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#290 - Young Male Rats Are 'Demasculinized' And 'Feminized' By Low Doses Of Dioxin, 16-Jun-1992

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

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


[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
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
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,
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 birnbaum; epa;
environmental hormones; richard peterson; breast milk; wi; androgens;
sexual differentiation; sperm count; niosh;

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