#323: New Perspectives on Toxics--Part 2: Male Reproductive System Is Harmed By Toxic Exposures, Causing Birth Defects, Sterility

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RACHEL'S HAZARDOUS WASTE NEWS #323
---February 3, 1993---
News and resources for environmental justice.
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The ancient Greeks observed that men heavily exposed to lead became sterile. But this knowledge was not passed to the Romans, who stored their drinking water and their wine in lead-lined containers. Romans also added lead to some of their drinks as a sweetener. Based on examination of lead in Roman bones, some historians conclude that the Roman upper classes probably couldn't reproduce themselves, contributing to the fall of Rome.[1]

Until very recently, scientists paid little attention to the effects of environmental agents on human reproduction. The modern period began in 1941 when blindness, deafness and death were reported among the offspring of pregnant women exposed to rubella (German measles). The thalidomide catastrophe in 1954-1961 brought home the potential dangers of chemicals, in this case a prescription drug. (See RHWN #322.) The birth of nearly 20,000 defective children following a Rubella epidemic in the early 1960s confirmed the association of environmental factors and birth defects.[2]

As recently as the early 1970s, few state governments were maintaining records of birth defects. In 1974 the federal government established the first national register of birth defects, monitoring hospital records that account for about 15% of all births.[3] Even today this program monitors only birth defects observed in newborns, which probably represent only about a sixth of the total defects that actually occur because many defects do not become apparent for several years.[2]

As of 1980, approximately 200,000 birth defects were estimated to have occurred in the U.S., accounting for about 7 percent of all live births. In addition, more than 560,000 infant deaths, spontaneous abortions, stillbirths and miscarriages were recorded due to defective fetal development.[2]

In 1990, the federal Centers for Disease Control (CDC) reported trends in birth defects between 1979 and 1987 in the U.S. They looked at 38 specific defects and found that 29 of the 38 had increased, two had decreased and 7 had remained stable.[3] The largest increases (29 percent and 20.2 percent) occurred in defects of the heart; no doubt some of this increase is due to better detection methods. However, there was also a 9.6 percent increase in eye defects and a 2.7 percent increase in cleft lip, so it seems likely that real increases are occurring.

As we reported last week,#322 the traditional view of birth defects highlights the role of women and disregards the role of men, even when there is good evidence showing men exposed to toxic chemicals father defective children. The traditional reason for ignoring such research is that, until recently, there has been no satisfactory theory to explain how male exposures could affect offspring, so a cause-and-effect relationship could not be established. The argument was that women are born with all the eggs they will ever have, so each egg can be exposed to toxins over a long period. Men on the other hand, produce new sperm constantly, so any individual sperm has only a brief opportunity to be exposed to toxins.

Another reason for ignoring the effect of toxins on male reproduction was the "macho sperm" theory, which said that only the fittest sperm were hardy enough to go the distance necessary to fertilize an egg.

[4] According to this theory, defective sperm could never reach an egg to fertilize it, so men couldn't be responsible for producing defective children. Now research has shown that the female reproductive tract has ways of moving sperms along whether they are healthy or defective.

Researchers used to believe that there was an effective barrier between blood vessels and the tissues where sperm originates in the testes. It is now known that the barrier is not effective against many chemicals.

Then of course there's a cultural bias, reaching back to the Salem witch trials, to blame women for trouble. "You don't have to be Sigmund Freud to figure out that there are cultural factors to say why we have paid so much attention to the female and so little to the male," says Dr. Devra Lee Davis, an epidemiologist with the National Research Council.

Research during the past decade has shown that there are two basic ways that chemicals can affect male reproduction.[5,6] Chemicals can directly affect the testes, where sperm originates. The numbers of sperm can be diminished, or some sperm can be damaged, or sperm may even carry toxins directly into the egg. Alternatively, toxins can attack the male nervous system, or endocrine system, affecting the flow of hormones that act as messengers regulating the complex chemical processes that must all work well for conception to occur.

No matter what the mechanism of damage may be, there is a growing body of evidence showing that male exposure to toxins can produce defective children. Here is a sampling:

** A nationwide study of 99,186 pregnancies in Finland showed an increased likelihood of spontaneous abortion if the father was occupationally exposed to rubber chemicals, solvents used in the manufacture of rubber products, solvents used in oil refineries, or ethylene oxide.[7]** A study of 22,192 children born with birth defects in British Columbia showed that paternal occupation as a fire fighter was related to the occurrence of heart defects. Fire fighters are often heavily exposed to carbon monoxide and to polycyclic aromatic hydrocarbons (PAHs)--the nasty chemicals in smoke and soot.[8]** A study of paternal occupation among 149 patients with Wilm's tumor (a childhood cancer of the kidney) showed that a significantly greater number of the fathers were exposed to lead on the job, compared to fathers of a control group of children without the disease.[9]** A study of 6000 men in Finland showed that paternal exposure to organic solvents nearly tripled the likelihood of spontaneous abortion as a pregnancy outcome, compared to controls not exposed to organic solvents. Painters, wood workers (for example, carpenters in the construction, furniture industry and the boat industry) were found to be at risk. The solvent toluene stood out as a particularly bad actor in his study. [10]** A study of anesthetists in the West Midlands region of England (half men, half women) showed that, during a 20-year period, 9.3% of their children were born with defects, and 31% of the anesthetists reported having trouble begetting children. Furthermore nearly all the children were born underweight. The gender of the anesthetists did not affect the likelihood of problems in their children, but female children seems to suffer greater birth defects. [11]** A recent review of several studies of paternal occupational exposures in relation to childhood cancer in the offspring showed consistently that work in hydrocarbon-related occupations (the petroleum and chemical industries), especially exposure to paint, is associated with brain cancer. Male exposure to paint is also linked to leukemias in offspring. [12]

What does all this evidence mean? It means neither men NOR women can be safely exposed to toxic chemicals. Instead of banning women from the workplace, the workplace should be cleaned up.

--Peter Montague, Ph.D.

===============

[1] S.C. Gilfillan, "Lead Poisoning and the Fall of Rome," JOURNAL OF OCCUPATIONAL MEDICINE Vol. 7 (Feb. 1965), pgs. 53-[60.]60.

[2] Raymond D. Harbison, "Teratogens," in John Doull and others, editors, CASARETT AND DOULL'S TOXICOLOGY 2nd edition (N.Y.: Macmillan, 1980), pgs. 158-175.

[3] Larry D. Edmonds and Levy M. James, "Temporal Trends in the Prevalence of Congenital Malformations at Birth Based on the Birth defects Monitoring Program, United States, [1979-1987."] MORBIDITY AND MORTALITY WEEKLY REPORTS CDC SURVEILLANCE SUMMARIES Vol. 39, No. SS-4 (December, 1990), pgs. 19-23.

[4] Sandra Blakeslee, "Research on Birth Defects Turns to Flaws in Sperm," NEW YORK TIMES (January 1, 1991), pgs. 1, 36.

[5] Lowell Sever and Nancy A. Hessol, "Toxic Effects of Occupational and Environmental Chemicals on the Testes," in J.A. Thomas and others, editors, ENDOCRINE TOXICOLOGY (N.Y.: Raven Press, 1985), pgs. 211-248.

[6] Harold Zenick, "Mechanisms of Environmental Agents by Class Associated With Adverse Male Reproductive Outcomes," in REPRODUCTION: THE NEW FRONTIER IN OCCUPATIONAL AND ENVIRONMENTAL HEALTH RESEARCH (N.Y.: Alan R. Liss, Inc., [1984),] pgs. 335-361.

[7] Marja-Lusa Lindbohm and others, "Effects of Paternal Occupational Exposure in Spontaneous Abortions," AMERICAN JOURNAL OF PUBLIC HEALTH (August, 1991), pgs. 1029-1033.

[8] Andrew F. Olshan and others, "Birth Defects Among Offspring of Firemen," AMERICAN JOURNAL OF EPIDEMIOLOGY Vol.
[131] (1990), pgs. 312-321.

[9] Arlene F. Kantor and others, "Occupations of fathers of patients with Wilm's tumour," JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH Vol. 33 (1979), pgs. 253-256.

[10] Helena Taskinen and others, "Spontaneous abortions and congenital malformations among the wives of men occupationally exposed to organic solvents," SCANDINAVIAN JOURNAL OF WORK, ENVIRONMENT AND HEALTH Vol. 15 (1989), pgs. 345-352.

[11] P. J. Tomlin, "Health problems of anesthetists and their families in the West Midlands," BRITISH MEDICAL JOURNAL (24 March, 1979), pgs. 779-784.

[12] David A. Savitz and Jianjua Chen, "Parental Occupation and Childhood Cancer: Review of Epidemiological Studies," ENVIRONMENTAL HEALTH PERSPECTIVES Vol. 88 (1990), pgs. 325-337.

Descriptor terms: reproductive hazards; health; birth defects; lead; rubella; endocrine disruptors; solvents; pahs; occupational safety and health; men; males; fathers; children; spontaneous abortion; petroleum industry;

#372: PCBs Diminish Penis Size

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RACHEL'S HAZARDOUS WASTE NEWS #372 
---January 13, 1994---
News and resources for environmental justice.
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Environmental Research Foundation
P.O. Box 5036, Annapolis, MD 21403
Fax (410) 263-8944; Internet: erf@igc.apc.org ==========
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Boys in Taiwan exposed to PCBs while in their mothers' womb develop smaller penises as they mature, compared to normal boys in Taiwan, according to a brief article this month in SCIENTIFIC AMERICAN. [1] PCBs (polychlorinated biphenyls) are a group of industrial chemicals manufactured and released into the environment in megaton quantities by Monsanto and its licensees between 1929 and 1976. [2]

The finding of small penises among PCB-exposed human males tends to confirm that humans and wildlife are affected similarly by exposure to "endocrine-disrupting chemicals" such as PCBs, dioxin, DDT, and dozens of others. (See RHWN #249, #263, #264, #323, #327, #334, #337, #364, #365.) The endocrine system, in wildlife and humans, is a complex set of bodily organs and tissues whose activities are coordinated by chemical messengers, called hormones, that control growth, development and behavior. In recent years, evidence has accumulated that several dozen pesticides and other industrial chemicals mimic, or interfere with, hormones and thus disrupt the endocrine system. In both wildlife and humans, it is the reproductive system that seems most prone to disruption by hormone-like industrial pollutants.

SCIENCE NEWS reported this month that male alligators exposed to pesticides in Florida are having difficulty reproducing, partly because their penises are not developing to normal size. [3] SCIENCE NEWS presented evidence from several sources that males of many wildlife species (birds, fish, amphibians, and mammals) are being "feminized" by exposure to low levels of pesticides and other industrial chemicals that have been released into the environment in huge quantities since World War II.

The boys in Taiwan were born to mothers who unwittingly consumed PCB-contaminated rice oil during a 10-month period in 1979. As many as 2000 people consumed the contaminated oil. The children consumed no contaminated oil themselves; they were exposed before birth to PCBs that were carried by their mothers' blood and crossed the placenta; they may have also been exposed shortly after birth by drinking their mothers' milk. The rice oil contained 100 parts per million (ppm) PCBs and 0.1 ppm PCDFs [polychlorinated dibenzofurans, a potent dioxin-like poison]. [4] A new mother in the U.S. today has an average of one ppm PCBs in her breast milk.

The children in Taiwan have been observed medically for many years. They are known as the "yucheng" (or "oil disease") children. A similar PCB contamination event ("yusho") occurred in Japan in 1968.

When 115 yucheng children were examined in 1985 they were less developed than a control group of children on 32 of 33 different measures. They were delayed, compared to controls, in the age at which they performed tasks such as saying phrases and sentences, turning pages, carrying out requests, pointing to body parts, holding pencils, and catching a ball.

The yucheng children also had a variety of physical defects at birth, including dark colored heads, faces and genitals, and abnormal nails that were often dark and ridged, split, or folded. [5]

These children provided the first direct evidence that PCBs are teratogenic [birth-defect-producing] in humans. Since then, other studies have shown that American children with "normal" levels of PCBs in their blood show slight physical, mental and emotional retardation.

In North Carolina, 912 infants have been followed from birth. Their mothers had no unusual PCB exposures but, like all Americans, they carry PCBs in their body tissues. Among 866 North Carolina infants tested, higher PCBs in mother's milk was correlated with hypotonicity [loss of muscle tone] and abnormally weak reflexes. Subsequent studies of 802 of the North Carolina children at ages 6 months and 12 months revealed those with higher levels of PCBs had poorer performance on tests requiring fine motor coordination.

Researchers reviewing the history of these children conclude, "There is thus consistent evidence that prenatal exposure to levels of PCBs commonly encountered in the U.S. produces detectable effects on motor maturation and some evidence of impaired infant learning." [6] In North Carolina, about 5% of the children have so far shown measurable effects related to PCB exposure, and in a Michigan study of children whose mothers ate fish from Lake Michigan (almost all of which are contaminated with PCBs), somewhat more than 5% of the children are showing effects.

At age 4, children in the Michigan group with higher PCBs levels weighed 10% (4 pounds) less than children with lower PCB levels. The effect was particularly significant in girls. In addition, the Michigan children were ranked according to an "activity" index, and higher PCB levels were correlated with children who were unusually "quiet and inactive." These effects on growth and behavior were specifically correlated with exposure to PCBs before birth and not with exposure after birth. This leads researchers to conclude that PCBs attack the central nervous system more successfully during its earlier developmental stages. [7]

The information from Taiwan about male genital development tends to confirm that PCB exposure in the womb has effects different from, and more powerful than, those caused by PCB exposure in later life. The same seems to be true in wildlife as well. Alligator eggs exposed to DDT or a related pesticide, dicophol, produce male alligators with abnormal sex hormones (estrogen and testosterone) in their blood, leading to growth of penises one-third to one-half normal size, and subsequent reproductive failure.

The Florida panther, an endangered species, is also failing to reproduce itself. There are only 30 to 50 panthers remaining, and the reason for the decline has been a mystery. Now researchers have reported that between 1985 and 1990, 67 percent of male panthers were born with one or more undescended testicles, a condition known as cryptorchidism. In England and the U.S., cryptorchidism has more than doubled in men during the last four decades. [8] Furthermore, some Florida panthers are sterile and others produce abnormal or deformed sperm. It was reported last year that sperm count in men in industrialized countries has dropped 50% during the past 50 years. [9]

Two years ago, researchers at University of Wisconsin reported that low prenatal [before birth] exposures to dioxin feminized the behavior of male rats during adulthood, and sharply reduced their production of sperm. [10] "Indeed," says Janet Raloff in SCIENCE NEWS, "the researchers concluded, the developing male reproductive system appears to be more sensitive to the effects of this hormone-like toxicant [dioxin] than any other organ or organ-system studied." [3]

The ability of industrial chemicals to damage the reproductive systems of wildlife has been observed since the 1950s when DDT was linked to eggshell thinning in many bird species, [11] but humans have been slow to get the message. Petrochemical corporations and agricultural giants continually dump billions of pounds of endocrine-disrupting toxins into the environment each year. Government goes along.

Scientists continue to study birds, uncovering new evidence of reproductive damage. Dr. Michael Fry at University of California, Davis, has been studying Western gulls on Santa Barbara Island, where in recent years he has begun to observe "lesbian gulls," meaning female-female pairing. He attributes this behavior partly to male gulls' growing indifference to sex. Examination reveals that the male gulls have feminized sex organs and have been "chemically castrated" by DDT and other environmental pollutants, Fry says.

Perhaps the new information about small penises in alligators and humans will finally get the attention of someone high up in Washington.

--Peter Montague, Ph.D.

===============

[1] Marguerite Holloway, "Dioxin Indictment," SCIENTIFIC AMERICAN Vol. 270 (January 1994), pg. 25.

[2] Kristin Bryan Thomas and Theo Colborn, "Organo-chlorine Endocrine Disruptors in Human Tissue," in 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). pgs. 342-343.

[3] Janet Raloff, "The Gender Benders," SCIENCE NEWS Vol. 145 (January 8, 1994), pgs. 24-27. And see J. Raloff, "Perinatal dioxin feminizes male rats," SCIENCE NEWS Vol. 141 (May 30, 1992), pg. 359, and Janet Raloff, "EcoCancers," SCIENCE NEWS Vol. 144 (July 3, 1993), pgs. 10-13. See also: Bette Hileman, "The Great Lakes Cleanup Effort," C&EN [CHEMICAL & ENGINEERING NEWS] February 8, 1988, pgs. 22-39; and: Bette Hileman, "Concerns Broaden over Chlorine and Chlorinated Hydrocarbons," C&EN [CHEMICAL & ENGINEERING NEWS] April 19, 1993, pgs. 11-20.

[4] Walter J. Rogan and others, "Congenital Poisoning by Polychlorinated Biphenyls and Their Contaminants in Taiwan," SCIENCE Vol. 241 (July 15, 1988), pgs. 334-336.

[5] Gina Kolata, "PCB Exposure Linked to Birth Defects in Taiwan," NEW YORK TIMES August 2, 1988, pg. C3.

[6] Hugh A. Tilson and others, "Polychlorinated Biphenyls and the Developing Nervous System: Cross-Species Comparisons," NEUROTOXICOLOGY AND TERATOLOGY Vol. 12 (1990), pgs. 239-248.

[7] Joseph L. Jacobson and others, "Effects of Exposure to PCBs and Related Compounds on Growth and Activity in Children," NEUROTOXICOLOGY AND TERATOLOGY Vol. 12 (1990), pgs. 319-326.

[8] A. Giwercman and N.E. Skakkebaek, "The human testis--an organ at risk?" INTERNATIONAL JOURNAL OF ANDROLOGY Vol. 15 (1992), pgs. 373-375.

[9] Elisabeth Carlsen and others, "Evidence for decreasing quality of semen during past 50 years," BRITISH MEDICAL JOURNAL Vol. 305 (1992), pgs. 609-613.

[10] Thomas A. Mably and others, "IN UTERO and Lactational Exposure of Male Rats to 2,3,7,8-Tetrachlorodibenzo-P-dioxin. 1. Effects on Androgenic Status." TOXICOLOGY AND APPLIED PHARMACOLOGY Vol. 114 (May, 1992), pgs. 97-107. And: Thomas A. Mably and others, "IN UTERO and Lactational Exposure of Male Rats to 2,3,7,8-Tetrachlorodibenzo-P-dioxin. 2. Effects on Sexual Behavior and the Regulation of Luteinizing Hormone Secretion in Adulthood." TOXICOLOGY AND APPLIED PHARMACOLOGY Vol. 114 (May, 1992), pgs. 108-117. And: Thomas A. Mably and others, "IN UTERO and Lactational Exposure of Male Rats to 2,3,7,8-Tetrachlorodibenzo-P-dioxin. 3. Effects on Spermatogenesis and Reproductive Capability." TOXICOLOGY AND APPLIED PHARMACOLOGY Vol. 114 (May, 1992), pgs. 118-126.

[11] For example, see Robert Risebrough and Virginia Brodine, "More Letters in the Wind," in Sheldon Novick and Dorothy Cottrell, editors, OUR WORLD IN PERIL: AN ENVIRONMENT REVIEW (Greenwich, Conn.: Fawcett, 1971), pgs. 243-255.

Descriptor terms: taiwan; china; pcbs; sexual development; reproductive system; endocrine system; monsanto; wildlife; penis; penises; hormones; endocrine disruptors; pesticides; alligators; fl; florida; pcdfs; polychlorinated dibenzofurans; polychlorinated biphenyls; breast milk; yucheng; yusho; japan; developmental disorders; teratogens; birth defects; north carolina; us; michigan; lake michigan; fish; estrogen; testosterone; florida panther; undescended testicles; cryptorchidism; sperm; rats; dioxin; ddt; dde; dicophol; western gulls; santa barbara island; ca; california;

#438: Warning on Male Reproductive Health

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RACHEL'S ENVIRONMENT & HEALTH WEEKLY #438
---April 20, 1995---
News and resources for environmental justice.
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Environmental Research Foundation
P.O. Box 5036, Annapolis, MD 21403
Fax (410) 263-8944; Internet: erf@rachel.clark.net ==========
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The Danish Environmental Protection Agency in Copenhagen, Denmark released a report April 18th entitled MALE REPRODUCTIVE HEALTH AND ENVIRONMENTAL CHEMICALS WITH ESTROGENIC EFFECTS. The 175-page English-language report, which we have obtained, says male reproductive health is deteriorating in many countries, and that the most likely cause is exposure to low levels of industrial chemicals that contaminate food, water, and many consumer products.

The Danish report says many industrial chemicals mimic sex hormones (chiefly the female hormone, estrogen) and thus interfere with the normal development of creatures (including humans) that become exposed before, or shortly after, birth. The report identifies many consumer products as sources of such hormone-like chemicals: pesticides, detergents, cosmetics, paints, and packaging materials, including plastic containers and food wraps. [1] The report calls for an aggressive, coordinated international research effort to describe the extent of the problem, and to design programs of "prevention and intervention."

Meanwhile in the U.S., the Chemical Manufacturers Association (CMA) has funded a report by a scientist who says these problems are not real. "The suggestion that industrial estrogenic chemicals contribute to an increased incidence of breast cancer in women and male reproductive problems is not plausible," the CMA's 6-page study concludes. [2]

In contrast, the Danish report says, "It is now evident that several aspects of male reproductive health have changed dramatically for the worse over the past 30-50 years. The most fundamental change has been the striking decline in sperm counts in the ejaculate of normal men; recent evidence from Paris indicates that this decrease amounts to about two percent per year over the last two decades. The result is that many, otherwise normal, men now have sperm counts so low that their fertility is likely to be impaired. Over the last half-century, the incidence of testicular cancer has increased progressively in many countries to become now the most common cancer in young men. Other disorders of the male reproductive tract may also be increasing in incidence, with several European countries reporting a progressive rise in hypospadias (a malformation of the external genitalia) and an apparently emerging trend towards an increasing incidence of testicular maldescent [undescended testicles]....

"While the etiologies [causes] underlying these apparent changes are currently not clear, both clinical and laboratory research suggest that all of the described changes in male reproductive health appear inter-related and may have a common origin in fetal life or childhood. This means that the increase in some of the disorders seen today originated 20-40 years ago and that the prevalence of such defects in male babies born today will not become manifest for another 20-40 years or more," the report says.

The Danish report was prepared by 19 scientists and physicians, including 13 from Denmark, two from France, one from England, one from Scotland, and two from the U.S.

The report says that declining reproductive health has also been widely observed in wildlife: "Trends in the reproductive health of species other than man also raise the possibility of environmental factors as partial etiologic [causal] contributions in a decline noted in the male reproductive health of wildlife. For example, wild panthers in the United States have been reported to have an increase in undescended testes and a decrease in semen quality, whereas male alligators in some lakes in Florida have been shown to have abnormalities in their sex hormone levels (tending towards femaleness) and to have smaller than normal genitalia. Male fish in some parts of the United Kingdom have been shown to express a 'female-like response' when studied in a relatively natural setting. Earlier studies of fish eating birds in the United States demonstrated nests containing male hatchlings that were apparently feminized. A recent report of lactating [milk-producing] male fruit bats suggested that the males were, in some way, exposed to a female sex hormone. Recent laboratory studies showed that when estrogenic forms of polychlorinated biphenyls (PCBs) were painted on turtle eggs, the male hatchlings were sex-reversed to females. Taken together, this growing body of evidence suggests that environmental factors that resemble female sex hormones may be having an adverse effect on the reproductive capacity and wellbeing of diverse species," the report says.

The report summarizes evidence indicating that all of these problems have a common origin: the exposure of male fetuses to estrogen-like chemicals before birth. "The wealth of experimental [laboratory animal] results and associated clinical [human] reports suggests strongly that prenatal exposure to exogenous [external] estrogens may play an etiologic role in the trends observed in male reproductive health," the report says.

The report lists many ways in which humans become exposed to chemicals that mimic hormones: "Estrogen effects are not restricted to a small group of therapeutic agents but appear in several groups of compounds that are in daily use in industry, agriculture or in the home," the report says. "A major problem is determining which chemicals are estrogenic... At present, tens of thousands [of] man-made chemicals are used, yet the effects on the endocrine [hormone] system have been studied for only a few of these. The estrogenic activity of most chemicals (e.g., alkylphenols, phthalate esters, bisphenol-A) has been detected by accident, not by intent; that is, no systematic screening, even on individual groups of chemicals, has been attempted. Hence it is highly possible that other estrogenic chemicals remain unidentified... Thus, the present situation is that man and wildlife are exposed to a very wide range of chemicals, and for the majority of them we do not know whether these chemicals are, or are not, estrogenic, whether their effects are additive, or even what the true exposure to these chemicals is."

The report points out that even weakly estrogenic chemicals may be of concern if they remain in the bodies of humans and wildlife for long periods. Natural hormones are created by the body, circulate in the blood stream very briefly to carry out a particular task, and are then destroyed by natural mechanisms. In contrast, many industrial chemicals that enter the body are not readily broken down so they circulate in the blood for long periods --in some cases many years --mimicking natural hormones.

The Danish report lists the following chemicals and classes of chemicals as known to have estrogenic activity:

Organochlorine pesticides: DDT, DDD, DDE, dicofol, perthane, methoxychlor, chlordane, oxychlordane, trans-nonachlor, heptachlor, heptachlorepoxide, aldrin, dieldrin, hexachlorobenzene, hexachlorocyclohexanes, lindane (gamma HCH), mirex, and toxaphene. Although these chemicals have been banned in several industrial countries, including the U.S., some of them are still manufactured [in the U.S. or overseas, by U.S. corporations--PM] and sold in developing countries where they are "widely used" today, the Danish report says.

Other known estrogenic chemicals include:

** Many of the 109 types of PCBs (polychlorinated biphenyls); 

** Dioxins and furans (unwanted by-products of all incinerators; paper-making mills; metal smelters; and the manufacture of some chemicals and pesticides); 

** Alkylphenols, the breakdown products of alkylphenol polyethoxylates (APEs) which are widely used in detergents, paints, herbicides and cosmetics. Some 300 million kilograms (660 million pounds) of APEs are produced each year and ultimately released into the environment. 

** Phytoestrogens, or plant-produced estrogens, including isoflavones and coumestans found in rye, wheat, cabbage, sprouts, spinach and soybeans. "Soybean is far and away the richest source of plant estrogens and is used ubiquitously [everywhere] in the food industry as a protein source including the production of infant milk formula substitutes," the Danish report says. Depending upon the dose, phytoestrogens have an estrogenic, or an anti-estrogenic, effect, the Danish report says. Unlike many of the other estrogenic chemicals identified in the Danish report, phytoestrogens do not bioaccumulate or biomagnify, but are readily metabolized and excreted. 

** Many common chemicals found in plastics, in-cluding bisphenol-A, phthalate esters (butylbenzyl phthalate and di-n-butylphthalate): "Phthalates are the most abundant man-made environmental pollutants, and human intake per day via various routes, especially via the diet, is measured in tens of milligrams," says the Danish report. Some plastics contain up to 40% phthalate esters (by weight). These esters leach out of, or volatilize out of, the plastics as time passes. Many foods in the U.S. and elsewhere are packaged in phthalate-containing plastics. Even blood for transfusions is sometimes packaged in phthalate-containing plastics. 

** Herbicides, such as the popular crab-grass and dandelion killer, 2,4-D, and the now-banned 2,4,5-T, both of which were widely used by U.S. forces in Vietnam. (See REHW #436.) Other herbicides with estrogenic effects include: alachlor; amitrole; atrazine; metribuzin; and trifluralin. 

** Fungicides: benomyl and its principal breakdown product, carbendazim, used on apples and bananas, among other food crops; and ethylene bis dithiocarbamates (EBDCs, including mancozeb, maneb, metiram, and zineb). 

** Hexachlorobenzene. Although this pesticide was banned in many countries in the 1970s, it "continues to be released to the environment as a byproduct and contaminant in many other chlorinated chemicals including chlorinated solvents," the Danish report says. 

** Tributyltin compounds. Tributyltin compounds, until very recently, were used in large quantities as antifouling paints on ships, boats, and mariculture pen nets. Now banned in many countries. 

** Malathion, heavily sprayed around residential areas of the U.S. to kill nuisance mosquitoes.

And finally the Danish report warns that exposure to low levels of many chemicals may be harming the reproductive health of humans and wildlife by mechanisms that have nothing to do with estrogen: "Although not the subject of this report, in considering and evaluating the possible role of estrogenic chemicals in male reproductive disorders, it should not be forgotten that many chemicals may have a detrimental effect on male reproductive health through other mechanisms than an estrogenic effect," the Danish report says.

 --Peter Montague

===============

[1] Our thanks to Lisa Finaldi of Greenpeace International for helping us obtain a copy of the Danish EPA report.

[2] Stephen H. Safe, "Environment and Dietary Estrogens and Human Health: Is There a Problem?" ENVIRONMENTAL HEALTH PERSPECTIVES Vol. 103, No. 4 (April, 1995), pgs. 346-351.

Descriptor terms: endocrine disrupters; strogen; hormones; reproductive system; pesticides; detergents; cosmetics; paints; packaging materials; plastics; packaging; cma; chemical manufacturers association; denmark; sperm count; hypospadias; undescended testicles; testicular cancer; cryptorchidism; wildlife; panthers; alligators; penis size; fish; birds; bats; turtles; pcbs; chlorine; organochlorine compounds; pesticides; DDT; DDD; DDE; dicofol; perthane; methoxychlor; chlordane; oxychlordane; trans-nonachlor; heptachlor; heptachlorepoxide; aldrin; dieldrin; hexachlorobenzene; hexachlorocyclohexanes; lindane (gamma HCH); mirex; toxaphene; dioxin; furans; alkylphenols; alkylphenol polyethoxylates; apes; metal smelting; paper mills; incineration; phytoestrogens; bisphenol-A; phthalate esters; herbicides; 2,4-d; 2,4,5-t; agent orange; vietnam veterans; alachlor; amitrole; atrazine; metribuzin; trifluralin; benomyl; carbendazim; ethylene bis dithiocarbamates; ebdcs; mancozeb; maneb; metiram; zineb; hexachlorobenzene; tributyltin; malathion;


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#290: Young Male Rats Are 'Demasculinized' and 'Feminized' By Low Doses of Dioxin

=======================Electronic Edition========================

RACHEL'S HAZARDOUS WASTE NEWS #290
---June 17, 1992---
News and resources for environmental justice.
------
Environmental Research Foundation
P.O. Box 5036, Annapolis, MD 21403
Fax (410) 263-8944; Internet: erf@igc.apc.org ==========
RACHEL-4CM = DIOXIN FOCUSED DIRECTORY Remote Access Chemical Hazards Electronic Library. Dioxinnz.com =======================Original Source========================

Three new studies by researchers at University of Wisconsin reveal that very low doses of dioxin alter the sexual development of young male rats, causing demasculinization and feminization. [1,2,3]

Dr. Linda S. Birnbaum, a scientist with U.S. EPA [Environmental Protection Agency] calls the new studies "highly significant."[4] Birnbaum is one of the chief scientists conducting the EPA's formal reassessment of the toxicity of dioxin (see RHWN #269, #270, #275). As we reported earlier (RHWN #279), many scientists, including Birnbaum, now consider dioxin an "environmental hormone." The new Wisconsin studies support that view.

The Wisconsin researchers, led by Dr. Richard E. Peterson, showed that dioxin interferes with the sexual development of male rats exposed to dioxin before, and shortly after, birth. Pregnant female rats were given a single oral dose of dioxin on the 15th day of pregnancy; their male offspring showed reduced levels of male hormones in their blood and a variety of sexual aberrations that stayed with them as they matured. The young males are demasculinized and feminized by doses of dioxin too low to cause any measurable toxicity in the mother rat. The sexual changes in the young males are both physiological and behavioral, and last into adulthood.

Dioxin passes through the placenta and enters the fetus, so the rat fetuses received part of the mother's dose almost immediately. After birth, the baby rats continued to receive a small dose of dioxin through their mother's milk. Peterson says the baby rats received the bulk of their dose through milk. In rats and humans both, females rid their bodies of dioxin chiefly by excreting it in their milk. Dioxin is soluble in fats and oils, and milk is high in fat.

Dioxin is the common name for a family of 75 toxins, the most potent of which is TCDD [2,3,7,8-tetrachlorodibenzo-P-dioxin]. The Wisconsin researchers used TCDD in their experiments.

Dioxin is not made intentionally for any industrial purpose, but is produced as a byproduct of the combustion of chlorine-containing wastes, the bleaching of paper, and the manufacture of some pesticides. The burning of municipal solid waste, and of many hazardous wastes, releases dioxin into the environment, as does paper manufacture. Government officials responsible for the quality of the environment in the Great Lakes have called for a phase-out of chlorine, to reduce dioxin levels in wildlife and humans around the Lakes. (See RHWN #284.)

In the Wisconsin experiments, young males whose mothers were given as little as 0.064 micrograms of dioxin per kilogram of body weight showed consistently reduced levels of male hormones, plus a variety of physical and behavioral changes, including:

--reduced testosterone levels and probably a reduced response to testosterone. Testosterone is a powerful hormone controlling various aspects of sexual development in males. 

--smaller accessory sex organs, including smaller testicles; 

--slower sexual maturation; 

--distinctly feminine-style regulation of one hormone related to testosterone production; 

--greater willingness to assume a receptive-female posture when approached by a sexually stimulated male.

These effects "strongly suggest, though do not conclusively prove, that TCDD impairs sexual differentiation in the CNS [central nervous system]," according to Peterson and co-workers. They go on to say that, "The present study provides the first evidence that TCDD impairs sexual differentiation of the CNS." Sexual differentiation--the full development of a female instead of a male, or vice versa--is affected by hormones circulating in the blood before and after birth.

Furthermore, these studies "strongly suggest" that "the demasculinization and feminization caused by IN UTERO and lactational TCDD exposure are irreversible," the Wisconsin researchers say. IN UTERO means "in the womb" and lactational means "from milk."

Other effects revealed by these studies include:

--Even the lowest dose tested (0.064 micrograms of dioxin per kilogram of the mother's body weight), yielded consistent reductions in a male offspring's daily sperm production. 

--The developing male reproductive system is more sensitive to the effects of this hormone-like toxicant [dioxin] that any other organ or organ-system studied. 

--the unborn or newborn is about 100 times more sensitive to dioxin than the sexually mature animal.

What do these studies mean for humans?

The Wisconsin researchers speculate, "Thus the findings from this study raise the possibility that TCDD could potentially affect sexually dimorphic behavior in man if exposure were to occur during fetal development." "Sexually dimorphic behavior" refers to the bodily and behavioral differences between men and women.

Peterson and co-workers point out that male rats typically inseminate a female rat with up to 10 times as many sperm as are typically needed to ensure impregnation. Humans, by contrast, typically release only about as many sperm as would be required for fertilization. "As a result," Peterson and his co-workers write, human reductions in sperm production "similar in magnitude to that in rats would be expected to reduce fertility in man." In other words, rats can continue to reproduce despite a reduction in sperm count because they produce an excess of sperm, but humans do not produce excess sperm so a reduction in human sperm count would likely reduce humans' ability to reproduce.[5]

"The real question is how general these effects are," Birnbaum says. Her EPA lab will repeat the Peterson studies with another strain of rats and eventually other species. And if these effects occur in another species? "I would get very concerned [about the potential human-health implications]," Birnbaum told SCIENCE 

NEWS reporter Janet Raloff.

At a public hearing on EPA's dioxin reassessment at EPA headquarters in Washington April 28, a representative of the American Paper Institute argued that only the study of humans can reveal anything meaningful about humans. Birnbaum responded somewhat testily, spelling out a dozen ways in which studies of rats and mice reveal useful information about dioxin's potential effects on humans.

June 10 at a Congressional hearing on dioxin in Washington, Assistant U.S. Surgeon General Barry L. Johnson, announced that a new study by the National Institute for Occupational Safety and Health (NIOSH) has found that workers exposed to high levels of dioxin have abnormally low levels of testosterone (male hormone) in their blood streams.[6] This finding is consistent with the rat studies of Peterson and co-workers. We have learned that this new NIOSH study was presented at a scientific meeting on June 10, but 

NIOSH sources have so far not released details of the new study to the general public.

At the Congressional hearing June 10, under questioning from Representative Ted Weiss (D-NY), Barry Johnson said that if it were faced with the Times Beach, Missouri, situation today, the U.S. Public Health Service would do exactly what it did 10 years ago, which is to evacuate people from their homes. He said the Times Beach evacuation was the appropriate response and would be repeated under similar circumstances today. Another official of U.S. Public Health Service, Vernon L. Houk, made headlines 14 months ago saying if he had the decision to make over again, he would not evacuate people from Times Beach. Times Beach is a town near St. Louis where an unscrupulous waste hauler spread dioxin-contaminated oil around as a dust suppressant in the 1970s. Horses and other animals became sick and died, and the Public Health Service evacuated the town in the early 1980s.

During the Congressional hearing Dr. Houk's views were further contradicted by the testimony of Dr. Marilyn Fingerhut of NIOSH, who studied the health of 5172 workers exposed to dioxin on the job. (See RHWN #219.) Dr. Houk made headlines a year ago when he said that, if dioxin causes cancer in humans at all, it is only "a weak carcinogen." (See RHWN #249.) Dr. Fingerhut contradicted this view, reporting that, among workers who had been exposed to dioxin for at least a year at least 20 years ago, there was 46% more cancer than among average U.S. males. During the hearing, Representative Weiss characterized Dr. Houk's views on dioxin as "quirky" and "cockamamie."

--Peter Montague, Ph.D.

===============

[1] Thomas A. Mably and others, "IN UTERO and Lactational Exposure of Male Rats to 2,3,7,8-Tetrachlorodibenzo-P-dioxin. 1. Effects on Androgenic Status." TOXICOLOGY AND APPLIED PHARMACOLOGY Vol. 114 (May, 1992), pgs. 97-107.

[2] Thomas A. Mably and others, "IN UTERO and Lactational Exposure of Male Rats to 2,3,7,8-Tetrachlorodibenzo-P-dioxin. 2. Effects on Sexual Behavior and the Regulation of Luteinizing Hormone Secretion in Adulthood." TOXICOLOGY AND APPLIED PHARMACOLOGY Vol. 114 (May, 1992), pgs. 108-117.

[3] Thomas A. Mably and others, "IN UTERO and Lactational Exposure of Male Rats to 2,3,7,8-Tetrachlorodibenzo-P-dioxin. 3. Effects on Spermatogenesis and Reproductive Capability." TOXICOLOGY AND APPLIED PHARMACOLOGY Vol. 114 (May, 1992), pgs. [118-126.]118-126.

[4] J. Raloff, "Perinatal dioxin feminizes male rats," SCIENCE NEWS Vol. 141 (May 30, 1992), pg. 359.

[5] In unrelated studies, Congress's Office of Technology Assessment (OTA) reported several years ago that Americans in their prime reproductive years (ages 20 to 24) have experienced an increase in infertility in recent years. See "Reproductive Dysfunction in the Population," in U.S. Congress, Office of Technology Assessment, REPRODUCTIVE HEALTH HAZARDS IN THE WORKPLACE [OTA-BA-266] (Washington, DC: U.S. Government Printing Office, 1985), pgs. 341-364. At the time of this 1985 OTA report, low doses of dioxin were not known to interfere with reproductive systems of rats or humans.

[6] Barry L. Johnson, "Testimony... Before the Subcommittee on Human Resources and Intergovernmental Relations, Committee on Government Operations, House of Representatives, June 10, [1992,"] pg. 8. Johnson is Assistant U.S. Surgeon General with the U.S. Public Health Service.

Descriptor terms: dioxin; sexual development; linda s. birnbaum; epa; environmental hormone; richard e. peterson; mother's milk; tcdd; wisconsin; male hormones; sexual differentiation; sperm count; niosh;

#173: Dioxin--Part 2: Gauging the Toxicity of Dioxin.

=======================Electronic Edition========================

RACHEL'S HAZARDOUS WASTE NEWS #173
---March 21, 1990---
News and resources for environmental justice.
------
Environmental Research Foundation
P.O. Box 5036, Annapolis, MD 21403
Fax (410) 263-8944; Internet: erf@igc.apc.org ==========
RACHEL-4CM = DIOXIN FOCUSED DIRECTORY Remote Access Chemical Hazards Electronic Library. Dioxinnz.com =================================Original Source========================

[Continuing our series on dioxin. Page numbers in parentheses refer to the ATSDR (the federal Agency for Toxic Substances and Disease Registry) Toxicological Profile for dioxin, cited in our last paragraph, below.]

It has become fashionable to pooh-pooh dioxin. We believe there are two reasons why this is occurring. First, some scientists have been publishing studies indicating that humans exposed to dioxin do not have an increased risk of cancer. As we saw in RHWN #171, some of the most important of these studies have now been exposed as fraudulent. The second reason is that dioxin is so toxic that it is difficult to express its potency in normal terms; therefore the media frequently print scary claims without offering much evidence, leading some people to conclude (incorrectly) that there isn't much substance to any claims about the extreme toxicity of dioxin.

In this series, we hope to lay the groundwork for an understanding of dioxin, to help people put dioxin into perspective. Some of what follows may seem a bit more technical than you are accustomed to reading in this newsletter; but stick with it, and you'll see why we have taken this approach.

The scientific and medical evidence presented by ATSDR forces us to conclude that dioxin deserves our greatest respect. It seems to be one of the two or three most toxic chemicals ever discovered, and it is produced as a byproduct of several different industrial processes. For years, industry has been dumping dioxin into the environment in large quantities without paying attention to the consequences. This does not mean there have been no consequences; it just means no one has made any systematic effort to tally them up.

Dioxin is a family of chemicals (75 in all) that does not occur naturally, nor is it intentionally manufactured by any industry (pg. 1). The most toxic dioxin is called 2,3,7,8-TCDD. Dioxins are produced as byproducts of the manufacture of some herbicides (for example, 2,4,5-T), wood preservatives made from trichlorophenols, and some germicides (for example, hexachlorophene). Dioxins are also produced by the manufacture of pulp and paper, by the combustion of wood in the presence of chlorine, by fires involving chlorinated benzenes and biphenyls (e.g., PCBs), by the exhaust of automobiles burning leaded fuel, and by municipal solid waste incinerators.

ATSDR says, "2,3,7,8-TCDD is highly toxic to all laboratory animals tested...." (pg. 11). Even the most conservative of toxicologists says, "TCDD has been called the most toxic synthetic chemical known to man. If its acute toxicity to the guinea pig, and even the rat and mouse, is the criterion, the statement is probably correct.... TCDD is unquestionably a chemical of supreme toxicity to experimental animals. Moreover, severe chronic effects from low dosages have also been demonstrated in experimental animals. Therefore, the concern about its effects on human health and the environment is understandable."[1]

In cases of high exposure of humans through industrial accidents, 2,3,7,8-TCDD causes a severe acne (called chloracne) which is not just a skin ailment; chloracne is a systemic disease that is more disfiguring than teenage acne and its effects last for years (in some cases, decades) after exposure (pgs. 3, 39).

There is "suggestive evidence" that 2,3,7,8-TCDD causes liver damage in humans (pgs. 3, 52-53). It definitely causes severe liver damage in animals.

In animals, 2,3,7,8-TCDD is toxic to the immune system; such effects have not been proven in humans (pgs. 3, 40, 54-56). In animals, 2,3,7,8-TCDD causes reproductive disorders, including spontaneous abortions. Monkeys are particuarly sensitive to reproductive effects from exposure to 2,3,7,8-TCDD. Such effects have not been proven in humans (pgs. 3, 17, 58-59). In animals, dioxin causes genetic damage (pgs. 60-61).

Both the U.S. Environmental Protection Agency (EPA) and the International Agency for Research on Cancer (IARC) have concluded that dioxin is a "probable human carcinogen" (pgs. 7, 61-68, 94). As we saw in RHWN #171, scientists within EPA have asked that this question be reviewed again because some of the key studies of dioxin and cancer were fraudulent, and EPA has relied on these fraudulent studies to set current standards.

How can we judge the toxicity of dioxin (or of any chemical, for that matter)? One way is to look at the standards that have been set by regulatory agencies.

In the case of dioxin, EPA has calculated a "safe" dose, taking into consideration dioxin's ability to cause cancer. The "safe" dose is expressed in extremely small units: femtograms. There are 28 grams in an ounce, and one femtogram is 0.000,000,000,000,001 grams, or one quadrillionth of a gram, or 10**-15 (or, 10 raised to the power of negative 15) grams.

EPA believes that ingesting (eating) 6.4 femtograms (6.4 x 10**-15 grams) of 2,3,7,8-TCDD per kilogram of body weight per day would cause cancer in one in a million people so exposed (pg. 95). Since an average adult weighs 62 kilograms or 137 pounds (average men weigh 70 kilograms [154 pounds] and average women weigh 55 kg [120 pounds]), the EPA is saying that 397 femtograms of 2,3,7,8-TCDD consumed in food each day would kill one-in-a-million humans so exposed. Over a year's time, 397 femtograms per day add up to 145,000 femtograms; over a 70-year lifetime, this would add up to 10.1 million femtograms, so 10.1 million femtograms (or 0.01 micrograms) is the maximum amount you could safely get into your body during your entire lifetime, EPA believes.

How can we express this in terms that people can grasp?

Let's compare it to one single aspirin tablet. One aspirin tablet weighs 5 grains (or 325 milligrams, or 325 trillion femtograms), so to express one "safe" lifetime dose of 2,3,7,8-TCDD, you would take a single aspirin tablet and divide it into 32 million (actually 32,172,218) miniscule pieces. Then one of those tiny pieces would represent one "safe" lifetime dose of 2,3,7,8-TCDD.

Another comparison: A single grain of table salt weighs approximately 0.1 milligrams or 100 billion femtograms, so to get an amount of table salt that weighs the same amount as one "safe" lifetime dose of 2,3,7,8-TCDD, you would divide a single grain of table salt into 9,900 microscopic pieces. One of those tiny pieces would represent a "safe" lifetime dose of dioxin.

The U.S. Food and Drug Administration (FDA) has its own way of calculating the same one-in-a-million cancer risk and they believe the EPA has overestimated the hazard by a factor of 10. In other words, FDA believes you could represent a "safe" dose of 2,3,7,8-TCDD by dividing a single grain of table salt into 990 pieces, with one of those pieces representing a safe lifetime dose. The federal Centers for Disease Control (CDC) in Atlanta has done its own calculation, concluding that the cancer hazard from dioxin is about half-way between the EPA's estimate and the FDA's estimate. EPA says 6.4 femtograms per kilogram of body weight per day is the safe dose; CDC says the correct number is 27.6; FDA says it's 57.2 (pg. 95). No matter which agency does the calculation, there's no escaping the fact that dioxin is considered supremely toxic.

One other way to understand the toxicity of dioxin is to compare the dioxin "reference dose" established by EPA to the "reference dose" they have set for other common toxic materials. The "reference dose" is the highest amount they believe you could eat regularly without incurring any disease (not considering cancer).

The reference dose for dioxin is 0.000,000,001 milligrams per kilogram of body weight per day (mg/kg/day) (pg. 94); the reference dose for the toxic metal cadmium[2] is 0.001 mg/kg/day and the "reference dose" for the toxic metal arsenic[3] is the same as for cadmium.[2] Thus we can see that EPA considers dioxin in food 1,000,000 times (one million times) more toxic than cadmium or arsenic[3], not counting the cancer hazard from dioxin. Yes, dioxin is toxic, no doubt about it.

[Part 3 continued issue #175 ]

--Peter Montague, Ph.D.

Also see: Dioxin--Part 1: Gauging the Toxicity of Dioxin. #171

===============

[1] Fred H. Tschirley, "Dioxin," SCIENTIFIC AMERICAN Vol. 254 (February, 1986), pg. 34."

[2] Agency for Toxic Substances and Disease Registry, TOXICOLOGICAL PROFILE FOR CADMIUM (Springfield, VA: National Technical Information Service [NTIS], 5285 Port Royal Rd., Springfield, VA 22161; phone (703) 487-4650), pg. 76.; NTIS number PB89-194476. $21.95.

[3] Agency for Toxic Substances and Disease Registry, TOXICOLOGICAL PROFILE FOR ARSENIC (Springfield, VA: National Technical Information Service [NTIS], 5285 Port Royal Rd., Springfield, VA 22161; phone (703) 487-4650), pg. 92.; NTIS number PB89-185706. $21.95.

Get: Agency for Toxic Substances and Disease Registry, TOXICOLOGICAL PROFILE FOR 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (Springfield, VA: National Technical Information Service [NTIS], 5285 Port Royal Rd., Springfield, VA 22161; phone (703) 4874650); NTIS number PB89-214522. $21.95.

Descriptor terms: dioxin; atsdr; herbicides; wood preservatives; trichlorophenols; hexachlorophene; pulp and paper; pcbs; msw; incineration; skin disorders; liver; fda; health effects; sudies; reproductive disorders; miscarriages; genetic disorders; cancers; risk assessment; chloroacne;