals created as by-products of many industrial processes, such as incinerators, where chlorine combines with carbon at high temperatures. PCBs are dioxin-like industrial chemicals manufactured by Monsanto between 1929 and 1976 and now found almost everywhere on the planet. See RACHEL'S #237.)
An earlier study of Inuit children had found an increase in otitis media (ear infections) among those exposed to hormone-disrupting chlorinated chemicals through their mother's milk. The Inuit live in the extreme northern part of the planet, about as far away from industrial sources as anyone can get, but many organochlorine chemicals march steadily northward as time passes because cool weather "distills" them out of the atmosphere. (This distillation process was described eloquently in the book OUR STOLEN FUTURE -- see RACHEL'S #486 and see www.ourstolenfuture.org.)
The authors of the Dutch study point out that the proper response to their findings would be to reduce the discharge of hormone-disrupting chemicals into the environment, not curtail breast feeding. EHP Vol. 108, No. 12 (December 2000), pgs. 1203-1207.
** A pilot study of 29 men in Massachusetts showed an association between levels of PCBs and DDE in their blood and reduced sperm count, reduced sperm motility (ability to move), and sperm shape. (DDE is a breakdown byproduct of the pesticide DDT.) Based on the findings of the pilot study, a larger study has begun. EHP Vol. 110, No. 3 (March, 2002), pgs. 229-233.
Environmental Organochlorines and Semen Quality: Results of a Pilot Study
Environmental Health Perspectives Volume 110, Number 3, March 2002
Russ Hauser,1 Larisa Altshul,1 Zuying Chen,2 Louise Ryan,1 James Overstreet,3 Isaac Schiff,2 and David C. Christiani11Environmental Health Department, Occupational Health Program, and Biostatistics Department, Harvard School of Public Health, Boston, Massachusetts, USA; 2Vincent Memorial Obstetrics and Gynecology Service, Andrology Laboratory and In Vitro Fertilization Unit, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, USA; 3Institute of Toxicology and Environmental Health, University of California, Davis, California, USA
Abstract
There have been numerous studies that suggest that sperm concentrations (sperm counts) are declining in men. However, other studies suggest that sperm counts are not declining or may be increasing in some areas. Although there is disagreement on whether there is a downward temporal trend in sperm counts, the studies provide evidence that sperm counts vary by geographic location. It has been hypothesized that the geographic variation in sperm concentrations may be due to environmental exposures, lifestyle factors, or some unknown causes. To determine whether contemporary ambient levels of polychlorinated biphenyls (PCBs) and p,p´-DDE are associated with altered semen quantity and quality, we selected a study population without specific exposure to PCBs or p,p´-DDE. The present study presents the results from a pilot study on the relationship between serum PCBs and p,p´-DDE and semen quality in 29 subjects recruited from the Massachusetts General Hospital Andrology Laboratory. Of the 29 subjects, 3 had sperm concentrations < 20 million/mL, 7 had < 50% motile sperm, 9 had < 4% normal morphology, and 6 were below normal in more than one semen parameter. The 18 subjects with normal spermatozoa concentration, motility, and morphology were used as comparison subjects. The mean (SE) concentration of the sum of PCBs and p,p´-DDE was 242 ng/g lipids (34.0) and 354 ng/g lipids (120), respectively, for men with below normal motility as compared to 202 ng/g lipids (16.6) and 240 ng/g lipids (31.1), respectively, for the comparison subjects. The data showed general trends that were suggestive of an association between PCBs and p,p´-DDE and abnormal motility, as well as with sperm concentration and morphology. A full-scale study is currently in progress. Key words: male reproductive health, organochlorines, pesticides, polychlorinated biphenyls, semen quality, sperm concentration. Environ Health Perspect 110:229-233 (2002). [Online 5 February 2002] http://ehpnet1.niehs.nih.gov/docs/2002/110p229-233hauser/abstract.html
Address correspondence to R. Hauser, Occupational Health Program, Harvard School of Public Health, Building 1, Room 1405, 665 Huntington Avenue, Boston, MA 02115 USA. Telephone: (617) 432-3326. Fax: (617) 432-0219. E-mail: rhauser@hohp.harvard.edu
In 1992, an analysis of 62 published studies reported that American men today produce only half as much sperm as their grandfather's did. In 1997, a re-analysis of the original 62 studies, using a different statistical technique, confirmed the finding -- 50% average sperm loss among U.S. and European/Australian men, 1938-1990, though no evident decline among non-Western males. Within the U.S., regional variations occur, but the average decline is 50% nationwide.
Now a third analysis has been published, which includes an additional 47 English-language studies, and extends the time-period slightly, from 1934 to 1996. The basic finding remains unchanged: a 50% reduction in sperm count among U.S. and European/Australian men but not among non-Western men. EHP Vol. 108, No. 10 (October 2000), pgs. 961-966.
The Question of Declining Sperm Density Revisited: An Analysis of 101 Studies Published 1934-1996
Environmental Health Perspectives Volume 108, Number 10, October 2000
Shanna H. Swan,1 Eric P. Elkin,2 and Laura Fenster31Family and Community Medicine, University of Missouri, Columbia, Missouri, USA 2California Public Health Institute, Berkeley, California, USA 3Reproductive Epidemiology Section, California Department of Health Services, Emeryville, California, USA
Abstract
In 1992 Carlsen et al. reported a significant global decline in sperm density between 1938 and 1990 [Evidence for Decreasing Quality of Semen during Last 50 Years. Br Med J 305:609-613 (1992)]. We subsequently published a reanalysis of the studies included by Carlsen et al. [Swan et al. Have Sperm Densities Declined? A Reanalysis of Global Trend Data. Environ Health Perspect 105:1228-1232 (1997)]. In that analysis we found significant declines in sperm density in the United States and Europe/Australia after controlling for abstinence time, age, percent of men with proven fertility, and specimen collection method. The declines in sperm density in the United States (approximately 1.5%/year) and Europe/Australia (approximately 3%/year) were somewhat greater than the average decline reported by Carlsen et al. (approximately 1%/year). However, we found no decline in sperm density in non-Western countries, for which data were very limited. In the current study, we used similar methods to analyze an expanded set of studies. We added 47 English language studies published in 1934-1996 to those we had analyzed previously. The average decline in sperm count was virtually unchanged from that reported previously by Carlsen et al. (slope = -0.94 vs. -0.93). The slopes in the three geographic groupings were also similar to those we reported earlier. In North America, the slope was somewhat less than the slope we had found for the United States (slope = -0.80; 95% confidence interval (CI), -1.37--0.24). Similarly, the decline in Europe (slope = -2.35; CI, -3.66--1.05) was somewhat less than reported previously. As before, studies from other countries showed no trend (slope = -0.21; CI, -2.30-1.88). These results are consistent with those of Carlsen et al. and our previous results, suggesting that the reported trends are not dependent on the particular studies included by Carlsen et al. and that the observed trends previously reported for 1938-1990 are also seen in data from 1934-1996. Key words: epidemiology, geography, regression analysis, semen quality, sperm density, trend. Environ Health Perspect 108:961-966 (2000). [Online 5 September 2000] http://ehpnet1.niehs.nih.gov/docs/2000/108p961-966swan/abstract.html
Address correspondence to S.H. Swan, Department of Family and Community Medicine, University of Missouri-Columbia, MA306 Medical Sciences Building, Columbia, MO 65212 USA. Telephone: (573) 882-3126. Fax: (573) 884-6172. E-mail: swans@health.missouri.edu
** A new study shows that the common plasticizer, DEHP [Di(2-ethylhexyl) phthalate], blocks the normal action of male sex hormone (androgen) and disrupts the normal growth of penis, testicles, prostate, and semen tubes (seminal vesicles) in male rats. (A plasticizer is a chemical added to hard plastics, such as vinyl or PVC, to make them soft.) Furthermore, DEHP caused malformed penises and caused male rats to lose interest in female rats. The authors report that, at lower doses than were used in this study, DEHP diminished the size of rats' testicles. The authors conclude, "These results imply that the acceptable daily intake for DEHP is only 3 micrograms of DEHP per kilogram of body weight per day." They report that typical exposure to DEHP in the U.S. ranges from 4 micrograms to 30 micrograms per kilogram of body weight per day. Thus typical human exposures in the U.S. far exceed the level of DEHP thought to be safe. The authors also point out that DEHP may produce additive effects when combined with other chemicals that behave in a similar manner. EHP Vol. 109, No. 3 (March 2001), pgs. 229-237.
Abnormalities of Sexual Development in Male Rats with in Utero and Lactational Exposure to the Antiandrogenic Plasticizer Di(2-ethylhexyl) Phthalate
Environmental Health Perspectives v.109, n.3, Mar02.
Robert W. Moore,1,2 Thomas A. Rudy,1 Tien-Min Lin,1 Kinarm Ko,3 and Richard E. Peterson1,2,31School of Pharmacy, 2Environmental Toxicology Center, and 3Endocrinology-Reproductive Physiology Program, University of Wisconsin, Madison, Wisconsin, USA
Abstract
Several members of the phthalate ester family have antiandrogenic properties, yet little is known about how exposure to these ubiquitous environmental contaminants early in development may affect sexual development. We conducted experiments to determine effects of in utero and lactational exposure to the most prevalent phthalate ester, di(2-ethylhexyl) phthalate (DEHP), on male reproductive system development and sexual behavior. Sprague-Dawley rats were dosed with corn oil or DEHP (0, 375, 750, or 1,500 mg/kg/day, per os) from gestation day 3 through postnatal day (PND) 21. Dose-related effects on male offspring included reduced anogenital distance, areola and nipple retention, undescended testes, and permanently incomplete preputial separation. Testis, epididymis, glans penis, ventral prostate, dorsolateral prostate, anterior prostate, and seminal vesicle weights were reduced at PND 21, 63, and/or 105-112. Additional dose-related effects included a high incidence of anterior prostate agenesis, a lower incidence of partial or complete ventral prostate agenesis, occasional dorsolateral prostate and seminal vesicle agenesis, reduced sperm counts, and testicular, epididymal, and penile malformations. Many DEHP-exposed males were sexually inactive in the presence of receptive control females, but sexual inactivity did not correlate with abnormal male reproductive organs. These results suggest that in utero and lactational DEHP exposure also inhibited sexually dimorphic central nervous system development. No major abnormalities were found in any of eight control litters, but DEHP caused severe male reproductive system toxicity in five of eight litters at 375 mg/kg/day, seven of eight litters at 750 mg/kg/day, and five of five litters at 1,500 mg/kg/day. These results demonstrate that the male reproductive system is far more sensitive to DEHP early in development than when animals are exposed as juveniles or adults. The effects of DEHP on male reproductive organs and sexual behaviors and the lack of significant effects on time to vaginal opening and first estrus in their littermates demonstrate that DEHP (and/or its metabolites) affects development of the male reproductive system primarily by acting as an antiandrogen. The pattern of effects of in utero and lactational DEHP exposure differed from patterns caused by other phthalate esters, and the preponderance of anterior prostate agenesis appears to be unique among all chemicals. These results suggest that DEHP acts partly by mechanisms distinct from those of other antiandrogens. Key words: antiandrogens, di(2-ethylhexyl) phthalate, in utero exposure, lactational exposure, male reproductive system development, masculine sexual behaviors, reproductive organ agenesis. Environ Health Perspect 109:229-237 (2001). [Online 28 February 2001] http://ehpnet1.niehs.nih.gov/docs/2001/109p229-237moore/abstract.html
Address correspondence to R.W. Moore, School of Pharmacy, University of Wisconsin, 425 N. Charter Street, Madison, WI 53706 USA. Telephone: (608) 265-2531. Fax: (608) 265-3316. E-mail: rwmoore@pharmacy.wisc.edu
** Diesel exhaust is a complex mixture of hydrocarbons and metals. In young rats, exposure to diesel exhaust has been shown to reduce the levels of certain hormones in the blood and to diminish the production of sperm. A new study exposed 90 female rats (72 pregnant, 18 not pregnant) to diesel exhaust for 13 days (from day 7 to day 20 of pregnancy). In the offspring of the pregnant rats, the development of testicles, ovaries and the thymus gland (an important part of the immune system in mammals) was "delayed and disturbed," the authors say. They go on, "Our study provides evidence for the first time that inhalation of diesel exhaust during pregnancy masculinizes fetuses through accumulation of testosterone in mother rats." The authors wonder what effects diesel exhaust might have on the immune system in later life. (EHP Vol. 109, No. 2 [February 2001], pgs. 111-119.) Immune disorders such as asthma and diabetes are rapidly increasing in industrialized nations.
The Masculinization of the Fetus During Pregnancy Due to Inhalation of Diesel Exhaust.
Environmental Health Perspectives v.109, n.2, Feb01.
Nobue Watanabe and Masayuki KuritaDepartment of Environmental Health, Tokyo Metropolitan Research Laboratory of Public Health, Tokyo, Japan
Abstract
This study was conducted to determine the impact of diesel exhaust inhalation on the fetus. Seventy-two pregnant rats and 18 nonpregnant rats were divided into three groups: a group exposed to total diesel engine exhaust containing 5.63 mg/m3 particulate matter, 4.10 ppm nitrogen dioxide, and 8.10 ppm nitrogen oxide; a group exposed to filtered exhaust without particulate matter; and a group exposed to clean air. The exposure period was from day 7 until day 20 of pregnancy. In addition, 15 pregnant rats were treated with aromatase inhibitors or testosterone to clarify the process by which diesel exhaust exerts its toxicity. The anogenital distance was significantly longer in male and female fetuses from both exhaust-exposed groups than in those of the control. Differentiation of the testis, ovary, and thymus was delayed and disturbed. Maternal testosterone and progesterone levels, which increased due to pregnancy whether or not the rats were exposed, were significantly higher and lower, respectively, in the pregnant rats exposed to total exhaust and filtered exhaust. The serum adrenocorticotropic hormone (ACTH) level and urinary excretion of 17-hydroxycorticosteroids (OHCS) did not differ among the pregnant groups. These results indicate that elevated testosterone did not result from elevated maternal adrenal function. The feto-placental-ovarian unit and inhibition of aromatase activity and synthesis caused by diesel exhaust inhalation might have played an essential role in the accumulation of testosterone. Since both exhaust-exposed groups showed almost the same reactions toward the inhalation, the gaseous phase must have included the relevant toxicants. Key words: diesel exhaust, feto-placental-ovarian unit, fetus, masculinization, ovary, pregnancy, rats, testis, testosterone, thymus. Environ Health Perspect 109:111-119 (2001). [Online 11 January 2001] http://ehpnet1.niehs.nih.gov/docs/2001/109p111-119watanabe/abstract.html
Address correspondence to N. Watanabe, Department of Environmental Health, Tokyo Metropolitan Research Laboratory of Public Health, 24-1 Hyakunincho 3 chome, shinjuku-ku, Tokyo 169-0073, Japan. Telephone: (81) 3-3363-3231. Fax: (81) 3-3368-4060. E-mail: nobuew@tokyo-eiken.go.jp
** Hypospadias is arrested development of the penis, and it occurs in about 1 out of every 125 live male births in the U.S. With hypospadias, the normal opening of the penis occurs not at the tip but on the underside, sometimes as far back as the scrotum. In the most extreme cases, hypospadias can make it difficult to tell whether a newborn is a boy or a girl. The problem can only be corrected surgically. The cause of hypospadias is unknown.
The important discovery in 1995, that some environmental chemicals act as anti-androgens,[1] meaning they disrupt the normal function of male sex hormones, has led researchers to ask whether environmental anti-androgens may contribute to the occurrence of hypospadias.
Four pesticides (or pesticide breakdown byproducts) are now classified as anti-androgens: DDE (a breakdown byproduct of DDT), Vinclozolin, Procymidone, and Linuron. In addition, two phthalates, widely used in plastics and personal care products --DBP [dibutyl phthalate] and DEHP [Di(2-ethylhexyl) phthalate] --are anti- androgens. And dioxin and PCBs have anti-androgenic properties. These eight chemicals have all been shown to cause hypospadias in laboratory animals.
Hypospadias and other genital abnormalities were recently reported in mink and river otters on the Columbia River, and among populations of black bears and polar bears. With the exception of the black bears, which were not monitored for chemicals, all the abnormal animals had elevated levels of organochlorine chemicals in their bodies. EHP Vol. 109, No. 11 (November 2001), pgs. 1175-1183.
Hypospadias and Endocrine Disruption: Is There a Connection?
Environmental Health Perspectives v.109, n.11, Nov01.
Laurence S. Baskin,1 Katherine Himes,2 and Theo Colborn31Department of Urology, University of California, San Francisco, California, USA; 2Harvard University Medical School, Boston, Massachusetts, USA; 3Wildlife and Contaminants Program, World Wildlife Fund, Washington, D.C., USA
Abstract
Hypospadias is one of the most common congenital anomalies in the United States, occurring in approximately 1 in 250 newborns or roughly 1 in 125 live male births. It is the result of arrested development of the urethra, foreskin, and ventral surface of the penis where the urethral opening may be anywhere along the shaft, within the scrotum, or in the perineum. The only treatment is surgery. Thus, prevention is imperative. To accomplish this, it is necessary to determine the etiology of hypospadias, the majority of which have been classified as idiopathic. In this paper we briefly describe the normal development of the male external genitalia and review the prevalence, etiology, risk factors, and epidemiology of hypospadias. The majority of hypospadias are believed to have a multifactorial etiology, although a small percentage do result from single gene mutations. Recent findings suggest that some hypospadias could be the result of disrupted gene expression. Discoveries about the antiandrogenic mechanisms of action of some contemporary-use chemicals have provided new knowledge about the organization and development of the urogenital system and may provide additional insight into the etiology of hypospadias and direction for prevention. Key words: antiandrogens, differentiation, external genitalia, gene expression, urogenital development. Environ Health Perspect 109:1175-1183 (2001). [Online 7 November 2001] http://ehpnet1.niehs.nih.gov/docs/2001/109p1175-1183baskin/abstract.html
Address correspondence to T. Colborn, Wildlife and Contaminants Program, World Wildlife Fund, 1250 24th Street NW, Washington, DC 20037 USA. Telephone: (202) 778-9643. Fax: (202) 530-0743. E-mail: colborn@wwfus.org
** Although chlorinated chemical discharges from pulp (paper) mills have decreased substantially during the past decade with the adoption of nonchlorine bleaching systems (especially outside the U.S.), harmful effects on fish downstream are still regularly observed, including depression of hormone levels in blood, delayed maturation, smaller gonad size, and confusion of sexual characteristics -- for example, females developing an elongated anal fin that is characteristic of males. This study took advantage of a "natural experiment\rdblquote -- a pulp mill closed for a period of time, then started up again. Researchers examined the ratio of male to female eels hatched in waters below pulp mills that were operating, then when the mills closed temporarily. While the mill was operating, the sex ratio was significantly altered (only 42% males instead of the usual 50%) but returned to normal when the mill temporarily closed. EHP Vol. 110, No. 8 (August 2002), pgs. 739-742.
Male-Biased Sex Ratios of Fish Embryos Near a Pulp Mill: Temporary Recovery after a Short-Term Shutdown
Environmental Health Perspectives Volume 110, Number 8, August 2002
D. G. Joakim Larsson and Lars FörlinDepartment of Zoology/Zoophysiology, Göteborg University, Göteborg, Sweden
Abstract
In a previous study we showed that broods from the viviparous eelpout (Zoarces viviparus) were significantly male biased in 1998 in the vicinity of a large kraft pulp mill on the Swedish Baltic coast. One suggested hypothesis was that masculinizing compounds in the effluent were affecting gonadal differentiation of the embryos, resulting in skewed sex ratios. In this article, we present further evidence for a causal relationship between the exposure to the effluent and the male-biased sex ratios. Analyses of historical samples showed that the eelpout produced male-biased broods close to the mill in 1997 in addition to 1998. During 1999, the mill was shut down for 17 days, coinciding with the period when the gonads of the eelpout embryos differentiate. Subsequently, in the fall of 1999, the sex ratios were no longer male biased; however, the following year (2000), a significant male bias reappeared. Investigations at 13 sites for up to 4 years showed a relatively stable sex ratio around 50/50, with the exceptions by the mill and with few observations of deviating ratios at other sites. Several reports document endocrine disturbances in fish near pulp and paper mills, including the expression of male secondary sex characters in female fish. The repeatedly identified male bias at the investigated mill, the normalization after mill shutdown, and the reappearance the following year indicate that pulp mill effluents also can affect sex ratios of nearby fish. Key words: androgenic, endocrine disruptors, gonadal differentiation, masculinization, ovary, testis. Environ Health Perspect 110:739-742 (2002). [Online 11 June 2002] http://ehpnet1.niehs.nih.gov/docs/2002/110p739-742larsson/abstract.html
Address correspondence to J. Larsson, Department of Physiology/Endocrinology, Sahlgrenska Academy, Göteborg University, Box 434, SE-405 30, Göteborg, Sweden. Telephone: +46-31-7733589. Fax: +46-31-7733531. E-mail: joakim.larsson@fysiologi.gu.se
** The salmon populations of the northwestern U.S. have been declining for decades, some to the point where they have already gone extinct; others are listed as endangered. This study examined female salmon on the Hanford Reach of the Columbia River and found that an astonishing 84% of them had a genetic marker that is normally only found in male salmon. The long-term effect of this sex reversal would be to reduce the number of females in each successive generation, eventually driving the species to extinction. The researchers do not know what has caused the sex shift in such a large proportion of wild salmon on the Columbia River. They point out that some pesticides (atrazine, carbofuran, lindane, methyl parathion, and dieldrin) are known to behave like estrogen in rainbow trout and are present in the Columbia River, though at levels considered too low to create this problem. Thus the mystery remains unsolved. EHP Vol. 109, No. 1 (January 2001), pgs. 67-69.
High Incidence of a Male-Specific Genetic Marker in Phenotypic Female Chinook Salmon from the Columbia River.
Environmental Health Perspectives v.109, n.1, Jan01.
James J. Nagler,1 Jerry Bouma,1 Gary H. Thorgaard,2 and Dennis D. Dauble31Department of Biological Sciences and Center for Reproductive Biology, University of Idaho, Moscow, Idaho, USA 2School of Biological Sciences and Center for Reproductive Biology, Washington State University, Pullman, Washington, USA 3Battelle Pacific Northwest National Laboratory, Richland, Washington, USA
Abstract
Numerous populations of anadromous salmonids in the northwestern United States have been declining for many years, resulting in Endangered Species Act listings and in some cases extinction. The degradation of river ecosystems has been proposed as one of the major reasons for the inability of salmon to maintain their populations. However, the specific factors interfering with the reproduction and survival of salmon during the freshwater phase of their life cycle have not been fully described. This study was initiated to determine the incidence of phenotypic sex reversal in wild, fall chinook salmon (Oncorhynchus tshawytcha) that returned to spawn in the Columbia River. Fish were sampled at different locations within this watershed to determine whether they were faithfully expressing their genotype. We report a high incidence (84%) of a genetic marker for the Y chromosome in phenotypic females sampled from the wild, which was not observed in female fish raised in hatcheries. It appears likely that female salmon with a male genotype have been sex reversed, creating the potential for an abnormal YY genotype in the wild that would produce all-male offspring and alter sex ratios significantly. Key words: chinook salmon, genetic marker, genotype, phenotype, sex linkage. Environ Health Perspect 109:67-69(2001). [Online 15 December 2000] http://ehpnet1.niehs.nih.gov/docs/2001/109p67-69nagler/abstract.html
Address correspondence to J.J. Nagler, Department of Biological Sciences, University of Idaho, Moscow, ID 83844-3051 USA. Telephone: (208) 885-4382. Fax: (208) 885-7905. E-mail: jamesn@uidaho.edu
** Among male tadpoles exposed to dibutyl phthalate (DBP) at low levels, about 7% of the males developed ovaries, thus confirming previous studies showing that DBP is a hormone disrupter. DBP is widely used in PVC pipe. The authors conclude that DBP is "an environmentally dangerous hormone" that disrupts the development of testicles in male animals. EHP Vol. 108, No. 12 (December 2000), pgs. 1189-1193.
Effects of Dibutyl Phthalate as an Environmental Endocrine Disruptor on Gonadal Sex Differentiation of Genetic Males of the Frog Rana rugosa. Environmental Health Perspectives V.108, N.12, Dec00
** A survey of bullfrogs and green frogs in New Hampshire found deformed frogs at 13 of 16 sites that were checked. Examination of hormone levels in deformed and normal frogs revealed that normal frogs have 3 times as much male sex hormone (androgen) in their blood, compared to the deformed frogs. Normal frogs also had three times as much of a hormone called gonadotropin-releasing hormone (GnRH) which is produced by the brain. This study suggests that hormone-disrupting chemicals may be one of multiple causes that are producing malformed frogs, and declines in frog populations, at many locations around the world. EHP Vol. 108, No. 11 (November 2000), pgs. 1085-1090.
Limb Malformations and Abnormal Sex Hormone Concentrations in Frogs
Environmental Health Perspectives v.108, n.11, Nov00
Stacia A. Sower,1 Karen L. Reed,1 and Kimberly J. Babbitt21Department of Biochemistry and Molecular Biology, 2Department of Natural Resources, University of New Hampshire, Durham, New Hampshire, USA
Abstract
Declines in amphibian populations, and amphibians with gross malformations, have prompted concern regarding the biological status of many anuran species. A survey of bullfrogs, Rana catesbeiana, and green frogs, Rana clamitans, conducted in central and southern New Hampshire showed malformed frogs at 81% of the sites sampled (13 of 16 sites). Brain gonadotropin-releasing hormone (GnRH) and the synthesis of androgens and estradiol, hormones essential to reproductive processes, were measured from limb-malformed and normal (no limb malformation) frogs. Normal frogs had significantly higher concentrations (nearly 3-fold) of in vitro produced androgens and of brain GnRH than malformed frogs. Because most malformations are thought to occur during development, we propose that environmental factors or endocrine-disrupting chemicals that may cause developmental abnormalities also act during early development to ultimately cause abnormally reduced GnRH and androgen production in adult frogs. The consequences of reduced GnRH and androgens on anuran reproductive behavior and population dynamics are unknown but certainly may be profound and warrant further research. Key words: amphibians, androgens, endocrine-disrupting chemicals, environmental influences, frogs, gonadotropin-releasing hormone. Environ Health Perspect 108:1085-1090 (2000). [Online 25 October 2000] http://ehpnet1.niehs.nih.gov/docs/2000/108p1085-1090sower/abstract.html
Address correspondence to S.A. Sower, Department of Biochemistry and Molecular Biology, Rudman Hall, University of New Hampshire, Durham, NH 03824 USA. Telephone: (603) 862-2103. Fax: (603) 862-4013. E-mail: sasower@cisunix.unh.edu
From this brief examination of one peer-reviewed journal over the past two years, the conclusion seems inescapable that industrial chemicals in the environment can and do interfere with the hormones of wildlife and humans, causing widespread harm. Furthermore, it is clear that large numbers of scientists agree that this is so because they are spending their lives researching these problems instead of pursuing more lucrative opportunities. Unfortunately, the full extent of these problems remains unknown, and unknowable, for practical reasons that will become clear in RACHEL'S #753.
[continued.]
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[1] W.R. Kelce and others, "Persistent DDT metabolite p-p'-DDE is a potent androgen receptor antagonist," NATURE Vol. 375, No. 6532 (1995), pgs. 581-585.
source: http://www.rachel.org/bulletin/bulletin.cfm?Issue_ID=2244
Part 4, n.753 3oct02
DISRUPTING LIFE'S MESSAGES
[In this series, we have been reviewing studies published during the past two years in ENVIRONMENTAL HEALTH PERSPECTIVES, a peer-reviewed journal published by the U.S. National Institutes of Health. Our purpose has been to discover whether mainstream scientists believe that industrial chemicals, released into the environment, can interfere with the hormones of wildlife and humans, leading to widepsread harm. It is abundantly clear that they do. To keep abreast of the torrent of new studies of hormone disruption appearing in dozens of journals, check in regularly at http://www.ourstolenfuture.org.
Now the question becomes, "What does all this information about hormone disruption mean?" One person eminently qualified to comment on that question is Dr. J.P. Myers, a zoologist and co-author (with Theo Colborn and Dianne Dumanoski) of OUR STOLEN FUTURE, the book that pushed "hormone disruption" to the top of the international environment-and-health agenda. The following essay first appeared in the February, 2002, issue of OUR PLANET, the journal of environmental sustainability published by the United Nations Environment Program. See http://www.ourplanet.com. We added the footnotes.]
Disrupting Life's Messages
by John Peterson Myers*
A revolution in scientific understanding of the impacts of contamination on health is under way. As it unfolds, it is likely dramatically to alter our understanding of the consequences of pollutants for human well-being, and to require fundamental changes in how chemicals are regulated. The revolution arises from scientific discoveries which establish that many chemicals both from the natural world and synthesized in laboratories interfere with the natural chemical messaging systems that direct the biological development of plants and animals, including humans.
Virtually all biological development is under the control of various chemical messaging systems that convey instructions from the genes to their targets, thereby directing development. Hormones, neurotransmitters and growth factors, among others, are key elements of these message systems. Their successful transmission of genetic instructions is vital to normal healthy development, as they control almost if not every aspect of the process from what sex a baby will become to how many fingers it will have, to whether its brain is capable of intelligent reasoning or whether its immune system will be able to resist disease.
Science has now established that a wide array of chemicals can disrupt these genetically based messages without damaging the genes themselves. Much attention has focused on disruption of hormonal signalling, which has become known as endocrine disruption.
The roots of research in this arena go back to the 1930s, but it has burgeoned in the last ten years because of very significant investments of funds by European, Japanese and North American governments. New results are published virtually every week. These new findings are rich in detail, fascinating in what they reveal about biological mechanisms, and sometimes breathtaking in their implications.
For example, a study published in July 2001 by the United States Centers for Disease Control reported a strong relationship between DDT contamination in mothers and the likelihood of pre-term birth of their infants.[1] Using biological samples stored since the 1960s, the authors report that their findings indicate that the United States experienced an epidemic of pre-term birth during the hey-day of DDT use, and that this persistent pollutant may have caused up to 15 per cent of infant mortality in America during that period.
Several important broad trends in the pattern of research findings can be identified from the thousands of studies on endocrine disruption published since the early 1990s.
First, the research confirms that contamination by hormonally active compounds is globally ubiquitous. No one is unexposed, even in the womb. The same is true for most, if not all living organisms, especially those higher in ecological food chains and thus consuming foods in which the contaminants have become concentrated by bioaccumulation. Contamination is partly so widespread because of the global redistribution of pollutants transported through air and water. The inadvertent but pervasive inclusion of hormonally active compounds in consumer products such as many cosmetics and plastics also contributes.
Empirical confirmation
Second, effects of exposure can be observed at levels dramatically lower than those thought relevant to health a decade ago. Scientists are measuring the endocrine-disruption impacts of contaminants like arsenic, dioxin and bisphenol A (a basic component of polycarbonate plastic) in the low parts-per-billion. This was unmeasurable two decades ago (scientific instruments simply were not that accurate) and highly controversial until recent review and empirical confirmation.
Third, the findings indicate that virtually all chemical messaging systems are vulnerable, in principle, to message disruption. Work in this area focused for decades on interference with oestrogen. As the focus has expanded to other hormones, one or more disrupting contaminants have been discovered for every system studied carefully, including the thyroid system (crucial for brain development), the retinoid system (involved in very basic control of development), and the glucocorticoids (important for metabolism and tumour suppression, among other things). In the summer of 2001, new results reinforced this trend dramatically, with a report that the ecological symbiosis between leguminaceous plants like beans and the bacteria responsible for nitrogen fixation is vulnerable to disruption by contaminants.[2] This symbiosis, mediated by chemical communication between the plant and the bacteria, is a vital component of the global nitrogen cycle.
Fourth, the health effects of concern have expanded dramatically beyond those of the traditional focus for toxicology. Laboratory studies unequivocally demonstrate effects on disease resistance, cognitive function and fertility resulting from low-level exposures.
These findings should be of deep concern to people, organizations and agencies focused on human economic development and equity. It is clear, for example, that background levels of contamination can make children less resistant to infectious agents. Further research in this area may force a radical reassessment of the toll of contamination, as this implies that many deaths and diseases would have been avoided had contaminants not reduced resistance.
Similarly, the research suggests that widespread exposure to neurologically active contaminants as might occur, for example, in agricultural areas in the developing world with intensive pesticide use may lead to community-wide erosion of cognitive abilities. In a world in which information is a key economic currency, this contamination burden could consign those affected to the economic margins forever. \tab\b Conceptual shifts
These emerging trends are forcing toxicologists toward several conceptual shifts that will lead to fundamental changes in the ways that chemicals are managed. The most important of these involves a change in the way that toxicologists think about what is relevant to human health.
Traditional toxicology focuses on damage, such as cell death, mutations, cancer or genotoxicity. Message disruption can cause these, but the effects may also be of a very different, but equally important, nature. Most challenging to traditional toxicology, message disruption does not work by overwhelming the body's (or the cell's) defences. It works by hijacking the developmental process, adding to or subtracting from the body's own control mechanisms at remarkably low levels of exposure. By subtly (or blatantly) altering the path of development, message disruption leads the victim to a different future. The difference may be small, as in the loss of a few IQ points, or it may be large, as in a completely dysfunctional immune system.
Toxicology has focused traditionally on the impact of high levels of exposure on small numbers of people. This new approach requires considering widespread, low-level exposures experienced by many people -- exposure levels that many had come to write-off as "background" and, by implication, irrelevant.
Taken together, these new scientific findings add to growing pressure to change the basic rules of chemical regulation. Once again, we have been blind-sided. Our ability to synthesize chemicals got far ahead of our scientific understanding of their impacts.
Traditional risk assessment allowed them to be commercialized and distributed, causing pervasive contamination. Risk assessment's partner in developing protective standards, epidemiology, by definition works only after an epidemic. Even then, its tools are remarkably insensitive in studies of the effects of endocrine disruption, and strongly biased toward negative results even when there are real effects.
The answer, still imperfect, lies in implementing precautionary measures that impose far more stringent requirements on old and new products alike. As the Swedish Chemicals Policy Committee has recognized, certain attributes should be knock-out criteria.[3] Persistent bioaccumulative compounds, for example should be eliminated from use even without demonstrating toxicological risk. Endocrine-disrupting materials should be removed from consumer products and their environmental release should be phased out. More generally, the demonstration of potentially harmful biological impacts in laboratory studies should reverse the burden of proof in developing regulations from one in which harm must be demonstrated before a product is withdrawn, to an approach where safety is ensured beyond reasonable doubt before widespread deployment is allowed. These steps will help ensure that the benefits we all enjoy from modern chemistry do not come back to haunt us.
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* John Peterson Myers, co-author of OUR STOLEN FUTURE (hard cover: Dutton, 1996; ISBN 0525939822; paperback: Plume, 1997; ISBN 0452274141), is Senior Advisor to the United Nations Foundation and Senior Fellow, Commonweal.
[1] M.P. Longnecker, M.A. Klebanoff, H. Zhou, J.W. Brock, "Association between maternal serum concentration of the DDT metabolite DDE and preterm and small-for-gestational-age babies at birth, " THE LANCET Vol. 358 (2001), pgs. 110-114.
[2] J.E. Fox, M. Starcevic, K.Y. Kow, M.E. Burow and J.A. McLachlan, "Nitrogen fixation: Endocrine disrupters and flavonoid signalling," NATURE Vol. 413 (2001), pgs. 128-129.
[3] Swedish chemicals policy recommendations were reported in Lotta Fredholm, "Chemical Testing: Sweden to Get Tough on Lingering Compounds," SCIENCE Vol. 290, No. 5497 (Dec. 1, 2000), pgs. 1663-1666.
NOTICE
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