[Pharmwaste] equine estrogens in effluent article

[Tenace, Laurie]

In the mix: equine estrogens used in HRT
http://pubs.acs.org/doi/full/10.1021/es900664y
Environ. Sci. Technol., Article ASAP
DOI: 10.1021/es900664y
Publication Date (Web): April 1, 2009
Copyright © 2009 American Chemical Society
Equine estrogens, presumably derived from human hormone replacement therapy
(HRT) medications, are pervasive in effluents from sewage treatment works
(STW) in the U.K., according to a comprehensive study published in ES&T (DOI
10.1021/es803135q). The study demonstrates, both in vitro and in vivo, that
these compounds can have substantial effects on the reproductive systems of
fish.

In most HRT regimens, women ingest estrogens derived from the urine of
pregnant mares. The researchers routinely detected one of these equine
estrogens, equilenin (Eqn), and a metabolite, 17β-dihydroequilenin (17β-Eqn),
in STW discharge from multiple facilities, says lead author Charles Tyler of
the University of Exeter (U.K.).

The researchers tested Eqn and 17β-Eqn in vitro using cell-based assays and
determined that both compounds were able to activate human and fish estrogen
receptors. In fact, in fish, 17β-Eqn was more potent than the estradiol (E2)
standard, Tyler says.

In vivo, the group exposed juvenile rainbow trout and carp to a range of
concentrations of Eqn, 17β-Eqn, or other estrogens, including E2. In these
concentration response experiments the researchers measured the production of
vitellogenin, an egg yolk protein that provides the energy building blocks
for the subsequent embryos. Vitellogenin is normally produced only by female
fish, explains Tyler. Yet exposure of trout or carp for 21 days to Eqn or
17β-Eqn induced a vitellogenic response in both sexes. The researchers
performed various associated biochemical and molecular analyseslooking at
activation of estrogen receptors, for exampleand showed that Eqn and 17β-Eqn
switch on estrogen-inducible genes.

Next, they exposed fish directly to STW effluent and determined the extent to
which the equine estrogens were taken up by the fish. Over a 10-day period,
these estrogens bioconcentrated over 1-million-fold in fish bile. Although
they did not measure accumulation of Eqn or 17β-Eqn in gonads in this study,
Tyler notes that other estrogens that bioconcentrate in the bile also
accumulate in the gonads.

Although the researchers observed responses in both trout and carp, the
reactions were greater in trout. "Trout are exquisitely sensitive to these
compounds," notes Tyler.

"They do a nice job of synthesizing data from chemical measurements and
bioassay information," comments James Gray, a scientist with the U.S.
Geological Survey. Gray's laboratory also monitors for Eqn but rarely, if
ever, finds it, he says. "I am somewhat surprised by the consistent presence
of Eqn and 17β-Eqn in the influents and effluents." Gray says he is less
convinced by the researchers' dismissal of industrial or agricultural runoff
as sources in the aquatic environment. The study shows the presence of the
compounds in wastewater, but the paper doesn't present any data to suggest
that other sources don't also contribute, Gray notes. "But I think that is a
minor point," Gray adds.

"By being interdisciplinary, this paper provides a broad picture of these
estrogens," says John Sumpter of Brunel University (U.K.). It "demonstrates
that another class of human pharmaceuticals ... can reach the aquatic
environment, and do so at concentrations that raise concern." Natural steroid
estrogens, synthetic estrogens such as ethynyl estradiol, xenoestrogens such
as nonylphenol, and now HRT estrogens are all present in the aquatic
environment. It is hard to answer the question of which estrogenic chemical
or chemicals cause the widespread feminization of fish that has been reported
worldwide, Sumpter says. A complex mixture that varies from location to
location seems to be the answer, he adds.

Currently, Tyler's group is studying the transfer of estrogens from water
into organisms other than fish, including the dipper (Cinclus cinclus), a
semiaquatic bird that is higher up on the food chain. Dippers live alongside
fast-moving rivers and spend most of their time feeding on aquatic
invertebrates and fish, organisms that may be exposed to STW discharge.

Estrogens, natural and synthetic, are incredibly potent compounds, observes
Tyler. He suggests that the focus should be on improving discharge and
treatment technologies to minimize the entry of estrogens into our waterways.



If you are surprised that birth control pills are made from pregnant mare
urine, here's an article by the AVMA:
http://www.avma.org/onlnews/javma/apr02/s041502d.asp 
Laurie

Laurie Tenace
Environmental Specialist
Waste Reduction Section
Florida Department of Environmental Protection
2600 Blair Stone Rd., MS 4555
Tallahassee FL 32399-2400
P: 850.245.8759
F: 850.245.8811
Laurie.Tenace at dep.state.fl.us 

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

Unwanted Medicine:
http://www.dep.state.fl.us/waste/categories/medications/default.htm



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