[Pharmwaste] FW: [hcwh] full text of JAMA article on endocrine disruptors

Wed, 20 Jul 2005 13:10:29 -0400

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Here's the JAMA article, thanks to Pete Myers and Kelly Heekin. Although =
it's
not talking about endocrine disruptors in water supplies, it is =
important to
note that this is another complication of the whole pharmaceutical waste
issue - the exposure can be coming from many other sources than =
contaminated
water.

=20

If you are interested, Health Care Without Harm has information on =
dioxin and
phthalates on its web site at: http://www.noharm.org/pvcDehp/issue

=20

=20

Laurie

=20

Laurie J. Tenace

Environmental Specialist

Florida Department of Environmental Protection

2600 Blair Stone Road, MS 4555

Tallahassee, Florida 32399-2400

PH: (850) 245-8759

FAX: (850) 245-8811

Laurie.Tenace@dep.state.fl.us

=20

view our mercury web pages at:=20

http://www.dep.state.fl.us/waste/categories/mercury/default.htm

=20

=20

  _____ =20

From: Kelly Heekin [mailto:kheekin@hcwh.org]=20
Sent: Wednesday, July 20, 2005 12:57 PM
To: hcwh
Subject: [hcwh] full text of JAMA article on endocrine disruptors

=20

(hcwh@lists.hcwh.org)

Thanks to Pete Myers for passing this on. Below is the full text of an
article on endocrine disruptors in the Journal of the American Medical
Association:

Endocrine-Disrupting Chemicals Probed as Potential Pathways to Illness=20

Richard Trubo=20

JAMA. 2005;294:291-293.=20

San Diego-For the last 60 years, humans have been exposed to an =
increasing
number of synthetic compounds in the environment. In fact, more than 80 =
000
chemicals are used commercially in the United States, found in products
ranging from toys and detergents to pesticides and food packaging.
Accumulating evidence that some of these widely used chemicals may have
hormonelike effects on the body is heightening concerns about their =
potential
long-term health risks, particularly when developing fetuses and =
neonates are
exposed.=20

At a day-long symposium at the Endocrine Society meeting here in June,
leading investigators shared the latest findings on the effects of these
synthetic chemicals-as well as of naturally occurring substances such as
phytoestrogens-that have been reported to have hormonelike activity and =
may
be associated with an increased susceptibility to disease and =
dysfunction.
The potential danger is greatest for "the fragile fetus" (a term coined =
more
than a decade ago by University of California at Berkeley =
endocrinologist
Howard Bern, PhD) and the neonate, which are particularly sensitive to
perturbations by endocrine-disrupting chemicals.=20

But such effects are often not apparent for years. "Exposure to =
chemicals
with endocrine-disrupting activity during critical stages of =
differentiation
may have permanent consequences that may not be expressed or detected =
until
later in life," said Retha R. Newbold, MS, head of developmental
endocrinology studies in the Laboratory of Molecular Toxicology at the
National Institute of Environmental Health Sciences. There is now =
greater
recognition, she added, that the developing organism may be especially
vulnerable to endocrine-disrupting chemicals because of such factors as
deficiencies in DNA repair mechanisms, detoxification enzymes that are =
not
completely functional, and a blood-brain barrier that is still being =
formed.=20

EXPOSURE TO PHTHALATES=20

Phthalates, a ubiquitous group of chemicals used in hundreds of =
products,
including soft vinyl plastic toys, shampoos, soaps, nail polish, vinyl
flooring, and pharmaceuticals, are being scrutinized for potentially =
harmful
effects during development. Shanna Swan, PhD, an epidemiologist and =
professor
of obstetrics and gynecology at the University of Rochester School of
Medicine and Dentistry, described her recent study of the effects of
phthalates in humans, the first to show a significant relationship =
between
maternal exposure to phthalates and adverse reproductive development in =
male
offspring. =
<http://jama.ama-assn.org/cgi/content/full/294/3/291#JMN50080F1> =20

The scope of human exposure to phthalates had previously been shown in =
data
from the National Health and Nutrition Examination Survey (NHANES =
1999-2000),
in which more than 75% of urine samples tested had measurable levels of
phthalate metabolites (Silva et al. Environ Health Perspect.
2004;112:331-338). Research at the Harvard School of Public Health had
provided human data showing a dose-response relationship between urine =
levels
of phthalate metabolites and sperm motility and concentrations (Duty et =
al.
Epidemiology. 2003;14:269-277).=20

Swan and her colleagues evaluated women who had been recruited to =
participate
in a multicenter pregnancy cohort study (the Study for Future Families).
Focusing on 85 eligible mother-son pairs, the researchers determined the
presence and levels of nine phthalate metabolites in the urine of =
mothers
during late pregnancy. Then, in the male offspring of these women,
researchers measured the so-called anogenital distance (AGD)-the =
distance
from the center of the anal opening to the anterior base of the penis or =
the
clitoris. The AGD, she said, is a sexually dimorphic measure; in =
rodents, it
has been found to be a sensitive indicator of masculinization, with AGDs
about twice as long in males as in females.=20

Findings by Swan's group showed a significant inverse association =
between
human AGD and concentrations of four phthalate metabolites. The higher =
the
levels of these four metabolites in maternal prenatal urine, the shorter =
the
infant's relative AGD. Eleven of 12 boys with the highest combined =
phthalate
exposure had AGDs below the 25th percentile for age and weight. A =
shorter AGD
was associated with incomplete testicular descent and smaller penile =
volume.
These findings, she said, are similar to those seen in rodent studies =
and
suggest that endocrine-disrupting compounds may play a role in the
undervirilization of males.=20

According to Swan, the pattern of genital changes observed in the boys =
in her
study are consistent with the "phthalate syndrome" described in rodents
exposed prenatally to phthalates. In addition to decreased AGD, the =
syndrome
is characterized by testicular, epididymal, and gubernacular cord =
agenesis.=20

RISKS OF BISPHENOL A=20

Another substance under scrutiny is the estrogenic compound bisphenol A
(BPA), which is found in products like baby bottles, food containers, =
and
dental sealants. About 6.4 billion pounds of it are manufactured =
worldwide
each year, and a recent report from the Centers for Disease Control and
Prevention noted that 95% of urine samples in a reference population of =
394
adults in the United States had measurable levels of BPA (Calafat et al.
Environ Health Perspect. 2005;113:391-395).=20

While the plastics industry has described BPA as highly durable, =
scientists
like Frederick vom Saal, PhD, contend that under everyday conditions, =
BPA in
products like polycarbonate plastic containers and tin cans leaches into =
food
and beverages. "A number of studies show that structural damage to a =
variety
of organs occurs as a result of fetal exposure to very low doses of =
bisphenol
A," added vom Saal, professor of biological sciences at University of
Missouri-Columbia. "When BPA in the low parts per trillion range is in
contact with human or animal cells, it will alter cell function. The =
range of
human exposure is as much as 100 to 1000 times higher than this."=20

In a recent study, estrogenic chemicals including BPA (10 =B5g/kg per =
day) were
fed to pregnant mice, a dose that is lower than the typical exposure in
pregnant women. Researchers found that BPA was associated with prostate
changes in the developing fetal mouse that are predictive of an =
increased
risk of cancer later in life (Timms et al. Proc Natl Acad Sci U S A.
2005;102:7014-7019).=20

A separate animal study, published on May 26 in the online edition of
Endocrinology, evaluated perinatal exposure to very low doses of BPA and =
the
effect of this compound on pubertal development of the mammary gland. =
The
study found persistent changes in mammary gland morphogenesis that may =
be
suggestive of an increased risk of breast cancer. Study coauthor Ana M. =
Soto,
PhD, professor in the department of anatomy and cellular biology at =
Tufts
University School of Medicine, said that these findings are =
"particularly
worrisome since the incidence of breast cancer has increased in the =
developed
world and has increased parallel to the introduction of endocrine =
disruptors
such as BPA into the environment."=20

CROSSING GENERATIONS=20

Endocrine disruptors may do more than pose risks in the offspring of =
mothers
exposed during pregnancy. Michael K. Skinner, PhD, director of the =
Center for
Reproductive Biology at Washington State University, described exposing
pregnant rats at mid gestation (the time of gonadal sex determination in =
the
embryo) to two endocrine-disrupting compounds-the antiandrogenic =
fungicide
vinclozolin (used in wine vineyards) and the estrogenic pesticide
methoxychlor (used to replace DDT). This transient embryonic exposure =
caused
an adult disease of subfertility related to increased apoptosis of
spermatogenic cells (Anway et al. Science. 2005;308:1466-1469).=20

In the vinclozolin group (which involved a dose of vinclozolin [100 =
mg/kg per
day] that is relatively low compared with most in vivo studies but =
higher
than environmental levels), the animals were then bred for four =
subsequent
generations. "Surprisingly, each generation of animal had the same =
disease
state, even though those animals were never exposed to the toxin," said
Skinner. "So it appears we have endocrine receptor-induced disease =
that's
permanent to the lineage. With an environmental toxin, we've induced a
disease state that is inherited in greater than 90% of all the males in
subsequent generations, even though the exposure occurred only once in =
the
original gestating mother."=20

Skinner referred to this finding as "a new paradigm" for thinking about =
the
hazards of environmental toxins. In explaining the possible mechanism =
for
this transgenerational effect, he pointed to altered DNA methylation
(attachments of methyl groups to DNA) and permanent, epigenetic =
reprogramming
(changes in the expression of a gene or genes achieved by factors other =
than
changes in the DNA sequence) of the male germline.=20

CAUTION WITH GENISTEIN?=20

Not all substances capturing the interest of researchers studying
endocrine-disrupting compounds are synthetic. One plant compound of =
interest,
genistein, is a natural phytoestrogen and the major isoflavone in soy
products. In fact, infants consuming soy-based infant formulas are =
taking in
levels high enough to raise red flags about possible risks of =
developmental
exposure.=20

In a recent animal study published on June 1 in the online edition of =
Biology
of Reproduction, investigators administered genistein to neonates in =
doses of
0.5, 5, or 50 mg/kg per day. In animals receiving the highest dose of
genistein for the first 5 days after birth, there were morphological =
changes
in the ovary (including the presence of multi-oocyte follicles) that =
were
associated with a 35% incidence of uterine tumors in animals at 18 =
months of
age.=20

"These animals had premature reproductive senescence," said Newbold. =
"Their
ovaries were malformed and not completely functional."=20

According to one report, the daily exposure of human infants to =
isoflavones
in soy-based infant formulas is 6 to 11 times higher (based on body =
weight)
than the dose that produces hormonal effects in adults consuming soy =
foods
(Setchell et al. Lancet. 1997;350:23-27). But for now, said Newbold,
researchers don't know how animal findings about genistein translate to =
the
human population. "I think we have to be cautious," she added. "Humans =
are
exposed to a number of estrogenic or endocrine-disrupting compounds and =
it
makes sense to decrease those exposures as much as possible."=20

INDUSTRY RESPONSE=20

In the aftermath of the release of Swan's study of phthalates, the =
American
Chemistry Council's Phthalate Esters Panel issued a statement asserting,
"Initial analyses indicate that the [Swan] study has many weaknesses,
suggesting that the study may not stand up under rigid scientific =
scrutiny.
The authors themselves stated that the results need to be validated."=20

Meanwhile, a Web site sponsored by the Bisphenol A Global Industry Group =
of
the American Plastics Council highlights a 2004 review by a panel of
researchers convened by the Harvard Center for Risk Analysis-and funded =
by
the American Plastics Council-in which the panel "found no consistent
affirmative evidence of low-dose BPA effects for any endpoint."=20

Even so, a bill has been introduced in the California state legislature =
(AB
319) by Assembly member Wilma Chan (D, Oakland) that would ban the use =
of BPA
and phthalates in toys and childcare products designed for infants and
children younger than 3 years of age. Hearings on the bill are pending.=20

"The EPA [Environmental Protection Agency] is struggling with the idea =
of
what levels are acceptable for each of these compounds," said Newbold.
"Everybody is taking them seriously-but we need a lot more research."=20

---
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<div class=3DSection1>

Here&#8217;s the JAMA article, =
thanks to Pete
Myers and Kelly Heekin. Although it&#8217;s not talking about endocrine
disruptors in water supplies, it is important to note that this is =
another
complication of the whole pharmaceutical waste issue &#8211; the =
exposure can
be coming from many other sources than contaminated =
water.

<p class=3DMsoNormal><font size=3D2 color=3Dnavy face=3DArial><span =
style=3D'font-size:
10.0pt;font-family:Arial;color:navy'>&nbsp;</span></font></p>

<p class=3DMsoNormal><font size=3D2 color=3Dnavy face=3DArial><span =
style=3D'font-size:
10.0pt;font-family:Arial;color:navy'>If you are interested, Health Care =
Without
Harm has information on dioxin and phthalates on its web site at: <a
href=3D"http://www.noharm.org/pvcDehp/issue">http://www.noharm.org/pvcDeh=
p/issue</a></span></font></p>

<p class=3DMsoNormal><font size=3D2 color=3Dnavy face=3DArial><span =
style=3D'font-size:
10.0pt;font-family:Arial;color:navy'>&nbsp;</span></font></p>

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10.0pt;font-family:Arial;color:navy'>&nbsp;</span></font></p>

<p class=3DMsoNormal><font size=3D2 color=3Dnavy face=3DArial><span =
style=3D'font-size:
10.0pt;font-family:Arial;color:navy'>Laurie</span></font></p>

<p class=3DMsoNormal><font size=3D2 color=3Dnavy face=3DArial><span =
style=3D'font-size:
10.0pt;font-family:Arial;color:navy'>&nbsp;</span></font></p>

<div>

Laurie J. Tenace

<p class=3DMsoNormal><font size=3D2 color=3Dnavy face=3DArial><span =
style=3D'font-size:
10.0pt;font-family:Arial;color:navy'>Environmental =
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<p class=3DMsoNormal><b><font size=3D2 face=3DTahoma><span =
style=3D'font-size:10.0pt;
font-family:Tahoma;font-weight:bold'>From:</span></font></b><font =
size=3D2
face=3DTahoma><span style=3D'font-size:10.0pt;font-family:Tahoma'> Kelly =
Heekin
[mailto:kheekin@hcwh.org] <br>
<b><span style=3D'font-weight:bold'>Sent:</span></b> Wednesday, July 20, =
2005
12:57 PM<br>
<b><span style=3D'font-weight:bold'>To:</span></b> hcwh<br>
<b><span style=3D'font-weight:bold'>Subject:</span></b> [hcwh] full text =
of JAMA
article on endocrine disruptors</span></font></p>

</div>

<p class=3DMsoNormal><font size=3D3 face=3D"Times New Roman"><span =
style=3D'font-size:
12.0pt'>&nbsp;</span></font></p>

<p class=3DMsoNormal><font size=3D3 face=3D"Times New Roman"><span =
style=3D'font-size:
12.0pt'>(hcwh@lists.hcwh.org)</span></font></p>

<div>

Thanks to Pete Myers for passing this on. Below is =
the full
text of an article on endocrine disruptors in the Journal of the =
American
Medical Association:

</div>

<p class=3DMsoNormal><b><font size=3D4 color=3D"#003366" =
face=3DVerdana><span
style=3D'font-size:13.5pt;font-family:Verdana;color:#003366;font-weight:b=
old'>Endocrine-Disrupting
Chemicals Probed as Potential Pathways to Illness </span></font></b></p>

<p><font size=3D2 face=3DVerdana><span =
style=3D'font-size:10.0pt;font-family:Verdana'>Richard
Trubo </span></font></p>

<p><i><font size=3D2 face=3DVerdana><span =
style=3D'font-size:10.0pt;font-family:Verdana;
font-style:italic'>JAMA.</span></font></i><font size=3D2 =
face=3DVerdana><span
style=3D'font-size:10.0pt;font-family:Verdana'>&nbsp;2005;294:291-293. =
</span></font></p>

San Diego&#8212;</=
span>For the
last 60 years, humans have been exposed to an increasing =
number of
synthetic compounds in the environment. In fact, more than
80&nbsp;000 chemicals are used commercially in the United =
States, found in products ranging from toys and detergents to =
pesticides
and food packaging. Accumulating evidence that some of these =
widely
used chemicals may have hormonelike effects on the body is
heightening concerns about their potential long-term health =
risks,
particularly when developing fetuses and neonates are =
exposed.

<p><font size=3D2 face=3DVerdana><span =
style=3D'font-size:10.0pt;font-family:Verdana'>At
a day-long symposium at the Endocrine Society meeting here<sup> </sup>in =
June,
leading investigators shared the latest findings on<sup> </sup>the =
effects of
these synthetic chemicals&#8212;as well as of<sup> </sup>naturally =
occurring
substances such as phytoestrogens&#8212;that<sup> </sup>have been =
reported to
have hormonelike activity and may be associated<sup> </sup>with an =
increased
susceptibility to disease and dysfunction.<sup> </sup>The potential =
danger is
greatest for &quot;the fragile fetus&quot; (a<sup> </sup>term coined =
more than
a decade ago by University of California<sup> </sup>at Berkeley =
endocrinologist
Howard Bern, PhD) and the neonate,<sup> </sup>which are particularly =
sensitive
to perturbations by endocrine-disrupting<sup> </sup>chemicals.<sup> =
</sup></span></font></p>

But
such effects are often not apparent for years. &quot;Exposure =
to
chemicals with endocrine-disrupting activity during critical =
stages
of differentiation may have permanent consequences that may =
not be
expressed or detected until later in life,&quot; said Retha =
R.
Newbold, MS, head of developmental endocrinology studies in =
the
Laboratory of Molecular Toxicology at the National Institute =
of
Environmental Health Sciences. There is now greater recognition, =
she
added, that the developing organism may be especially vulnerable =
to
endocrine-disrupting chemicals because of such factors as =
deficiencies
in DNA repair mechanisms, detoxification enzymes that are not
completely functional, and a blood-brain barrier that is =
still being
formed.

<p><b><font size=3D2 color=3D"#003366" face=3DVerdana><span =
style=3D'font-size:10.0pt;
font-family:Verdana;color:#003366;font-weight:bold'>EXPOSURE TO =
PHTHALATES</span></font></b><font
size=3D2 face=3DVerdana><span =
style=3D'font-size:10.0pt;font-family:Verdana'> </span></font><br>
<br>
<font size=3D2 face=3DVerdana><span =
style=3D'font-size:10.0pt;font-family:Verdana'>Phthalates,
a ubiquitous group of chemicals used in hundreds<sup> </sup>of products,
including soft vinyl plastic toys, shampoos, soaps,<sup> </sup>nail =
polish,
vinyl flooring, and pharmaceuticals, are being<sup> </sup>scrutinized =
for
potentially harmful effects during development.<sup> </sup>Shanna Swan, =
PhD, an
epidemiologist and professor of obstetrics<sup> </sup>and gynecology at =
the
University of Rochester School of Medicine<sup> </sup>and Dentistry, =
described
her recent study of the effects of<sup> </sup>phthalates in humans, the =
first
to show a significant relationship<sup> </sup>between maternal exposure =
to
phthalates and adverse reproductive<sup> </sup>development in male =
offspring.</span></font><a
href=3D"http://jama.ama-assn.org/cgi/content/full/294/3/291#JMN50080F1"><=
/a><sup><font
size=3D2 face=3DVerdana><span =
style=3D'font-size:10.0pt;font-family:Verdana'> </span></font></sup></p>

The
scope of human exposure to phthalates had previously been =
shown in
data from the National Health and Nutrition Examination =
Survey
(NHANES 1999-2000), in which more than 75% of urine samples =
tested
had measurable levels of phthalate metabolites (Silva et al. =
Environ Health Perspect.
2004;112:331-338). Research at the Harvard School of Public =
Health
had provided human data showing a dose-response relationship =
between
urine levels of phthalate metabolites and sperm motility and
concentrations (Duty et al. Epidemiology.
2003;14:269-277).

Swan
and her colleagues evaluated women who had been recruited to
participate in a multicenter pregnancy cohort study (the =
Study for
Future Families). Focusing on 85 eligible mother-son pairs, =
the
researchers determined the presence and levels of nine =
phthalate
metabolites in the urine of mothers during late pregnancy. =
Then, in
the male offspring of these women, researchers measured the
so-called anogenital distance (AGD)&#8212;the distance from =
the
center of the anal opening to the anterior base of the penis =
or the
clitoris. The AGD, she said, is a sexually dimorphic measure; =
in
rodents, it has been found to be a sensitive indicator of
masculinization, with AGDs about twice as long in males as in
females.

Findings
by Swan&#8217;s group showed a significant inverse =
association
between human AGD and concentrations of four phthalate =
metabolites.
The higher the levels of these four metabolites in maternal =
prenatal
urine, the shorter the infant&#8217;s relative AGD. Eleven of =
12
boys with the highest combined phthalate exposure had AGDs =
below the
25th percentile for age and weight. A shorter AGD was =
associated
with incomplete testicular descent and smaller penile volume. =
These
findings, she said, are similar to those seen in rodent =
studies and
suggest that endocrine-disrupting compounds may play a role =
in the
undervirilization of males.

According
to Swan, the pattern of genital changes observed in the boys =
in her
study are consistent with the &quot;phthalate syndrome&quot; =
described
in rodents exposed prenatally to phthalates. In addition to
decreased AGD, the syndrome is characterized by testicular, =
epididymal,
and gubernacular cord agenesis.

<p><b><font size=3D2 color=3D"#003366" face=3DVerdana><span =
style=3D'font-size:10.0pt;
font-family:Verdana;color:#003366;font-weight:bold'><br>
RISKS OF BISPHENOL A</span></font></b><font size=3D2 =
face=3DVerdana><span
style=3D'font-size:10.0pt;font-family:Verdana'> </span></font></p>

Another
substance under scrutiny is the estrogenic compound bisphenol =
A
(BPA), which is found in products like baby bottles, food
containers, and dental sealants. About 6.4 billion pounds of =
it are
manufactured worldwide each year, and a recent report from =
the
Centers for Disease Control and Prevention noted that 95% of =
urine
samples in a reference population of 394 adults in the United =
States had measurable levels of BPA (Calafat et al. Environ Health Perspect.
2005;113:391-395).

While
the plastics industry has described BPA as highly durable, =
scientists
like Frederick vom Saal, PhD, contend that under everyday
conditions, BPA in products like polycarbonate plastic =
containers
and tin cans leaches into food and beverages. &quot;A number =
of
studies show that structural damage to a variety of organs =
occurs as
a result of fetal exposure to very low doses of bisphenol =
A,&quot;
added vom Saal, professor of biological sciences at =
University of
Missouri-Columbia. &quot;When BPA in the low parts per =
trillion
range is in contact with human or animal cells, it will alter =
cell
function. The range of human exposure is as much as 100 to =
1000
times higher than this.&quot;

In
a recent study, estrogenic chemicals including BPA (10 =B5g/kg =
per
day) were fed to pregnant mice, a dose that is lower than the
typical exposure in pregnant women. Researchers found that =
BPA was
associated with prostate changes in the developing fetal =
mouse that
are predictive of an increased risk of cancer later in life =
(Timms
et al. Proc Natl Acad Sci U S =
A.
2005;102:7014-7019).

A
separate animal study, published on May 26 in the online edition =
of Endocrinology, evaluated =
perinatal
exposure to very low doses of BPA and the effect of this =
compound on
pubertal development of the mammary gland. The study found
persistent changes in mammary gland morphogenesis that may be
suggestive of an increased risk of breast cancer. Study =
coauthor Ana
M. Soto, PhD, professor in the department of anatomy and =
cellular
biology at Tufts University School of Medicine, said that =
these
findings are &quot;particularly worrisome since the incidence =
of
breast cancer has increased in the developed world and has =
increased
parallel to the introduction of endocrine disruptors such as =
BPA
into the environment.&quot;

<p><b><font size=3D2 color=3D"#003366" face=3DVerdana><span =
style=3D'font-size:10.0pt;
font-family:Verdana;color:#003366;font-weight:bold'><br>
CROSSING GENERATIONS</span></font></b><font size=3D2 =
face=3DVerdana><span
style=3D'font-size:10.0pt;font-family:Verdana'> </span></font></p>

Endocrine
disruptors may do more than pose risks in the offspring of =
mothers
exposed during pregnancy. Michael K. Skinner, PhD, director =
of the
Center for Reproductive Biology at Washington State =
University,
described exposing pregnant rats at mid gestation (the time =
of
gonadal sex determination in the embryo) to two =
endocrine-disrupting
compounds&#8212;the antiandrogenic fungicide vinclozolin =
(used in
wine vineyards) and the estrogenic pesticide methoxychlor =
(used to
replace DDT). This transient embryonic exposure caused an =
adult
disease of subfertility related to increased apoptosis of
spermatogenic cells (Anway et al. Science.
2005;308:1466-1469).

In
the vinclozolin group (which involved a dose of vinclozolin =
[100
mg/kg per day] that is relatively low compared with most in =
vivo
studies but higher than environmental levels), the animals =
were then
bred for four subsequent generations. &quot;Surprisingly, =
each
generation of animal had the same disease state, even though =
those
animals were never exposed to the toxin,&quot; said Skinner. =
&quot;So
it appears we have endocrine receptor&#8211;induced disease =
that&#8217;s
permanent to the lineage. With an environmental toxin, =
we&#8217;ve
induced a disease state that is inherited in greater than 90% =
of all
the males in subsequent generations, even though the exposure
occurred only once in the original gestating =
mother.&quot;

Skinner
referred to this finding as &quot;a new paradigm&quot; for thinking =
about
the hazards of environmental toxins. In explaining the =
possible
mechanism for this transgenerational effect, he pointed to =
altered
DNA methylation (attachments of methyl groups to DNA) and =
permanent,
epigenetic reprogramming (changes in the expression of a gene =
or
genes achieved by factors other than changes in the DNA =
sequence) of
the male germline.

<p><b><font size=3D2 color=3D"#003366" face=3DVerdana><span =
style=3D'font-size:10.0pt;
font-family:Verdana;color:#003366;font-weight:bold'><br>
CAUTION WITH GENISTEIN?</span></font></b><font size=3D2 =
face=3DVerdana><span
style=3D'font-size:10.0pt;font-family:Verdana'> </span></font></p>

Not
all substances capturing the interest of researchers studying =
endocrine-disrupting
compounds are synthetic. One plant compound of interest, =
genistein,
is a natural phytoestrogen and the major isoflavone in soy =
products.
In fact, infants consuming soy-based infant formulas are =
taking in
levels high enough to raise red flags about possible risks of
developmental exposure.

In
a recent animal study published on June 1 in the online edition =
of Biology of Reproduction, =
investigators
administered genistein to neonates in doses of 0.5, 5, or 50 =
mg/kg
per day. In animals receiving the highest dose of genistein =
for the
first 5 days after birth, there were morphological changes in =
the
ovary (including the presence of multi-oocyte follicles) that =
were
associated with a 35% incidence of uterine tumors in animals =
at 18
months of age.

&quot;These
animals had premature reproductive senescence,&quot; said =
Newbold.
&quot;Their ovaries were malformed and not completely =
functional.&quot;

According
to one report, the daily exposure of human infants to =
isoflavones in
soy-based infant formulas is 6 to 11 times higher (based on =
body
weight) than the dose that produces hormonal effects in =
adults
consuming soy foods (Setchell et al. Lancet.
1997;350:23-27). But for now, said Newbold, researchers =
don&#8217;t know
how animal findings about genistein translate to the human =
population.
&quot;I think we have to be cautious,&quot; she added. &quot;Humans =
are
exposed to a number of estrogenic or endocrine-disrupting =
compounds
and it makes sense to decrease those exposures as much as
possible.&quot;

<p><b><font size=3D2 color=3D"#003366" face=3DVerdana><span =
style=3D'font-size:10.0pt;
font-family:Verdana;color:#003366;font-weight:bold'><br>
INDUSTRY RESPONSE</span></font></b><font size=3D2 face=3DVerdana><span
style=3D'font-size:10.0pt;font-family:Verdana'> </span></font></p>

In
the aftermath of the release of Swan&#8217;s study of phthalates, =
the
American Chemistry Council&#8217;s Phthalate Esters Panel =
issued a
statement asserting, &quot;Initial analyses indicate that the =
[Swan]
study has many weaknesses, suggesting that the study may not =
stand
up under rigid scientific scrutiny. The authors themselves =
stated
that the results need to be validated.&quot; =

<p><font size=3D2 face=3DVerdana><span =
style=3D'font-size:10.0pt;font-family:Verdana'>Meanwhile,
a Web site sponsored by the Bisphenol A Global Industry<sup> </sup>Group =
of the
American Plastics Council highlights a 2004 review<sup> </sup>by a panel =
of
researchers convened by the Harvard Center for<sup> </sup>Risk
Analysis&#8212;and funded by the American Plastics Council&#8212;in<sup> =
</sup>which
the panel &quot;found no consistent affirmative evidence of<sup> =
</sup>low-dose
BPA effects for any endpoint.&quot;<sup> </sup></span></font></p>

Even
so, a bill has been introduced in the California state =
legislature
(AB 319) by Assembly member Wilma Chan (D, Oakland) that =
would ban
the use of BPA and phthalates in toys and childcare products
designed for infants and children younger than 3 years of =
age.
Hearings on the bill are pending.

&quot;The
EPA [Environmental Protection Agency] is struggling with the =
idea of
what levels are acceptable for each of these compounds,&quot; =
said
Newbold. &quot;Everybody is taking them seriously&#8212;but =
we need
a lot more research.&quot;

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