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Environmental Estrogens (EEs)
Hormonally Active Agents (HAAs)
Hormone Disrupting Chemicals
Xeno-Estrogens
Research
EPA recognizes that organochlorine pesticides, such as lindane, may cause
endocrine disruption that may be associated with human or ecological risk
concerns. The Agency is currently developing a strategy to look at the
remaining registered organochlorine pesticides as a group to examine their role
as potential endocrine disruptors. Although EPA is closing the Special Review of
lindane for kidney effects, the findings from a comprehensive examination of
this group of chemicals could lead to further regulatory action on lindane. (For
further information see: Lindane - Decision Not to Initiate a Special Review on
Kidney Effects, 60 Federal Register 38329, July 26, 1995) [Internet: http://www.epa.gov/fedrgstr/EPA-PEST/1995/July/Day-26/pr-347.html]
Hormonally Active Agents in the Environment
In humans, results of cognitive and neurobehavioral studies of mother-infant
cohorts accidently exposed to high concentrations of PCBs and PCDFs and of
mother-infant cohorts eating contaminated fish and other food products
containing mixtures of PCBs, dioxin, and pesticides (such as DDE, dieldrin, and lindane)
provide evidence that prenatal exposure to these HAAs can affect the developing
nervous system. Similarly, monkeys exposed to PCBs in utero and during lactation
have deficits in cognitive function when assessed at 14 months post-exposure and
rats and mice exposed prenatally to PCBs suffer impaired locomotor ability and
learning.
http://www.nap.edu/html/hormonal_agents/
Lindane is an organochlorine pesticide which is under a great deal of
regulatory pressure around the world. On the 13th July 2000 an EU regulatory
committee voted to ban agricultural uses of Lindane in Europe - though it can
still be used in some other products, such as ant killer [26]. It is a
persistent pollutant, and is found in human breast milk [27]. The oestrogenic
properties of lindane have been demonstrated in several systems, including the
production of vitellogenin (egg yolk protein) and zona radiata (egg shell
protein) in primary hepatocyctes (liver cells) from Atlantic salmon (Salmo
salar L.) [28]. Lindane has also been shown to damage human spermatozoa
at concentrations as low as those found in female genital tract secretions [29].
Introduction to Hormone Disrupting Chemicals
Does yo-yo dieting pose cancer threat?
Indeed, contends Davis, the fact that lindane is still used on
children to kill head lice "is appalling."
http://www.sciencenews.org/sn_arc97/3_15_97/fob1.htm
The Effects of estrogenic pesticides on the
development of the reproductive tissue in Mammals and Birds
Estrogenic pesticides can have detrimental reproductive effects
on adult animals. Chronic exposure of rhesus monkeys to dioxin causes a
dosage-dependent increase in the severity and occurrence of endometriosis. (Rier
et al., 1995) Endometriosis is characterized by chronic pain, infertility and
adhesion formation. Estrogens cause the proliferation of endometrial cells in
proestrus and also cause the proliferation and bleeding of ectopic endometrial
cells.(Stancel et al., 1995) The pain and ovarian cysts make the monkey
incapable to breed. Similar condition can be found in six million woman. In
another study, kepone was administered to sexually active rats just before
ovulation and after ovulation.(Brown et al., 1991) In both cases, the rats
showed a rapid decrease in precopulatory and receptivity behaviours. ovulation
was also suppressed. In a study by Bradlow and his colleagues(1995), they found
that organochlorine pesticides increase the breakdown of estrogen into
16u-Hydroxyestrone, which cause uncontrolled cell proliferation. This cell
proliferation is one the leading cause of pesticide induce breast and
endometrial cancers. Adult males also can suffered for the accumulation of
pesticides in their diet and bodies. An investigation into the reproductive
performance of man exposed to pesticides in the work showed that there was
significant decrease frequency of live births and stillbirths, neonatal deaths
and congenital defects in the children of exposed man compared to control
group.(Rupa et al., 1991) The men also have decreased fertility and increased
incidence of abnormal sperm and dead sperm. A study by Leonard Nelson (1990)
show that dieldrin and mirex stimulates swimming in sea urchin sperm and lindane
inhibits sperm motility. In different study showed that mirex caused testicular
atrophy in humans.(Nelson, 1990) In birds, organochlorine accumulation causes
eggshell thinning by inhibition of calcium ATPase as well as decreased
incubation attentiveness, territorial defence and impairment of chick- rearing
behaviours.(Fry, 1995) All this deficiencies cause a reduction in the
reproductive fitness of the birds. An number of studies were conducted on adult
male rats on the effects of different pesticide on testicular function. The
pesticide methoxychlor cause decrease sperm motility, body weight and slight
decrease in sperm count.(Linder et al., 1992) The fungicide benomyl produced
premature release of germ cells, testicular swelling and occlusion of efferent
ductules. Seminiferous tubular atrophy was also observed.(Hess et al., 1991) In
one study showed that lindane feed to twenty-one day old male rats resulted in
the inhibition of spermatogenesis, proliferation of Leydig cells and
degeneration of seminiferous tubule lumens at the highest dosage
level.(Chowdhury et al., 1987)
http://kali.usask.ca/essay96/B364-10.html
Substances interfering with the endocrine system
A footnote on page 1 of the Wingspread Statement says,
"Chemicals known to disrupt the endocrine system include: DDT and its
degradation products, DEHP (di(2-ethylhexyl)phthalate), dicofol, HCB (hexachlorobenzene),
kelthane, kepone, lindane and other hexachlorocyclohexane congeners,
methoxychlor, octachlorostyrene, synthetic pyrethroids, triazine herbicides,
EBDC fungicides, certain PCB congeners, 2,3,7,8-TCDD and other dioxins,
2,3,7,8-TCDF and other furans, cadmium, lead, mercury, tributyltin and other
organo-tin compounds, alkyl phenols (non-biodegradable detergents and
anti-oxidants present in modified polystyrene and PVCs), styrene dimers and
trimers, soy products, and laboratory animal and pet food products."
http://db.rtk.net/E3621T132
Assessing reproductive toxicity based on
zonagenetic assays of xenoestrogens, and new concepts concerning animal
gestation
B.Th. Walther
Dept. of Molecular Biology, Univ. of Bergen, N-5020 Bergen, NORWAY
Female sexual maturation proceeds by pivotal hepatic biosynthetic processes
under the control of estrogens. In fish, oogenesis involves both zonagenesis and
vitellogenesis, forming the bulk of the eggshell (zona) and yolk, respectievely
(Walther 1993). Estradiol induces mRNAs for zona radiata proteins (zrp;
Oppen-Berntsen et al. 1990) and for vitellogenin (vtg), by interacting with
hepatic estrogen receptor, followed by protein synthesis.
Such inductions also occur in primary cultures of hepatocytes from juvenile
Atlantic salmon, which secrete zrp and vtg into the culture medium (Oppen-Berntsen
et al. 1992). In vivo, zrp and vtg are transported in the blood for
specific uptake by the ovaries (Oppen-Berntsen et al. 1994). Recent evidence
shows that zonagenesis occurs in response to lower levels of estradiol than are
required to initiate vitellogenesis in juvenile Atlantic salmon (Celius &
Walther 1998). Zonagenesis may be initiated already at levels approximating
those sufficient for induction of hepatic estrogen receptor (ER). Furthermore,
at high levels of estradiol, vitellogenesis appears to be somewhat delayed
compared to zonagenesis. The finding of zonagenesis induced at putatively
constitutive ER-levels, points to initiation of puberty by non-classical steroid
signal pathways (Celius & Walther, unpubl.).
In analogy to Sumpter & Jobling (1995), we used in vitro induction of
zonagenesis to assess the estrogenic potential by xenobiotics and mycotoxins (Celius
et al. 1999). Zonagenesis provides an alternate and supplementary assay for
rapid assessment of xenoestrogenicity, as shown in vivo for xenobiotics
such as nonylphenol (Arukwe et al. 1997). Nonylphenol, lindane, bisphenol
A, and DDT, as well as zearalenone, and both isomers of zearalenol, all induced
zonagenesis in vitro, albeit with various potencies. The relative
activities of the zearalenol isomers compared to their in vivo activity.
Results from this assay may rationalize how various xenobiotics, despite their
highly disparate molecular structures (e.g. lindane & DDT), may all
exhibit the biological property of estrogenicity.
Finally, the reproductive relevance of zonagenesis is discussed in the context
of the evolution of vertebrate gestation, and of sexual reproduction (Walther
1993; 1998). Zonagenesis may protect vertebrate gestation in fish, reptiles and
mammals, but zrp-deposition reflects the evolution of the female reproductive
tract (Walther 1999). If zonagenesis exists in all vertebrates, it may be a
common biomarker for xenoestrogenic action in vertebrates. Since zonagenesis was
thought to be more limited than vitellogenesis, this conclusion is surprising.
http://www.eawag.ch/courses/eedc/abstracts.html
ENDOCRINE DISRUPTORS: EPIDEMIOLOGIC APPROACHES Release Date:
June 12, 2000 RFA: OH-01-001 National Institute for Occupational Safety and
Health (NIOSH), Center for Disease Control and Prevention (CDC) National Center
for Environmental Research (NCER), U.S. Environmental Protection Agency (EPA)
National Cancer Institute (NCI), National Institutes of Health National
Institute of Environmental Health Sciences (NIEHS), National Institutes of
Health Letter of Intent Receipt Date: August 11, 2000 Application Receipt Date:
September 22, 2000 THIS RFA USES THE "MODULAR GRANT" AND
"JUST-IN-TIME" CONCEPTS. IT INCLUDES DETAILED MODIFICATIONS TO
STANDARD APPLICATION INSTRUCTIONS THAT MUST BE USED WHEN PREPARING APPLICATIONS
IN RESPONSE TO THIS RFA.
http://grants.nih.gov/grants/guide/rfa-files/RFA-OH-01-001.html
BIRTH DEFECTS OF THE PENIS AND TESTICLES RISING IN EUROPE,
THE U.S., AND JAPAN
Paulozzi LJ. International trends in rates of hypospadias and
cryptorchidism. Environmental Health Perspectives 1999; 107 (4):
297-302.
Data from the International Clearinghouse for Birth Defects Monitoring
Systems on rates of cryptorchidism and hypospadias reveal trends in the
diagnosis of these two defects over the past few decades. Marked increases in
the diagnosis of hypospadias occurred in two American birth defects registries,
and in Scandinavia and Japan, with some evidence of leveling-off after 1985.
Increases in hypospadias were not seen in less affluent nations. Increases in
cryptorchidism were only seen in two U.S. systems and in South America. It is
not clear if these trends reflect increasing diagnosis and reporting of these
male genital defects, or if there is a real increase. Both cryptorchidism and
hypospadias reflect disruption of the normal maturation process of the male
reproductive tract during a specific period of vulnerability during gestation.
Estrogenic or anti-androgenic agents, including some environmental chemicals,
can cause these defects in laboratory animals.
http://www.med.harvard.edu/chge/toxics11.html#birth
Professor Jean Golding and her colleagues at Bristol's Institute of Child
Health, in research commissioned by the BBC in Bristol, has suggested that
hypospadias is more common in the male offspring of vegetarian mothers.
Hypospadias is the name given to a physical abnormality of the penis which is
correctable through surgery. Hypospadias has been linked with an increased risk
of testicular cancer (cancer of the "balls") as well as reduced sperm
production. It is now thought that the incidence of hypospadias may be increased
in the children of mothers who eat a vegetarian diet. Assuming that these
results are not due to a statistical error, it is believed that the reason for
this increased incidence could caused by the pesticides used to protect fruit
and vegetables from pests.
The report, which was broadcast on Newsnight (BBC2 on 25th February
1999) and was reported in the Guardian (26th February 1999, page 8), if
corroborated by other studies, would, of course, be very significant. It is
already known that exposure to pesticides can increase the risk of physical
abnormalities affecting the urogenital area in boys. It is believed that these
abnormalities are caused by the artificial oestrogens which some pesticides are
thought to produce in the vegetables themselves. In the light of increasing
concerns expressed over the pesticide Lindane, which is being
associated with breast cancer, this should be a matter is serious concern to us
all. Recent research has also linked artificial oestrogens with reduced
fertility in men.
http://members.aol.com/kscuk/NEWS07.HTM
hypospadias
According to a recent hypothesis, environmental pollutants such as
organochlorines may be contributing to higher rates of structural abnormalities
in the male such as hypospadias. This is thought to be related to the
influence of such chemicals on steroid hormone function. Increased rates of
testicular cancer, and generally reduced male reproductive health have also been
noted by Danish observers. This is an intriguing theory, but clarification
regarding the contribution of genetics, social, and other environmental factors
is necessary.
Lindane has been used for many years in the treatment of lice and
scabies. It is an example of an organochlorine pesticide. Lindane is
capable of being absorbed into maternal blood and can also cross the placenta. A
preferable agent may be a pyrethrin-containing pediculicide which is poorly
absorbed through intact skin.
Birth Research Unit General Hospital Kandy, Sri Lanka
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